FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schulz, A Cohen-Pfeffer, J Crystal, R de los Reyes, E Eto, Y Guelbert, N Heron, B Mikhailova, S Miller, N Mink, JW Perez-Poyato, MS Simonati, A Sims, K Williams, RE AF Schulz, Angela Cohen-Pfeffer, Jessica Crystal, Ronald de los Reyes, Emily Eto, Yoshikatsu Guelbert, Norberto Heron, Benedicte Mikhailova, Svetlana Miller, Nicole Mink, Jonathan W. Socorro Perez-Poyato, Maria Simonati, Alessandro Sims, Katherine Williams, Ruth E. TI NEURONAL CEROID LIPOFUSCINOSIS-2 (CLN2) DISEASE, A TYPE OF BATTEN DISEASE CAUSED BY TPP1 ENZYME DEFICIENCY: CURRENT KNOWLEDGE OF THE NATURAL HISTORY FROM INTERNATIONAL EXPERTS SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD) CY APR 03-06, 2016 CL Ponte Vedra Beach, FL SP Soc Inherited Metab Disorders C1 [Schulz, Angela] Univ Med Ctr Hamburg Eppendorf, Dept Paediat, Hamburg, Germany. [Cohen-Pfeffer, Jessica; Miller, Nicole] BioMarin Pharmaceut Inc, Global Med Affairs, Novato, CA USA. [Crystal, Ronald] Weill Cornell Med Coll, Dept Med Genet, New York, NY USA. [de los Reyes, Emily] Nationwide Childrens Hosp, Dept Pediat Neurol, Columbus, OH USA. [Eto, Yoshikatsu] Southern Tohoku Brain Res Ctr, Adv Clin Res Ctr, Kawasaki, Kanagawa, Japan. [Guelbert, Norberto] Hosp Ninos Cordoba, Cordoba, Argentina. [Heron, Benedicte] CHU Paris Est Hop Enfants Armand Trousseau, Serv Neuropediat, Paris, France. [Mikhailova, Svetlana] Russian Pediat Reg Hosp, Dept Med Genet, Moscow, Russia. [Mink, Jonathan W.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Socorro Perez-Poyato, Maria] Hosp Univ Marques de Valdecilla, Unit Pediat Neurol, Santander, Cantabria, Spain. [Simonati, Alessandro] Univ Verona, Dept Neurol & Movement Sci Neurol, I-37100 Verona, Italy. [Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Williams, Ruth E.] Guys & St Thomas NHS Fdn Trust, Childrens Neurosci, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2016 VL 117 IS 3 MA 101 BP 283 EP 284 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DH3JP UT WOS:000372683600120 ER PT J AU Williams, RE Cohen-Pfeffer, J Adams, H Blohm, M de los Reyes, E Denecke, J Drago, K Fairhurst, C Frazier, M Guelbert, N Kiss, S Kofler, A Lawson, J Lehwald, L Leung, MA Mikhailova, S Mink, J Nickel, M Shediac, R Sims, K Specchio, N Topcu, M von Lobbecke, I West, A Schulz, A AF Williams, Ruth E. Cohen-Pfeffer, Jessica Adams, Heather Blohm, Martin de los Reyes, Emily Denecke, Jonas Drago, Kristen Fairhurst, Charlie Frazier, Margie Guelbert, Norberto Kiss, Szilard Kofler, Annamaria Lawson, John Lehwald, Lenora Leung, Mary-Anne Mikhailova, Svetlana Mink, Jonathan Nickel, Miriam Shediac, Renee Sims, Katherine Specchio, Nicola Topcu, Meral von Lobbecke, Ina West, Andrea Schulz, Angela TI EXPERT OPINION ON THE MANAGEMENT OF CLN2 DISEASE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD) CY APR 03-06, 2016 CL Ponte Vedra Beach, FL SP Soc Inherited Metab Disorders C1 [Williams, Ruth E.; Fairhurst, Charlie; Leung, Mary-Anne] Evelina London Childrens Hosp, London, England. [Cohen-Pfeffer, Jessica; Shediac, Renee] BioMarin Pharmaceut Inc, Novato, CA USA. [Adams, Heather; Mink, Jonathan] Univ Rochester, Sch Med, Rochester, NY USA. [Blohm, Martin; Denecke, Jonas; Nickel, Miriam; Schulz, Angela] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [de los Reyes, Emily; Lehwald, Lenora] Nationwide Childrens Hosp, Columbus, OH USA. [Drago, Kristen] Journeycare Children, Chicago, IL USA. [Frazier, Margie] BDSRA, Columbus, OH USA. [Guelbert, Norberto] Childrens Hosp Cordoba, Cordoba, Argentina. [Kiss, Szilard] Weill Cornell Med Coll, New York, NY USA. [Kofler, Annamaria; Specchio, Nicola] IRCCS, Bambino Gesu Childrens Hosp, Rome, Italy. [Lawson, John] Sydney Childrens Hosp, Sydney, NSW, Australia. [Mikhailova, Svetlana] Russian Reg Pediat Hosp, Moscow, Russia. [Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Topcu, Meral] Hacettepe Univ, Ankara, Turkey. [West, Andrea] BDFA, Farnborough, Hants, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2016 VL 117 IS 3 MA 122 BP 293 EP 293 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DH3JP UT WOS:000372683600141 ER PT J AU Blakeley, JO Coons, SJ Corboy, JR Leidy, NK Mendoza, TR Wefel, JS AF Blakeley, Jaishri O. Coons, Stephen Joel Corboy, John R. Leidy, Nancy Kline Mendoza, Tito R. Wefel, Jeffrey S. TI Clinical outcome assessment in malignant glioma trials: measuring signs, symptoms, and functional limitations SO NEURO-ONCOLOGY LA English DT Article DE clinical outcome assessment; clinical trials; endpoints; malignant glioma ID QUALITY-OF-LIFE; NEWLY-DIAGNOSED GLIOBLASTOMA; KARNOFSKY PERFORMANCE STATUS; MODULE EORTC QLQ-BN20; RANDOMIZED PHASE-III; BRAIN-TUMOR MODULE; HIGH-GRADE GLIOMAS; EUROPEAN-ORGANIZATION; NEUROCOGNITIVE FUNCTION; COGNITIVE FUNCTION AB The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA measures that are feasible and have appropriate psychometric properties for use in this patient population as well as highlight where further development is needed. C1 [Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21287 USA. [Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21287 USA. [Coons, Stephen Joel] Crit Path Inst, 1730 E River Rd, Tucson, AZ USA. [Corboy, John R.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, 12631 East 17th Ave B185, Aurora, CO USA. [Leidy, Nancy Kline] Evidera, 7101Wisconsin Ave,Suite 1400, Bethesda, MD USA. [Mendoza, Tito R.; Wefel, Jeffrey S.] Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Bld, Houston, TX 77030 USA. RP Blakeley, JO (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.; Blakeley, JO (reprint author), Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21287 USA.; Blakeley, JO (reprint author), Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21287 USA. EM jblakel3@jhmi.edu NR 57 TC 0 Z9 0 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAR PY 2016 VL 18 SU 2 BP 13 EP 20 DI 10.1093/neuonc/nov291 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DH9KO UT WOS:000373115200002 ER PT J AU Helfer, JL Wen, PY Blakeley, J Gilbert, MR Armstrong, TS AF Helfer, Jennifer L. Wen, Patrick Y. Blakeley, Jaishri Gilbert, Mark R. Armstrong, Terri S. TI Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda MD) SO NEURO-ONCOLOGY LA English DT Article DE brain tumor; clinical outcome assessment; endpoints; high-grade gliomas; patient-reported outcomes ID NEWLY-DIAGNOSED GLIOBLASTOMA; SYMPTOM INVENTORY; RANDOMIZED-TRIAL; MODULE; CANCER; MYELOFIBROSIS; RUXOLITINIB; BEVACIZUMAB; VALIDATION; THERAPY AB On October 15, 2014, a workshop was held on the use of clinical outcome assessments in clinical trials for high-grade glioma of the brain. This workshop was sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, consisting of the National Brain Tumor Society, the Society for Neuro-Oncology, the Musella Foundation for Brain Tumor Research and Information, and Accelerate Brain Cancer Cure. It was planned and carried out with participation from the US Food and Drug Administration. The workshop also included stakeholders from all aspects of the brain tumor community, including clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and the National Cancer Institute. This report summarizes the presentations and discussions of that workshop and the proposals that emerged to move the field forward and toward greater inclusion of these endpoints in future clinical trials for high-grade gliomas. C1 [Helfer, Jennifer L.] Natl Brain Tumor Soc, 55 Chapel St,Suite 200, Newton, MA 02458 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Blakeley, Jaishri] Johns Hopkins Univ, Brain Canc Program, Dept Neurooncol, Baltimore, MD USA. [Gilbert, Mark R.] NCI, Ctr Canc Res, Neurooncol Branch, Bethesda, MD 20892 USA. [Armstrong, Terri S.] Univ Texas Houston, Hlth Sci Ctr, Sch Nursing, Dept Family Hlth, Houston, TX USA. RP Helfer, JL (reprint author), Natl Brain Tumor Soc, 55 Chapel St,Suite 200, Newton, MA 02458 USA. EM jhelfer@braintumor.org RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU Angiochem; Astra Zeneca; Genentech/Roche; GlaxoSmith Kline; Merck; Novartis; Sanofi-Aventis; Vascular Biogenics; Abbvie FX P.Y.W. has received research support from Angiochem, Astra Zeneca, Genentech/Roche, GlaxoSmith Kline, Merck, Novartis, Sanofi-Aventis, and Vascular Biogenics; serves on the advisory board of Abbvie, Celldex, Foundation Medicine, Genentech/Roche, Novartis, SigmaTau, Vascular Biogenics, Midatech, and Momenta; and has been a speaker for Merck. J.B. reports grants from GlaxoSmith Kline and served as a paid consultant for Abbvie. T.S.A. served as a consultant for Abbvie, Immunocellular Therapeutics, and Tocagen. J.L.H. and M.R.G. report no conflicts. NR 23 TC 0 Z9 0 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAR PY 2016 VL 18 SU 2 BP 26 EP 36 DI 10.1093/neuonc/nov270 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DH9KO UT WOS:000373115200004 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI While We're at It, Let's Whack the FDA SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bchabner@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAR PY 2016 VL 21 IS 3 BP 259 EP 260 DI 10.1634/theoncologist.2016-0041 PG 2 WC Oncology SC Oncology GA DH9MR UT WOS:000373120700001 PM 26869585 ER PT J AU Greer, JA Amoyal, N Nisotel, L Fishbein, JN MacDonald, J Stagl, J Lennes, I Temel, JS Safren, SA Pirl, WF AF Greer, Joseph A. Amoyal, Nicole Nisotel, Lauren Fishbein, Joel N. MacDonald, James Stagl, Jamie Lennes, Inga Temel, Jennifer S. Safren, Steven A. Pirl, William F. TI A Systematic Review of Adherence to Oral Antineoplastic Therapies SO ONCOLOGIST LA English DT Review DE Patient adherence; Medication adherence; Oral drug administration; Antineoplastic agents; Chemotherapy; Endocrine therapy ID CHRONIC MYELOID-LEUKEMIA; BREAST-CANCER PATIENTS; ADJUVANT ENDOCRINE THERAPY; GASTROINTESTINAL STROMAL TUMORS; PATIENTS ANASTROZOLE COMPLIANCE; HORMONAL-THERAPY; AROMATASE INHIBITORS; POSTMENOPAUSAL WOMEN; ANTICANCER AGENTS; IMATINIB THERAPY AB Background. Oral antineoplastic therapies not only improve survival but also reduce the burden of care for patients. Yet patients and clinicians face new challenges in managing adherence to these oral therapies. We conducted a systematic literature review to assess rates and correlates of adherence to oral antineoplastic therapies and interventions aimed at improving adherence. Methods. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of the Ovid MEDLINE database from January 1, 2003 to June 30, 2015, using relevant terminology for oral antineoplastic agents. We included observational, database, and intervention studies. At least two researchers evaluated each paper to ensure accuracy of results and determine risk of bias. Results. We identified 927 records from the search and screened 214 abstracts. After conducting a full-text review of 167 papers, we included in the final sample 51 papers on rates/correlates of adherence to oral antineoplastic therapy and 12 papers on intervention studies to improve adherence. Rates of adherence varied widely, from 46% to 100%, depending on patient sample, medication type, follow-up period, assessment measure, and calculation of adherence. Of the intervention studies, only 1 of the randomized trials and 2 of the cohort studies showed benefit regarding adherence, with the majority suffering high risk of bias. Conclusions. Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer. C1 [Greer, Joseph A.; Amoyal, Nicole; Nisotel, Lauren; Fishbein, Joel N.; MacDonald, James; Stagl, Jamie; Lennes, Inga; Temel, Jennifer S.; Pirl, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greer, Joseph A.; Amoyal, Nicole; Nisotel, Lauren; Fishbein, Joel N.; MacDonald, James; Stagl, Jamie; Lennes, Inga; Temel, Jennifer S.; Pirl, William F.] Harvard Univ, Sch Med, Boston, MA USA. [Safren, Steven A.] Univ Miami, Coral Gables, FL 33124 USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey Bldg,Suite 10B,55 Fruit St, Boston, MA 02114 USA. EM jgreer2@mgh.harvard.edu OI Jacobs, Jamie M./0000-0001-9740-624X FU Patient-Centered Outcomes Research Institute [IHS-1306-03616] FX Funding for this study was supported by the Patient-Centered Outcomes Research Institute (IHS-1306-03616, PI: Greer). PROSPERO registration number is CRD42014014785. NR 92 TC 3 Z9 3 U1 2 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAR PY 2016 VL 21 IS 3 BP 354 EP 376 DI 10.1634/theoncologist.2015-0405 PG 23 WC Oncology SC Oncology GA DH9MR UT WOS:000373120700015 PM 26921292 ER PT J AU McInnis, KC Ramey, LN AF McInnis, Kelly C. Ramey, Lindsay N. TI High-Risk Stress Fractures: Diagnosis and Management SO PM&R LA English DT Review ID YOUNG MALE-ADULTS; FEMORAL-NECK; BONE STRESS; 5TH-METATARSAL FRACTURES; SURGICAL-TREATMENT; MEDIAL MALLEOLUS; VITAMIN-D; CONSERVATIVE MANAGEMENT; RADIOGRAPHIC EVALUATION; MILITARY RECRUITS AB Stress fractures are common overuse injuries in athletes. They occur during periods of increased training without adequate rest, disrupting normal bone reparative mechanisms. There are a host of intrinsic and extrinsic factors, including biochemical and biomechanical, that put athletes at risk. In most stress fractures, the diagnosis is primarily clinical, with imaging indicated at times, and management focused on symptom-free relative rest with advancement of activity as tolerated. Overall, stress fractures in athletes have an excellent prognosis for return to sport, with little risk of complication. There is a subset of injuries that have a greater risk of fracture progression, delayed healing, and nonunion and are generally more challenging to treat with nonoperative care. Specific locations of high-risk stress fracture include the femoral neck (tension side), patella, anterior tibia, medial malleolus, talus, tarsal navicular, proximal fifth metatarsal, and great toe sesamoids. These sites share a characteristic region of high tensile load and low blood flow. High-risk stress fractures require a more aggressive approach to evaluation, with imaging often necessary, to confirm early and accurate diagnosis and initiate immediate treatment. Treatment consists of nonweight-bearing immobilization, often with a prolonged period away from sport, and a more methodic and careful reintroduction to athletic activity. These stress fractures may require surgical intervention. A high index of suspicion is essential to avoid delayed diagnosis and optimize outcomes in this subset of stress fractures. C1 [McInnis, Kelly C.; Ramey, Lindsay N.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [McInnis, Kelly C.] Harvard Univ, Sch Med, Ctr Sports Med, Boston, MA USA. [McInnis, Kelly C.] Massachusetts Gen Hosp, Sports Med Serv, 175 Cambridge St, Boston, MA 02114 USA. [Ramey, Lindsay N.] Harvard Univ, Sch Med, Boston, MA USA. RP McInnis, KC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.; McInnis, KC (reprint author), Harvard Univ, Sch Med, Ctr Sports Med, Boston, MA USA.; McInnis, KC (reprint author), Massachusetts Gen Hosp, Sports Med Serv, 175 Cambridge St, Boston, MA 02114 USA. EM kcmcinnis@partners.org NR 105 TC 4 Z9 4 U1 16 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAR PY 2016 VL 8 IS 3 SU S BP S113 EP S124 DI 10.1016/j.pmrj.2015.09.019 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DH5UZ UT WOS:000372858900014 PM 26972260 ER PT J AU Reiff, ES Little, SE Dobson, L Wilkins-Haug, L Bromley, B AF Reiff, Emily S. Little, Sarah E. Dobson, Lori Wilkins-Haug, Louise Bromley, Bryann TI What is the role of the 11-to 14-week ultrasound in women with negative cell-free DNA screening for aneuploidy? SO PRENATAL DIAGNOSIS LA English DT Article ID INCREASED NUCHAL TRANSLUCENCY; FETAL STRUCTURAL ANOMALIES; CHROMOSOMAL MICROARRAY; ABNORMALITIES; GESTATION; DIAGNOSIS; 1ST-TRIMESTER; FETUSES; SCAN AB ObjectiveThis study aimed to examine the role of the 11- to 14-week ultrasound in women with negative cell-free DNA screening. MethodsA retrospective cohort study of women at increased risk for aneuploidy based on age or medical history and negative cell-free DNA screening between March 2012 and March 2014 was conducted. Patients were included if they had an 11- to 14-week ultrasound and obstetrical care at our center(s). Primary outcome was an unexpected finding at ultrasound. Imaging findings were compared with obstetrical outcome by medical record review. ResultsStudy group was composed of 1739 patients. An unexpected finding was identified in 60/1739 (3.5%). An abnormal fetal finding occurred in 37 living fetuses (2.1%); 33 had a nuchal translucency (NT)3mm, including four isolated' cystic hygroma and three with a structural abnormality. Four fetuses had a structural anomaly without a thick NT. Karyotype confirmed euploidy in 98.7% of available cases. Pregnancy termination was chosen by 63.6% of those with cystic hygroma or anomaly at the 11- to 14-week scan. Unexpected multiples were identified in 13 (0.7%) women and a fetal demise in 10 (0.6%). ConclusionUnexpected findings at the 11- to 14-week scan occur in 3.5% of patients with negative cell-free DNA. Recognition provides options for comprehensive testing, consultation, and management. (c) 2016 John Wiley & Sons, Ltd. What's already known about this topic? Noninvasive prenatal screening for aneuploidy by cell-free DNA has superior performance metrics for detection of targeted trisomies when compared with standard aneuploidy screening methods and does not require an 11- to 14-week fetal scan. What does this study add? The 11- to 14-week scan demonstrates unexpected findings in 3.5% of patients with negative noninvasive prenatal screening by cell-free DNA including 2.1% with fetal findings that place them at increased risk for other genetic and/or structural anomalies. C1 [Reiff, Emily S.; Little, Sarah E.; Dobson, Lori; Wilkins-Haug, Louise; Bromley, Bryann] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. [Reiff, Emily S.; Bromley, Bryann] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Bromley, Bryann] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Reiff, Emily S.; Little, Sarah E.; Wilkins-Haug, Louise; Bromley, Bryann] Harvard Univ, Sch Med, Boston, MA USA. [Bromley, Bryann] Diagnost Ultrasound Associates PC, Boston, MA USA. RP Reiff, ES (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA.; Reiff, ES (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.; Reiff, ES (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM ereiff@partners.org NR 35 TC 4 Z9 4 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 EI 1097-0223 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAR PY 2016 VL 36 IS 3 BP 260 EP 265 DI 10.1002/pd.4774 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA DH1OR UT WOS:000372555000009 PM 26748490 ER PT J AU Zgibor, JC Schlenk, EA Vater, L Kola, S Vander Bilt, J Woody, S Jacob, ME Lo-Ciganic, WH Brenckle, A Brandenstein, J Kwoh, CK Boudreau, R Albert, S Conroy, M Rodgers, E Newman, AB AF Zgibor, Janice C. Schlenk, Elizabeth A. Vater, Laura Kola, Sushma Vander Bilt, Joni Woody, Sarah Jacob, Mini E. Lo-Ciganic, Wei-Hsuan Brenckle, Allison Brandenstein, Jane Kwoh, C. Kent Boudreau, Robert Albert, Steven Conroy, Margaret Rodgers, Elizabeth Newman, Anne B. TI Partnership Building and Implementation of an Integrated Healthy-Aging Program SO PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION LA English DT Article DE Community; partnership; exercise; preventive behavior; prevention; healthy aging ID LOWER-EXTREMITY FUNCTION; PREVENTION PROGRAM; PHYSICAL-ACTIVITY; EXERCISE PROGRAM; SELF-MANAGEMENT; CHRONIC DISEASE; 10 KEYS; COMMUNITY; ARTHRITIS; DISABILITY AB Background: Evidence-based interventions exist for prevention of chronic disease in older adults. Partnering with community organizations may provide a mechanism for disseminating these interventions. Objective: To describe the partnership and program implementation by the Arthritis Foundation (AF) and the University of Pittsburgh. Methods: The AF Exercise Program (AFEP; an existing evidence-based program) was enhanced with the "10 Keys"(TM) to Healthy Aging (a prevention-focused program bundling the most common risk factors for chronic disease and disability in older adults and applies behavior change strategies to enhance prevention). The program was delivered in 20 sessions over 10 weeks by community health workers in a cluster-randomized trial. Lessons Learned: Partnering with an organization having an existing infrastructure supports program delivery at the community level. This partnership provided programming in 54 sites across Pittsburgh and surrounding communities. Conclusions: This collaborative partnership created a productive synergy maximizing strengths in both research and program delivery. C1 [Zgibor, Janice C.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL 33620 USA. [Schlenk, Elizabeth A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15260 USA. [Vater, Laura] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Kola, Sushma] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Vander Bilt, Joni; Boudreau, Robert; Rodgers, Elizabeth; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Woody, Sarah] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA. [Jacob, Mini E.] VA Boston Healthcare Syst, New England GRECC, Boston, MA USA. [Jacob, Mini E.] Boston Univ, Hlth & Disabil Res Inst, Sch Publ Hlth, Boston, MA 02215 USA. [Jacob, Mini E.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Cambridge, MA 02138 USA. [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. [Brenckle, Allison; Brandenstein, Jane] Arthrit Fdn, Pittsburgh, PA USA. [Kwoh, C. Kent] Coll Med, Dept Med, Div Rheumatol & Clin Rheumatol, Boston, MA USA. [Kwoh, C. Kent] Univ Arizona, Arthrit Ctr, Tucson, AZ 85721 USA. [Albert, Steven] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Conroy, Margaret] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. RP Zgibor, JC (reprint author), Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL 33620 USA. OI Albert, Steven/0000-0001-6786-9956; Schlenk, Elizabeth/0000-0001-7361-1951; Boudreau, Robert/0000-0003-0162-5187 FU Centers for Disease Control and Prevention, Health Promotion and Disease Prevention Research Center [U48DP001918] FX This study was funded by the Centers for Disease Control and Prevention, Health Promotion and Disease Prevention Research Center, U48DP001918. NR 32 TC 0 Z9 0 U1 4 U2 4 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1557-0541 EI 1557-055X J9 PROG COMM HLTH PARTN JI Prog. Community Health Partnersh. PD SPR PY 2016 VL 10 IS 1 BP 123 EP 132 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DH3JB UT WOS:000372682200016 PM 27018361 ER PT J AU Vohringer, PA Perlis, RH AF Voehringer, Paul A. Perlis, Roy H. TI Discriminating Between Bipolar Disorder and Major Depressive Disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Diagnosis; Nosology; Misdiagnosis; Bipolar disorder; Major depressive disorder; Irritability ID COMORBIDITY SURVEY REPLICATION; TREATMENT ENHANCEMENT PROGRAM; LIFETIME PREVALENCE; ANTIDEPRESSANT USE; CLINICAL-FEATURES; SPECTRUM DISORDER; II DISORDER; STEP-BD; UNIPOLAR; ONSET AB Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder. C1 [Voehringer, Paul A.] Tufts Univ, Sch Med, Dept Psychiat, 800 Washington St, Boston, MA 02111 USA. [Voehringer, Paul A.] Univ Chile, Dept Psychiat, Av Independencia 1027, Santiago 8071146, Chile. [Perlis, Roy H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost,Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost,Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM rperlis@mgh.harvard.edu OI Vohringer, Paul A/0000-0002-2460-4680 NR 53 TC 1 Z9 1 U1 4 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2016 VL 39 IS 1 BP 1 EP + DI 10.1016/j.psc.2015.10.001 PG 11 WC Psychiatry SC Psychiatry GA DH8GV UT WOS:000373032400002 PM 26876315 ER PT J AU Phillippe, M Adeli, S AF Phillippe, Mark Adeli, Sharareh TI Cell-Free DNA Production by Human Trophoblast Cells SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Phillippe, Mark; Adeli, Sharareh] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA T-073 BP 124A EP 124A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200232 ER PT J AU Mitchell, C Gaur, N Kalsy, A AF Mitchell, Caroline Gaur, Nidhi Kalsy, Anuj TI Lactobacillus Crispatus Protects Vaginal Epithelial Cells from Leptotrichia Amnionii-Induced Damage. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Mitchell, Caroline; Gaur, Nidhi; Kalsy, Anuj] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA T-214 BP 167A EP 167A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200372 ER PT J AU Reed, SD Newton, KM Larson, JC Anawalt, BD Booth-LaForce, CC Woods, NF Landis, CA Freeman, EW Joffe, H Carpenter, JS Guthrie, KA AF Reed, Susan D. Newton, Katherine M. Larson, Joseph C. Anawalt, Bradley D. Booth-LaForce, Catherine C. Woods, Nancy F. Landis, Carol A. Freeman, Ellen W. Joffe, Hadine Carpenter, Janet S. Guthrie, Katherine A. TI Daily Salivary Cortisol Patterns in Midlife Women with Hot Flashes. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Reed, Susan D.; Anawalt, Bradley D.; Booth-LaForce, Catherine C.; Woods, Nancy F.; Landis, Carol A.] Univ Washington, Seattle, WA 98195 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Larson, Joseph C.; Guthrie, Katherine A.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Freeman, Ellen W.] Perleman SOM, Philadelphia, PA USA. [Joffe, Hadine] Harvard, Dana Farber, Brigham & Womens, Boston, MA USA. [Carpenter, Janet S.] Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA T-248 BP 177A EP 178A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200406 ER PT J AU Bellio, C Foster, R Growdon, WB Rueda, BR AF Bellio, Chiara Foster, Rosemary Growdon, Whitfield B. Rueda, Bo R. TI PARP Inhibitors for Treatment of Ovarian Cancer: The Downside of Good Intentions. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Bellio, Chiara; Foster, Rosemary; Growdon, Whitfield B.; Rueda, Bo R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bellio, Chiara; Foster, Rosemary; Growdon, Whitfield B.; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA T-252 BP 179A EP 179A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200410 ER PT J AU Elias, KM Lindsey, JS Ng, NWC Ginsburg, ES Drapkin, R Anchan, RM AF Elias, Kevin M. Lindsey, Jennifer S. Ng, Nicholas W. C. Ginsburg, Elizabeth S. Drapkin, Ronny Anchan, Raymond M. TI Protection Against Chemotherapy Induced Premature Ovarian Failure Using Granulosa Cell-Derived Induced Pluripotent Stem Cells. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Elias, Kevin M.; Lindsey, Jennifer S.; Ng, Nicholas W. C.; Ginsburg, Elizabeth S.; Anchan, Raymond M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Elias, Kevin M.; Ginsburg, Elizabeth S.; Drapkin, Ronny; Anchan, Raymond M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 6 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA T-260 BP 181A EP 181A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200418 ER PT J AU Peress, DA Miller, ES Bortoletto, P Gossett, DR AF Peress, Danielle A. Miller, Emily S. Bortoletto, Pietro Gossett, Dana R. TI Is Third Stage Oxytocin Administration Associated with an Increased Risk of Retained Placentas? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Peress, Danielle A.; Miller, Emily S.; Gossett, Dana R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bortoletto, Pietro] Brigham & Womens Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA F-010 BP 189A EP 189A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200445 ER PT J AU Liff, I Adeli, S Romero, R Phillippe, M AF Liff, Ingrid Adeli, Sharareh Romero, Roberto Phillippe, Mark TI Mechanism Underlying Progesterone Prolongation of Gestation in the Mouse SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Liff, Ingrid; Adeli, Sharareh; Phillippe, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Romero, Roberto] Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA F-074 BP 209A EP 209A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200509 ER PT J AU Cardozo, ER Karmon, AE Gatune, L Foster, R Rueda, BR Styer, AK AF Cardozo, Eden R. Karmon, Anatte E. Gatune, Leah Foster, Rosemary Rueda, Bo R. Styer, Aaron K. TI The Impact of MicroRNA 21a-5p on Mediators of Extracellular Matrix Formation in Uterine Leiomyoma SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Cardozo, Eden R.; Karmon, Anatte E.; Gatune, Leah; Foster, Rosemary; Rueda, Bo R.; Styer, Aaron K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cardozo, Eden R.; Karmon, Anatte E.; Foster, Rosemary; Rueda, Bo R.; Styer, Aaron K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA F-206 BP 250A EP 250A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200641 ER PT J AU Hariton, E Bortoletto, P Cardozo, ER Hochberg, EP Sabatini, ME AF Hariton, Eduardo Bortoletto, Pietro Cardozo, Eden R. Hochberg, Ephraim P. Sabatini, Mary E. TI The Role of Oncofertility Clinics in Facilitating Access to Reproductive Specialists. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Hariton, Eduardo; Bortoletto, Pietro; Cardozo, Eden R.; Hochberg, Ephraim P.; Sabatini, Mary E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA F-251 BP 263A EP 263A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200686 ER PT J AU Naqvi, M Bryant, A Kaimal, A AF Naqvi, Mariam Bryant, Allison Kaimal, Anjali TI Second Stage Length and Third and Fourth Degree Lacerations Among Nulliparous Women SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Naqvi, Mariam; Bryant, Allison; Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA S-031 BP 279A EP 279A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200738 ER PT J AU Naqvi, M Scourtas, A Hanmer, K Khattaby, I Roberts, D AF Naqvi, Mariam Scourtas, Aristana Hanmer, Kaitlin Khattaby, Ingy Roberts, Drucilla TI Placental Pathology and Ischemic Perinatal Stroke. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation CY MAR 16-19, 2016 CL Montreal, CANADA SP Soc Reprod Invest C1 [Naqvi, Mariam; Scourtas, Aristana; Hanmer, Kaitlin; Khattaby, Ingy; Roberts, Drucilla] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2016 VL 23 SU 1 MA S-183 BP 325A EP 326A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DH6CS UT WOS:000372879200889 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the legacy of kidney disease - Focus on childhood SO SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION LA English DT Editorial Material ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; BLOOD-PRESSURE; GLOBAL HEALTH; CHILDREN AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. C1 [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA. [Schaefer, Franz] Heidelberg Univ, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens, Med Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Vet Affairs VA Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA.; Ingelfinger, JR (reprint author), World Kidney Day, Int Federat Kidney Fdn, Int Soc Nephrol, Rue Fabr 1B, B-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1319-2442 EI 2320-3838 J9 SAUDI J KIDNEY DIS T JI Saudi J. Kidney Dis. Transplant. PD MAR-APR PY 2016 VL 27 IS 2 BP 219 EP 226 DI 10.4103/1319-2442.178201 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DI1YN UT WOS:000373293000001 PM 26997373 ER PT J AU Biehn, TL Contractor, AA Elhai, JD Tamburrino, M Fine, TH Cohen, G Shirley, E Chan, PK Liberzon, I Calabrese, JR Galea, S AF Biehn, Tracey L. Contractor, Ateka A. Elhai, Jon D. Tamburrino, Marijo Fine, Thomas H. Cohen, Gregory Shirley, Edwin Chan, Philip K. Liberzon, Israel Calabrese, Joseph R. Galea, Sandro TI Latent dimensions of posttraumatic stress disorder and their relations with alcohol use disorder SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Posttraumatic stress disorder; Alcohol use disorder; Cormorbidity; Confirmatory factor analysis ID SUBSTANCE-USE DISORDERS; CONFIRMATORY FACTOR-ANALYSIS; PTSD SYMPTOMS; UNDERLYING DIMENSIONS; COMORBIDITY; SOLDIERS; DRINKING; TRAUMA; SAMPLE; MODEL AB The objective of this study was to evaluate the relationship between factors of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) using confirmatory factor analysis (CFA) in order to further our understanding of the substantial comorbidity between these two disorders. CFA was used to examine which factors of PTSD's dysphoria model were most related to AUD in a military sample. Ohio National Guard soldiers with a history of overseas deployment participated in the survey (n = 1215). Participants completed the PTSD Checklist and a 12-item survey from the National Survey on Drug Use used to diagnosis AUD. The results of the CFA indicated that a combined model of PTSD's four factors and a single AUD factor fit the data very well. Correlations between PTSD's factors and a latent AUD factor ranged from correlation coefficients of 0.258-0.285, with PTSD's dysphoria factor demonstrating the strongest correlation. However, Wald tests of parameter constraints revealed that AUD was not more correlated with PTSD's dysphoria than other PTSD factors. All four factors of PTSD's dysphoria model demonstrate comparable correlations with AUD. The role of dysphoria to the construct of PTSD is discussed. C1 [Biehn, Tracey L.] St Cloud VA Hlth Care Syst, 4801 Vet Dr, St Cloud, MN 56303 USA. [Biehn, Tracey L.; Contractor, Ateka A.; Elhai, Jon D.] Univ Toledo, Dept Psychol, Mail Stop 948,2801 W Bancroft St, Toledo, OH 43606 USA. [Elhai, Jon D.; Tamburrino, Marijo; Fine, Thomas H.] Univ Toledo, Dept Psychiat, Mail Stop 948,2801 W Bancroft St, Toledo, OH 43606 USA. [Cohen, Gregory; Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Cohen, Gregory; Shirley, Edwin] Case Western Reserve Univ, Univ Hosp, Dept Psychiat, Case Med Ctr, Cleveland, OH 44106 USA. [Liberzon, Israel] Univ Michigan, Dept Psychiat, Mental Hlth Serv, VA Ann Arbor Hlth Syst, Ann Arbor, MI 48109 USA. [Calabrese, Joseph R.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Contractor, Ateka A.] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Healthcare Syst, Boston, MA USA. RP Biehn, TL (reprint author), St Cloud VA Hlth Care Syst, 4801 Vet Dr, St Cloud, MN 56303 USA.; Biehn, TL (reprint author), Univ Toledo, Dept Psychol, Mail Stop 948,2801 W Bancroft St, Toledo, OH 43606 USA. EM tlbiehn02@gmail.com OI Liberzon, Israel/0000-0002-4990-556X FU Department of Defense Congressionally Directed Medical Research Program, "Combat Mental Health Initiative" [W81XWH-O7-1-0409] FX This project was funded by the Department of Defense Congressionally Directed Medical Research Program W81XWH-O7-1-0409, the "Combat Mental Health Initiative." NR 63 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD MAR PY 2016 VL 51 IS 3 BP 421 EP 429 DI 10.1007/s00127-015-1135-x PG 9 WC Psychiatry SC Psychiatry GA DI1CA UT WOS:000373232400011 PM 26520448 ER PT J AU Celano, CM Healy, B Suarez, L Levy, DE Mastromauro, C Januzzi, JL Huffman, JC AF Celano, Christopher M. Healy, Brian Suarez, Laura Levy, Douglas E. Mastromauro, Carol Januzzi, James L. Huffman, Jeff C. TI Cost-Effectiveness of a Collaborative Care Depression and Anxiety Treatment Program in Patients with Acute Cardiac Illness SO VALUE IN HEALTH LA English DT Article DE anxiety; cardiovascular disease; collaborative care; cost-effectiveness; depression ID RANDOMIZED-CONTROLLED-TRIAL; BYPASS GRAFT-SURGERY; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; PANIC DISORDER; HEALTH STATES; INTERVENTION; MANAGEMENT; VALIDITY AB Objective: To use data from a randomized trial to determine the cost-effectiveness of a collaborative care (CC) depression and anxiety treatment program and to assess effects of the CC program on health care utilization. Methods: The CC intervention's impact on health related quality of life, depression-free days (DFDs), and anxiety-free days (AFDs) over the 24-week postdischarge period was calculated and compared with the enhanced usual care (EUC) condition using independent samples t tests and random-effects regression models. Costs for both the CC and EUC conditions were calculated on the basis of staff time, overhead expenses, and treatment materials. Using this information, incremental cost-effectiveness ratios were calculated. A cost-effectiveness acceptability plot was created using nonparametric bootstrapping with 10,000 replications, and the likelihood of the CC intervention's cost-effectiveness was assessed using standard cutoffs. As a secondary analysis, we determined whether the CC intervention led to reductions in postdischarge health care utilization and costs. Results: The CC intervention was more costly than the EUC intervention ($209.86 vs. $34.59; z = -11.71; P < 0.001), but was associated with significantly greater increases in quality adjusted life-years (t = -2.49; P = 0.01) and DFDs (t = -2.13; P = 0.03), but not AFDs (t = -1.92; P = 0.057). This translated into an incremental cost-effectiveness ratio of $3337.06 per quality adjusted life-year saved, $13.36 per DFD, and $13.74 per AFD. Compared with the EUC intervention, the CC intervention was also associated with fewer emergency department visits but no differences in overall costs. Conclusions: This CC intervention was associated with clinically relevant improvements, was cost-effective, and was associated with fewer emergency department visits in the 24 weeks after discharge. C1 [Celano, Christopher M.; Healy, Brian; Levy, Douglas E.; Januzzi, James L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Celano, Christopher M.; Suarez, Laura; Mastromauro, Carol; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Healy, Brian; Januzzi, James L.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Celano, CM (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM ccelano@partners.org FU American Heart Association [10GRNT3450015] FX American Heart Association Grant-in-Aid (grant no. 10GRNT3450015 to J.C. Huffman). NR 40 TC 3 Z9 3 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2016 VL 19 IS 2 BP 185 EP 191 DI 10.1016/j.jval.2015.12.015 PG 7 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA DH8WY UT WOS:000373078800009 PM 27021752 ER PT J AU Singh, S Rejai, S Antongiorgi, Z Gonzalez, N Stelzner, M AF Singh, Sumit Rejai, Sepehr Antongiorgi, Zarah Gonzalez, Nestor Stelzner, Matthias TI Misconnections in the Critically Ill: Injection of High-Dose Gadolinium into an External Ventricular Drain SO A & A CASE REPORTS LA English DT Article ID INTRATHECAL GADOLINIUM; GADOPENTETATE DIMEGLUMINE; ENCEPHALOPATHY; CISTERNOGRAPHY AB We report an unfortunate case of accidental administration of intrathecal gadolinium through an external ventricular drain in a postcraniotomy patient during magnetic resonance imaging of the brain. The incident occurred after the venous contrast line was connected mistakenly to the ventricular drainage catheter. The patient subsequently developed confusion, aphasia, and right facial droop with new computed tomography evidence of diffuse cerebral edema and stroke. Review of the magnetic resonance image revealed the inappropriate presence of subarachnoid gadolinium. Despite all interventions, the patient developed irreversible neurologic disability. We address the clinical sequelae, management strategies, and factors contributing to the catheter misconnection that led to this event. C1 [Singh, Sumit; Rejai, Sepehr; Antongiorgi, Zarah] Univ Calif Los Angeles, Med Ctr, Dept Anesthesiol & Perioperat Med, Los Angeles, CA 90024 USA. [Gonzalez, Nestor] Univ Calif Los Angeles, Med Ctr, Neurosurg, Los Angeles, CA 90024 USA. [Stelzner, Matthias] Univ Calif Los Angeles, Med Ctr, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. RP Singh, S (reprint author), Univ Calif Los Angeles, Dept Anesthesiol & Perioperat Med, 757 Westwood Plaza, Los Angeles, CA 90024 USA. EM SPSingh@mednet.ucla.edu OI Gonzalez, Nestor/0000-0002-8277-6317 NR 14 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD MAR 1 PY 2016 VL 6 IS 5 BP 121 EP 123 DI 10.1213/XAA.0000000000000230 PG 3 WC Anesthesiology SC Anesthesiology GA DH2OT UT WOS:000372626400004 PM 26462163 ER PT J AU Melillo, B Liang, SY Park, J Schon, A Courter, JR LaLonde, JM Wendler, DJ Princiotto, AM Seaman, MS Freire, E Sodroski, J Madani, N Hendrickson, WA Smith, AB AF Melillo, Bruno Liang, Shuaiyi Park, Jongwoo Schoen, Arne Courter, Joel R. LaLonde, Judith M. Wendler, Daniel J. Princiotto, Amy M. Seaman, Michael S. Freire, Ernesto Sodroski, Joseph Madani, Navid Hendrickson, Wayne A. Smith, Amos B., III TI Small-Molecule CD4-Mimics: Structure-Based Optimization of HIV-1 Entry Inhibition SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV; gp120; CD4; entry inhibitor; structure-based drug design; thermodynamics; X-ray crystallography; viral inhibition; protein-protein interactions ID STRUCTURE-BASED DESIGN; CD4; VALIDATION; DOCKING AB The optimization, based on computational, thermodynamic, and crystallographic data, of a series of small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120 of human immunodeficiency virus (HIV) has been achieved. Importantly, biological evaluation revealed that the small-molecule CD4 mimics (4-7) inhibit HIV-1 entry into target cells with both significantly higher potency and neutralization breadth than previous congeners, while maintaining high selectivity for the target virus. Their binding mode was characterized via thermodynamic and crystallographic studies. C1 [Melillo, Bruno; Park, Jongwoo; Courter, Joel R.; Wendler, Daniel J.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Liang, Shuaiyi; Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Seaman, Michael S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Park, Jongwoo] LG Chem, Daejeon, South Korea. [Courter, Joel R.] Seattle Genet, Bothell, WA 98021 USA. [LaLonde, Judith M.] Teva Pharmaceut USA Inc, Horsham, PA 19044 USA. [Wendler, Daniel J.] Max Planck Florida Inst Neurosci, Jupiter, FL 33458 USA. RP Smith, AB (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. EM smithab@sas.upenn.edu FU Program Project (NIH) [GM 56550] FX Funding was provided by a Program Project (NIH GM 56550) to J.L., E.F., W.A.H., A.B.S., and J.S. NR 18 TC 10 Z9 10 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAR PY 2016 VL 7 IS 3 BP 330 EP 334 DI 10.1021/acsmedchemlett.5b00471 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DG4LE UT WOS:000372042900025 PM 26985324 ER PT J AU Bourgeois, S Bounoure, L Mouro-Chanteloup, I Aronovicz, YC Brown, D Wagner, CA AF Bourgeois, S. Bounoure, L. Mouro-Chanteloup, I. Aronovicz, Y. Colin Brown, D. Wagner, C. A. TI The ammonia transporter RhCG modulates vacuolar H+-ATPase function in renal collecting duct cells SO ACTA PHYSIOLOGICA LA English DT Meeting Abstract C1 [Bourgeois, S.; Bounoure, L.; Wagner, C. A.] Univ Zurich, Inst Physiol, CH-8006 Zurich, Switzerland. [Mouro-Chanteloup, I.; Aronovicz, Y. Colin] INSERM, UMR665, Paris, France. [Mouro-Chanteloup, I.; Aronovicz, Y. Colin] Univ Paris Diderot, Paris, France. [Brown, D.] Massachusetts Gen Hosp, Dept Med, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, D.] Harvard Univ, Sch Med, 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 1748-1708 EI 1748-1716 J9 ACTA PHYSIOL JI Acta Physiol. PD MAR PY 2016 VL 216 SU 707 SI SI MA OS13-1 PG 1 WC Physiology SC Physiology GA DG7TA UT WOS:000372285400175 ER PT J AU Dubois, B Hampel, H Feldman, HH Scheltens, P Aisen, P Andrieu, S Bakardjian, H Benali, H Bertram, L Blennow, K Broich, K Cavedo, E Crutch, S Dartigues, JF Duyckaerts, C Epelbaum, S Frisoni, GB Gauthier, S Genthon, R Gouw, AA Habert, MO Holtzman, DM Kivipelto, M Lista, S Molinuevo, JL O'Bryant, SE Rabinovici, GD Rowe, C Salloway, S Schneider, LS Sperling, R Teichmann, M Carrillo, MC Cummings, J Jack, CR AF Dubois, Bruno Hampel, Harald Feldman, Howard H. Scheltens, Philip Aisen, Paul Andrieu, Sandrine Bakardjian, Hovagim Benali, Habib Bertram, Lars Blennow, Kaj Broich, Karl Cavedo, Enrica Crutch, Sebastian Dartigues, Jean-Francois Duyckaerts, Charles Epelbaum, Stephane Frisoni, Giovanni B. Gauthier, Serge Genthon, Remy Gouw, Alida A. Habert, Marie-Odile Holtzman, David M. Kivipelto, Miia Lista, Simone Molinuevo, Jose-Luis O'Bryant, Sid E. Rabinovici, Gil D. Rowe, Christopher Salloway, Stephen Schneider, Lon S. Sperling, Reisa Teichmann, Marc Carrillo, Maria C. Cummings, Jeffrey Jack, Cliff R., Jr. CA IWG Amer Alzheimer's Assoc Preclinical TI Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Preclinical; Asymptomatic; Diagnostic criteria; Biomarkers; Pathophysiology; Genetics; CSF biomarkers; Blood biomarkers; MRI; Amyloid PET; Tau PET ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; CEREBROSPINAL-FLUID BIOMARKERS; BLOOD-BASED BIOMARKERS; NORMAL OLDER-ADULTS; BETA-AMYLOID 1-42; SECONDARY PREVENTION TRIALS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; GINKGO-BILOBA EXTRACT AB During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Dubois, Bruno; Hampel, Harald; Epelbaum, Stephane; Teichmann, Marc] Univ Paris 06, Pitie Salpetriere Univ Hosp, AP HP, Inst Memory & Alzheimers Dis IM2A, Paris, France. [Dubois, Bruno; Hampel, Harald; Epelbaum, Stephane; Teichmann, Marc] Univ Paris 06, Pitie Salpetriere Univ Hosp, AP HP, Brain & Spine Inst ICM,Frontlab,Dept Neurol,UMR S, Paris, France. [Hampel, Harald; Cavedo, Enrica; Lista, Simone] AXA Res Fund, Paris, France. [Hampel, Harald; Cavedo, Enrica; Lista, Simone] UPMC, Paris, France. [Feldman, Howard H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Dept Neurol & Alzheimer Ctr, Amsterdam, Netherlands. [Scheltens, Philip] Neurosci Campus, Dept Neurol & Alzheimer Ctr, Amsterdam, Netherlands. [Aisen, Paul] Univ Southern Calif San Diego, San Diego, CA USA. [Andrieu, Sandrine; Gouw, Alida A.] Univ Toulouse 3, Toulouse Univ Hosp, INSERM, UMR1027, F-31062 Toulouse, France. [Bakardjian, Hovagim] Inst Neurosci Translat Paris, IIIU A ICM, Paris, France. [Benali, Habib] UPMC UM CR2, CNRS UMR 7371, INSERM U1146, Site Pitie Salpetriere, Paris, France. [Bertram, Lars] Med Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt L, D-23538 Lubeck, Germany. [Bertram, Lars] Med Univ Lubeck, Inst Integrat & Expt Genom, Lubeck Interdisciplinary Platform Genome Analyt L, D-23538 Lubeck, Germany. [Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London, England. [Blennow, Kaj] Univ Gothenburg, Molndal Hosp, Sahlgrenska Univ Hosp, Clin Neurochem Lab,Dept Neurosci & Physiol, Molndal, Sweden. [Broich, Karl] Fed Inst Drugs & Med Devices, Bonn, Germany. [Cavedo, Enrica] IRCCS Ctr San Giovanni di Dio Fatebenefratelli, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy. [Crutch, Sebastian] UCL, UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England. [Dartigues, Jean-Francois] Univ Bordeaux, INSERM U1219, Bordeaux, France. [Duyckaerts, Charles] Univ Paris 06, AP HP, Alzheimer Prion Team, ICM, Paris, France. [Frisoni, Giovanni B.] Univ Hosp Geneva, Geneva, Switzerland. [Frisoni, Giovanni B.] Univ Geneva, Geneva, Switzerland. [Frisoni, Giovanni B.] IRCCS Fatebenefratelli, Brescia, Italy. [Gauthier, Serge] McGill Ctr Studies Aging, Douglas Mental Hlth Res Inst, Montreal, PQ, Canada. [Genthon, Remy] Hop La Pitie Salpetriere, Fdn Rech Alzheimer, Paris, France. [Gouw, Alida A.] Vrije Univ Amsterdam Med Ctr, MEG Ctr, Dept Clin Neurophysiol, Amsterdam, Netherlands. [Habert, Marie-Odile] Univ Paris 06, Sorbonne Univ, CNRS, INSERM,Lab Imagerie Biomed, Paris, France. [Habert, Marie-Odile] Hop La Pitie Salpetriere, AP HP, Dept Nucl Med, Paris, France. [Holtzman, David M.] Washington Univ, Dept Neurol, Hope Ctr Neurol Disorders, St Louis, MO USA. [Holtzman, David M.] Washington Univ, Dept Neurol, Knight Alzheimers Dis Res Ctr St, St Louis, MO USA. [Kivipelto, Miia] Karolinska Univ Hosp, Dept Geriatr Med, Karolinska Inst, Ctr Alzheimer Res, Stockholm, Sweden. [Kivipelto, Miia] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland. [Molinuevo, Jose-Luis] Hosp Clin Barcelona, IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain. [Molinuevo, Jose-Luis] Pasqual Maragall Fdn, Barcelonabeta Brain Res Ctr, Barcelona, Spain. [O'Bryant, Sid E.] Univ N Texas, Hlth Sci Ctr, Ctr Alzheimers & Neurodegenerat Dis Res, Denton, TX 76203 USA. [Rabinovici, Gil D.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Rowe, Christopher] Univ Melbourne, Austin Hlth, Dept Mol Imaging, Melbourne, Vic 3010, Australia. [Salloway, Stephen] Brown Univ, Alpert Med Sch, Butler Hosp, Memory & Aging Program, Providence, RI 02912 USA. [Salloway, Stephen] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Salloway, Stephen] Brown Univ, Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Memory Disorders Unit,Ctr Alzheimer Res & Treatme, Boston, MA 02115 USA. [Sperling, Reisa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Memory Disorders Unit,Ctr Alzheimer Res & Treatme, Boston, MA USA. [Carrillo, Maria C.] Alzheimers Assoc Div Med & Sci Relat, Chicago, IL USA. [Cummings, Jeffrey] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA. [Jack, Cliff R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. RP Dubois, B (reprint author), Univ Paris 06, Pitie Salpetriere Univ Hosp, AP HP, Inst Memory & Alzheimers Dis IM2A, Paris, France.; Dubois, B (reprint author), Univ Paris 06, Pitie Salpetriere Univ Hosp, AP HP, Brain & Spine Inst ICM,Frontlab,Dept Neurol,UMR S, Paris, France. EM bruno.dubois@aphp.fr RI Bertram, Lars/K-3889-2015; Frisoni, Giovanni B/K-1360-2016; , Enrica/K-2652-2016; OI Feldman, Howard/0000-0002-9258-4538; Bertram, Lars/0000-0002-0108-124X; Frisoni, Giovanni B/0000-0002-6419-1753; , enrica/0000-0003-2127-816X; , Enrica/0000-0003-2306-0164; Molinuevo, Jose Luis/0000-0003-0485-6001; O'Bryant, Sid/0000-0003-0582-5266 FU AXA Research Fund; Fondation Universite Pierre et Marie Curie; "Fondation pour la Recherche sur Alzheimer", Paris, France; program "Investissements d'avenir" [ANR-10-IAIHU-06]; European Medical Information Framework (EMIF); National Institute on Aging; French International Foundation for Research in Alzheimer's disease (IFRAD); Alzheimer's Association FX H.H. is supported by the AXA Research Fund, the Fondation Universite Pierre et Marie Curie, and the "Fondation pour la Recherche sur Alzheimer", Paris, France. The research leading to these results has received funding from the program "Investissements d'avenir" ANR-10-IAIHU-06. S.L. is supported by the European Medical Information Framework (EMIF). R.S. is supported by the National Institute on Aging and Alzheimer's Association.r The authors acknowledge the helpful contribution of Zaven Khachaturian as an advisor to the Working Group in charge of the article. The meeting was supported by the French International Foundation for Research in Alzheimer's disease (IFRAD). NR 297 TC 38 Z9 38 U1 15 U2 46 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAR PY 2016 VL 12 IS 3 BP 292 EP 323 DI 10.1016/j.jalz.2016.02.002 PG 32 WC Clinical Neurology SC Neurosciences & Neurology GA DH3VP UT WOS:000372715200010 PM 27012484 ER PT J AU Goldberg, J Magruder, KM Forsberg, CW Friedman, MJ Litz, BT Vaccarino, V Heagerty, PJ Gleason, TC Huang, GD Smith, NL AF Goldberg, Jack Magruder, Kathryn M. Forsberg, Christopher W. Friedman, Matthew J. Litz, Brett T. Vaccarino, Viola Heagerty, Patrick J. Gleason, Theresa C. Huang, Grant D. Smith, Nicholas L. TI Prevalence of Post-Traumatic Stress Disorder in Aging Vietnam-Era Veterans: Veterans Administration Cooperative Study 569: Course and Consequences of Post-Traumatic Stress Disorder in Vietnam-Era Veteran Twins SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Epidemiology; geriatric/aging/elderly; PTSD/posttraumatic stress disorder; twin studies; trauma ID DIAGNOSTIC INTERVIEW CIDI; ADMINISTERED PTSD SCALE; LATE-LIFE PTSD; COMBAT EXPOSURE; REGISTRY; HEALTH; CHECKLIST; VERSION AB Objective: The prevalence of post-traumatic stress disorder (PTSD) among aging Vietnam-era veterans is not well characterized. Methods: In a cross-sectional study, 5,598 male Vietnam-era veterans and members of the Vietnam Era Twin Registry were assessed for PTSD using the Composite International Diagnostic Interview. Current symptoms were measured with the PTSD Checklist (PCL). PTSD was estimated according to age (<60 or >= 60) and Vietnam theater service. Results: The lifetime prevalence of PTSD in theater veterans aged at least 60 years was 16.9% (95% CI: 13.9%-20.5%) and higher than the 5.5% (95% CI: 4.3%-7.0%) among nontheater veterans. Among veterans younger than 60 years, the comparable prevalence was 22.0% for theater (95% CI: 16.7%-28.4%) and 15.7% for nontheater (95% CI: 13.4%-18.2%) veterans. Similar results were found for theater service and current PTSD prevalence (past 12 months). PCL scores were significantly higher in theater compared with nontheater veterans in both younger and older cohorts. In both the younger and older cohorts significant differences in lifetime and current PTSD prevalence and PCL scores persisted in theater service discordant twin pairs. Conclusion: Vietnam service is related to elevated PTSD prevalence and current symptom burden in aging veterans. More than 30 years after the end of the Vietnam conflict, many veterans continue to suffer from PTSD, which highlights the need for continuing outreach throughout the life course. C1 [Goldberg, Jack; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Magruder, Kathryn M.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Friedman, Matthew J.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, White River Jct, VT USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA. [Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Vaccarino, Viola] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Vaccarino, Viola] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Gleason, Theresa C.; Huang, Grant D.] VA Off Res & Dev, Clin Sci Res & Dev, Cooperat Studies Program, Washington, DC USA. RP Goldberg, J (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr S 152 E, 1600 South Columbian Way, Seattle, WA 98108 USA. EM jack.goldberg@va.gov FU Cooperative Studies Program of the Office of Research and Development, Clinical Science Research and Development, of the U.S. Department of Veterans Affairs; National Institutes of Health [K24 HL077506] FX The Cooperative Studies Program of the Office of Research and Development, Clinical Science Research and Development, of the U.S. Department of Veterans Affairs provided financial support for Cooperative Study 569 and the development and maintenance of the VET Registry. Dr. Viola Vaccarino was supported in part by a National Institutes of Health award (K24 HL077506). NR 35 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2016 VL 24 IS 3 BP 181 EP 191 DI 10.1016/j.jagp.2015.05.004 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DG8CF UT WOS:000372309300002 PM 26560508 ER PT J AU Beristianos, MH Yaffe, K Cohen, B Byers, AL AF Beristianos, Matthew H. Yaffe, Kristine Cohen, Beth Byers, Amy L. TI PTSD and Risk of Incident Cardiovascular Disease in Aging Veterans SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE PTSD; cardiovascular disease; veterans ID POSTTRAUMATIC-STRESS-DISORDER; CORONARY-HEART-DISEASE; PERIPHERAL ARTERIAL-DISEASE; MENTAL-HEALTH PROBLEMS; VIETNAM VETERANS; US VETERANS; SYMPTOMS; AFGHANISTAN; PREVALENCE; IRAQ AB Objectives: To determine if late-life posttraumatic stress disorder (PTSD) is associated with cardiovascular disease in a sample of older veterans, and whether the association is independent of medical and psychiatric comorbities. Design: Retrospective cohort study conducted using the Department of Veterans Affairs (VA) National Patient Care Database (2000-2011). Setting: VA medical centers in the United States. Participants: A total of 138,341 veterans 55 years and older without cardiovascular disease at study baseline (2000-2003). Measurements: PTSD and cardiovascular disease (as defined by diagnoses of: cerebrovascular disease [CVD], congestive heart failure [CHF], myocardial infarction [MI], and peripheral vascular disease [PVD]) were identified by ICD-9 codes during study baseline (2000-2003) and follow-up (2004-2011), respectively. Results: 3% of veterans (N = 4,041) had a baseline diagnosis of PTSD. Unadjusted increased risk of incidence of CVD was 80%, CHF was 56%, MI was 82%, and PVD was 60% in veterans with PTSD compared with those without PTSD. After adjustment for demographics, medical comorbidities, substance use, and psychiatric comorbidities, veterans with late-life PTSD were at a 45% increased risk for incident CVD, 26% increased risk for incident CHF, 49% increased risk for incident MI, and 35% increased risk for PVD compared with veterans without late-life PTSD. Conclusions: Findings highlight the longitudinal impact of PTSD on increasing the incidence of cardiovascular disease in older adults. This study implies the need for greater monitoring and treatment of PTSD in older persons, particularly older veterans, to assist in preventing adverse outcomes, such as cardiovascular disease, over the long term. C1 [Beristianos, Matthew H.; Yaffe, Kristine; Byers, Amy L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cohen, Beth] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Beristianos, Matthew H.; Yaffe, Kristine; Cohen, Beth; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Beristianos, Matthew H.] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA USA. RP Beristianos, MH (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM Matthew.Beristianos@ucsf.edu FU U.S. Department of Defense [W81XWH-11-2-0189]; K24 Midcareer Investigator Award from the National Institute on Aging [AG031155]; National Heart, Lung, and Blood Institute [K23 HL 094765-0]; American Heart Association [12CRP11810021]; Takeda, Inc.; National Institute on Aging FX This study was funded by U.S. Department of Defense grant W81XWH-11-2-0189 (principal investigator: Dr. Byers). Dr. Yaffe is supported in part by a K24 Midcareer Investigator Award from the National Institute on Aging (AG031155). Dr. Cohen is supported in part by the National Heart, Lung, and Blood Institute grant K23 HL 094765-0 and grant 12CRP11810021 from the American Heart Association.; Mr. Beristianos, Dr. Cohen, and Dr. Byers report no financial relationships with commercial interests. Dr. Yaffe reports having served as a consultant to Novartis, Inc., and Pfizer for reasons not related to the current project. She serves on DSMB committees for Takeda, Inc., and a National Institute on Aging-sponsored study, and also serves on the Beeson Scientific Advisory Board. The authors have no competing interests, including specific financial interests or relationships or affiliations relevant to the subject of this article. NR 41 TC 6 Z9 6 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2016 VL 24 IS 3 BP 192 EP 200 DI 10.1016/j.jagp.2014.12.003 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DG8CF UT WOS:000372309300003 PM 25555625 ER PT J AU Diem, SJ Blackwell, TL Stone, KL Yaffe, K Tranah, G Cauley, JA Ancoli-Israel, S Redline, S Spira, AP Hillier, TA Ensrud, KE AF Diem, Susan J. Blackwell, Terri L. Stone, Katie L. Yaffe, Kristine Tranah, Greg Cauley, Jane A. Ancoli-Israel, Sonia Redline, Susan Spira, Adam P. Hillier, Teresa A. Ensrud, Kristine E. TI Measures of Sleep-Wake Patterns and Risk of Mild Cognitive Impairment or Dementia in Older Women SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE cognitive aging; sleep disorders; older women; dementia; actigraphy ID OSTEOPOROTIC FRACTURES; ALZHEIMERS-DISEASE; DECLINE; ADULTS; FRAGMENTATION; QUESTIONNAIRE; RELIABILITY; ACTIGRAPHY; DURATION; RHYTHMS AB Objective: Sleep disturbances are common in older adults. Little is known about the sleep of cognitively intact older adults and its relationship to subsequent cognitive impairment. The objective of this study was to examine the association between objective sleep-wake measures and risk of incident cognitive impairment. Methods: In this prospective cohort study encompassing four U.S. sites, 1,245 women (mean age: 82.6 years) without dementia participated in the Study of Osteoporotic Fractures and completed actigraphy at the baseline visit and comprehensive cognitive assessment at follow-up. The association between sleep-wake patterns measured by actigraphy and risk of incident mild cognitive impairment (MCI) and dementia was examined. Results: A total of 473 women (38%) developed cognitive impairment during an average (SD) follow-up of 4.9 (0.6) years; 290 (23.3%) developed MCI and 183 (14.7%) developed dementia. After controlling for multiple potential confounders, women in the lowest quartile of average sleep efficiency (<74%) had a 1.5-fold higher odds of developing MCI or dementia compared with women in the highest quartile of sleep efficiency (>86%) (odds ratio: Q1 versus Q4 1.53; 95% CI: 1.07, 2.19; Wald chi(2) [1, N = 1,223] = 5.34 for p for trend = 0.03). Longer average sleep latency, but not total sleep time, was also associated with higher odds of developing cognitive impairment. Greater variability in both sleep efficiency and total sleep time was associated with an increased odds of developing MCI or dementia. Conclusion: Lower average sleep efficiency, longer average sleep latency, and greater variability in sleep efficiency and total sleep time are associated with increased odds of developing cognitive impairment. Further research is needed to explore the mechanisms underlying these associations. C1 [Diem, Susan J.; Ensrud, Kristine E.] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Diem, Susan J.; Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55415 USA. [Blackwell, Terri L.; Stone, Katie L.; Tranah, Greg] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Spira, Adam P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Diem, SJ (reprint author), Univ Minnesota, 1100 Washington Ave S, Minneapolis, MN 55415 USA. EM sdiem@umn.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institute on Aging [RO1 AG005407, RO1 AR35582, ROA AR35583, RO1 AR35584, RO1 AG005394, RO1 AG027574, RO1 AG027576, KO1 AG033195] FX The Study of Osteoporotic Fractures is supported by grants RO1 AG005407, RO1 AR35582, ROA AR35583, RO1 AR35584, RO1 AG005394, RO1 AG027574, RO1 AG027576, and KO1 AG033195 from the National Institute on Aging. The funding agencies had no direct role in the conduct of the study; the collection, management, analyses and interpretation of the data; or preparation or approval of the manuscript. All authors have nothing to disclose. NR 49 TC 2 Z9 2 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2016 VL 24 IS 3 BP 248 EP 258 DI 10.1016/j.jagp.2015.12.002 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DG8CF UT WOS:000372309300009 PM 26964485 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Problem-based learning discussion: Medical treatment of pediatric chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article; Proceedings Paper CT North American Rhinology and Allergy Conference CY FEB 05-07, 2015 CL Boca Raton, FL ID ENDOSCOPIC SINUS SURGERY; CYSTIC-FIBROSIS; LONG-TERM; CONTROLLED-TRIAL; RETROSPECTIVE ANALYSIS; NASAL POLYPS; CHILDREN; OUTCOMES; MANAGEMENT; METAANALYSIS AB This problem-based learning case focused on the approach to evaluation and management of a 5-year old girl who was "always sick" with sinus infections. The discussion unfolds in a "real life" scenario, i.e., based on information available to the clinician initially and after the acquisition of laboratory data, and, ultimately, after sinus surgery. Emphasis is placed on the differential diagnosis of the patient's symptoms, discussion of the initial management strategy for chronic rhinosinusitis (CRS), evolution from acute rhinosinusitis to CRS, the prevalence of and differential diagnosis of nasal polyps in children, treatment considerations specific for CRS with nasal polyps, the significance of Pseudomonas aeruginosa sinus infection, the significance of an abnormal sweat chloride test in a young child with nasal polyposis, special considerations in children with CRS who have cystic fibrosis, treatment considerations after endoscopic sinus surgery, and, finally, prognostic factors that impact the outcomes of endoscopic sinus surgery. This problem-based learning case highlights many facets of managing refractory CRS in children. C1 [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org NR 60 TC 1 Z9 1 U1 1 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2016 VL 30 IS 2 BP 113 EP 121 DI 10.2500/ajra.2016.30.4270 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA DG8PL UT WOS:000372346000017 PM 26980392 ER PT J AU Schlosser, RJ Storck, K Cortese, BM Uhde, TW Rudmik, L Soler, ZM AF Schlosser, Rodney J. Storck, Kristina Cortese, Bernadette M. Uhde, Thomas W. Rudmik, Luke Soler, Zachary M. TI Depression in chronic rhinosinusitis: A controlled cohort study SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; QUALITY-OF-LIFE; INVENTORY-II; DIABETES-MELLITUS; DISEASE SEVERITY; SYMPTOMS; OUTCOMES; HEALTH; IMPACT; ASSOCIATION AB Background: Depression in patients with chronic rhinosinusitis (CRS) is underdiagnosed but significantly impacts treatment outcomes and health care utilization. Objective: To compare undiagnosed depression in a CRS cohort with a healthy, non-CRS control cohort. Methods: A case-control study of patients with symptomatic CRS and a non-CRS control cohort was performed. Demographic and comorbidity factors were correlated to depression-specific outcomes by using the Beck Depression Inventory II (BDI). Results: We enrolled 42 patients with CRS and 88 control patients with no history of CRS. Physician-diagnosed depression was equivalent in CRS and control patients (6% and 9%, respectively). BDI-detected depression was higher among patients with CRS compared with controls (31% versus 14.8%, respectively; p = 0.031). BDI scores were higher in patients with CRS even when controlling for comorbid asthma, allergy, and aspirin sensitivity. When examined by polyp status, the patients without polyps had more depression than did the controls (38% versus 14.8%; p = 0.048). The somatic subscale scores of the BDI were worse in patients with CRS (p = 0.004), whereas the cognitive subscale trended toward significance (p = 0.081). Conclusion: Depression may be more common in CRS than previously recognized, especially in patients without polyps. Somatic subscale scores of the BDI are increased in CRS and may impact future treatment outcomes. C1 [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. [Schlosser, Rodney J.; Storck, Kristina; Soler, Zachary M.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Cortese, Bernadette M.; Uhde, Thomas W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Rudmik, Luke] Univ Calgary, Dept Surg, Div Otolaryngol Head & Neck Surg, Calgary, AB, Canada. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu FU Flight Attendant Medical Research Institute [ID113042_CIA]; National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, Bethesda, Maryland [R01 DC005805, R03 DC013651-01]; National Institute of Mental Health [K01 MH090548]; Entellus; IntersectENT; OptiNose FX Supported by a grant from the Flight Attendant Medical Research Institute (ID113042_CIA). Z.M. Soler is also supported by grants from the National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, Bethesda, Maryland (R01 DC005805; R03 DC013651-01). B.M. Cortese is supported by a grant from the National Institute of Mental Health (K01 MH090548).; Z.M. Soler is a consultant for Olympus, which is not affiliated with this manuscript, and has grant support from Entellus and IntersectENT. R.J. Schlosser is supported by grants from OptiNose, Entellus, and IntersectENT, which are not associated with this manuscript, and is a consultant for Olympus, Meda, and Arrinex, which are not affiliated with this study. The remaining authors have no conflicts of interest pertaining to this article NR 33 TC 4 Z9 4 U1 1 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2016 VL 30 IS 2 BP 128 EP 133 DI 10.2500/ajra.2016.30.4290 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DG8PL UT WOS:000372346000019 PM 26980393 ER PT J AU Xia, W Chiu, YH Afeiche, MC Williams, PL Ford, JB Tanrikut, C Souter, I Hauser, R Chavarro, JE AF Xia, Wei Chiu, Yu-Han Afeiche, Myriam C. Williams, Paige L. Ford, Jennifer B. Tanrikut, Cigdem Souter, Irene Hauser, Russ Chavarro, Jorge E. CA EARTH Study Team TI Impact of men's dairy intake on assisted reproductive technology outcomes among couples attending a fertility clinic SO ANDROLOGY LA English DT Article DE assisted reproductive technology; cohort studies; dairy intake; infertility; men ID FOOD FREQUENCY QUESTIONNAIRE; YOUNG DANISH MEN; SEMEN QUALITY; DIETARY-INTAKE; UNITED-STATES; SOY FOOD; INFERTILITY; POPULATION; REPRODUCIBILITY; PARAMETERS AB Intake of full-fat dairy has been linked to lower semen quality but whether this leads to decreased fertility is unknown. To address this question, we prospectively evaluated the association of men's dairy intake with treatment outcomes of subfertile couples undergoing assisted reproductive technology (ART). We followed 142 men from couples undergoing infertility treatment with ART at an academic fertility centre between 2007 and 2014. Couples completed dietary assessments prior to treatment, and the female partners underwent a total of 248 ART cycles. Multivariable generalized linear mixed models were used to examine the association of dairy intake with fertilization, implantation, clinical pregnancy and live birth rates adjusting for age, body mass index, smoking status, total exercise time, dietary patterns, alcohol, caffeine, total energy intake, and female dairy intake. Intake of dairy foods, regardless of their fat content, was not associated with fertilization, implantation, clinical pregnancy or live birth rates. The adjusted live birth rates (95% confidence interval) for couples in increasing quartiles of men's dairy intake were 0.42 (0.25, 0.60), 0.25 (0.13, 0.42), 0.26 (0.15, 0.41), and 0.44 (0.27, 0.63) (p linear trend=0.73). Results remained similar after adjustment for female partner intake of dairy foods. Overall, men's dairy intake was not associated with treatment outcomes of couples undergoing ART. C1 [Xia, Wei; Chiu, Yu-Han; Chavarro, Jorge E.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA USA. [Xia, Wei] Huazhong Univ Sci & Technol, Tongji Med Coll, Family Planning Res Inst, Wuhan 430074, Peoples R China. [Xia, Wei] Huazhong Univ Sci & Technol, Tongji Med Coll, Reprod Med Ctr, Wuhan 430074, Peoples R China. [Afeiche, Myriam C.; Ford, Jennifer B.; Hauser, Russ] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tanrikut, Cigdem] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Tanrikut, Cigdem; Souter, Irene; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA USA. [Souter, Irene; Hauser, Russ] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA USA. EM jchavarr@hsph.harvard.edu FU NIH [R01ES009718, R01ES022955, P30ES000002, P30DK46200]; China Scholarship Council FX The authors acknowledge all members of the EARTH study team, specifically the Harvard T.H. Chan School of Public Health research nurses Jennifer B. Ford and Myra G. Keller, research staff Ramace Dadd and Patricia Morey, physicians and staff at Massachusetts General Hospital Fertility Center and extend a special thanks to all the study participants. This work was supported by NIH grants R01ES009718, R01ES022955, P30ES000002 and P30DK46200. Dr Xia was supported by the China Scholarship Council. NR 36 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD MAR PY 2016 VL 4 IS 2 BP 277 EP 283 DI 10.1111/andr.12151 PG 7 WC Andrology SC Endocrinology & Metabolism GA DG9PT UT WOS:000372417000011 PM 26825777 ER PT J AU Lin, JE Neylan, TC Epel, E O'Donovan, A AF Lin, Joy E. Neylan, Thomas C. Epel, Elissa O'Donovan, Aoife TI Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Childhood adversity; Adulthood trauma; C-reactive protein; Immune system; Inflammation ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; EARLY-LIFE STRESS; ELEVATED INFLAMMATION; MENTAL-HEALTH; CARDIOVASCULAR-DISEASE; PSYCHIATRIC-DISORDERS; PSYCHOLOGICAL STRESS; GENE-EXPRESSION; RISK AB Mounting evidence highlights specific forms of psychological stress as risk factors for ill health. Particularly strong evidence indicates that childhood adversity and adulthood trauma exposure increase risk for physical and psychiatric disorders, and there is emerging evidence that inflammation may play a key role in these relationships. In a population-based sample from the Health and Retirement Study (n = 11,198, mean age 69 +/- 10), we examine whether childhood adversity, adulthood trauma, and the interaction between them are associated with elevated levels of the systemic inflammatory marker high sensitivity C-reactive protein (hsCRP). All models were adjusted for age, gender, race, education, and year of data collection, as well as other possible confounds in follow-up sensitivity analyses. In our sample, 67% of individuals had experienced at least one traumatic event during adulthood, and those with childhood adversity were almost three times as likely to have experienced trauma as an adult. Childhood adversities and adulthood traumas were independently associated with elevated levels of hsCRP (beta = 0.03, p = 0.01 and beta = 0.05, p < 0.001, respectively). Those who had experienced both types of stress had higher levels of hsCRP than those with adulthood trauma alone, Estimate = -0.06, 95% CI [-0.003, -0.12], p = 0.04, but not compared to those with childhood adversity alone, Estimate = -0.06, 95% CI [0.03, -0.16], p = 0.19. There was no interaction between childhood and adulthood trauma exposure. To our knowledge, this is the first study to examine adulthood trauma exposure and inflammation in a large population-based sample, and the first to explore the interaction of childhood adversity and adulthood trauma with inflammation. Our study demonstrates the prevalence of trauma-related inflammation in the general population and suggests that childhood adversity and adulthood trauma are independently associated with elevated inflammation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lin, Joy E.] Univ Calif San Francisco, Sch Med, 500 Parnassus Ave, San Francisco, CA 94143 USA. [Neylan, Thomas C.; Epel, Elissa; O'Donovan, Aoife] Univ Calif San Francisco, Dept Psychiat, 500 Parnassus Ave, San Francisco, CA 94143 USA. [Lin, Joy E.; Neylan, Thomas C.; O'Donovan, Aoife] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. RP Lin, JE (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 4150 Clement St 116C-1, San Francisco, CA 94121 USA. EM joy.lin@ucsf.edu; thomas.neylan@ucsf.edu; elissa.epel@ucsf.edu; aoife.odonovan@ucsf.edu FU National Institute on Aging [NIA U01AG009740]; National Center for Advancing Translational Sciences Career Development Award at the University of California, San Francisco [KL2 TR000143]; Society in Science-Branco Weiss Fellowship; UCSF Dean's Office Medical Student Research Program FX The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and was conducted by the University of Michigan. A.O.D. was supported by a National Center for Advancing Translational Sciences Career Development Award at the University of California, San Francisco (KL2 TR000143) and a Society in Science-Branco Weiss Fellowship. J.E.L. was supported by the UCSF Dean's Office Medical Student Research Program. The authors would like to acknowledge Tom Metzler for statistical support in preparation of this manuscript. NR 79 TC 1 Z9 1 U1 4 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAR PY 2016 VL 53 BP 105 EP 112 DI 10.1016/j.bbi.2015.11.015 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA DG9BJ UT WOS:000372377500012 PM 26616398 ER PT J AU Franco, W Gutierrez-Herrera, E Kollias, N Doukas, A AF Franco, W. Gutierrez-Herrera, E. Kollias, N. Doukas, A. TI Review of applications of fluorescence excitation spectroscopy to dermatology SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Review ID IRRITANT CONTACT-DERMATITIS; IN-VIVO FLUORESCENCE; HUMAN-SKIN; EPIDERMAL PROLIFERATION; NONINVASIVE EVALUATION; REACTION-PRODUCTS; DANSYL CHLORIDE; COLLAGEN; AGE; AUTOFLUORESCENCE AB Endogenous molecules that exhibit fluorescence hold the potential to serve as reporters of tissue structure, activity and physiology. Fluorescence excitation spectroscopy is one means to measure and express tissue's innate fluorescence. This review focuses on the application of endogenous fluorescence ultraviolet excitation spectroscopy to dermatology. C1 [Franco, W.; Gutierrez-Herrera, E.; Doukas, A.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kollias, N.] Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada. [Gutierrez-Herrera, E.] Univ Nacl Autonoma Mexico, Ctr Ciencias Aplicadas & Desarrollo Tecnol, Mexico City 04510, DF, Mexico. RP Franco, W (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM wfranco@mgh.harvard.edu NR 34 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAR PY 2016 VL 174 IS 3 BP 499 EP 504 DI 10.1111/bjd.14221 PG 6 WC Dermatology SC Dermatology GA DH5DJ UT WOS:000372805100018 PM 26471781 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Sex differences in characteristics, utilization, and outcomes of patient undergoing total elbow arthroplasty: a study of the US nationwide inpatient sample SO CLINICAL RHEUMATOLOGY LA English DT Article DE Discharge; Hospital stay; Mortality; Outcomes; Sex; TEA; Total elbow arthroplasty; Utilization ID SURGEON PROCEDURE VOLUME; TOTAL KNEE ARTHROPLASTY; UNITED-STATES; SHOULDER ARTHROPLASTY; HIP-REPLACEMENT; HOME; ASSOCIATION; DISCHARGE; MORTALITY; SUPPORT AB The aim of this study was to compare patient characteristics, utilization rates, and outcomes after total elbow arthroplasty (TEA) by sex. We used the nationwide inpatient sample from 1998 to 2011 to study sex-related time trends in patient characteristics, comorbidity, and outcomes after TEA. We used chi-squared test, analysis of variance, and the Cochran-Armitage test to assess differences in utilization rates and characteristics over time by sex and logistic regression to compare mortality, discharge disposition, and the length of hospital stay by sex. Overall TEA utilization 0.45 in 1998 to 0.96 per 100,000 in 2011 (p < 0.0001). The utilization rates were significantly higher in females compared to males throughout the study period: 0.62 vs. 0.29 in 1998 (p < 0.0001) and 1.31 vs. 0.70 in 2011 (p < 0.0001). Compared to males, females undergoing TEA were more likely to be white (79.7 vs. 71.4 %; p < 0.0001), have rheumatoid arthritis (16.7 vs. 8.1 %; p < 0.0001), and have Deyo-Charlson index of 2 or more (11.3 vs. 5.9 %; p < 0.0001) and were older (63.5 vs. 51.4 years; p < 0.0001). Compared to males undergoing TEA, females had significantly lower mortality, 0.1 vs. 0.4 % (p = 0.03); lower proportion were discharged to home, 81.9 vs. 89.6 % (p < 0.0001), and fewer had has index hospital stay above the median, 30.0 vs. 33.0 % (p = 0.01); most differences were significant after multivariable adjustment. TEA utilization in the USA more than doubled in the last 14 years, with rates higher in females than males. Females had better outcomes after TEA than men. Preoperative risk communication should be sex-specific based on these data. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging (NIA); National Cancer Institute (NCI) FX This material is the result of work supported by the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA), and National Cancer Institute (NCI). NR 19 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD MAR PY 2016 VL 35 IS 3 BP 723 EP 731 DI 10.1007/s10067-014-2778-9 PG 9 WC Rheumatology SC Rheumatology GA DG9UJ UT WOS:000372429000022 PM 25316506 ER PT J AU Burge, SK Katerndahl, DA Wood, RC Becho, J Ferrer, RL Talamantes, M AF Burge, Sandra K. Katerndahl, David A. Wood, Robert C. Becho, Johanna Ferrer, Robert L. Talamantes, Melissa TI Using Complexity Science to Examine Three Dynamic Patterns of Intimate Partner Violence SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE spouse abuse; battered women; domestic violence; nonlinear dynamics; longitudinal studies ID PRIMARY-CARE; LYAPUNOV EXPONENTS; TIME-SERIES; RELIABILITY; SEVERITY; VALIDITY; SYSTEMS; HEALTH; CHAOS; MOOD AB Introduction: The partner violence literature describes 3 dominant models of dynamics of partner aggression: cycle of violence, family systems theory, and Duluth model (power and control wheel). Complexity science describes 3 patterns of system dynamics: periodic, chaotic, and random. Are these parallel patterns? In this analysis, investigators calculated dynamic patterns (periodic, chaotic, and random) using 84 daily reports of male-to-female aggression and assessed the "fit" between time-series-derived patterns of male partners' violent behaviors and literature-based models of violence dynamics. Method: Participants were 200 women in moderately violent intimate relationships who completed a telephone survey about their relationships every day for 12 weeks. They also completed baseline and end-of-study surveys and maintained telephone contact with the study team weekly. Of 200 participants, 135 women provided enough data to be assigned to period, chaotic, or random groups. Results: Group membership included 16 women in periodic, 40 in chaotic, and 79 in random groups. Consistent with the cycle of violence, periodic women found violence to be predictable and controllable. Consistent with the Duluth model, women in the random group found violence to be unpredictable and out of their control, occurring with high frequency. The chaotic group had the lowest frequency and severity of violence, lowest stress and arguments, and the highest marital satisfaction. Discussion: The most common dynamic pattern in partner violence is random, which exhibits high frequency and unpredictability of aggression. Complexity science suggests interventions in random systems have unpredictable outcomes, posing great challenges for clinicians who work with victims of violence. C1 [Burge, Sandra K.; Katerndahl, David A.; Wood, Robert C.; Becho, Johanna; Ferrer, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr,Mail Code 7795, San Antonio, TX 78229 USA. [Talamantes, Melissa] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Burge, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr,Mail Code 7795, San Antonio, TX 78229 USA. EM burge@uthscsa.edu FU "Dynamics of Human Behavior" program, National Science Foundation [0525026] FX This study was funded with a grant from the "Dynamics of Human Behavior" program, National Science Foundation, Award 0525026. Automated data collection was provided by the University of Colorado, Department of Family Medicine Information Services group. We thank Stephanie Mitchell, Kelli Giacomini, and Wilson Pace for their invaluable assistance with IVR. We also express appreciation to Norma Cantu and Diandrea Garza for their commitment to screening and enrolling women for this study. NR 39 TC 1 Z9 1 U1 1 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD MAR PY 2016 VL 34 IS 1 BP 4 EP 14 DI 10.1037/fsh0000170 PG 11 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA DG8WG UT WOS:000372363700002 PM 26618639 ER PT J AU Kentta, TV Nearing, BD Porthan, K Tikkanen, JT Viitasalo, M Nieminen, MS Salomaa, V Oikarinen, L Jula, A Kontula, K Newton-Cheh, C Huikuri, HV Verrier, RL AF Kentta, Tuomas V. Nearing, Bruce D. Porthan, Kimmo Tikkanen, Jani T. Viitasalo, Matti Nieminen, Markku S. Salomaa, Veikko Oikarinen, Lasse Jula, Antti Kontula, Kimmo Newton-Cheh, Chris Huikuri, Heikki V. Verrier, Richard L. TI Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms SO HEART RHYTHM LA English DT Editorial Material DE Sudden cardiac death; Ventricular arrhythmias; Depolarization; Repolarization; Electrocardiogram; Heterogeneity ID T-WAVE MORPHOLOGY; QT DISPERSION; MYOCARDIAL-INFARCTION; REPOLARIZATION HETEROGENEITY; VENTRICULAR REPOLARIZATION; CARDIOVASCULAR MORTALITY; RISK STRATIFICATION; ARRHYTHMIA RISK; INTERVAL; POPULATION AB BACKGROUND Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. OBJECTIVE We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). METHODS Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean +/- SEM age 50.9 +/- 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. RESULTS During the follow-up period of 7.7 +/- 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V-4-V-6) were univariately associated with SCD (P < .001 for each). When adjusted with standard clinical risk markers, JWH and TWH remained independent predictors of SCD. Increased TWH (>= 102 mu V) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (>= 123 mu V) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (>= 470 mu V), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). CONCLUSION Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population. C1 [Kentta, Tuomas V.; Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Oulu, Med Res Ctr Oulu, Oulu, Finland. [Kentta, Tuomas V.; Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Hosp Oulu, Oulu, Finland. [Kentta, Tuomas V.; Nearing, Bruce D.; Verrier, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nearing, Bruce D.; Verrier, Richard L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Porthan, Kimmo; Viitasalo, Matti; Nieminen, Markku S.; Oikarinen, Lasse] Univ Helsinki, Cent Hosp, Div Cardiol, Heart & Lung Ctr, Helsinki, Finland. [Tikkanen, Jani T.] Haartman Hosp, Emergency Dept, Helsinki, Finland. [Salomaa, Veikko; Jula, Antti] Natl Inst Hlth & Welf, Helsinki, Finland. [Kontula, Kimmo] Univ Helsinki, Dept Med, Helsinki, Finland. [Newton-Cheh, Chris] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Chris] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Chris] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Verrier, RL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 99 Brookline Ave,RN 301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu NR 35 TC 3 Z9 3 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2016 VL 13 IS 3 BP 713 EP 720 DI 10.1016/j.hrthm.2015.11.035 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG8XV UT WOS:000372367800015 PM 26616400 ER PT J AU Libbus, I Nearing, BD Amurthur, B KenKnight, BH Verrier, RL AF Libbus, Imad Nearing, Bruce D. Amurthur, Badri KenKnight, Bruce H. Verrier, Richard L. TI Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study SO HEART RHYTHM LA English DT Editorial Material DE Heart failure; T-wave alternans; Baroreceptor sensitivity; Vagus nerve stimulation; Autonomic regulation therapy; Heart rate turbulence; Ventricular tachycardia; Heart rate variability; Autonomic tone; Autonomic reflexes ID VAGUS NERVE-STIMULATION; PHYSIOLOGICAL INTERPRETATION; CLINICAL-USE; SUDDEN; SYSTEM; DEATH; STANDARDS; MORTALITY; EPILEPSY; HOLTER AB BACKGROUND Autonomic regulation therapy (ART) with chronic vagus nerve stimulation improves ventricular function in patients with chronic heart failure, but its effects on quantitative T-wave alternans (TWA), ventricular tachycardia (VT), baroreflex sensitivity, and autonomic tone remained unknown. OBJECTIVE Effects on TWA, a marker of risk of life-threatening arrhythmias; heart rate turbulence (HRT), an indicator of baroreflex sensitivity; heart rate variability; and VT incidence were studied in 25 patients with chronic symptomatic heart failure and reduced ejection fraction enrolled in the ANTHEM-HF study (NCT01823887). METHODS Twenty-four-hour ambulatory electrocardiographic recordings made before ART system (Cyberonics, Inc., Houston, TX) implantation involving the left or right vagus nerve and after 6 and 12 months of chronic therapy (10-Hz frequency, 250-mu s pulse width, maximum tolerable current amplitude after 10 weeks of titration) at low-intensity (<2 mA; n = 10, 40%) or high-intensity (>= 2 mA; n = 15, 60%) stimulation levels were analyzed. RESULTS At 12 months, peak TWA levels were reduced by 29% from 71.0 +/- 4.6 to 50.5 +/- 1.8 mu V (P < .0001). The number of patients with severely abnormal TWA (>= 60 mu V) was reduced by 76% from 17 to 4 (P < .0005), and the number of patients with nonsustained VT decreased by 73% from 11 to 3 (P < .025). HRT slope (P < .025), high frequency heart rate variability (HRV) (P =.05), and square root of the mean squared differences of successive normal-to-normal interval HRV (P =.013) increased. The mean heart rate derived from 24-hour Hotter electrocardiograms decreased by 10% from 77 +/- 2 to 69 +/- 2 beats/min (P = .0002). HRT onset was unchanged. CONCLUSION Chronic ART in patients with symptomatic heart failure improves cardiac electrical stability, as reflected by reduced TWA levels and heart rate, suppresses VT, and increases baroreceptor sensitivity. These observations deserve study in a larger population. C1 [Libbus, Imad; Amurthur, Badri; KenKnight, Bruce H.] Cyberonics Inc, Houston, TX USA. [Nearing, Bruce D.; Verrier, Richard L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Verrier, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Sch Med,Harvard Thomdike Electrophysiol Inst, 99 Brookline Ave,RN 301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu NR 24 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2016 VL 13 IS 3 BP 721 EP 728 DI 10.1016/j.hrthm.2015.11.030 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG8XV UT WOS:000372367800016 PM 26601770 ER PT J AU Afeiche, MC Chiu, YH Gaskins, AJ Williams, PL Souter, I Wright, DL Hauser, R Chavarro, JE AF Afeiche, M. C. Chiu, Y. -H. Gaskins, A. J. Williams, P. L. Souter, I. Wright, D. L. Hauser, R. Chavarro, J. E. CA EARTH Study Team TI Dairy intake in relation to in vitro fertilization outcomes among women from a fertility clinic SO HUMAN REPRODUCTION LA English DT Article DE diet; dairy; in vitro fertilization outcomes; assisted reproductive technology; live birth rate ID GROWTH-FACTOR-I; MILK CONSUMPTION; DIETARY PATTERNS; SEMEN QUALITY; PREGNANCY; FOOD; MEN; QUESTIONNAIRE; INFERTILITY; PRODUCTS AB Is dairy food consumption associated with live birth among women undergoing infertility treatment? There was a positive association between total dairy food consumption and live birth among women a parts per thousand yen35 years of age. Dairy food intake has been previously related to infertility risk and measures of fertility potential but its relation to infertility treatment outcomes are unknown. Our study population comprised a total of 232 women undergoing 353 in vitro fertilization (IVF) treatment cycles between February 2007 and May 2013, from the Environment and Reproductive Health study, an ongoing prospective cohort. Diet was assessed before assisted reproductive technology (ART) treatment using a validated food frequency questionnaire. Study outcomes included ovarian stimulation outcomes (endometrial thickness, estradiol levels and oocyte yield), fertilization rates, embryo quality measures and clinical outcomes (implantation, clinical pregnancy and live birth rates). We used generalized linear mixed models with random intercepts to account for multiple ART cycles per woman while simultaneously adjusting for age, caloric intake, BMI, race, smoking status, infertility diagnosis, protocol type, alcohol intake and dietary patterns. The age- and calorie-adjusted difference in live birth between women in the highest (> 3.0 servings/day) and lowest (< 1.34 servings/day) quartile of dairy intake was 21% (P = 0.02). However, after adjusting for additional covariates, this association was observed only among women a parts per thousand yen35 years (P, interaction = 0.04). The multivariable-adjusted live birth (95% CI) in increasing quartiles of total dairy intake was 23% (11, 42%), 39% (24, 56%), 29% (17, 47%) and 55% (39, 69%) (P, trend = 0.02) among women a parts per thousand yen35 years old, and ranged from 46 to 54% among women < 35 years old (P, trend = 0.69). There was no association between dairy intake and any of the intermediate outcomes. The lack of a known biological mechanism linking dairy intake to infertility treatment outcomes calls for caution when interpreting these results and for additional work to corroborate or refute them. Dairy intake does not appear to harm IVF outcomes and, if anything, is associated with higher chances of live birth. This work was supported by NIH grants R01-ES009718 and R01ES000002 from NIEHS, P30 DK046200 from NIDDK and T32HD060454 from NICHD. M.C.A. was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. She is currently employed at the Nestl, Research Center, Switzerland and completed this work while at the Harvard School of Public Health. The other authors declare no conflicts of interest. C1 [Afeiche, M. C.; Hauser, R.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chiu, Y. -H.; Gaskins, A. J.; Chavarro, J. E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chiu, Y. -H.; Gaskins, A. J.; Williams, P. L.; Hauser, R.; Chavarro, J. E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, P. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Souter, I.; Wright, D. L.; Hauser, R.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Souter, I.; Wright, D. L.; Hauser, R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chavarro, J. E.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Chavarro, J. E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Afeiche, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM mafeiche@hsph.harvard.edu FU NIH [R01-ES009718]; NIEHS [R01ES000002]; NIDDK [P30 DK046200]; NICHD [T32HD060454]; Ruth L. Kirschstein National Research Service Award from NIDDK [T32 DK 007703-16] FX This work was supported by NIH grants R01-ES009718 and R01ES000002 from NIEHS, P30 DK046200 from NIDDK, and T32HD060454 from NICHD. M.C.A. was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. NR 31 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 2016 VL 31 IS 3 BP 563 EP 571 DI 10.1093/humrep/dev344 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DG9QN UT WOS:000372419000009 PM 26787645 ER PT J AU Neilan, TG Kwong, R AF Neilan, Tomas G. Kwong, Raymond TI How to Distinguish Between Myocarditis and Sarcoidosis Based on CMR Imaging REPLY SO JACC-CARDIOVASCULAR IMAGING LA English DT Letter ID LATE GADOLINIUM ENHANCEMENT; CARDIAC SARCOIDOSIS C1 [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Cardiol, 55 Fruit St,Yawkey 5, Boston, MA 02114 USA. RP Neilan, TG (reprint author), Massachusetts Gen Hosp, Dept Cardiol, 55 Fruit St,Yawkey 5, Boston, MA 02114 USA. EM tneilan@partners.org NR 5 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2016 VL 9 IS 3 BP 327 EP 328 DI 10.1016/j.jcmg.2015.05.016 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DH0EN UT WOS:000372455400021 PM 26965735 ER PT J AU Schulman, JM Oh, DH Sanborn, JZ Pincus, L McCalmont, TH Cho, RJ AF Schulman, Joshua M. Oh, Dennis H. Sanborn, J. Zachary Pincus, Laura McCalmont, Timothy H. Cho, Raymond J. TI Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation SO JAMA DERMATOLOGY LA English DT Article ID GORLIN SYNDROME; MEDULLOBLASTOMA AB IMPORTANCE Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is a rare genodermatosis in which numerous indolent, well-differentiated basal cell carcinomas develop primarily on the face and genitals, without other features characteristic of basal cell nevus syndrome. The cause is unknown. The purpose of the study was to identify a genetic basis for the syndrome and a mechanism by which the associated tumors develop. OBSERVATIONS Whole-exome sequencing of 5 tumors and a normal buccal mucosal sample from a patient with MHIBCC was performed. A conserved splice-site mutation in 1 copy of the suppressor of fused gene (SUFU) was identified in all tumor and normal tissue samples. Additional distinct deletions of the trans SUFU allele were identified in all tumor samples, none of which were present in the normal sample. CONCLUSIONS AND RELEVANCE A germline SUFU mutation was present in a patient with MHIBCC, and additional acquired SUFU mutations underlie the development of infundibulocystic basal cell carcinomas. The downstream location of the SUFU gene within the sonic hedgehog pathway may explain why its loss is associated with relatively well-differentiated tumors and suggests that MHIBCC will not respond to therapeutic strategies, such as smoothened inhibitors, that target upstream components of this pathway. C1 [Schulman, Joshua M.; Oh, Dennis H.; Pincus, Laura; McCalmont, Timothy H.; Cho, Raymond J.] Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,S431, San Francisco, CA 94115 USA. [Schulman, Joshua M.; Pincus, Laura; McCalmont, Timothy H.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94115 USA. [Oh, Dennis H.] San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA USA. [Sanborn, J. Zachary] NantOmics LLC, Santa Cruz, CA USA. RP Cho, RJ (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,S431, San Francisco, CA 94115 USA. EM chorj@derm.ucsf.edu FU Well Aging Research Center, Samsung Advanced Institute of Technology; National Cancer Institute, National Institutes of Health [K08 CA169865] FX This study was supported by the Well Aging Research Center, Samsung Advanced Institute of Technology, under the auspices of Sang Chul Park, MD, PhD, and by grant K08 CA169865 from the National Cancer Institute, National Institutes of Health (Dr Cho). NR 15 TC 2 Z9 2 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAR PY 2016 VL 152 IS 3 BP 323 EP 327 DI 10.1001/jamadermatol.2015.4233 PG 5 WC Dermatology SC Dermatology GA DH0GH UT WOS:000372460300019 PM 26677003 ER PT J AU Morone, NE Greco, CM Moore, CG Rollman, BL Lane, B Morrow, LA Glynn, NW Weiner, DK AF Morone, Natalia E. Greco, Carol M. Moore, Charity G. Rollman, Bruce L. Lane, Bridget Morrow, Lisa A. Glynn, Nancy W. Weiner, Debra K. TI A Mind-Body Program for Older Adults With Chronic Low Back Pain A Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID SELF-EFFICACY; PSYCHOMETRIC PROPERTIES; NATIONAL-HEALTH; SCALE; METAANALYSIS; MINDFULNESS; VALIDATION; MEDITATION; DISABILITY; INTENSITY AB IMPORTANCE Treatment of chronic low back pain (LBP) in older adults is limited by the adverse effects of analgesics. Effective nonpharmacologic treatment options are needed. OBJECTIVE To determine the effectiveness of a mind-body program at increasing function and reducing pain in older adults with chronic LBP. DESIGN, SETTING, AND PARTICIPANTS This single-blind, randomized clinical trial compared a mind-body program (n = 140) with a health education program (n = 142). Community-dwelling older adults residing within the Pittsburgh metropolitan area were recruited from February 14, 2011, to June 30, 2014, with 6-month follow-up completed by April 9, 2015. Eligible participants were 65 years or older with functional limitations owing to their chronic LBP (>= 11 points on the Roland and Morris Disability Questionnaire) and chronic pain (duration >= 3 months) of moderate intensity. Data were analyzed from March 1 to July 1, 2015. INTERVENTIONS The intervention and control groups received an 8-week group program followed by 6 monthly sessions. The intervention was modeled on the Mindfulness-Based Stress Reduction program; the control program, on the "10 Keys" to Healthy Aging. MAIN OUTCOMES AND MEASURES Follow-up occurred at program completion and 6 months later. The score on the Roland and Morris Disability Questionnaire was the primary outcome and measured functional limitations owing to LBP. Pain (current, mean, and most severe in the past week) was measured with the Numeric Pain Rating Scale. Secondary outcomes included quality of life, pain self-efficacy, and mindfulness. Intent-to-treat analyses were conducted. RESULTS Of 1160 persons who underwent screening, 282 participants enrolled in the trial (95 men [33.7%] and 187 women [66.3%]; mean [SD] age, 74.5 [6.6] years). The baseline mean (SD) Roland and Morris Disability Questionnaire scores for the intervention and control groups were 15.6 (3.0) and 15.4 (3.0), respectively. Compared with the control group, intervention participants improved an additional -1.1 (mean, 12.1 vs 13.1) points at 8 weeks and -0.04 (mean, 12.2 vs 12.6) points at 6 months (effect sizes, -0.23 and -0.08, respectively) on the Roland and Morris Disability Questionnaire. By 6 months, the intervention participants improved on the Numeric Pain Rating Scale current and most severe pain measures an additional -1.8 points (95% CI, -3.1 to -0.05 points; effect size, -0.33) and -1.0 points (95% CI, -2.1 to 0.2 points; effect size, -0.19), respectively. The changes in Numeric Pain Rating Scale mean pain measure after the intervention were not significant (-0.1 [95% CI, -1.1 to 1.0] at 8 weeks and -1.1 [95% CI, -2.2 to -0.01] at 6 months; effect size, -0.01 and -0.22, respectively). CONCLUSIONS AND RELEVANCE A mind-body program for chronic LBP improved short-term function and long-term current and most severe pain. The functional improvement was not sustained, suggesting that future development of the intervention could focus on durability. C1 [Morone, Natalia E.; Rollman, Bruce L.; Lane, Bridget] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. [Morone, Natalia E.; Rollman, Bruce L.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Morone, Natalia E.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Greco, Carol M.] Univ Pittsburgh, Sch Med, UPMC, Dept Psychiat,Ctr Integrat Med, Pittsburgh, PA 15213 USA. [Moore, Charity G.] Carolinas HealthCare Syst, Dickson Adv Analyt, Charlotte, NC USA. [Morrow, Lisa A.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Glynn, Nancy W.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. RP Morone, NE (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. EM moronene@upmc.edu OI Glynn, Nancy/0000-0003-2265-0162 FU National Institutes of Health [R01 AG034078] FX This study was supported by grant R01 AG034078 from the National Institutes of Health. NR 29 TC 12 Z9 12 U1 5 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2016 VL 176 IS 3 BP 329 EP 337 DI 10.1001/jamainternmed.2015.8033 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DG7ZP UT WOS:000372302500010 PM 26903081 ER PT J AU Auer, R Vittinghoff, E Yaffe, K Kunzi, A Kertesz, SG Levine, DA Albanese, E Whitmer, RA Jacobs, DR Sidney, S Glymour, MM Pletcher, MJ AF Auer, Reto Vittinghoff, Eric Yaffe, Kristine Kuenzi, Arnaud Kertesz, Stefan G. Levine, Deborah A. Albanese, Emiliano Whitmer, Rachel A. Jacobs, David R., Jr. Sidney, Stephen Glymour, M. Maria Pletcher, Mark J. TI Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age The Coronary Artery Risk Development in Young Adults (CARDIA) Study SO JAMA INTERNAL MEDICINE LA English DT Article ID POPULATION-BASED COHORT; HEAVY CANNABIS USERS; SOCIOECONOMIC-STATUS; DRUG-USE; DECLINE; HEALTH; IQ; INTERFERENCE; EXPOSURE; MIDLIFE AB IMPORTANCE Marijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function. OBJECTIVE To study the association between cumulative lifetime exposure to marijuana use and cognitive performance in middle age. DESIGN, SETTING, AND PARTICIPANTS We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 black and white men and women aged 18 to 30 years at baseline from March 25, 1985, to June 7, 1986 (year 0), and followed up over 25 years from June 7, 1986, to August 31, 2011, to estimate cumulative years of exposure to marijuana (1 year = 365 days of marijuana use) using repeated measures and to assess associations with cognitive function at year 25. Linear regression was used to adjust for demographic factors, cardiovascular risk factors, tobacco smoking, use of alcohol and illicit drugs, physical activity, depression, and results of the mirror star tracing test (a measure of cognitive function) at year 2. Data analysis was conducted from June 7, 1986, to August 31, 2011. MAIN OUTCOMES AND MEASURES Three domains of cognitive function were assessed at year 25 using the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). RESULTS Among 3385 participants with cognitive function measurements at the year 25 visit, 2852 (84.3%) reported past marijuana use, but only 392 (11.6%) continued to use marijuana into middle age. Current use of marijuana was associated with worse verbal memory and processing speed; cumulative lifetime exposure was associated with worse performance in all 3 domains of cognitive function. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worse verbal memory. For each 5 years of past exposure, verbal memory was 0.13 standardized units lower (95% CI, -0.24 to -0.02; P =.02), corresponding to a mean of 1 of 2 participants remembering 1 word fewer from a list of 15 words for every 5 years of use. After adjustment, we found no associations with lower executive function (-0.03 [95% CI, -0.12 to 0.07]; P =.56) or processing speed (-0.04 [95% CI, -0.16 to 0.08]; P =.51). CONCLUSIONS AND RELEVANCE Past exposure to marijuana is associated with worse verbal memory but does not appear to affect other domains of cognitive function. C1 [Auer, Reto; Vittinghoff, Eric; Yaffe, Kristine; Glymour, M. Maria; Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Auer, Reto; Kuenzi, Arnaud] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94143 USA. [Kertesz, Stefan G.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med & Acute Care Res, Birmingham, AL USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Levine, Deborah A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Levine, Deborah A.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Levine, Deborah A.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Levine, Deborah A.] Univ Michigan, Stroke Program, Ann Arbor, MI 48109 USA. [Albanese, Emiliano] Univ Geneva, Dept Psychiat, Geneva, Switzerland. [Whitmer, Rachel A.; Sidney, Stephen] Kaiser Permanente, Div Res, Oakland, CA USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Auer, R (reprint author), Univ Lausanne, Dept Ambulatory Care & Community Med, Rue Bugnon 44, CH-1011 Lausanne, Switzerland. EM reto.auer@hospvd.ch OI Glymour, M. Maria/0000-0001-9644-3081 FU National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA [AG0005]; NHLBI [AG0005] FX The Coronary Artery Risk Development in Young Adults (CARDIA) study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (grants HHSN268201300025C and HHSN268201300026C), Northwestern University (grant HHSN268201300027C), University of Minnesota (grant HHSN268201300028C), Kaiser Foundation Research Institute (grant HHSN268201300029C), and The Johns Hopkins University School of Medicine (grant HHSN268200900041C). The CARDIA study is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between the NIA and the NHLBI (AG0005). NR 45 TC 12 Z9 12 U1 9 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2016 VL 176 IS 3 BP 352 EP 361 DI 10.1001/jamainternmed.2015.7841 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DG7ZP UT WOS:000372302500014 PM 26831916 ER PT J AU Widera, E Talebreza, S AF Widera, Eric Talebreza, Shaida TI Variability in Hospice Care at the Very End of Life SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Widera, Eric] Univ Calif San Francisco, Dept Internal Med, Div Geriatr, San Francisco, CA 94143 USA. [Widera, Eric] San Francisco VA Med Ctr, 4150 Clement St,Campus Box 181G, San Francisco, CA 94121 USA. [Talebreza, Shaida] Univ Utah, Sch Med, Dept Internal Med, Div Geriatr, Salt Lake City, UT USA. [Talebreza, Shaida] George E Wahlen Salt Lake City Vet Affairs Med Ct, Salt Lake City, UT USA. [Talebreza, Shaida] Inspirat Hosp, Salt Lake City, UT USA. RP Widera, E (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Campus Box 181G, San Francisco, CA 94121 USA. EM eric.widera@ucsf.edu NR 2 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2016 VL 176 IS 3 BP 370 EP 371 DI 10.1001/jamainternmed.2015.7931 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DG7ZP UT WOS:000372302500017 PM 26856885 ER PT J AU Kim, TY Schafer, AL AF Kim, Tiffany Y. Schafer, Anne L. TI Variability in DXA Reporting and Other Challenges in Osteoporosis Evaluation SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID PREVENTION; FRACTURE; THERAPY C1 [Kim, Tiffany Y.; Schafer, Anne L.] San Francisco VA Med Ctr, Endocrine Res Unit, 1700 Owens St,Room 367, San Francisco, CA 94158 USA. RP Schafer, AL (reprint author), San Francisco VA Med Ctr, Endocrine Res Unit, 1700 Owens St,Room 367, San Francisco, CA 94158 USA. EM anne.schafer@ucsf.edu FU CSRD VA [IK2 CX000549] NR 7 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2016 VL 176 IS 3 BP 393 EP 395 DI 10.1001/jamainternmed.2015.7550 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DG7ZP UT WOS:000372302500025 PM 26746871 ER PT J AU Lehman, C AF Lehman, Constance TI Potential Benefits of Computer-Aided Detection for Cancer Identification and Treatment Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID SCREENING MAMMOGRAPHY C1 [Lehman, Constance] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Ste 240, Boston, MA 02114 USA. RP Lehman, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Ste 240, Boston, MA 02114 USA. EM clehman@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2016 VL 176 IS 3 BP 411 EP 411 DI 10.1001/jamainternmed.2015.8474 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DG7ZP UT WOS:000372302500038 PM 26954046 ER PT J AU Sun, JK Aiello, LP AF Sun, Jennifer K. Aiello, Lloyd Paul TI The Future of Ultrawide Field Imaging for Diabetic Retinopathy Pondering the Retinal Periphery SO JAMA OPHTHALMOLOGY LA English DT Editorial Material C1 [Sun, Jennifer K.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Beetham Eye Inst,Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2016 VL 134 IS 3 BP 247 EP 248 DI 10.1001/jamaophthalmol.2015.5384 PG 2 WC Ophthalmology SC Ophthalmology GA DH1JN UT WOS:000372540300005 PM 26720171 ER PT J AU Kang, JH Willett, WC Rosner, BA Buys, E Wiggs, JL Pasquale, LR AF Kang, Jae H. Willett, Walter C. Rosner, Bernard A. Buys, Emmanuel Wiggs, Janey L. Pasquale, Louis R. TI Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study SO JAMA OPHTHALMOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; FOOD FREQUENCY QUESTIONNAIRE; NORMAL-TENSION GLAUCOMA; VISUAL-FIELD CHARACTERISTICS; OCULAR BLOOD-FLOW; OSTEOPOROTIC FRACTURES; INTRAOCULAR-PRESSURE; POSTURE CHANGE; EXERCISE; RISK AB IMPORTANCE Nitric oxide signaling alterations in outflow facility and retinal blood flow autoregulation are implicated in primary open-angle glaucoma (POAG). Nitric oxide donation has emerged as a POAG therapeutic target. An exogenous source of nitric oxide is dietary nitrates. OBJECTIVE To evaluate the association between dietary nitrate intake, derived mainly from green leafy vegetables, and POAG. DESIGN, SETTING, AND PARTICIPANTS We followed up participants biennially in the prospective cohorts of the Nurses' Health Study (63 893 women; 1984-2012) and the Health Professionals Follow-up Study (41 094 men; 1986-2012) at each 2-year risk period. Eligible participants were 40 years or older, were free of POAG, and reported eye examinations. EXPOSURES The primary exposure was dietary nitrate intake. Information on diet and potential confounders was updated with validated questionnaires. MAIN OUTCOMES AND MEASURES The main outcome was the incidence of POAG and POAG subtypes; 1483 cases were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP) (>22 or <22 mm Hg) or by visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Cohort-specific and pooled multivariable rate ratios (MVRRs) and 95% CIs were estimated. RESULTS During 1 678 713 person-years of follow-up, 1483 incident cases of POAG were identified. The mean (SD) age for the 1483 cases was 66.8 (8.3). Compared with the lowest quintile of dietary nitrate intake (quintile 1: approximately 80 mg/d), the pooled MVRR for the highest quintile (quintile 5: approximately 240 mg/d) was 0.79 (95% CI, 0.66-0.93; P for trend = .02). The dose response was stronger (P for heterogeneity = .01) for POAG with early paracentral VF loss (433 cases; quintile 5 vs quintile 1 MVRR = 0.56; 95% CI, 0.40-0.79; P for trend < .001) than for POAG with peripheral VF loss only (835 cases; quintile 5 vs quintile 1 MVRR = 0.85; 95% CI, 0.68-1.06; P for trend = .50). The association did not differ (P for heterogeneity = .75) by POAG subtypes defined by IOP (997 case patients with IOP >= 22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.82; 95% CI, 0.67-1.01; P for trend = .11; 486 case patients with IOP <22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.71; 95% CI, 0.53-0.96; P for trend = .12). Green leafy vegetables accounted for 56.7% of nitrate intake variation. Compared with consuming 0.31 servings per day, the MVRR for consuming 1.45 or more servings per day was 0.82 for all POAG (95% CI, 0.69-0.97; P for trend = .02) and 0.52 for POAG with paracentral VF loss (95% CI, 0.29-0.96; P for trend < .001). CONCLUSIONS AND RELEVANCE Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis. C1 [Kang, Jae H.; Willett, Walter C.; Rosner, Bernard A.; Pasquale, Louis R.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. [Kang, Jae H.; Willett, Walter C.; Rosner, Bernard A.; Pasquale, Louis R.] Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Buys, Emmanuel] Massachusetts Gen Hosp, Res Inst, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wiggs, Janey L.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. RP Kang, JH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.; Kang, JH (reprint author), Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu FU National Institutes of Health [R21 EY022766]; Arthur Ashley Foundation; Harvard Glaucoma Center of Excellence; Harvard Medical Distinguished Ophthalmology Scholar Award; [UM1 CA186107]; [UM1 CA167552]; [EY09611]; [EY015473] FX This work was supported by grants UM1 CA186107, UM1 CA167552, EY09611, and EY015473 (Dr Pasquale) and grant R21 EY022766 (Dr Wiggs) from the National Institutes of Health and the Arthur Ashley Foundation, the Harvard Glaucoma Center of Excellence (Drs Pasquale and Wiggs), and a Harvard Medical Distinguished Ophthalmology Scholar Award (Dr Pasquale). NR 87 TC 1 Z9 1 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2016 VL 134 IS 3 BP 294 EP 303 DI 10.1001/jamaophthalmol.2015.5601 PG 10 WC Ophthalmology SC Ophthalmology GA DH1JN UT WOS:000372540300016 PM 26767881 ER PT J AU Silva, PS Cavallerano, JD Haddad, NMN Tolls, D Thakore, K Patel, B Sehizadeh, M Tolson, AM Sun, JK Aiello, LP AF Silva, Paolo S. Cavallerano, Jerry D. Haddad, Nour Maya N. Tolls, Dorothy Thakore, Komal Patel, Bina Sehizadeh, Mina Tolson, Ann M. Sun, Jennifer K. Aiello, Lloyd Paul TI Comparison of Nondiabetic Retinal Findings Identified With Nonmydriatic Fundus Photography vs Ultrawide Field Imaging in an Ocular Telehealth Program SO JAMA OPHTHALMOLOGY LA English DT Article ID SCANNING LASER OPHTHALMOSCOPY; DIABETIC-RETINOPATHY; LESIONS; ANGIOGRAPHY AB IMPORTANCE Ultrawide field imaging (UWFI) is increasingly being used in teleophthalmology settings. Given the greater area of the retina imaged, we evaluated the ability of UWFI vs nonmydriatic fundus photography (NMFP) to detect nondiabetic retinal findings in a teleophthalmology program. OBSERVATION We conducted a retrospective single-center comparative cohort study from January 1, 2011, to June 30, 2013, imaging 3864 and 3971 consecutive teleophthalmology patients (7728 and 7942 eyes) using NMFP and UWFI, respectively. Standard diabetic retinopathy evaluation and nondiabetic findings were compared between the 2 imaging modalities. In patients without diabetic retinopathy (2243 by NMFP and 2252 by UWFI), the rate of identification of nondiabetic findings by NMFP (451 patients [20.1%]) and UWFI (490 [21.8%]) were comparable (P = .19). Ultrawide field imaging increased the identification of choroidal nevi by 27%(406 eyes [5.3%] by NMFP vs 545 eyes [6.9%] by UWFI; P < .001) and chorioretinal atrophy or scarring by 116%(50 eyes [0.6%] by NMFP vs 101 eyes [1.3%] by UWFI; P < .001). No peripheral retinal findings were identified with NMFP, while UWFI detected 25 retinal tears (0.3%; P < .001), 54 lattice and peripheral degenerations (0.7%; P < .001), and 142 cases of vitreous detachment or floaters (1.8%; P < .001). Data analysis was performed from November 1, 2013, to May 1, 2014. CONCLUSIONS AND RELEVANCE In eyes without diabetic retinopathy, approximately 20% may have ocular findings identified on retinal imaging, which emphasizes the role of retinal imaging in patients with diabetes mellitus type 1 and type 2 regardless of the severity of retinopathy. In this cohort, UWFI increased the identification of peripheral retinal and vitreous pathologic findings. C1 [Silva, Paolo S.; Cavallerano, Jerry D.; Haddad, Nour Maya N.; Tolls, Dorothy; Thakore, Komal; Patel, Bina; Sehizadeh, Mina; Tolson, Ann M.; Sun, Jennifer K.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, One Joslin Pl, Boston, MA 02215 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Silva, Paolo S.] Univ Philippines, Philippine Eye Res Inst, Teleophthalmol & Image Reading Ctr, Manila, Philippines. [Patel, Bina] New England Coll Optometry, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, One Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu FU Massachusetts Lions Eye Research Fund FX This study was supported by the Massachusetts Lions Eye Research Fund (Drs Silva and Aiello). Temporary loan of 2 ultrawide field imaging devices was provided to the Joslin Diabetes Center by Optos plc. NR 15 TC 3 Z9 3 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2016 VL 134 IS 3 BP 330 EP 334 DI 10.1001/jamaophthalmol.2015.5605 PG 5 WC Ophthalmology SC Ophthalmology GA DH1JN UT WOS:000372540300020 PM 26795026 ER PT J AU Stryjewski, TP Papakostas, TD Vavvas, D AF Stryjewski, Tomasz P. Papakostas, Thanos D. Vavvas, Demetrios TI Proliferative Hypertensive Retinopathy SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Stryjewski, Tomasz P.; Papakostas, Thanos D.; Vavvas, Demetrios] Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. [Papakostas, Thanos D.; Vavvas, Demetrios] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Vavvas, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2016 VL 134 IS 3 BP 345 EP 346 DI 10.1001/jamaophthalmol.2015.5583 PG 3 WC Ophthalmology SC Ophthalmology GA DH1JN UT WOS:000372540300026 PM 26767543 ER PT J AU Suh, I Yingling, C Randolph, GW Duh, QY AF Suh, Insoo Yingling, Charles Randolph, Gregory W. Duh, Quan-Yang TI A Novel Method of Neuromonitoring in Thyroidectomy and Parathyroidectomy Using Transcutaneous Intraoperative Vagal Stimulation SO JAMA SURGERY LA English DT Letter ID RECURRENT LARYNGEAL NERVE; INJURY; IONM C1 [Suh, Insoo; Duh, Quan-Yang] Univ Calif San Francisco, Dept Surg, Endocrine Surg Sect, Mt Zion Med Ctr, 1600 Divisadero St,Room A-725, San Francisco, CA 94115 USA. [Suh, Insoo; Duh, Quan-Yang] Vet Affairs Med Ctr, Surg Serv, San Francisco, CA 94121 USA. [Yingling, Charles] Golden Gate Neuromonitoring, San Francisco, CA USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Suh, I (reprint author), Univ Calif San Francisco, Dept Surg, Endocrine Surg Sect, Mt Zion Med Ctr, 1600 Divisadero St,Room A-725, San Francisco, CA 94115 USA. EM insoo.suh@ucsf.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2016 VL 151 IS 3 BP 290 EP 292 DI 10.1001/jamasurg.2015.3249 PG 4 WC Surgery SC Surgery GA DG7TI UT WOS:000372286200023 PM 26535804 ER PT J AU Waltz, P Luciano, J Peitzman, A Zuckerbraun, BS AF Waltz, Paul Luciano, Jason Peitzman, Andrew Zuckerbraun, Brian S. TI Femoral Hernias in Patients Undergoing Total Extraperitoneal Laparoscopic Hernia Repair: Including Routine Evaluation of the Femoral Canal in Approaches to Inguinal Hernia Repair SO JAMA SURGERY LA English DT Letter C1 [Waltz, Paul; Luciano, Jason; Peitzman, Andrew; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, VA Pittsburgh Healthcare Syst, F1267 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2016 VL 151 IS 3 BP 292 EP 293 DI 10.1001/jamasurg.2015.3402 PG 3 WC Surgery SC Surgery GA DG7TI UT WOS:000372286200024 PM 26558846 ER PT J AU Lehman, CD Lee, JM DeMartini, WB Hippe, DS Rendi, MH Kalish, G Porter, P Gralow, J Partridge, SC AF Lehman, Constance D. Lee, Janie M. DeMartini, Wendy B. Hippe, Daniel S. Rendi, Mara H. Kalish, Grace Porter, Peggy Gralow, Julie Partridge, Savannah C. TI Screening MRI in Women With a Personal History of Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROSPECTIVE MULTICENTER COHORT; HIGH FAMILIAL RISK; FOLLOW-UP; CONSERVATION THERAPY; MAMMOGRAPHY; TRIAL; SURVEILLANCE; TAMOXIFEN; ULTRASOUND; SOCIETY AB Screening MRI is recommended for individuals at high risk for breast cancer, based on genetic risk or family history (GFH); however, there is insufficient evidence to support screening MRI for women with a personal history (PH) of breast cancer. We compared screening MRI performance in women with PH vs GFH of breast cancer. We analyzed case-series registry data, collected at time of MRI and at 12-month follow-up, from our regional Clinical Oncology Data Integration project. MRI performance was compared in women with PH with those with GFH. Chi-square testing was used to identify associations between age, prior history of MRI, and clinical indication with MRI performance; logistic regression was used to determine the combined contribution of these variables in predicting risk of a false-positive exam. All statistical tests were two-sided. Of 1521 women who underwent screening MRI from July 2004 to November 2011, 915 had PH and 606 had GFH of breast cancer. Overall, MRI sensitivity was 79.4% for all cancers and 88.5% for invasive cancers. False-positive exams were lower in the PH vs GFH groups (12.3% vs 21.6%, P < .001), specificity was higher (94.0% vs 86.0%, P < .001), and sensitivity and cancer detection rate were not statistically different (P > .99). Age (P < .001), prior MRI (P < .001), and clinical indication (P < .001) were individually associated with initial false-positive rate; age and prior MRI remained statistically significant in multivariable modeling (P = .001 and P < .001, respectively). MRI performance is superior in women with PH compared with women with GFH. Screening MRI warrants consideration as an adjunct to mammography in women with a PH of breast cancer. C1 [Lehman, Constance D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Janie M.; Hippe, Daniel S.; Kalish, Grace; Partridge, Savannah C.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Lee, Janie M.; Partridge, Savannah C.] Seattle Canc Care Alliance, Seattle, WA USA. [DeMartini, Wendy B.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Rendi, Mara H.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Porter, Peggy; Gralow, Julie] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Gralow, Julie] Univ Washington, Med Ctr, Dept Med Oncol, Seattle, WA 98195 USA. RP Lehman, CD (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging, Avon Comprehens Breast Evaluat Ctr, Suite 240,55 Fruit St, Boston, MA 02114 USA. EM clehman@mgh.harvard.edu NR 40 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAR PY 2016 VL 108 IS 3 AR djv349 DI 10.1093/jnci/djv349 PG 8 WC Oncology SC Oncology GA DH2BP UT WOS:000372589400015 ER PT J AU Marler, S Ferguson, BJ Lee, EB Peters, B Williams, KC McDonnell, E Macklin, EA Levitt, P Gillespie, CH Anderson, GM Margolis, KG Beversdorf, DQ Veenstra-VanderWeele, J AF Marler, Sarah Ferguson, Bradley J. Lee, Evon Batey Peters, Brittany Williams, Kent C. McDonnell, Erin Macklin, Eric A. Levitt, Pat Gillespie, Catherine Hagan Anderson, George M. Margolis, Kara Gross Beversdorf, David Q. Veenstra-VanderWeele, Jeremy TI Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Serotonin; 5-HT; Gastrointestinal (GI); IL-6; Medical comorbidities; Autism Treatment Network ID MENTAL-RETARDATION; METAANALYSIS; CHILDREN; BEHAVIOR AB Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD. C1 [Marler, Sarah; Peters, Brittany] Vanderbilt Univ, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Ferguson, Bradley J.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Interdisciplinary Neurosci Program, Columbia, MO USA. [Lee, Evon Batey] Vanderbilt Univ, Dept Pediat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Lee, Evon Batey] Vanderbilt Univ, Dept Psychol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Lee, Evon Batey] Vanderbilt Univ, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Williams, Kent C.] Nationwide Childrens, Dept Gastroenterol Hepatol & Nutr, Columbus, OH USA. [McDonnell, Erin; Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Levitt, Pat] Childrens Hosp Los Angeles, Inst Developing Mind, Dev Neurogenet, Los Angeles, CA 90027 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Neurogenet, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Neurosci, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Pharm, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Psychol, Los Angeles, CA 90033 USA. [Gillespie, Catherine Hagan] Univ Missouri, Coll Vet Med, Dept Vet Pathobiol, Columbia, MO USA. [Anderson, George M.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Margolis, Kara Gross] Columbia Univ, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, New York, NY 10027 USA. [Beversdorf, David Q.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorder, Interdisciplinary Neurosci Program, Dept Radiol, Columbia, MO USA. [Beversdorf, David Q.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorder, Interdisciplinary Neurosci Program, Dept Neurol, Columbia, MO USA. [Beversdorf, David Q.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorder, Interdisciplinary Neurosci Program, Dept Psychol Sci, Columbia, MO USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Dept Psychiat, 1051 Riverside Dr,Mail Unit 78, New York, NY 10032 USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Sackler Inst Dev Psychobiol, 1051 Riverside Dr,Mail Unit 78, New York, NY 10032 USA. [Veenstra-VanderWeele, Jeremy] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Veenstra-VanderWeele, Jeremy] New York Presbyterian Hosp, Ctr Autism & Developing Brain, White Plains, NY USA. RP Veenstra-VanderWeele, J (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr,Mail Unit 78, New York, NY 10032 USA.; Veenstra-VanderWeele, J (reprint author), Columbia Univ, Sackler Inst Dev Psychobiol, 1051 Riverside Dr,Mail Unit 78, New York, NY 10032 USA.; Veenstra-VanderWeele, J (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA.; Veenstra-VanderWeele, J (reprint author), New York Presbyterian Hosp, Ctr Autism & Developing Brain, White Plains, NY USA. EM sarah.marler@vanderbilt.edu; fergusonbj@health.missouri.edu; evon.lee@vanderbilt.edu; brittany.peters@vanderbilt.edu; kent.williams@nationwidechildrens.org; eimcdonnell@mgh.harvard.edu; emacklin@mgh.harvard.edu; plevitt@med.usc.edu; haganc@missouri.edu; george.anderson@yale.edu; kjg2133@cumc.columbia.edu; beversdorfd@health.missouri.edu; jeremy.vvw@gmail.com RI Beversdorf, David/M-2786-2016; OI Beversdorf, David/0000-0002-0298-0634; Macklin, Eric/0000-0003-1618-3502 FU [UA3MC11054] FX We would like to thank the children and families who participated in this study. This research was supported by a Grant given to the Autism Treatment Network, Autism Intervention Research Network on Physical Health by the Health Resources Services Administration (HRSA Grant# UA3MC11054). This article was reviewed by the funding body prior to submission. NR 24 TC 2 Z9 3 U1 5 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2016 VL 46 IS 3 BP 1124 EP 1130 DI 10.1007/s10803-015-2646-8 PG 7 WC Psychology, Developmental SC Psychology GA DG7RO UT WOS:000372281600035 PM 26527110 ER PT J AU Perrotta, L Kandala, J Di Biase, L Valleggi, A Michelotti, F Pieragnoli, P Ricciardi, G Mascioli, G Lakkireddy, D Pillarisetti, J Emdin, M Natale, A Singh, JP Padeletti, L AF Perrotta, Laura Kandala, Jagdesh Di Biase, Luigi Valleggi, Alessandro Michelotti, Federica Pieragnoli, Paolo Ricciardi, Giuseppe Mascioli, Giosue Lakkireddy, Dhanunjaya Pillarisetti, Jayasree Emdin, Michele Natale, Andrea Singh, Jagmeet P. Padeletti, Luigi TI Prognostic Impact of QRS Axis Deviation in Patients Treated With Cardiac Resynchronization Therapy SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; heart failure; left bundle branch block; QRS axis deviation ID BUNDLE-BRANCH-BLOCK; RANDOMIZED CONTROLLED-TRIALS; LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE; MORPHOLOGY; DURATION; OUTCOMES; METAANALYSIS; PREDICTORS; CARDIOLOGY AB Prognosis of QRS Axis Deviation in CRT-D IntroductionQRS duration and morphology are currently recognized as recommended criteria for the selection of CRT candidates. It has recently been shown that patients with left bundle branch block (LBBB) derive substantial clinical benefit from CRT. The aim of this study is to investigate the prognostic impact of QRS axis deviation (AD) in HF patients with LBBB undergoing CRT. Methods and ResultsWe retrospectively evaluated 707 HF patients with LBBB who underwent CRT at five centers. Baseline QRS axis was defined as normal (NA: -30 degrees to 90 degrees), right axis deviation (RAD: 90 degrees to 180 degrees) and left axis deviation (LAD: <-30 degrees). The primary endpoint was a composite of all cause death/HF hospitalization. The risk of endpoint by AD was evaluated with both Kaplan-Meier and Cox proportional hazard analysis. Among 707 patients (73% M, median age: 71 [62,77] years), 323 (46%) had NA, 359 (51%) LAD, and 25 (3.5%) RAD. Baseline clinical characteristics were similar between the three groups. Over a mean follow-up of 32 25 months, 141 deaths occurred (21%) and 36% (n = 255) met with the composite endpoint. A significantly higher proportion of RAD patients (52%) reached the endpoint (LAD 40%, NA 30%). KM analysis showed that RAD and LAD patients had worse event free survival and in multivariate analysis both LAD (HR: 1.40; 95% CI: 1.05-1.86; P = 0.021) and RAD (HR: 2.49; 95% CI: 1.31-4.74; P = 0.005) were independently associated with worse clinical outcome. ConclusionsRight or left axis deviation in the presence of LBBB in HF patients undergoing CRT are independent predictors of poor prognosis. C1 [Perrotta, Laura; Michelotti, Federica; Pieragnoli, Paolo; Ricciardi, Giuseppe; Padeletti, Luigi] Univ Florence, Viale Morgagni 85, I-50134 Florence, Italy. [Kandala, Jagdesh; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Di Biase, Luigi; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Valleggi, Alessandro; Emdin, Michele] Fdn Monasterio, Pisa, Italy. [Michelotti, Federica; Mascioli, Giosue] Gavazzeni Hosp, Bergamo, Italy. [Lakkireddy, Dhanunjaya; Pillarisetti, Jayasree] Univ Kansas, Bloch Heart Rhythm Ctr, Div Cardiovasc Dis, Cardiovasc Res Inst,Hosp & Med Ctr, Kansas City, KS USA. [Padeletti, Luigi] IRCCS MultiMed, Milan, Italy. RP Perrotta, L (reprint author), Univ Florence, Viale Morgagni 85, I-50134 Florence, Italy. EM laura_perrotta81@hotmail.com OI Di Biase, Luigi/0000-0001-6508-4047 FU EHRA (European Heart Rhythm Association) fellowship grant; Biotronik; Boston Scientific; Sorin; St. Jude Medical; Medtronic FX L. Perrotta was supported by an EHRA (European Heart Rhythm Association) fellowship grant.; L. Di Biase serves as a consultant/advisory board member of Biosense Webster, St. Jude Medical, Hansen, Medtronic, Biotronik, and Boston Scientific. A. Natale reports honoraria from Biosense Webster and serving as consultant/advisory board member of Janssen, Boston Scientific, Medtronic, and St. Jude Medical. J. P. Singh serves as an advisor/consultant for Biotronik, Boston Scientific, Medtronic, Sorin, St. Jude Medical, Respicardia, and CardioInsight; he has received honoraria for participating in educational symposiums sponsored by Biotronik, Boston Scientific, Sorin, and St. Jude Medical; and received grants for clinical research from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical. L. Padeletti is consultant for Medtronic, St. Jude Medical, Biotronik, and Boston Scientific. NR 19 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAR PY 2016 VL 27 IS 3 BP 315 EP 320 DI 10.1111/jce.12887 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DH2WT UT WOS:000372648600014 PM 26640084 ER PT J AU Maron, BA Stephens, TE Farrell, LA Oldham, WM Loscalzo, J Leopold, JA Lewis, GD AF Maron, Bradley A. Stephens, Thomas E. Farrell, Laurie A. Oldham, William M. Loscalzo, Joseph Leopold, Jane A. Lewis, Gregory D. TI Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE aldosterone; exercise; heart failure; cardiac reserve; reduced ejection fraction ID SMOOTH-MUSCLE-CELLS; HYPERTENSION; HEMODYNAMICS; SILDENAFIL; ENDOTHELIN; FIBROSIS; RECEPTOR AB BACKGROUND: Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aimed to characterize ET-1 and transpulmonary aldosterone levels in HFrEF and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO(2)). METHODS: Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively. RESULTS: Radial ET-1 levels (median [interquartile range]) were higher in HFrEF patients compared with controls (17.5 [11.5-31.4] vs 11.5 [4.4-19.0] pg/ml, p = 0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] radial arterial levels) was present in HFrEF (p < 0.001) but not in controls (p = 0.24). Compared with controls, aldosterone levels (median [interquartile range]) were increased in HFrEF patients in the PA (364 [250-489] vs 581 [400-914] ng/dl, p < 0.01) and radial compartments (366 [273-466] vs 702 [443-1223] ng/dl, p < 0.001). Akin to ET-1, a transpulmonary increase (median [interquartile range]) in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [-54 to 40] vs 61.6 [-13.6 to 165] ng/dl, p = 0.01) and peak exercise (-20.7 [-39.6 to 79.1] vs 25.8 [-29.2 to 109.3] ng/dl, p = 0.02). The adjusted pVO(2) correlated inversely with aldosterone levels at peak activity in the PA (r = -0.31, p = 0.01) and radial artery (r = -0.32, p = 0.01). CONCLUSIONS: These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone arid pVO(2). Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve capacity in HFrEF. Published by Elsevier Inc. C1 [Maron, Bradley A.; Stephens, Thomas E.; Loscalzo, Joseph; Leopold, Jane A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Maron, Bradley A.; Stephens, Thomas E.; Farrell, Laurie A.; Oldham, William M.; Loscalzo, Joseph; Leopold, Jane A.; Lewis, Gregory D.] Harvard Univ, Sch Med, Boston, MA USA. [Maron, Bradley A.] Vet Affairs Boston Healthcare Syst, Dept Cardiol, West Roxbury, MA USA. [Farrell, Laurie A.; Lewis, Gregory D.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Oldham, William M.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, 800 Fruit St, Boston, MA 02114 USA. EM glewis@partners.orrg FU Gilead Sciences Inc; National Institutes of Health [HL061795, HL108630, HL048743, GM107618, R01-105301, U01-1252151, R01-HL1-19154, U10-HL1-10337, T32-HL-007633, K08-HL1-11207-01A1]; American Heart Association [15GRNT25080016]; Pulmonary Hypertension Association; Gilead Research Scholars Fund; Cardiovascular Medical Research and Education Foundation; Klarman Foundation (Boston, MA) at Brigham; Women's Hospital FX B.A.M. receives funding from Gilead Sciences Inc to study pulmonary hypertension. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.; This work was supported by National Institutes of Health (HL061795, HL108630, HL048743, and GM107618 to J.L.; R01-105301 and U01-1252151 to J.A.L.; R01-HL1-19154, U10-HL1-10337, and Hassenfeld Clinical Scholar Award to G.D.L.; T32-HL-007633 to W.M.O.; K08-HL1-11207-01A1 to B.A.M.), and the American Heart Association (15GRNT25080016), Pulmonary Hypertension Association, Gilead Research Scholars Fund, Cardiovascular Medical Research and Education Foundation, and the Klarman Foundation (Boston, MA) at Brigham and Women's Hospital to B.A.M. NR 24 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAR PY 2016 VL 35 IS 3 BP 342 EP 351 DI 10.1016/j.healun.2015.10.019 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DH3JI UT WOS:000372682900011 PM 26586488 ER PT J AU Kansagara, D Chiovaro, JC Kagen, D Jencks, S Rhyne, K O'Neil, M Kondo, K Relevo, R Motu'apuaka, M Freeman, M Englander, H AF Kansagara, Devan Chiovaro, Joseph C. Kagen, David Jencks, Stephen Rhyne, Kerry O'Neil, Maya Kondo, Karli Relevo, Rose Motu'apuaka, Makalapua Freeman, Michele Englander, Honora TI So many options, where do we start? An overview of the care transitions literature SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; ACUTE CORONARY SYNDROME; HEART-FAILURE; FOLLOW-UP; HOSPITAL DISCHARGE; SYSTEMATIC REVIEWS; METAANALYSIS; HOME; INTERVENTIONS; READMISSIONS AB BACKGROUNDHealth systems are faced with a large array of transitional care interventions and patient populations to whom such activities might apply. PURPOSETo summarize the health and utilization effects of transitional care interventions, and to identify common themes about intervention types, patient populations, or settings that modify these effects. DATA SOURCESPubMed and Cochrane Database of Systematic Reviews (January 1950-May 2014), reference lists, and technical advisors. STUDY SELECTIONSystematic reviews of transitional care interventions that reported hospital readmission as an outcome. DATA EXTRACTIONWe extracted transitional care procedures, patient populations, settings, readmissions, and health outcomes. We identified commonalities and compiled a narrative synthesis of emerging themes. DATA SYNTHESISAmong 10 reviews of mixed patient populations, there was consistent evidence that enhanced discharge planning and hospital-at-home interventions reduced readmissions. Among 7 reviews in specific patient populations, transitional care interventions reduced readmission in patients with congestive heart failure and general medical populations. In general, interventions that reduced readmission addressed multiple aspects of the care transition, extended beyond hospital stay, and had the flexibility to accommodate individual patient needs. There was insufficient evidence on how caregiver involvement, transition to sites other than home, staffing, patient selection practices, or care settings modified intervention effects. CONCLUSIONSSuccessful interventions are comprehensive, extend beyond hospital stay, and have the flexibility to respond to individual patient needs. The strength of evidence should be considered low because of heterogeneity in the interventions studied, patient populations, clinical settings, and implementation strategies. Journal of Hospital Medicine 2016;11:221-230. (c) 2015 Society of Hospital Medicine. C1 [Kansagara, Devan; Chiovaro, Joseph C.; Kagen, David; Rhyne, Kerry; Freeman, Michele] VA Portland Hlth Care Syst, Dept Med, Portland, OR USA. [Kansagara, Devan; Chiovaro, Joseph C.; Kagen, David; Rhyne, Kerry; Englander, Honora] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Kansagara, Devan; O'Neil, Maya; Kondo, Karli; Relevo, Rose; Motu'apuaka, Makalapua; Freeman, Michele] Portland VA Evidence Based Synth Program, Portland, OR USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration (VHA) [ESP 05-225, 01-0206]; Quality Enhancement Research Initiative, Department of Veterans Affairs [05-225] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration (VHA) Project ESP 05-225, VA#01-0206. Dr. Jencks' work on this project was supported in part by a grant from the Quality Enhancement Research Initiative (05-225), Department of Veterans Affairs. Dr. Jencks has reported prior consulting work with the following entities: Inovalon, Care Centrix, Affymax, Curaspan, Reinforced Care, Health Services Advisory Group, Delmarva Foundation, Connecticut Peer Review Organization, Maryland Health Services Cost Review Commission, Institute for Healthcare Improvement, American Association for Respiratory Care, Monaghan Medical, Iowa Society for Respiratory Care. NR 38 TC 5 Z9 5 U1 6 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAR PY 2016 VL 11 IS 3 BP 221 EP 230 DI 10.1002/jhm.2502 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DG8JQ UT WOS:000372330500011 PM 26551918 ER PT J AU Llibre, A Lopez-Macias, C Marafioti, T Mehta, H Partridge, A Kanzig, C Rivellese, F Galson, JD Walker, LJ Milne, P Phillips, RE Kelly, DF Freeman, GJ El Shikh, ME Klenerman, P Willberg, CB AF Llibre, Alba Lopez-Macias, Constantino Marafioti, Teresa Mehta, Hema Partridge, Amy Kanzig, Carina Rivellese, Felice Galson, Jacob D. Walker, Lucy J. Milne, Paul Phillips, Rodney E. Kelly, Dominic F. Freeman, Gordon J. El Shikh, Mohey Eldin Klenerman, Paul Willberg, Christian B. TI LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; C-TYPE LECTIN; OSTEOCLAST INHIBITORY LECTIN; FUNCTION IN-VITRO; HUMAN T-CELLS; IMMUNE-RESPONSES; HUMAN NKR-P1A; SOMATIC MUTATION; CUTTING EDGE; HELPER-CELLS AB Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the GC in humans. C1 [Llibre, Alba; Mehta, Hema; Partridge, Amy; Kanzig, Carina; Phillips, Rodney E.; Klenerman, Paul; Willberg, Christian B.] Univ Oxford, Peter Medawar Bldg Pathogen Res,South Parks Rd, Oxford OX1 3SY, England. [Lopez-Macias, Constantino] Specialties Hosp, Mexican Inst Social Secur, Natl Med Ctr Siglo 21, Med Res Unit Immunochem, Mexico City 06720, DF, Mexico. [Marafioti, Teresa] UCL, Dept Histopathol, London WC1E 6JJ, England. [Rivellese, Felice; El Shikh, Mohey Eldin] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Ctr Expt Med & Rheumatol, London EC1M 6BQ, England. [Galson, Jacob D.; Kelly, Dominic F.] Univ Oxford, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford Vaccine Grp,Dept Paediat, S Parks Rd, Oxford OX3 7LJ, England. [Walker, Lucy J.; Milne, Paul] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Klenerman, Paul; Willberg, Christian B.] Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 9DU, England. RP Willberg, CB (reprint author), Univ Oxford, Peter Medawar Bldg Pathogen Res,South Parks Rd, Oxford OX1 3SY, England.; El Shikh, ME (reprint author), Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Ctr Expt Med & Rheumatol, London EC1M 6BQ, England. EM m.elshikh@qmul.ac.uk; chris.willberg@ndm.ox.uk OI Willberg, Christian/0000-0001-5299-9344; Galson, Jacob/0000-0003-4916-800X FU University College London Hospitals/University College London National Institute for Health Research Comprehensive Biomedical Research Centre; National Institute for Health Research Biomedical Research Centre, Oxford; National Institutes of Health/National Institute of Allergy and Infectious Diseases U19 Bio-Defense Program (National Institutes of Health/National Institute of Allergy and Infectious Diseases) [1U19AI082630-01, U19 AI082630]; Wellcome Trust Senior Fellowship [WT091663MA]; Obra Social La Caixa FX This work was supported by grants from the University College London Hospitals/University College London National Institute for Health Research Comprehensive Biomedical Research Centre (to T.M.), the National Institute for Health Research Biomedical Research Centre, Oxford (to C.B.W. and P.K.), National Institutes of Health/National Institute of Allergy and Infectious Diseases U19 Bio-Defense Program (National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants 1U19AI082630-01 and U19 AI082630) (to C.B.W. and P.K.), and by Wellcome Trust Senior Fellowship WT091663MA (to P.K.) and Obra Social La Caixa (to A.L.). NR 71 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2016 VL 196 IS 5 BP 2085 EP 2094 DI 10.4049/jimmunol.1502462 PG 10 WC Immunology SC Immunology GA DG8LT UT WOS:000372336300013 PM 26829983 ER PT J AU Nowakowska, DJ Kissler, S AF Nowakowska, Dominika J. Kissler, Stephan TI Ptpn22 Modifies Regulatory T Cell Homeostasis via GITR Upregulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-DOSE INTERLEUKIN-2; OF-FUNCTION VARIANT; TYROSINE-PHOSPHATASE; ALLELIC VARIANT; B-CELLS; RECEPTOR; AUTOIMMUNITY; LIGAND; PROLIFERATION; SUPPRESSION AB PTPN22 gene variation associates with multiple autoimmune diseases, including type 1 diabetes and rheumatoid arthritis. Loss of function studies have demonstrated that PTPN22 impinges on the homeostatic behavior of regulatory T (Treg) cells, a lineage critical for immune tolerance. The frequency and absolute number of Treg cells is increased in Ptpn22-deficient mice, but the mechanism driving this increase is unknown. In this study, we show that Ptpn22 knockdown (KD) promoted the expansion of the Treg cell compartment by upregulating the glucocorticoid-induced TNFR family-related protein (GITR) and increasing GITR signaling. Ptpn22 KD did not accelerate cell division but instead prolonged Treg cell survival, as measured by a decrease in the frequency of apoptotic Treg cells. Loss of Ptpn22 caused a concomitant increase in the proportion of CD44(hi)CD62L(lo) effector Treg cells, at the expense of CD44(lo)CD62L(hi) central Treg cells. The increase in Treg cell numbers, but not their differentiation toward an effector phenotype, was dependent on GITR signaling, because blockade of GITR ligand prevented Treg cell expansion caused by Ptpn22 KD. These findings indicate that GITR plays a key role in regulating the overall size of the Treg cell pool. Our results suggest that the size and composition of the Treg cell compartment are independently controlled and have implications for the design of immunotherapies that seek to improve Treg cell function. C1 [Nowakowska, Dominika J.; Kissler, Stephan] Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. RP Kissler, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM Stephan.Kissler@joslin.harvard.edu OI , /0000-0003-3062-7800 FU JDRF Career Development Award [2-2010-383]; Iacocca Foundation; Diabetes Research Center award (National Institutes of Health) [P30DK036836] FX This work was supported in part by JDRF Career Development Award 2-2010-383 (to S.K.), by a Mary K. Iacocca fellowship from the Iacocca Foundation (to D.J.N.), and by a Diabetes Research Center award (National Institutes of Health Grant P30DK036836) to the Joslin Diabetes Center. NR 29 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2016 VL 196 IS 5 BP 2145 EP 2152 DI 10.4049/jimmunol.1501877 PG 8 WC Immunology SC Immunology GA DG8LT UT WOS:000372336300018 PM 26810223 ER PT J AU Khan, NS Kasperkovitz, PV Timmons, AK Mansour, MK Tam, JM Seward, MW Reedy, JL Puranam, S Feliu, M Vyas, JM AF Khan, Nida S. Kasperkovitz, Pia V. Timmons, Allison K. Mansour, Michael K. Tam, Jenny M. Seward, Michael W. Reedy, Jennifer L. Puranam, Sravanthi Feliu, Marianela Vyas, Jatin M. TI Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing beta-1,3 Glucan SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; ASPERGILLUS-FUMIGATUS; CANDIDA-ALBICANS; IMMUNE RECOGNITION; DENDRITIC CELLS; INNATE IMMUNITY; PROTEOLYTIC CLEAVAGE; CYTOKINE PRODUCTION; FUNGAL-INFECTIONS; HOST-DEFENSE AB Dectin-1 and TLR9 play distinct roles in the recognition and induction of innate immune responses to Aspergillus fumigatus and Candida albicans. Dectin-1 is a receptor for the major fungal cell wall carbohydrate beta-1,3 glucan that induces inflammatory cytokines and controls phagosomal maturation through spleen tyrosine kinase activation. TLR9 is an endosomal TLR that also modulates the inflammatory cytokine response to fungal pathogens. In this study, we demonstrate that beta-1,3 glucan beads are sufficient to induce dynamic redistribution and accumulation of cleaved TLR9 to phagosomes. Trafficking of TLR9 to A. fumigatus and C. albicans phagosomes requires Dectin-1 recognition. Inhibition of phagosomal acidification blocks TLR9 accumulation on phagosomes containing beta-1,3 glucan beads. Dectin-1-mediated spleen tyrosine kinase activation is required for TLR9 trafficking to beta-1,3 glucan-, A. fumigatus-, and C. albicans-containing phagosomes. In addition, Dectin-1 regulates TLR9-dependent gene expression. Collectively, our study demonstrates that recognition of beta-1,3 glucan by Dectin-1 triggers TLR9 trafficking to beta-1,3 glucan-containing phagosomes, which may be critical in coordinating innate antifungal defense. C1 [Khan, Nida S.; Timmons, Allison K.; Mansour, Michael K.; Tam, Jenny M.; Seward, Michael W.; Reedy, Jennifer L.; Puranam, Sravanthi; Feliu, Marianela; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. [Khan, Nida S.] Univ Massachusetts, Biomed Engn & Biotechnol, Lowell, MA 01854 USA. [Kasperkovitz, Pia V.] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Mansour, Michael K.; Reedy, Jennifer L.; Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Feliu, Marianela] Boston Univ, Nutr & Metab, Boston, MA 02118 USA. [Vyas, Jatin M.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jvyas@partners.org FU National Institutes of Health [5R01 A1 092084, 1R01 A1 097519]; National Institutes of Health/National Institute of Allergy and Infectious Diseases [1K08AI110655, T32 A1007061-35, KL2 TR001100] FX This work was supported by National Institutes of Health Grants 5R01 A1 092084 and 1R01 A1 097519 and National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants 1K08AI110655 (to M.K.M.), T32 A1007061-35 (to J.L.R.), and KL2 TR001100 (to J.L.R.). NR 61 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2016 VL 196 IS 5 BP 2249 EP 2261 DI 10.4049/jimmunol.1401545 PG 13 WC Immunology SC Immunology GA DG8LT UT WOS:000372336300027 PM 26829985 ER PT J AU Caballero-Franco, C Guma, M Choo, MK Sano, Y Enzler, T Karin, M Mizoguchi, A Park, JM AF Caballero-Franco, Celia Guma, Monica Choo, Min-Kyung Sano, Yasuyo Enzler, Thomas Karin, Michael Mizoguchi, Atsushi Park, Jin Mo TI Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38 alpha-Dependent Restraint of NF-kappa B Signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOTOXIN BETA-RECEPTOR; CHEMOKINE RECEPTOR; FOLLICLE FORMATION; LARGE-INTESTINE; INDUCER CELLS; PROTEIN-KINASE; T-CELLS; HOMEOSTASIS; P38-ALPHA; PROLIFERATION AB The protein kinase p38 alpha mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38 alpha in several different cell types have demonstrated that p38 alpha signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38 alpha. In this study, we show that p38 alpha regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38 alpha gene, we find that p38 alpha serves to limit NF-kappa B signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38 alpha-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. C1 [Caballero-Franco, Celia; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA. [Caballero-Franco, Celia; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Mizoguchi, Atsushi; Park, Jin Mo] Harvard Univ, Sch Med, 149 Thirteenth St, Charlestown, MA 02129 USA. [Guma, Monica; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Guma, Monica] Univ Calif San Diego, Sch Med, Div Rheumatol Allergy & Immunol, La Jolla, CA 92093 USA. [Enzler, Thomas] Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ 85724 USA. [Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Mizoguchi, Atsushi] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Park, JM (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA.; Park, JM (reprint author), Harvard Univ, Sch Med, 149 Thirteenth St, Charlestown, MA 02129 USA. EM jmpark@cbrc2.mgh.harvard.edu FU National Institutes of Health [AI074957, AI043477] FX This work was supported by National Institutes of Health Grants AI074957 (to J.M.P.) and AI043477 (to M.K.). NR 53 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2016 VL 196 IS 5 BP 2368 EP 2376 DI 10.4049/jimmunol.1501724 PG 9 WC Immunology SC Immunology GA DG8LT UT WOS:000372336300039 PM 26792803 ER PT J AU Scully, E Lockhart, A Huang, L Robles, Y Becerril, C Romero-Tejeda, M Albrecht, MA Palmer, CD Bosch, RJ Altfeld, M Kuritzkes, DR Lin, NH AF Scully, Eileen Lockhart, Ainsley Huang, Lisa Robles, Yvonne Becerril, Carlos Romero-Tejeda, Marisol Albrecht, Mary A. Palmer, Christine D. Bosch, Ronald J. Altfeld, Marcus Kuritzkes, Daniel R. Lin, Nina H. TI Elevated Levels of Microbial Translocation Markers and CCL2 Among Older HIV-1-Infected Men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-1; inflammation; monocytes; chemokine ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HIV-INFECTION; ATHEROSCLEROSIS; PREDICT; DISEASE; RISK AB The aging of the human immunodeficiency virus type 1 (HIV-1)-infected population obligates a focus on the interaction between aging, comorbid conditions, and HIV-1. We recruited a cohort of HIV-1-infected men aged <= 35 years or >= 50 years who were receiving fully suppressive antiretroviral therapy (ART). We analyzed plasma markers of inflammation; T-cell activation, exhaustion, proliferation; and innate cellular subsets and functional capacity. Levels of lipopolysaccharide and the plasma marker of chemokine (C-C motif) ligand 2 were significantly elevated in older HIV-infected men despite comparable cellular phenotypes. Compared with similarly age-stratified uninfected subjects, older HIV-1-infected adults were also more frequently in the upper quartile of soluble CD14 expression. C1 [Scully, Eileen; Lockhart, Ainsley; Romero-Tejeda, Marisol; Palmer, Christine D.; Altfeld, Marcus] MIT & Harvard, Ragon Inst MGH, Cambridge, MA USA. [Scully, Eileen; Robles, Yvonne; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Huang, Lisa; Becerril, Carlos] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Albrecht, Mary A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA USA. [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Altfeld, Marcus] Heinrich Pette Inst, Hamburg, Germany. [Lin, Nina H.] Boston Univ, Sch Med, Boston Med Ctr, Div Infect Dis, Boston, MA 02118 USA. RP Lin, NH (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Div Infect Dis, Boston, MA 02118 USA. EM nina.lin@bmc.org FU National Institute of Allergy and Infectious Diseases [5 K08 AI081545]; Harvard University Center for AIDS Research; National Institutes of Health (NIH) [P30 A1060354]; Ragon Institute Immune Monitoring Core; NIH [P01 AI074415] FX This work was supported by the National Institute of Allergy and Infectious Diseases (grant 5 K08 AI081545 to N. H. L.); the Harvard University Center for AIDS Research, a National Institutes of Health (NIH)-funded program (grant P30 A1060354; supplemental award to N. H. L.); and the Ragon Institute Immune Monitoring Core and NIH (grant P01 AI074415). NR 15 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2016 VL 213 IS 5 BP 771 EP 775 DI 10.1093/infdis/jiv501 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DG9XY UT WOS:000372438300013 PM 26494772 ER PT J AU Lyerly, MJ Wu, TC Mullen, MT Albright, KC Wolff, C Boehme, AK Branas, CC Grotta, JC Savitz, SI Carr, BG AF Lyerly, Michael J. Wu, Tzu-Ching Mullen, Michael T. Albright, Karen C. Wolff, Catherine Boehme, Amelia K. Branas, Charles C. Grotta, James C. Savitz, Sean I. Carr, Brendan G. TI The effects of telemedicine on racial and ethnic disparities in access to acute stroke care SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article DE Teleneurology; tele-stroke; healthcare access; racial minorities; ethnic minorities; telemedicine ID TISSUE-PLASMINOGEN ACTIVATOR; AMERICAN-HEART-ASSOCIATION; ACUTE ISCHEMIC-STROKE; UNITED-STATES; OUTCOMES; CENTERS; TIME; RECOMMENDATIONS; THROMBOLYSIS; TELESTROKE AB Racial and ethnic disparities have been previously reported in acute stroke care. We sought to determine the effect of telemedicine (TM) on access to acute stroke care for racial and ethnic minorities in the state of Texas. Data were collected from the US Census Bureau, The Joint Commission and the American Hospital Association. Access for racial and ethnic minorities was determined by summing the population that could reach a primary stroke centre (PSC) or telemedicine spoke within specified time intervals using validated models. TM extended access to stroke expertise by 1.5 million residents. The odds of providing 60-minute access via TM were similar in Blacks and Whites (prevalence odds ratios (POR) 1.000, 95% CI 1.000-1.000), even after adjustment for urbanization (POR 1.000, 95% CI 1.000-1.001). The odds of providing access via TM were also similar for Hispanics and non-Hispanics (POR 1.000, 95% CI 1.000-1.000), even after adjustment for urbanization (POR 1.000, 95% CI 1.000-1.000). We found that telemedicine increased access to acute stroke care for 1.5 million Texans. While racial and ethnic disparities exist in other components of stroke care, we did not find evidence of disparities in access to the acute stroke expertise afforded by telemedicine. C1 [Lyerly, Michael J.] Univ Alabama Birmingham, Dept Neurol, 1813 6th Ave South,RWUH M226, Birmingham, AL 35294 USA. [Lyerly, Michael J.] Birmingham Vet Affairs Med Ctr, Stroke Program, Birmingham, AL USA. [Wu, Tzu-Ching; Grotta, James C.; Savitz, Sean I.] Univ Texas Houston, Mem Hermann Med Ctr, Dept Neurol, Houston, TX USA. [Mullen, Michael T.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Albright, Karen C.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Hlth Serv & Outcomes Res Ctr Outcome & Effectiven, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Ctr Excellence Comparat Effectiveness Res Elimina, Minor Hlth & Hlth Dispar Res Ctr MHRC, Birmingham, AL 35294 USA. [Albright, Karen C.] Birmingham Vet Affairs Med Ctr, GRECC, Birmingham, AL USA. [Wolff, Catherine] Duke Univ, Sch Med, Durham, NC USA. [Boehme, Amelia K.] Columbia Univ, Dept Neurol, Gertrude Sergievsky Ctr, New York, NY USA. [Branas, Charles C.] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Carr, Brendan G.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Lyerly, MJ (reprint author), Univ Alabama Birmingham, Dept Neurol, 1813 6th Ave South,RWUH M226, Birmingham, AL 35294 USA. EM mjlyerly@uab.edu OI Lyerly, Michael/0000-0003-4236-1018 FU AHRQ HHS [5 T32 HS013852-10]; NIMHD NIH HHS [3 P60 MD000502-08S1, P60 MD000502]; None [HS013852] NR 52 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD MAR PY 2016 VL 22 IS 2 BP 114 EP 120 DI 10.1177/1357633X15589534 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DG4XG UT WOS:000372075900005 PM 26116854 ER PT J AU Vedire, K Joselow, AL Markham, CM Raugi, GJ AF Vedire, Kirtana Joselow, Andrew L. Markham, Craig M. Raugi, Gregory J. TI Teledermatology-directed surgical care is safe and reduces travel SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article DE Telemedicine; teledermatology; melanoma; severely dysplastic nevi; primary care clinicians ID GENERAL-PRACTITIONERS; MELANOMA; EXCISION; REFERRALS; PROGRAM AB Methods: We conducted a retrospective chart review and identified 186 Veterans in the VA Corporate Data Warehouse as having malignant melanomas or severely dysplastic nevi during the four-year period of observation from 1 July 2009 to 30 June 2013 and met inclusion and exclusion criteria for analysis. Results: Three hundred and sixty-six surgical procedures were performed for diagnosis and treatment of these conditions including biopsy and wide-local excision, of which 189 carefully selected cases were performed by primary care clinicians with 2.0% biopsy complication rate and a 7.7% wide-local excision complication rate. Cases not performed by primary care providers were referred to specialists (e.g. dermatologists, general surgeons or specialty surgeons) who had a 2.5% complication rate in biopsies and wide-local excision complication rate of 13.5% in severely dysplastic nevi and pTis and pT1a lesions and a 10.7% complication rate for lesions pT1b and greater. Discussion: These results show that a significant fraction of surgical procedures for diagnosis and treatment of malignant melanoma and severely dysplastic nevi can be safely performed in rural clinics by trained primary care providers. C1 [Vedire, Kirtana; Joselow, Andrew L.; Markham, Craig M.; Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Seattle Div, Washington, DC USA. [Joselow, Andrew L.] Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Raugi, Gregory J.] Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. RP Raugi, GJ (reprint author), VISN20 Teledermatol,Fed Off Bldg,Suite 630, Seattle, WA 98104 USA. EM gregory.raugi@va.gov FU US Department of Veterans Affairs; VISN20 Office of Rural Health Services; Office of Rural Health FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: US Department of Veterans Affairs, VISN20 Office of Rural Health Services, and the Office of Rural Health. NR 17 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD MAR PY 2016 VL 22 IS 2 BP 121 EP 126 DI 10.1177/1357633X15589861 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DG4XG UT WOS:000372075900006 PM 26116856 ER PT J AU Martinod, K Witsch, T Farley, K Gallant, M Remold-O'Donnell, E Wagner, DD AF Martinod, K. Witsch, T. Farley, K. Gallant, M. Remold-O'Donnell, E. Wagner, D. D. TI Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE extracellular traps; eukocyte elastase; neutrophils; serine proteases; venous thrombosis ID PULMONARY-FIBROSIS; INNATE IMMUNITY; NET FORMATION; DNA TRAPS; INHIBITOR; RELEASE; MOUSE; PAD4 AB Neutrophil elastase (NE) plays a role in extracellular trap formation (NETosis) triggered by microbes. The contribution of NE was evaluated in mouse NETosis models of sterile inflammation and thrombosis. NE is not required for mouse neutrophil NET production in vitro with non-infectious stimuli. NE deficiency had no significant effect on thrombosis in the inferior vena cava stenosis model. Summary Background Neutrophil serine proteases have been implicated in coagulation and neutrophil extracellular trap (NET) formation. In human neutrophils, neutrophil elastase (NE) translocates to the nucleus during NETosis and cleaves histones, thus aiding in chromatin decondensation. NE-/- mice were shown not to release NETs in response to microbes. However, mouse studies evaluating the role of NE in NET formation in sterile inflammation and thrombosis are lacking. Objective We wished to establish if neutrophils from NE-/- mice have a defect in NETosis, similar to peptidylarginine deiminase 4 (PAD4(-/-)) mice, and how this might have an impact on venous thrombosis, a model where NETs are produced and are crucial to thrombus development. Methods We performed in vitro NET assays using neutrophils from wild-type (WT), NE-/-, SerpinB1 (SB1)(-/-) and NE(-/-)SB1(-/-) mice. We compared WT and NE-/- animals using the inferior vena cava stenosis model of deep vein thrombosis (DVT). Results Neutrophil elastase deficiency resulted in a small reduction in ionomycin-induced NET formation in vitro without affecting histone citrullination. However, NET production in response to phorbol 12-myristate 13-acetate or platelet activating factor was normal in neutrophils from two independent NE-deficient mouse lines, and in NE(-/-)SB1(-/-) as compared with SB1(-/-) neutrophils. NE deficiency or inhibition did not prevent NETosis in vivo or DVT outcome. Conclusions Neutrophil elastase is not required for NET formation in mice. NE-/- mice, which form pathological venous thrombi containing NETs, do not phenocopy PAD4(-/-) mice in in vitro NETosis assays or experimental venous thrombosis. Our study suggests that NET-targeted therapies need to be highly effective to have an impact on DVT. C1 [Martinod, K.; Witsch, T.; Farley, K.; Gallant, M.; Remold-O'Donnell, E.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Martinod, K.; Witsch, T.; Farley, K.; Remold-O'Donnell, E.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Remold-O'Donnell, E.; Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,Third Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL102101, R01HL125501, 5T32HL066987-13]; National Institute of Allergy and Infectious Diseases [R21AI103407]; German Cardiac Society (Deutsche Gesellschaft fuer Kardiologie) FX We thank J. Roes (University College London) and H. Luo (Boston Children's Hospital) for providing neutrophil elastase-deficient mice to E.R.O. We also thank M. Demers and S. Ling Wong for helpful discussions. This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grants R01HL102101 and R01HL125501 (to D.D.W.) and 5T32HL066987-13 (K.M.), and the National Institute of Allergy and Infectious Diseases grant R21AI103407 (to E.R.O.). T.W. was a recipient of a fellowship of the German Cardiac Society (Deutsche Gesellschaft fuer Kardiologie). NR 28 TC 16 Z9 16 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAR PY 2016 VL 14 IS 3 BP 551 EP 558 DI 10.1111/jth.13239 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DH1DR UT WOS:000372525100017 PM 26712312 ER PT J AU Baruch, NF O'Donnell, EH Glanz, BI Benedict, RHB Musallam, AJ Healy, BC Rintell, D Chitnis, T AF Baruch, Natalie F. O'Donnell, Ellen H. Glanz, Bonnie I. Benedict, Ralph H. B. Musallam, Alexander J. Healy, Brian C. Rintell, David Chitnis, Tanuja TI Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Multiple sclerosis; pediatric; cognition; quality of life; outcomes ID QUALITY-OF-LIFE; DIGIT MODALITIES TEST; PSYCHOSOCIAL FEATURES; JUVENILE MS; NEUROPSYCHOLOGICAL ASSESSMENT; UNITED-STATES; IMPACT; DYSFUNCTION; IMPAIRMENT; CHILDHOOD AB Background: Little is known about long-term cognitive and patient-reported outcomes of pediatric-onset multiple sclerosis (POMS). Objective: The objective of this paper is to compare cognitive and patient-reported outcomes in adults with POMS vs. adult-onset MS (AOMS). Methods: We compared standardized patient-reported measures MSQOL54, MFIS, CES-D and SDMT in adult patients with MS onset prior to and after age 18, using data gathered in the Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study. Results: Fifty-one POMS and 550 AOMS patients were compared. SDMT scores were significantly lower in POMS after adjusting for age (-7.57 (-11.72, -3.43; p < 0.001), but not after adjusting for disease duration. Estimated group difference demonstrated lower normative z scores in POMS vs. AOMS in unadjusted analysis (-0.74 (95% CI: -1.18, -0.30; p = 0.0009) and after adjusting for disease duration (-0.60; 95%CI: -1.05, -0.15; p = 0.0097). Findings were unchanged in a subset of POMS diagnosed prior to age 18. In unadjusted and adjusted analyses, no significant differences were observed in health-related quality-of-life, fatigue, depression or social support between POMS and AOMS. Conclusions: Younger age of onset was associated with more impairment in information-processing speed in adults with POMS compared to AOMS, and remained significant when controlling for disease duration in age-normed analysis. The two groups were similar in terms of patient-reported outcomes, suggesting similar qualitative experiences of MS. C1 [Baruch, Natalie F.; Glanz, Bonnie I.; Musallam, Alexander J.; Healy, Brian C.; Rintell, David; Chitnis, Tanuja] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. [O'Donnell, Ellen H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Benedict, Ralph H. B.] SUNY Buffalo, Dept Neurol, Buffalo, NY 14260 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM tchitnis@partners.org NR 36 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD MAR PY 2016 VL 22 IS 3 BP 354 EP 361 DI 10.1177/1352458515588781 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DG7CM UT WOS:000372242400012 PM 26041802 ER PT J AU Bararia, D Kwok, HS Welner, RS Numata, A Sarosi, MB Yang, H Wee, S Tschuri, S Ray, D Weigert, O Levantini, E Ebralidze, AK Gunaratne, J Tenen, DG AF Bararia, Deepak Kwok, Hui Si Welner, Robert S. Numata, Akihiko Sarosi, Menyhart B. Yang, Henry Wee, Sheena Tschuri, Sebastian Ray, Debleena Weigert, Oliver Levantini, Elena Ebralidze, Alexander K. Gunaratne, Jayantha Tenen, Daniel G. TI Acetylation of C/EBP alpha inhibits its granulopoietic function SO NATURE COMMUNICATIONS LA English DT Article ID BINDING PROTEIN-ALPHA; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION; LYSINE ACETYLATION; HISTONE ACETYLTRANSFERASE; PROTEOMIC IDENTIFICATION; MOLECULAR-DYNAMICS; TRANSCRIPTION; DIFFERENTIATION AB CCAAT/enhancer-binding protein alpha (C/EBP alpha) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBP alpha at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBP alpha DNA-binding ability and modulates C/EBP alpha transcriptional activity. Acetylated C/EBP alpha is enriched in human myeloid leukaemia cell lines and acute myeloid leukaemia (AML) samples, and downregulated upon granulocyte-colony stimulating factor (G-CSF)-mediated granulocytic differentiation of 32Dcl3 cells. C/EBP alpha mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBP alpha-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBP alpha and demonstrate the importance of C/EBP alpha acetylation in myeloid differentiation. C1 [Bararia, Deepak; Kwok, Hui Si; Numata, Akihiko; Yang, Henry; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore. [Bararia, Deepak; Levantini, Elena; Ebralidze, Alexander K.; Tenen, Daniel G.] Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Bararia, Deepak; Tschuri, Sebastian; Weigert, Oliver] Univ Munich, Univ Hosp, Dept Internal Med 3, Marchioninistr 15, D-81377 Munich, Germany. [Bararia, Deepak; Tschuri, Sebastian; Weigert, Oliver] Univ Munich, Expt Leukamie & Lymphomforsch ELLF, Marchioninistr 15, D-81377 Munich, Germany. [Bararia, Deepak; Tschuri, Sebastian; Weigert, Oliver] German Canc Consortium DKTK, D-69120 Heidelberg, Germany. [Bararia, Deepak; Tschuri, Sebastian; Weigert, Oliver] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Kwok, Hui Si] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117456, Singapore. [Welner, Robert S.; Levantini, Elena; Ebralidze, Alexander K.; Tenen, Daniel G.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02215 USA. [Welner, Robert S.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Sarosi, Menyhart B.] Univ Leipzig, Fac Chem & Mineral, Inst Inorgan Chem, D-04103 Leipzig, Germany. [Wee, Sheena; Gunaratne, Jayantha] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Translat Biomed Prote Lab, Singapore 138673, Singapore. [Ray, Debleena] Duke NUS Grad Med Sch, Program Canc & Stem Cell Biol, Singapore 169857, Singapore. [Levantini, Elena] CNR, Inst Biomed Technol, I-56124 Pisa, Italy. [Gunaratne, Jayantha] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117594, Singapore. RP Bararia, D; Tenen, DG (reprint author), Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore.; Bararia, D; Tenen, DG (reprint author), Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA.; Bararia, D (reprint author), Univ Munich, Univ Hosp, Dept Internal Med 3, Marchioninistr 15, D-81377 Munich, Germany.; Bararia, D (reprint author), Univ Munich, Expt Leukamie & Lymphomforsch ELLF, Marchioninistr 15, D-81377 Munich, Germany.; Bararia, D (reprint author), German Canc Consortium DKTK, D-69120 Heidelberg, Germany.; Bararia, D (reprint author), German Canc Res Ctr, D-69120 Heidelberg, Germany.; Tenen, DG (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02215 USA. EM deepak.bararia@med.uni-muenchen.de; daniel.tenen@nus.edu.sg RI Sarosi, Menyhart/B-8886-2012 OI Sarosi, Menyhart/0000-0003-4222-0717 FU National Research Foundation Singapore; Singapore Translational Research Award from the Singapore National Medical Research Council [NMRC/STaR/0001/2008]; Singapore Ministry of Education; National Research Foundation; National Institutes of Health [CA66996, HL112719]; Max-Eder Program of the Deutsche Krebshilfe [110659]; European Social Fund (ESF) of the European Union (EU); Free State of Saxony; Singapore Ministry of Education under its Research Centres of Excellence initiative FX We thank Pere Puigserver (Dana Farber Cancer Institute, Boston, USA) for GCN5 and PCAF constructs, Georg W. Bornkamm (Helmholtz Center, Munich, Germany) for p300 construct. Wee Joo Chng (Cancer Science Institute, Singapore) for AML samples and cell lines, Yoon-Pin Lim (National University of Singapore, Singapore) and Shirly Chong Poh Kuan (National University of Singapore, Singapore) for synthetic peptides analysis used for rabbit immunization, Alan Friedman (John Hopkins University, Maryland, USA) for the pBabe-ER vector, Axel Imhof (Ludwig-Maximilians-University, Munich, Germany) for GST-tagged GCN5 HAT domain expression construct, Sharon Y. R. Dent (MD Anderson Cancer Center, Texas, USA) for Gcn5fl/fl mice, Motomi Osato (Cancer Science Institute, Singapore) for Vav-iCre mice, r many helpfuCelestina Chin Ai Qi (Cancer Science Institute, Singapore) for proofreading of the manuscript, and members of the Tenen laboratory fol discussions and technical support. This research is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative, Singapore Translational Research Award from the Singapore National Medical Research Council (NMRC/STaR/0001/2008 to D.G.T) and grants from the Singapore Ministry of Education and National Research Foundation and the National Institutes of Health (CA66996 and HL112719 to D.G.T). This research was supported by the Max-Eder Program of the Deutsche Krebshilfe (#110659 to O.W.). The molecular modelling studies were funded by the European Social Fund (ESF) of the European Union (EU) and the Free State of Saxony (M.B.S.). NR 63 TC 1 Z9 1 U1 4 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10968 DI 10.1038/ncomms10968 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DH3XY UT WOS:000372721300001 PM 27005833 ER PT J AU Kettunen, J Demirkan, A Wurtz, P Draisma, HHM Haller, T Rawal, R Vaarhorst, A Kangas, AJ Lyytikainen, LP Pirinen, M Pool, R Sarin, AP Soininen, P Tukiainen, T Wang, Q Tiainen, M Tynkkynen, T Amin, N Zeller, T Beekman, M Deelen, J van Dijk, KW Esko, T Hottenga, JJ van Leeuwen, EM Lehtimaki, T Mihailov, E Rose, RJ de Craen, AJM Gieger, C Kahonen, M Perola, M Blankenberg, S Savolainen, MJ Verhoeven, A Viikari, J Willemsen, G Boomsma, DI van Duijn, CM Eriksson, J Jula, A Jarvelin, MR Kaprio, J Metspalu, A Raitakari, O Salomaa, V Slagboom, PE Waldenberger, M Ripatti, S Ala-Korpela, M AF Kettunen, Johannes Demirkan, Ayse Wurtz, Peter Draisma, Harmen H. M. Haller, Toomas Rawal, Rajesh Vaarhorst, Anika Kangas, Antti J. Lyytikaeinen, Leo-Pekka Pirinen, Matti Pool, Rene Sarin, Antti-Pekka Soininen, Pasi Tukiainen, Taru Wang, Qin Tiainen, Mika Tynkkynen, Tuulia Amin, Najaf Zeller, Tanja Beekman, Marian Deelen, Joris van Dijk, Ko Willems Esko, Tonu Hottenga, Jouke-Jan van Leeuwen, Elisabeth M. Lehtimaki, Terho Mihailov, Evelin Rose, Richard J. de Craen, Anton J. M. Gieger, Christian Kahonen, Mika Perola, Markus Blankenberg, Stefan Savolainen, Markku J. Verhoeven, Aswin Viikari, Jorma Willemsen, Gonneke Boomsma, Dorret I. van Duijn, Cornelia M. Eriksson, Johan Jula, Antti Jarvelin, Marjo-Riitta Kaprio, Jaakko Metspalu, Andres Raitakari, Olli Salomaa, Veikko Slagboom, P. Eline Waldenberger, Melanie Ripatti, Samuli Ala-Korpela, Mika TI Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA SO NATURE COMMUNICATIONS LA English DT Article ID CORONARY-ARTERY-DISEASE; EVALUATING ROSUVASTATIN; GENETIC-DETERMINANTS; INTERVENTION TRIAL; JUPITER TRIAL; ASSOCIATION; LIPOPROTEIN(A); THERAPY; RISK; JUSTIFICATION AB Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk. C1 [Kettunen, Johannes; Wurtz, Peter; Kangas, Antti J.; Soininen, Pasi; Wang, Qin; Tiainen, Mika; Tynkkynen, Tuulia; Ala-Korpela, Mika] Univ Oulu, Fac Med, Computat Med, POB 5000, Oulu 90014, Finland. [Kettunen, Johannes; Sarin, Antti-Pekka; Perola, Markus; Eriksson, Johan; Jula, Antti; Salomaa, Veikko; Ripatti, Samuli] Natl Inst Hlth & Welf, POB 30, FI-00271 Helsinki, Finland. [Kettunen, Johannes; Soininen, Pasi; Wang, Qin; Tiainen, Mika; Tynkkynen, Tuulia; Ala-Korpela, Mika] Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Yliopistonranta 1C, Kuopio 70210, Finland. [Kettunen, Johannes; Savolainen, Markku J.; Jarvelin, Marjo-Riitta; Ala-Korpela, Mika] Univ Oulu, Bioctr Oulu, POB 5000, FI-90014 Oulu, Finland. [Demirkan, Ayse; van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Human Genet, POB 9600, NL-2300 RC Leiden, Netherlands. [Demirkan, Ayse; Amin, Najaf; van Leeuwen, Elisabeth M.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. [Draisma, Harmen H. M.; Pool, Rene; Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Boechorststr 1,Room 2B 29, NL-1081 BT Amsterdam, Netherlands. [Draisma, Harmen H. M.; Pool, Rene; Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] EMGO Inst Hlth & Care Res, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. [Draisma, Harmen H. M.] Neurosci Campus Amsterdam, Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. [Haller, Toomas; Esko, Tonu; Mihailov, Evelin; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia. [Rawal, Rajesh; Gieger, Christian; Waldenberger, Melanie] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. [Rawal, Rajesh; Gieger, Christian; Waldenberger, Melanie] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. [Vaarhorst, Anika; Beekman, Marian; Deelen, Joris; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, POB 9600, NL-2300 RC Leiden, Netherlands. [Lyytikaeinen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ, Univ Tampere Sch Med, Dept Clin Chem, Fimlab Labs, Kalevantie 4, Tampere 33014, Finland. [Pirinen, Matti; Sarin, Antti-Pekka; Perola, Markus; Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Inst Mol Med FIMM, Biomedicum 2,Tukholmankatu 8, FIN-00290 Helsinki, Finland. [Tukiainen, Taru] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, 55 Fruit St, Boston, MA 02114 USA. [Tukiainen, Taru] Broad Inst, Program Med & Populat Genet, 415 Main St, Cambridge, MA 02142 USA. [Tukiainen, Taru] Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Zeller, Tanja; Blankenberg, Stefan] Partner Site Hamburg Lubeck Kiel, German Ctr Cardiovasc Res DZHK eV, Martinistr 52, D-20246 Hamburg, Germany. [Zeller, Tanja; Blankenberg, Stefan] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Martinistr 52, D-20246 Hamburg, Germany. [van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Endocrinol, POB 9600, NL-2300 RC Leiden, Netherlands. [Rose, Richard J.; Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, POB 41,Maannerheimintie 172, FIN-00014 Helsinki, Finland. [Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA. [de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Geriatr & Gerontol, Postzone C7-Q,POB 9600, NL-2300 RC Leiden, Netherlands. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, POB 2000, FIN-33521 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, POB 2000, FIN-33521 Tampere, Finland. [Savolainen, Markku J.] Univ Oulu, Oulu Univ Hosp, Med Res Ctr, Internal Med, Aapistie 5A, FI-90220 Oulu, Finland. [Verhoeven, Aswin] Leiden Univ, Med Ctr, Ctr Prote & Metabol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. [Viikari, Jorma] Univ Turku, Dept Med, PB 52, Turku 20521, Finland. [Viikari, Jorma] Turku Univ Hosp, PB 52, Turku 20521, Finland. [Eriksson, Johan] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, PL 20,Tukholmankatu 8B, Helsinki 00029, Finland. [Eriksson, Johan] Helsingfors Univ, Folkhalsan Res Ctr, PB 63, Helsinki 00014, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London SW7 2AZ, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Fac Med, Ctr Life Course & Syst Epidemiol, PL 5000, Oulu 90014, Finland. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, OYS, POB 20, Oulu 90029, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth, POB 30,Mannerheimintie 166, Helsinki 00300, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Subst Abuse Serv, POB 30,Mannerheimintie 166, Helsinki 00300, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Kiinamyllynkatu 4-8, Turku 20521, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, Kiinamyllynkatu 4-8, Turku 20521, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Human Genet, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. [Ala-Korpela, Mika] Oulu Univ Hosp, Kajaanintie 50, Oulu 90220, Finland. [Ala-Korpela, Mika] Univ Bristol, Sch Social & Community Med, Computat Med, Senate House,Tyndall Ave, Bristol BS8 1TH, Avon, England. [Ala-Korpela, Mika] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England. [Demirkan, Ayse; van Dijk, Ko Willems] LUMC, Bldg 2,Einthovenweg 20, NL-2333 ZC Leiden, Netherlands. RP Kettunen, J (reprint author), Univ Oulu, Fac Med, Computat Med, POB 5000, Oulu 90014, Finland.; Kettunen, J (reprint author), Natl Inst Hlth & Welf, POB 30, FI-00271 Helsinki, Finland.; Kettunen, J (reprint author), Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Yliopistonranta 1C, Kuopio 70210, Finland.; Kettunen, J (reprint author), Univ Oulu, Bioctr Oulu, POB 5000, FI-90014 Oulu, Finland. EM johannes.kettunen@oulu.fi RI Pool, Rene/B-3652-2009; Waldenberger, Melanie/B-5355-2014; Slagboom, P. Eline/R-4790-2016; OI Pirinen, Matti/0000-0002-1664-1350; Pool, Rene/0000-0001-5579-0933; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Kaprio, Jaakko/0000-0002-3716-2455; Waldenberger, Melanie/0000-0003-0583-5093; Slagboom, P. Eline/0000-0002-2875-4723; Kettunen, Johannes/0000-0002-3345-491X; Gieger, Christian/0000-0001-6986-9554 NR 31 TC 8 Z9 8 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 11122 DI 10.1038/ncomms11122 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DH4DP UT WOS:000372736000001 PM 27005778 ER PT J AU Ananian, L AF Ananian, Lillian TI Relationship Based Care: Exploring the Manifestations of Health as Expanding Consciousness Within a Patient and Family Centered Medical Intensive Care Unit SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Ananian, Lillian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2016 VL 65 IS 2 BP E92 EP E93 PG 2 WC Nursing SC Nursing GA DG6SA UT WOS:000372215200253 ER PT J AU Carroll, D Albert, J Drucker, A AF Carroll, Diane Albert, Jenn Drucker, Adienne TI A National Study of Intravenous Medication Errors - Understanding How to Improve Intravenous Safety with Smart Pumps: An Academic Medical Center Experience SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Carroll, Diane; Albert, Jenn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drucker, Adienne] Partners HealthCare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2016 VL 65 IS 2 BP E101 EP E102 PG 2 WC Nursing SC Nursing GA DG6SA UT WOS:000372215200277 ER PT J AU Moriarty, H Winter, L Piersol, C Vause-Earland, T Robinson, K Newhart, B AF Moriarty, Helene Winter, Laraine Piersol, Catherine Vause-Earland, Tracey Robinson, Keith Newhart, Brian TI Patient-Centered and Family-Centered Outcomes in Intervention Research: Use of Target Outcomes in a Study with Veterans with Traumatic Brain Injury and Their Family Members SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Moriarty, Helene] Villanova Univ, Villanova, PA 19085 USA. [Winter, Laraine; Robinson, Keith; Newhart, Brian] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Piersol, Catherine; Vause-Earland, Tracey] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2016 VL 65 IS 2 BP E71 EP E71 PG 1 WC Nursing SC Nursing GA DG6SA UT WOS:000372215200194 ER PT J AU Perkins, JM Subramanian, SV Smith, GD Ozaltin, E AF Perkins, Jessica M. Subramanian, S. V. Smith, George Davey Ozaltin, Emreo TI Adult height, nutrition, and population health SO NUTRITION REVIEWS LA English DT Review DE genetics; height; intergenerational; life course; mortality; morbidity; nutrition; population health; socioeconomic status; stature ID BODY-MASS INDEX; LABOR-MARKET OUTCOMES; GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; INDIVIDUAL PARTICIPANT METAANALYSIS; GESTATIONAL-AGE INFANTS; MIDDLE-INCOME COUNTRIES; LOW-BIRTH-WEIGHT; RISK-FACTORS; PROSPECTIVE COHORT AB In this review, the potential causes and consequences of adult height, a measure of cumulative net nutrition, in modern populations are summarized. The mechanisms linking adult height and health are examined, with a focus on the role of potential confounders. Evidence across studies indicates that short adult height (reflecting growth retardation) in low- and middle-income countries is driven by environmental conditions, especially net nutrition during early years. Some of the associations of height with health and social outcomes potentially reflect the association between these environmental factors and such outcomes. These conditions are manifested in the substantial differences in adult height that exist between and within countries and over time. This review suggests that adult height is a useful marker of variation in cumulative net nutrition, biological deprivation, and standard of living between and within populations and should be routinely measured. Linkages between adult height and health, within and across generations, suggest that adult height may be a potential tool for monitoring health conditions and that programs focused on offspring outcomes may consider maternal height as a potentially important influence. C1 [Perkins, Jessica M.; Subramanian, S. V.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Perkins, Jessica M.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Perkins, Jessica M.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Subramanian, S. V.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Ozaltin, Emreo] World Bank, Hlth Nutr & Populat Global Practice, 1818 H St NW,MSN J 600, Washington, DC 20433 USA. RP Ozaltin, E (reprint author), World Bank, Hlth Nutr & Populat Global Practice, 1818 H St NW,MSN J 600, Washington, DC 20433 USA. EM eozaltin@worldbank.org RI Davey Smith, George/A-7407-2013 OI Davey Smith, George/0000-0002-1407-8314 FU Harvard Center of Population and Development Studies; Robert Wood Johnson Foundation; MRC Integrative Epidemiology Unit (IEU) at the University of Bristol [MC_UU_12013/1-9] FX This work was partially supported by a grant from the Harvard Center of Population and Development Studies. S.V.S. is partially supported by the Robert Wood Johnson Foundation Investigator Award in Health Policy Research. G.D S. works within the MRC Integrative Epidemiology Unit (IEU) at the University of Bristol. Grant Reference: MC_UU_12013/1-9. NR 223 TC 3 Z9 3 U1 4 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0029-6643 EI 1753-4887 J9 NUTR REV JI Nutr. Rev. PD MAR PY 2016 VL 74 IS 3 BP 149 EP 165 DI 10.1093/nutrit/nuv105 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DH2HN UT WOS:000372605600001 PM 26928678 ER PT J AU Junior, JA Katz, AM Ahn, R AF Junior, Jean A. Katz, Arlene M. Ahn, Roy TI The Perspectives of Young Women in Rural Western Kenya on Unconditional Cash Transfers SO POVERTY & PUBLIC POLICY LA English DT Article DE sub-Saharan Africa; Kenya; women; cash transfers; subjective well-being ID SUB-SAHARAN AFRICA; TRANSFER PROGRAM; QUALITATIVE RESEARCH; VULNERABLE CHILDREN; MENTAL-HEALTH; POVERTY; IMPACT; COUNTRIES; SERVICES; SUPPORT AB Unconditional cash transfers (UCTs) provide money to eligible individuals, without dictating how they spend the money or tasks they must do to receive it. This study explored how UCTs affected the lives of young, impoverished women in rural western Kenya. Qualitative methods were used, including in-depth interviews with 30 women: 10 receiving $1,000, 10 receiving $500, and 10 not receiving a UCT. UCTs were positively viewed by interviewees, and had nuanced and varied effects on aspirations, money management, relationships, and subjective well-being in social context. The perspectives of interviewees offer programmatic suggestions and question major assumptions concerning UCTs. The perspectives of interviewees offer programmatic suggestions and question major assumptions concerning UCTs. This qualitative study augments the primarily quantitative research on UCTs that has been done to date. C1 [Junior, Jean A.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Arlene M.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Ahn, Roy] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. RP Junior, JA (reprint author), Harvard Univ, Sch Med, Boston, MA USA. NR 75 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1944-2858 J9 Poverty Public Polic JI Poverty Public Policy PD MAR PY 2016 VL 8 IS 1 BP 72 EP 94 DI 10.1002/pop4.127 PG 23 WC Social Work SC Social Work GA DG9OH UT WOS:000372412700006 ER PT J AU Nelson, S Rustad, JK Catalano, G Stern, TA Kozel, FA AF Nelson, Scott Rustad, James K. Catalano, Glenn Stern, Theodore A. Kozel, F. Andrew TI Depressive Symptoms Before, During, and After Delirium: A Literature Review SO PSYCHOSOMATICS LA English DT Review ID CONFUSION ASSESSMENT METHOD; CORONARY-BYPASS SURGERY; HIP FRACTURE PATIENTS; POSTOPERATIVE DELIRIUM; ELDERLY-PATIENTS; CARDIAC-SURGERY; RISK-FACTORS; COGNITIVE IMPAIRMENT; PROSPECTIVE COHORT; FUNCTIONAL STATUS AB Background: Delirium and depression are often thought of as mutually exclusive conditions. However, several studies cite depression as a risk factor for delirium whereas others note that patients with delirium often manifest depressive symptoms. Whether these depressive symptoms persist after delirium resolves remains unclear. Objectives: This article reviews published studies that have investigated the relationship between depression and delirium. Methods: Literature searches on PubMed, CINAHL, Cochrane Library, and PsycInfo were conducted using search criteria "delirium" AND "depress*" as keywords or MeSH terms. Results: Of 722 search results, 10 prospective cohort studies were identified for inclusion. These studies were categorized regarding the time of assessment for depressive symptoms. Included studies varied greatly (regarding their index population, their methods of assessment, and their timing of assessments). Of the studies, 3 involved patients undergoing hip fracture repair. They demonstrated more severe depressive symptoms both during delirium and after delirium ended. Conversely, the other studies did not find any statistically significant correlations between the 2 conditions. Conclusions: The literature suggests a correlation between depression and delirium in patients with hip fracture. Whether other specific populations have higher comorbidity is unclear. Unfortunately, studies varied widely in their methods, precluding a meta-analysis. Nonetheless, our review provides a foundation for future research. C1 [Nelson, Scott; Rustad, James K.; Catalano, Glenn; Kozel, F. Andrew] James A Haley Vet Hosp & Clin, Mental Hlth & Behav Sci, Tampa, FL USA. [Nelson, Scott; Rustad, James K.; Catalano, Glenn; Kozel, F. Andrew] Univ S Florida, Dept Psychiat & Behav Sci, 12901 Bruce B Downs Blvd,MDC 41, Tampa, FL 33612 USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kozel, F. Andrew] James A Haley Vet Hosp & Clin, HSR&D Ctr Innovat Disabil & Rehabil Res CINDRR, Tampa, FL USA. RP Nelson, S (reprint author), Univ S Florida, Dept Psychiat & Behav Sci, 12901 Bruce B Downs Blvd,MDC 41, Tampa, FL 33612 USA. EM snelson5@health.usf.edu NR 64 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2016 VL 57 IS 2 BP 131 EP 141 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA DH4OY UT WOS:000372766500002 PM 26805588 ER PT J AU Burk, KS Singh, AK Vagefi, PA Sahani, D AF Burk, Kristine S. Singh, Ajay K. Vagefi, Parsia A. Sahani, Dushyant TI Pretransplantation Imaging Workup of the Liver Donor and Recipient SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Liver transplantation; Preliving donor liver transplant imaging; Hepatic artery anatomy and variants; Portal vein anatomy and variants; Hepatic vein anatomy and variants; Biliary anatomy and variants ID 2 ADULT RECIPIENTS; HEPATOCELLULAR-CARCINOMA; RIGHT HEPATECTOMY; TRANSPLANTATION; SPLIT; CT; DISEASE; OUTCOMES; ANATOMY; SURGERY AB Liver transplantation requires thorough preoperative imaging. Contrast enhanced computed tomography (CT) and MR imaging are the main modalities utilized for this purpose. Radiation-reducing protocols, advanced imaging techniques for evaluation of parenchymal fat and iron content, and 3-dimenionsal and volumetric reformations are routinely used. The helpful diagnostic radiologist has a complete understanding of indications for transplant, the indications for bridging and/or down-staging therapies for hepatocellular carcinoma, and the components of the transplant operation. With this information at hand, the radiologist can craft a thorough, yet succinct report that will help the surgeon plan and execute successful donor and recipient transplant operations. C1 [Burk, Kristine S.] Massachusetts Gen Hosp, Dept Radiol, Radiol Founders 205, 55 Fruit St, Boston, MA 02114 USA. [Singh, Ajay K.; Sahani, Dushyant] Massachusetts Gen Hosp, Dept Radiol, Radiol WHT 270, 55 Fruit St, Boston, MA 02114 USA. [Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Radiol, White 521c,55 Fruit St, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Radiol WHT 270, 55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 42 TC 0 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2016 VL 54 IS 2 BP 185 EP + DI 10.1016/j.rcl.2015.09.010 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH4QN UT WOS:000372770600002 PM 26896219 ER PT J AU Moreno, CC Mittal, PK Ghonge, NP Bhargava, P Heller, MT AF Moreno, Courtney Coursey Mittal, Pardeep K. Ghonge, Nitin P. Bhargava, Puneet Heller, Matthew T. TI Imaging Complications of Renal Transplantation SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Renal transplantation; Complications of renal transplantation; Renal artery stenosis; Renal vein thrombosis; Collecting system injury; Lymphocele; Urinoma; Posttransplant lymphoproliferative disorder ID CHRONIC ALLOGRAFT NEPHROPATHY; DELAYED GRAFT FUNCTION; ARTERY-STENOSIS; RISK-FACTORS; KIDNEY-TRANSPLANTATION; VASCULAR COMPLICATIONS; MULTIVARIATE-ANALYSIS; DOPPLER SONOGRAPHY; RESISTIVE INDEX; ACUTE REJECTION AB Renal transplant complications are categorized as those related to the transplant vasculature, collecting system, perinephric space, renal parenchyma, and miscellaneous complications including posttransplant lymphoproliferative disorder. Many of these renal transplant complications are diagnosed with imaging. Medical complications including rejection, acute tubular necrosis, and drug toxicity also can impair renal function. These medical complications are typically indistinguishable at imaging, and biopsy may be performed to establish a diagnosis. Normal transplant anatomy, imaging techniques, and the appearances of renal transplant complications at ultrasound, computed tomography, and MR imaging are reviewed. C1 [Moreno, Courtney Coursey; Mittal, Pardeep K.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. [Ghonge, Nitin P.] Indraprastha Apollo Hosp, Dept Radiol, Delhi Mathura Rd, New Delhi 110076, India. [Bhargava, Puneet] Univ Washington, Med Ctr, Dept Radiol, VA Puget Sound Hlth Care Syst, 1959 NE Pacific St,Room BB308,Box 357115, Seattle, WA 98195 USA. [Heller, Matthew T.] Univ Pittsburgh, Sch Med, Dept Radiol, 200 Lothrop St,Suite 174E PUH, Pittsburgh, PA 15213 USA. RP Moreno, CC (reprint author), Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM courtney.moreno@emoryhealthcare.org OI Mittal, Pardeep/0000-0002-3302-8590 NR 62 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2016 VL 54 IS 2 BP 235 EP + DI 10.1016/j.rcl.2015.09.007 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH4QN UT WOS:000372770600005 PM 26896222 ER PT J AU Backhus, LM Mulligan, MS Ha, R Shriki, JE Mohammed, TLH AF Backhus, Leah M. Mulligan, Michael S. Ha, Richard Shriki, Jabi E. Mohammed, Tan-Lucien H. TI Imaging in Lung Transplantation Surgical Considerations of Donor and Recipient SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Lung transplant; Transplant evaluation; Transplant surgery; Computed tomography ID IDIOPATHIC PULMONARY-FIBROSIS; TRAUMATIC CARDIOPULMONARY ARREST; VOLUME REDUCTION SURGERY; INTERNATIONAL-SOCIETY; CYSTIC-FIBROSIS; ORGAN DONATION; FLEISCHNER-SOCIETY; SIZE MISMATCH; BRAIN-DEATH; MANAGEMENT AB Modifications in recipient and donor criteria and innovations in donor management hold promise for increasing rates of lung transplantation, yet availability of donors remains a limiting resource. Imaging is critical in the work-up of donor and recipient including identification of conditions that may portend to poor posttransplant outcomes or necessitate modifications in surgical technique. This article describes the radiologic principles that guide selection of patients and surgical procedures in lung transplantation. C1 [Backhus, Leah M.; Ha, Richard] Stanford Univ, Dept Cardiothorac Surg, 300 Pasteur Dr,Falk Bldg, Stanford, CA 94304 USA. [Mulligan, Michael S.] Univ Washington, Dept Surg, Div Cardiothorac Surg, Seattle, WA 98195 USA. [Shriki, Jabi E.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Shriki, Jabi E.] VA Puget Sound Hlth Care Syst, Diagnost Imaging Serv, Seattle, WA USA. [Mohammed, Tan-Lucien H.] Univ Florida, Coll Med, Dept Radiol, Gainesville, FL 32610 USA. RP Backhus, LM (reprint author), Stanford Univ, Dept Cardiothorac Surg, 300 Pasteur Dr,Falk Bldg, Stanford, CA 94304 USA. EM lbackhus@stanford.edu NR 67 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2016 VL 54 IS 2 BP 339 EP + DI 10.1016/j.rcl.2015.09.013 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH4QN UT WOS:000372770600011 PM 26896228 ER PT J AU Bahney, CS Jacobs, L Tamai, R Hu, D Luan, TF Wang, MQ Reddy, S Park, M Limburg, S Kim, HT Marcucio, R Kuo, AC AF Bahney, Chelsea S. Jacobs, Linsey Tamai, Robert Hu, Diane Luan, Tammy F. Wang, Miqi Reddy, Sanjay Park, Michelle Limburg, Sonja Kim, Hubert T. Marcucio, Ralph Kuo, Alfred C. TI Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes SO TISSUE ENGINEERING PART A LA English DT Article ID MESENCHYMAL STEM-CELLS; IN-VIVO; CARTILAGE REPAIR; GENE-EXPRESSION; OSSIFICATION; HYDROGELS; DEFECTS; CULTURE AB Introduction: Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. Materials and Methods: We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-beta 1 (TGF-beta 1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. Results: Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. Conclusions: hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-beta superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach. C1 [Bahney, Chelsea S.; Hu, Diane; Marcucio, Ralph] Univ Calif San Francisco, Orthopaed Trauma Inst, San Francisco Gen Hosp, San Francisco, CA 94121 USA. [Jacobs, Linsey; Tamai, Robert; Luan, Tammy F.; Wang, Miqi; Reddy, Sanjay; Park, Michelle; Limburg, Sonja; Kim, Hubert T.; Kuo, Alfred C.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 112, San Francisco, CA 94121 USA. RP Kuo, AC (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 112, San Francisco, CA 94121 USA. EM kuoac@orthosurg.ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS) of the National Institutes of Health (NIH) [5F32AR062469]; Musculoskeletal Transplant Foundation; UCSF Graduate Education in Medical Sciences (GEMS); UCSF Department of Orthopaedic Surgery; San Francisco Veterans Affairs Medical Center FX Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS) of the National Institutes of Health (NIH) under the following award numbers: CSB (#5F32AR062469). Additional research support was provided by the Musculoskeletal Transplant Foundation (CSB: MTF Junior Investigator Award), the UCSF Graduate Education in Medical Sciences (GEMS), the UCSF Department of Orthopaedic Surgery, and the San Francisco Veterans Affairs Medical Center. NR 31 TC 0 Z9 1 U1 5 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD MAR 1 PY 2016 VL 22 IS 5-6 BP 427 EP 435 DI 10.1089/ten.tea.2014.0705 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA DH0FL UT WOS:000372457800005 PM 26830207 ER PT J AU Park, KM Hussein, KH Hong, SH Ahn, C Yang, SR Park, SM Kweon, OK Kim, BM Woo, HM AF Park, Kyung-Mee Hussein, Kamal Hany Hong, Seok-Ho Ahn, Cheol Yang, Se-Ran Park, Sung-Min Kweon, Oh-Kyeong Kim, Byeong-Moo Woo, Heung-Myong TI Decellularized Liver Extracellular Matrix as Promising Tools for Transplantable Bioengineered Liver Promotes Hepatic Lineage Commitments of Induced Pluripotent Stem Cells SO TISSUE ENGINEERING PART A LA English DT Article ID LONG-TERM CULTURE; PORCINE LIVER; ENDOTHELIAL-CELLS; GROWTH-FACTORS; HUMAN IPS; IN-VITRO; ORGAN; DISEASE; DIFFERENTIATION; PLATFORM AB Liver transplantation is the last resort for liver failure patients. However, due to the shortage of donor organs, bioengineered liver generated from decellularized whole liver scaffolds and induced pluripotent stem cell (iPSC)-derived hepatocytes (iPSC-Heps) is being studied as an alternative approach to treat liver disease. Nevertheless, there has been no report on both the interaction of iPSC-Heps with a liver extracellular matrix (ECM) and the analysis of recellularized iPSC-Heps into the whole liver scaffolds. In this study, we produced porcine iPSC-Heps, which strongly expressed the hepatic markers alpha-fetoprotein and albumin and exhibited hepatic functionalities, including glycogen storage, lipid accumulation, low-density lipoprotein uptake, and indocyanine green metabolism. Supplementation of ECM from porcine decellularized liver containing liver-derived growth factors stimulated the albumin expression of porcine iPSC-Heps during differentiation procedures. The iPSC-Heps were reseeded into decellularized liver scaffolds, and the recellularized liver was cultured using a continuous perfusion system. The recellularized liver scaffolds were transplanted into rats for a short term, and the grafts expressed hepatocyte markers and did not rupture. These results provide a foundation for development of bioengineered liver using stem cell and decellularized scaffolds. C1 [Park, Kyung-Mee; Hussein, Kamal Hany; Hong, Seok-Ho; Ahn, Cheol; Yang, Se-Ran; Park, Sung-Min; Woo, Heung-Myong] Kangwon Natl Univ, Stem Cell Inst KNU, Chunchon 200701, Gangwon, South Korea. [Park, Kyung-Mee; Hussein, Kamal Hany; Woo, Heung-Myong] Kangwon Natl Univ, Sch Vet Med, Chunchon 200701, Gangwon, South Korea. [Hong, Seok-Ho; Yang, Se-Ran; Park, Sung-Min] Kangwon Natl Univ, Sch Med, Chunchon 200701, Gangwon, South Korea. [Ahn, Cheol] Kangwon Natl Univ, Sch Biomed Technol, Chunchon 200701, Gangwon, South Korea. [Kweon, Oh-Kyeong] Seoul Natl Univ, Sch Vet Med, Seoul, South Korea. [Kim, Byeong-Moo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,GI Unit, Boston, MA USA. RP Woo, HM (reprint author), Kangwon Natl Univ, Sch Vet Med, Chunchon 200701, Gangwon, South Korea. EM woohm@kangwon.ac.kr FU "Cooperative Research Program for Agriculture Science & Technology Development" Rural Development Administration, Republic of Korea [PJ0110022015] FX This work was carried out with the support of "Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ0110022015)" Rural Development Administration, Republic of Korea NR 56 TC 1 Z9 2 U1 9 U2 19 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD MAR 1 PY 2016 VL 22 IS 5-6 BP 449 EP 460 DI 10.1089/ten.tea.2015.0313 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA DH0FL UT WOS:000372457800007 PM 26801816 ER PT J AU Lindau, A Hardtner, C Hergeth, SP Blanz, KD Dufner, B Hoppe, N Anto-Michel, N Kornemann, J Zou, J Gerhardt, LMS Heidt, T Willecke, F Geis, S Stachon, P Wolf, D Libby, P Swirski, FK Robbins, CS McPheat, W Hawley, S Braddock, M Gilsbach, R Hein, L von zur Muhlen, C Bode, C Zirlik, A Hilgendorf, I AF Lindau, Alexandra Haerdtner, Carmen Hergeth, Sonja P. Blanz, Kelly Daryll Dufner, Bianca Hoppe, Natalie Anto-Michel, Nathaly Kornemann, Jan Zou, Jiadai Gerhardt, Louisa M. S. Heidt, Timo Willecke, Florian Geis, Serjosha Stachon, Peter Wolf, Dennis Libby, Peter Swirski, Filip K. Robbins, Clinton S. McPheat, William Hawley, Shaun Braddock, Martin Gilsbach, Ralf Hein, Lutz von zur Muehlen, Constantin Bode, Christoph Zirlik, Andreas Hilgendorf, Ingo TI Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE Atherosclerosis; SYK; Monocytes; Macrophages; Progenitors; Proliferation; Egress ID TYROSINE KINASE INHIBITOR; STEM-CELL PROLIFERATION; RHEUMATOID-ARTHRITIS; ATHEROSCLEROTIC LESIONS; INADEQUATE RESPONSE; PARALLEL-GROUP; DOUBLE-BLIND; PHASE-III; ACCUMULATION; FOSTAMATINIB AB Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL-3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression. C1 [Lindau, Alexandra; Haerdtner, Carmen; Hergeth, Sonja P.; Blanz, Kelly Daryll; Dufner, Bianca; Hoppe, Natalie; Anto-Michel, Nathaly; Kornemann, Jan; Zou, Jiadai; Gerhardt, Louisa M. S.; Heidt, Timo; Willecke, Florian; Geis, Serjosha; Stachon, Peter; Wolf, Dennis; von zur Muehlen, Constantin; Bode, Christoph; Zirlik, Andreas; Hilgendorf, Ingo] Univ Heart Ctr Freiburg, Dept Cardiol & Angiol 1, Hugstetter Str 55, D-79106 Freiburg, Germany. [Blanz, Kelly Daryll] Univ Freiburg, Spemann Grad Sch Biol & Med, Hugstetter Str 55, D-79106 Freiburg, Germany. [Blanz, Kelly Daryll] Univ Freiburg, Fac Biol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Robbins, Clinton S.] Peter Munk Cardiac Ctr, Toronto, ON, Canada. [McPheat, William] AstraZeneca R&D, Gothenburg, Sweden. [Hawley, Shaun; Braddock, Martin] AstraZeneca R&D, Alderley Pk, Macclesfield, Cheshire, England. [Gilsbach, Ralf; Hein, Lutz] Univ Freiburg, Inst Expt & Clin Pharmacol & Toxicol, Hugstetter Str 55, D-79106 Freiburg, Germany. RP Zirlik, A; Hilgendorf, I (reprint author), Univ Heart Ctr Freiburg, Dept Cardiol & Angiol 1, Hugstetter Str 55, D-79106 Freiburg, Germany. EM andreas.zirlik@universitaets-herzzentrum.de; ingo.hilgendorf@universitaets-herzzentrum.de FU Department of Cardiology and Angiology I, University Heart Center Freiburg; Astra Zeneca; German Research Foundation [HI 1573/2-1]; Excellence Initiative of the German Research Foundation (Spemann Graduate School) [GSC-4] FX This work was supported by internal funds of the Department of Cardiology and Angiology I, University Heart Center Freiburg, and Astra Zeneca to A.Z., the German Research Foundation to I.H. (HI 1573/2-1) and the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School) to K.D.B. NR 20 TC 4 Z9 4 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8428 EI 1435-1803 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAR PY 2016 VL 111 IS 2 AR 20 DI 10.1007/s00395-016-0535-8 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG7LE UT WOS:000372265000011 PM 26891724 ER PT J AU Sinha, I Zhu, D Ojomo, K Gfrerer, L Sawh-Martinez, R Patel, A Chan, RK Watkins, JF AF Sinha, Indranil Zhu, Dagny Ojomo, Kristin Gfrerer, Lisa Sawh-Martinez, Rajendra Patel, Anup Chan, Rodney K. Watkins, James F. TI Functional and subjective assessment of burn contracture release in a mission setting SO BURNS LA English DT Article; Proceedings Paper CT Meeting of the American-Burn-Association CY 2015 CL Chicago, IL SP Amer Burn Assoc DE Burn reconstruction; Contractors; Surgical missions ID SF-36 HEALTH SURVEY; QUALITY-OF-LIFE; INJURY; TRANSLATION; ADAPTATION; PREVENTION; MANAGEMENT; BARRIERS; IMPACT; RETURN AB Objective: Burns and subsequent contractures are common in developing nations. Contracture release is performed to treat such patients with functional limitations. The aim of this study is to evaluate post-operative functional and psychosocial outcomes following contracture release in a mission setting. Methods: During a surgical mission in Mumbai, India, 39 patients burn contractures underwent surgical release. A total of 31 patients (64% female, mean age 27 years) chose to participate in the study. Patients were scored preoperatively and postoperatively using a SF-36 validated survey and AMA impairment guideline assessment. Results: Thirty-one patients completed questionnaires pre-operative and 6-weeks post operatively. Twenty-four patients completed a survey 3-months post operatively (77.4%). Among those enrolled, 67% were women with the majority sustaining <20% total body surface area burns (70.7%) but had multiple contractures (80.6%). SF-36 physical component score increased from a mean score of 49.8 preoperatively to 55.6 by 3 months following contracture release (P < 0.001). The SF-36 mental component score similarly increased from 38.8 to 51.1 by 3 months (P < 0.001). AMA Whole Person Impairment (WPI) scores improved from 40.3% impairment pre-operative to 26.6% at 6-weeks post-operative (P < 0.001). Conclusions: Patients SF-36 and WPI scores improved following burn contracture release, confirming both functional and psychologic improvement following surgery. During the acute post-operative period, this study suggests that contracture release in a mission setting is of benefit to patients. (C) 2015 Elsevier Ltd and ISBI. All rights reserved. C1 [Sinha, Indranil; Ojomo, Kristin] Brigham & Womens Hosp, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. [Sinha, Indranil; Ojomo, Kristin] Brigham & Womens Hosp, Div Trauma & Burn Surg, 75 Francis St, Boston, MA 02115 USA. [Zhu, Dagny] Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA. [Gfrerer, Lisa] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Sawh-Martinez, Rajendra; Patel, Anup] Yale Univ, Sch Med, Div Plast Surg, 333 Cedar St, New Haven, CT 06520 USA. [Chan, Rodney K.] San Antonio Mil Med Ctr, Clin Div, San Antonio, TX 78234 USA. [Chan, Rodney K.] San Antonio Mil Med Ctr, Burn Ctr, San Antonio, TX 78234 USA. [Watkins, James F.] VA Eastern Colorado Healthcare Syst, Div Trauma & Crit Care, Denver, CO 80220 USA. RP Sinha, I (reprint author), Dept Surg, Div Plast Surg, Div Trauma Burn Surg, 75 Francis St, Boston, MA 02115 USA. EM isinha@partners.org NR 29 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD MAR PY 2016 VL 42 IS 2 BP 466 EP 470 DI 10.1016/j.burns.2015.07.009 PG 5 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA DG6FW UT WOS:000372179600035 PM 26778704 ER PT J AU Allott, EH Howard, LE Aronson, WJ Terris, MK Kane, CJ Amling, CL Cooperberg, MR Freedland, SJ AF Allott, Emma H. Howard, Lauren E. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Cooperberg, Matthew R. Freedland, Stephen J. TI Racial Differences in the Association Between Preoperative Serum Cholesterol and Prostate Cancer Recurrence: Results from the SEARCH Database SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN; RISK; MEN; COHORT; ATHEROSCLEROSIS; MORTALITY; IMPACT; GRADE; CELLS AB Background: Black men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking. Methods: We identified 628 black and 1,020 non-black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race-stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia. Results: High cholesterol was associated with increased risk of recurrence in black [HRper10 (mg/dL) 1.06; 95% confidence interval (CI), 1.02-1.11] but not non-black men (HRper10 mg/dL 0.99; 95% CI, 0.95-1.03; P-interaction = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HRper10 mg/dL 1.02; 95% CI, 1.00-1.03 and 1.02; 95% CI, 1.00-1.02, respectively; P-interaction = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (P-interaction = 0.047). Conclusion: Elevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race. Impact: Significantly contrasting associations by race may provide insight into prostate cancer racial disparities. (C) 2016 AACR. C1 [Allott, Emma H.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Allott, Emma H.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Howard, Lauren E.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Kane, Christopher J.] Univ Calif San Diego Hlth Syst, Dept Urol, San Diego, CA USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. [Cooperberg, Matthew R.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA USA. [Freedland, Stephen J.] Cedars Sinai Med Ctr, 8635 West 3rd St,Suite 1070W, Los Angeles, CA 90048 USA. [Freedland, Stephen J.] Vet Affairs Med Ctr, Div Urol, Durham, NC USA. RP Freedland, SJ (reprint author), Cedars Sinai Med Ctr, 8635 West 3rd St,Suite 1070W, Los Angeles, CA 90048 USA. EM stephen.freedland@cshs.org FU NIH [1K24CA160653, P50CA92131]; University Cancer Research Fund of North Carolina FX This study was supported by grants from NIH [1K24CA160653 (to S.J. Freedland) and P50CA92131 (to W.J. Aronson)] and by the University Cancer Research Fund of North Carolina (to E.H. Allott). NR 32 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2016 VL 25 IS 3 BP 547 EP 554 DI 10.1158/1055-9965.EPI-15-0876 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6EA UT WOS:000372173900015 PM 26809276 ER PT J AU Boros, E Holland, JP Kenton, N Rotile, N Caravan, P AF Boros, Eszter Holland, Jason P. Kenton, Nathaniel Rotile, Nicholas Caravan, Peter TI Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of (89)Zirconium for Positron Emission Tomography (PET) Imaging SO CHEMPLUSCHEM LA English DT Article DE antitumor agents; imaging agents; macrocycles; radiopharmaceuticals; zirconium ID P-ISOTHIOCYANATOBENZYL-DESFERRIOXAMINE; EFFECTIVE CORE POTENTIALS; IMMUNO-PET; MONOCLONAL-ANTIBODIES; MOLECULAR CALCULATIONS; BIFUNCTIONAL CHELATE; SIDEROPHORE ANALOGS; ZR-89; ZIRCONIUM-89; CANCER AB Four novel chelators (L1-L4) and their (89)zirconium complexes were prepared and compared with the (89)zirconium desferrioxamineB (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The Zr-89-L4 complex showed similar stability to that of Zr-89-DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that Zr-89-L4 had similar pharmacokinetic behavior to that of Zr-89-DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 (L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with Zr-89-L5-trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2 +/- 2.25) and a high tumor specificity that was comparable to the performance of Zr-89-DFO-trastuzumab. C1 [Boros, Eszter; Kenton, Nathaniel; Rotile, Nicholas; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. [Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. RP Boros, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM eboros@nmr.mgh.harvard.edu FU NIH [K99HL125728, R01EB009062] FX Fang Qian, Dingyi Wen, Yuting Huang, Susan Foley, and Paul Weinreb of Biogen Inc. are acknowledged for MS analysis of antibody conjugates. Chongzhao Ran and Anna Moore are acknowledged for providing access to the Sofie Biosciences G4 PET scanner. Shadi Esfahani and Umar Mahmood are acknowledged for a donation of BT474 cells and providing guidance on tumor implantation. Neil Vasdev is acknowledged for providing 89Zr(oxalate) in house for early experiments. The NIH is acknowledged for funding support to E.B. (K99HL125728) and P.C. (R01EB009062). NR 46 TC 5 Z9 5 U1 13 U2 22 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 2192-6506 J9 CHEMPLUSCHEM JI ChemPlusChem PD MAR PY 2016 VL 81 IS 3 BP 274 EP 281 DI 10.1002/cplu.201600003 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA DG6EL UT WOS:000372175000003 PM 27630807 ER PT J AU Hsue, PY Tawakol, A AF Hsue, Priscilla Y. Tawakol, Ahmed TI Inflammation and Fibrosis in HIV Getting to the Heart of the Matter SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; cardiovascular diseases; fibrosis; HIV; heart failure; inflammation ID HUMAN-IMMUNODEFICIENCY-VIRUS; CARDIOVASCULAR MAGNETIC-RESONANCE; ARTERIAL INFLAMMATION; INFECTION; RISK; ECHOCARDIOGRAPHY; CYTOMEGALOVIRUS; COAGULATION; DYSFUNCTION; MYOCARDITIS C1 Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave, San Francisco, CA 94110 USA. EM Priscilla.Hsue@ucsf.edu FU NIAID NIH HHS [K24 AI112393, K24AI112393] NR 29 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2016 VL 9 IS 3 AR e004427 DI 10.1161/CIRCIMAGING.116.004427 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DG3PN UT WOS:000371982100001 PM 26951604 ER PT J AU Fifer, MA AF Fifer, Michael A. TI Through Thick and Thin What Are the Septal Thickness Limits for Alcohol Septal Ablation? SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE Editorials; catheter ablation; cardiomyopathy; hypertrophic obstructive; heart septal defects; ventricular; hypertrophy; left ventricular; magnetic resonance imaging; ventricular outflow obstruction; ventricular septum ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; TASK-FORCE; MANAGEMENT; GUIDELINES; PREDICTORS; DIAGNOSIS; MYECTOMY C1 [Fifer, Michael A.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiol Div, Boston, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM mfifer@mgh.harvard.edu NR 19 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD MAR PY 2016 VL 9 IS 3 AR e003588 DI 10.1161/CIRCINTERVENTIONS.116.003588 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG3QV UT WOS:000371985700001 PM 26884613 ER PT J AU Shinagare, AB Keraliya, A Somarouthu, B Tirumani, SH Ramaiya, NH Kantoff, PW AF Shinagare, A. B. Keraliya, A. Somarouthu, B. Tirumani, S. H. Ramaiya, N. H. Kantoff, P. W. TI Imaging yield from 133 consecutive patients with prostate cancer and low trigger PSA from a single institution SO CLINICAL RADIOLOGY LA English DT Article ID RADIONUCLIDE BONE-SCINTIGRAPHY; RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; FOLLOW-UP; COMPUTED-TOMOGRAPHY; INCREASED SURVIVAL; NATURAL-HISTORY; ANTIGEN LEVEL; MEN; PROGRESSION AB AIM: To investigate the yield of imaging in patients with relapsed prostate cancer (PC) with a low trigger prostate-specific antigen (PSA). MATERIALS AND METHODS: This institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study included all 133 patients (mean age 68 years; range 45-88; median 69 months since original diagnosis; interquartile range [IQR]: 32-139) with hormone-sensitive PC (HSPC, n = 28) or castration-resistant PC (CRPC, n = 105) and trigger PSA < 4 ng/ml, who underwent same-day bone scintigraphy and computed tomography (CT; total 224 time points) at Dana-Farber Cancer Institute from January to December 2013. Clinical and pathological data were obtained by manual review of the electronic medical records. All the included bone scintigraphs and CT images were reviewed by a fellowship-trained oncoradiologist to record the metastatic pattern and any clinically significant non-metastatic findings. RESULTS: Ninety-four of the 133 (71%) patients had metastatic disease (18/28 [64%] with HSPC, 76/105 [72%] with CRPC). Forty-one of the 133 (31%) patients developed new metastatic disease and 23/133 (17%) developed new clinically significant non-metastatic findings. The incidence of osseous, nodal, and visceral metastases, and clinically significant non-metastatic findings was similar across the HSPC and CRPC groups (p>0.05 for all). Fifty-seven of the 133 (43%) patients had findings seen only at CT, of which 37 had new extra-osseous findings. Only 2/133 (2%) had findings at bone scintigraphy not seen at CT, both in areas not covered on CT. CONCLUSION: Imaging frequently demonstrated new metastatic and non-metastatic findings in patients with a low trigger PSA. CT is valuable in these patients because extra-osseous findings not visible at bone scintigraphy are frequently seen. (C) 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Shinagare, A. B.; Keraliya, A.; Somarouthu, B.; Tirumani, S. H.; Ramaiya, N. H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Shinagare, A. B.; Keraliya, A.; Somarouthu, B.; Tirumani, S. H.; Ramaiya, N. H.; Kantoff, P. W.] Harvard Univ, Sch Med, 75 Francis St, Boston, MA 02115 USA. [Kantoff, P. W.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM ashinagare@partners.org NR 35 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD MAR PY 2016 VL 71 IS 3 BP E143 EP E149 DI 10.1016/j.crad.2015.12.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG3UK UT WOS:000371995700001 PM 26767544 ER PT J AU Mackin, RS Vigil, O Insel, P Kivowitz, A Kupferman, E Hough, CM Fekri, S Crothers, R Bickford, D Delucchi, KL Mathews, CA AF Mackin, R. Scott Vigil, Ofilio Insel, Philip Kivowitz, Alana Kupferman, Eve Hough, Christina M. Fekri, Shiva Crothers, Ross Bickford, David Delucchi, Kevin L. Mathews, Carol A. TI PATTERNS OF CLINICALLY SIGNIFICANT COGNITIVE IMPAIRMENT IN HOARDING DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE hoarding disorder; cognitive impairment; executive dysfunction; categorization; information processing speed; memory; attention ID OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM DIMENSIONS; OLDER-ADULTS; EXECUTIVE FUNCTION; DECISION-MAKING; DEPRESSION; INVENTORY; ATTENTION; VALIDITY; THERAPY AB ObjectivesThe cognitive characteristics of individuals with hoarding disorder (HD) are not well understood. Existing studies are relatively few and somewhat inconsistent but suggest that individuals with HD may have specific dysfunction in the cognitive domains of categorization, speed of information processing, and decision making. However, there have been no studies evaluating the degree to which cognitive dysfunction in these domains reflects clinically significant cognitive impairment (CI). MethodsParticipants included 78 individuals who met DSM-V criteria for HD and 70 age- and education-matched controls. Cognitive performance on measures of memory, attention, information processing speed, abstract reasoning, visuospatial processing, decision making, and categorization ability was evaluated for each participant. Rates of clinical impairment for each measure were compared, as were age- and education-corrected raw scores for each cognitive test. ResultsHD participants showed greater incidence of CI on measures of visual memory, visual detection, and visual categorization relative to controls. Raw-score comparisons between groups showed similar results with HD participants showing lower raw-score performance on each of these measures. In addition, in raw-score comparisons HD participants also demonstrated relative strengths compared to control participants on measures of verbal and visual abstract reasoning. ConclusionsThese results suggest that HD is associated with a pattern of clinically significant CI in some visually mediated neurocognitive processes including visual memory, visual detection, and visual categorization. Additionally, these results suggest HD individuals may also exhibit relative strengths, perhaps compensatory, in abstract reasoning in both verbal and visual domains. C1 [Mackin, R. Scott; Vigil, Ofilio; Kivowitz, Alana; Kupferman, Eve; Hough, Christina M.; Crothers, Ross; Bickford, David; Delucchi, Kevin L.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Mackin, R. Scott; Insel, Philip] San Francisco VA Med Ctr, San Francisco, CA USA. [Fekri, Shiva] Univ Colorado, Dept Psychol, Denver, CO 80202 USA. RP Mackin, RS (reprint author), Univ Calif San Francisco, Langley Porter Psychiat Inst, Dept Psychiat, 401 Parnassus Ave,Box F-0984, San Francisco, CA 94143 USA. EM Scott.Mackin@ucsf.edu RI Hough, Christina/K-2416-2016 OI Hough, Christina/0000-0002-8864-5262 FU NIMH [R21 MH087748, K08 MH081065, R01 0977669]; Patient-Centered Outcomes Research Institute (PCORI) Award [6000] FX Contract grant sponsor: NIMH; Grant numbers: R21 MH087748, K08 MH081065, R01 0977669. The Althea Foundation and a Patient-Centered Outcomes Research Institute (PCORI) Award; Contract number: 6000. NR 46 TC 3 Z9 3 U1 6 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAR PY 2016 VL 33 IS 3 BP 211 EP 218 DI 10.1002/da.22439 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DG6FY UT WOS:000372179800005 PM 26474146 ER PT J AU McGuire, JF Orr, SP Wu, MS Lewin, AB Small, BJ Phares, V Murphy, TK Wilhelm, S Pine, DS Geller, D Storch, EA AF McGuire, Joseph F. Orr, Scott P. Wu, Monica S. Lewin, Adam B. Small, Brent J. Phares, Vicky Murphy, Tanya K. Wilhelm, Sabine Pine, Daniel S. Geller, Daniel Storch, Eric A. TI FEAR CONDITIONING AND EXTINCTION IN YOUTH WITH OBSESSIVE-COMPULSIVE DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE fear conditioning; extinction; skin conductance; inhibitory learning; obsessive-compulsive disorder; children ID COGNITIVE-BEHAVIORAL THERAPY; ANXIETY DISORDERS; FUNCTIONAL IMPAIRMENT; TREATMENT RESPONSE; BIAS MODIFICATION; CHILD VERSION; ADOLESCENTS; PREDICTORS; ADULTS; RELIABILITY AB BackgroundFear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy (CBT). Youth with OCD may have impairments in fear acquisition and extinction that carry treatment implications. We examined these processes using a differential conditioning procedure. MethodsForty-one youth (19 OCD, 22 community comparisons) completed a battery of clinical interviews, rating scales, and a differential conditioning task that included habituation, acquisition, and extinction phases. Skin conductance response (SCR) served as the primary dependent measure. ResultsDuring habituation, no difference between groups was observed. During acquisition, differential fear conditioning was observed across participants as evidenced by larger SCRs to the CS+ compared to CS-; there were no between-group differences. Across participants, the number and frequency of OCD symptoms and anxiety severity was associated with greater reactivity to stimuli during acquisition. During extinction, a three-way interaction and follow-up tests revealed that youth with OCD showed a different pattern of SCR extinction compared to the community comparison group. ConclusionsYouth with OCD exhibit a different pattern of fear extinction relative to community comparisons. This may be attributed to impaired inhibitory learning and contingency awareness in extinction. Findings suggest the potential benefit of utilizing inhibitory-learning principles in CBT for youth with OCD, and/or augmentative retraining interventions prior to CBT to reduce threat bias and improve contingency detection. C1 [McGuire, Joseph F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Pl,48-228B, Los Angeles, CA 90095 USA. [Orr, Scott P.; Wilhelm, Sabine; Geller, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wu, Monica S.; Lewin, Adam B.; Phares, Vicky; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Wu, Monica S.; Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Psychiat & Behav Neurosci, Tampa, FL USA. [Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, All Childrens Hosp, Johns Hopkins Med, St Petersburg, FL 33701 USA. [Small, Brent J.] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Rockville, MD 20857 USA. [Storch, Eric A.] Rogers Behav Hlth Tampa Bay, Tampa, FL USA. [Storch, Eric A.] Univ S Florida, Dept Hlth Policy & Management, Tampa, FL USA. RP McGuire, JF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Pl,48-228B, Los Angeles, CA 90095 USA. EM jfmcguire@mednet.ucla.edu FU National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) [R01MH093381-02S1]; NIMH Intramural Research Program FX Contract grant sponsor: Support for this article comes in part from the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) as a research supplement to promote diversity in health-related research (R01MH093381-02S1). Dr. Pine is supported by the NIMH Intramural Research Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or NIH. NR 54 TC 4 Z9 4 U1 5 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAR PY 2016 VL 33 IS 3 BP 229 EP 237 DI 10.1002/da.22468 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DG6FY UT WOS:000372179800007 PM 26799264 ER PT J AU Achuko, O Walker, RJ Campbell, JA Dawson, AZ Egede, LE AF Achuko, Obinna Walker, Rebekah J. Campbell, Jennifer A. Dawson, Aprill Z. Egede, Leonard E. TI Pathways Between Discrimination and Quality of Life in Patients with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID REPORTED RACIAL-DISCRIMINATION; RANDOMIZED CONTROLLED-TRIAL; PERCEIVED DISCRIMINATION; SOCIAL DETERMINANTS; AFRICAN-AMERICAN; GLYCEMIC CONTROL; HEALTH-CARE; EVERYDAY DISCRIMINATION; PSYCHOLOGICAL DISTRESS; WEIGHT DISCRIMINATION AB Background: Discrimination is a social determinant that has been linked to poor physical and mental health outcomes. This study aimed to examine the pathway whereby discrimination influences quality of life in patients with type 2 diabetes. Subjects and Methods: Six hundred fifteen patients were recruited from two adult primary care clinics in the southeastern United States. Measures included perceived discrimination, perceived stress, social support, and social cohesion and were based on a theoretical model for the pathways by which perceived discrimination influences mental and physical health. Quality of life was measured using the SF-12 questionnaire. Results: The final model [chi(2)(106) = 157.35, P = 0.009, R-2 = 0.99, root mean square error of approximation = 0.03, comparative fit index = 0.99] indicates direct effects of higher perceived stress (r = -1.02, P < 0.05) and lower social support (r = 0.36, P < 0.001) significantly related to decreased mental health component score (MCS) of quality of life. Discrimination and social cohesion were not significantly directly related to MCS. However, higher discrimination (r = 0.47, P < 0.001), higher social cohesion (r = 0.14, P < 0.05), and lower social support (r = -0.43, P < 0.001) were significantly directly related to increased stress. No significant paths were found for the physical component score of quality of life. Conclusions: Perceived discrimination was significantly associated with stress and served as a pathway to influence the mental health component of quality of life (MCS). Social support had a direct and an indirect effect on MCS through a negative association with stress. These results suggest that future interventions should be developed to decrease stress and increase social support surrounding discrimination to improve the MCS of quality of life in patients with diabetes. C1 [Achuko, Obinna; Walker, Rebekah J.; Campbell, Jennifer A.; Dawson, Aprill Z.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA Hlth Serv Res & Dev COIN, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by grant K24DK093699-01 from the National Institute of Diabetes and Digestive and Kidney Disease (Principal Investigator: L.E.E.). NR 58 TC 0 Z9 0 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD MAR 1 PY 2016 VL 18 IS 3 BP 151 EP 158 DI 10.1089/dia.2015.0305 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DG6HE UT WOS:000372183700008 PM 26866351 ER PT J AU Marneros, AG AF Marneros, Alexander G. TI Increased VEGF-A promotes multiple distinct aging diseases of the eye through shared pathomechanisms SO EMBO MOLECULAR MEDICINE LA English DT Article DE age-related macular degeneration; aging; cataract; NLRP3 inflammasome; VEGF-A ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MEMBRANE ATTACK COMPLEX; AGE-RELATED CATARACT; DISMUTASE-NULL MICE; MACULAR-DEGENERATION; SUPEROXIDE-DISMUTASE; NLRP3 INFLAMMASOME; OXIDATIVE-STRESS AB While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and both neovascular and non-exudative AMD-like pathologies. In the lens, increased VEGF-A induces age-related opacifications that are associated with ERK hyperactivation, increased oxidative damage, and higher expression of the NLRP3 inflammasome effector cytokine IL-1. Similarly, increased VEGF-A induces oxidative stress and IL-1 expression also in the retinal pigment epithelium (RPE). Targeting NLRP3 inflammasome components or Il1r1 strongly inhibited not only VEGF-A-induced cataract formation, but also both neovascular and non-exudative AMD-like pathologies. Moreover, increased VEGF-A expression specifically in the RPE was sufficient to cause choroidal neovascularization (CNV) as in neovascular AMD, which could be inhibited by RPE-specific inactivation of Flk1, while Tlr2 inactivation strongly reduced CNV. These findings suggest a shared pathogenic role of VEGF-A-induced andNLRP3 inflammasome-mediated IL-1 activation for multiple distinct ocular aging diseases. C1 [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Marneros, Alexander G.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Marneros, AG (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.; Marneros, AG (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. EM amarneros@mgh.harvard.edu FU NEI [R01-EY019297]; BrightFocus Foundation FX For some technical assistance, I would like to thank Oscar Morales and Karin Strittmatter. This work was supported by grants to A.G.M. from the NEI (R01-EY019297) and from the BrightFocus Foundation. NR 66 TC 1 Z9 1 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAR PY 2016 VL 8 IS 3 BP 208 EP 231 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DG5WT UT WOS:000372151100004 PM 26912740 ER PT J AU Teplyuk, NM Uhlmann, EJ Gabriely, G Volfovsky, N Wang, Y Teng, J Karmali, P Marcusson, E Peter, M Mohan, A Kraytsberg, Y Cialic, R Chiocca, EA Godlewski, J Tannous, B Krichevsky, AM AF Teplyuk, Nadiya M. Uhlmann, Erik J. Gabriely, Galina Volfovsky, Natalia Wang, Yang Teng, Jian Karmali, Priya Marcusson, Eric Peter, Merlene Mohan, Athul Kraytsberg, Yevgenya Cialic, Ron Chiocca, E. Antonio Godlewski, Jakub Tannous, Bakhos Krichevsky, Anna M. TI Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic SO EMBO MOLECULAR MEDICINE LA English DT Article DE alternative splicing; brain tumor; microRNA; oligonucleotide therapeutics; stem cells ID CANCER-CELL-PROLIFERATION; PRE-MESSENGER-RNA; GENE-EXPRESSION; MIR-B-10 EXPRESSION; BRAIN-TUMORS; INVASION; GLIOMA; PROTEINS; PROMOTES; RESISTANCE AB MicroRNA-10b (miR-10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Although several miR-10b targets have been identified previously, the common mechanism conferring the miR-10b-sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5UTRs of its target genes, including MBNL1-3, SART3, and RSRC1. We have further assessed the inhibition of miR-10b in intracranial human GSC-derived xenograft and murine GL261 allograft models in athymic and immunocompetent mice. Three delivery routes for the miR-10b antisense oligonucleotide inhibitors (ASO), direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections, have been explored. In all cases, the treatment with miR-10b ASO led to targets' derepression, and attenuated growth and progression of established intracranial GBM. No significant systemic toxicity was observed upon ASO administration by local or systemic routes. Our results indicate that miR-10b is a promising candidate for the development of targeted therapies against all GBM subtypes. C1 [Teplyuk, Nadiya M.; Uhlmann, Erik J.; Gabriely, Galina; Wang, Yang; Peter, Merlene; Mohan, Athul; Kraytsberg, Yevgenya; Cialic, Ron; Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ann Romney Ctr Neurol Dis, Boston, MA USA. [Volfovsky, Natalia] Simons Fdn, New York, NY USA. [Teng, Jian; Tannous, Bakhos] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Karmali, Priya; Marcusson, Eric] Regulus Therapeut Inc, San Diego, CA USA. [Chiocca, E. Antonio; Godlewski, Jakub] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. RP Krichevsky, AM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ann Romney Ctr Neurol Dis, Boston, MA USA. EM akrichevsky@rics.bwh.harvard.edu OI Cialic, Ron/0000-0002-1589-2262 FU NIH/NCI [RO1CA138734]; Sontag Foundation; National Brain Tumor Society; Brain Science Foundation FX This work was supported by grants from NIH/NCI (RO1CA138734), Sontag Foundation Distinguished Scientist Award, and National Brain Tumor Society (to AMK), and Brain Science Foundation (to NT, AMK, and EJU). We thank Anant Jain, Deeptha Vasudevan, and Meenakshi Basu for technical assistance, Dr. Oleg Butovsky for assistance with IPA analysis, and Dr. Vivek Kaimal for assistance with microarray analysis. We thank Regulus Therapeutics, Inc., for providing miRNA inhibitors and antibody recognizing the ASO. We also thank Dr. Hiroaki Wakamoto for providing human GBM stem cells, Dr. Bozena Kaminska for mouse GL261 cells, and Dr. Glenn Morris for sharing the anti-MBNL2 antibody. NR 68 TC 8 Z9 9 U1 7 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAR PY 2016 VL 8 IS 3 BP 268 EP 287 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DG5WT UT WOS:000372151100007 PM 26881967 ER PT J AU Brown, HE Roffman, JL AF Brown, Hannah E. Roffman, Joshua L. TI Emerging Treatments in Schizophrenia: Highlights from Recent Supplementation and Prevention Trials SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED-TRIAL; ETHYL-EICOSAPENTAENOIC ACID; VITAMIN-D DEFICIENCY; ADD-ON THERAPY; DOUBLE-BLIND; NEGATIVE SYMPTOMS; FATTY-ACID; CELECOXIB AUGMENTATION; STABLE SCHIZOPHRENIA; ADJUNCTIVE THERAPY C1 [Brown, Hannah E.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Hannah E.] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. [Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Brown, HE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM hebrown@partners.org FU Pamlab FX Dr. Roffman has previously received a research grant from Pamlab. NR 61 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2016 VL 24 IS 2 BP e1 EP e7 PG 7 WC Psychiatry SC Psychiatry GA DG5CQ UT WOS:000372090900001 PM 26954600 ER PT J AU Hsu, J Price, M Spirt, J Vogeli, C Brand, R Chernew, ME Chaguturu, SK Mohta, N Weil, E Ferris, T AF Hsu, John Price, Mary Spirt, Jenna Vogeli, Christine Brand, Richard Chernew, Michael E. Chaguturu, Sreekanth K. Mohta, Namita Weil, Eric Ferris, Timothy TI Patient Population Loss At A Large Pioneer Accountable Care Organization And Implications For Refining The Program SO HEALTH AFFAIRS LA English DT Article ID SHARED SAVINGS PROGRAM; HEALTH-CARE; MEDICARE; PERFORMANCE; PATTERNS; RULES; ACOS AB There is an ongoing move toward payment models that hold providers increasingly accountable for the care of their patients. The success of these new models depends in part on the stability of patient populations. We investigated the amount of population turnover in a large Medicare Pioneer accountable care organization (ACO) in the period 2012-14. We found that substantial numbers of beneficiaries became part of or left the ACO population during that period. For example, nearly one-third of beneficiaries who entered in 2012 left before 2014. Some of this turnover reflected that of ACO physicians-that is, beneficiaries whose physicians left the ACO were more likely to leave than those whose physicians remained. Some of the turnover also reflected changes in care delivery. For example, beneficiaries who were active in a care management program were less likely to leave the ACO than similar beneficiaries who had not yet started such a program. We recommend policy changes to increase the stability of ACO beneficiary populations, such as permitting lower cost sharing for care received within an ACO and requiring all beneficiaries to identify their primary care physician before being linked to an ACO. C1 [Hsu, John] Massachusetts Gen Hosp, Mongan Inst, Clin Econ & Policy Anal Program, Boston, MA 02114 USA. [Hsu, John] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hsu, John; Chernew, Michael E.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Price, Mary; Spirt, Jenna; Vogeli, Christine] Massachusetts Gen Hosp, Mongan Inst, Boston, MA 02114 USA. [Brand, Richard] Univ Calif San Francisco, Biostat, San Francisco, CA 94143 USA. [Chaguturu, Sreekanth K.; Weil, Eric; Ferris, Timothy] Partners HealthCare, Populat Hlth, Boston, MA USA. [Chaguturu, Sreekanth K.; Ferris, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chaguturu, Sreekanth K.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Mohta, Namita] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Weil, Eric] Massachusetts Gen Phys Org, Boston, MA USA. [Weil, Eric] Massachusetts Gen Hosp, Div Gen Internal Med, Clin Affairs, Boston, MA 02114 USA. [Ferris, Timothy] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. [Ferris, Timothy] Harvard Univ, Sch Med, Boston, MA USA. RP Hsu, J (reprint author), Massachusetts Gen Hosp, Mongan Inst, Clin Econ & Policy Anal Program, Boston, MA 02114 USA.; Hsu, J (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA.; Hsu, J (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM jhsu2000@gmail.com FU National Institute on Aging [P01AG032952] FX An earlier version of this article was presented at the biennial conference of the International Health Economics Association, Milan, Italy, July 2015. Funding was provided by the National Institute on Aging (Grant No. P01AG032952). NR 34 TC 1 Z9 1 U1 2 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR PY 2016 VL 35 IS 3 BP 422 EP 430 DI 10.1377/hlthaff.2015.0805 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DG1KA UT WOS:000371825000009 PM 26953296 ER PT J AU Hogarth, MW Garton, FC Houweling, PJ Tukiainen, T Lek, M Macarthur, DG Seto, JT Quinlan, KGR Yang, N Head, SI North, KN AF Hogarth, Marshall W. Garton, Fleur C. Houweling, Peter J. Tukiainen, Taru Lek, Monkol Macarthur, Daniel G. Seto, Jane T. Quinlan, Kate G. R. Yang, Nan Head, Stewart I. North, Kathryn N. TI Analysis of the ACTN3 heterozygous genotype suggests that alpha-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion SO HUMAN MOLECULAR GENETICS LA English DT Article ID SKELETAL-MUSCLE; ATHLETIC PERFORMANCE; R577X POLYMORPHISM; GENE DUPLICATION; KNOCKOUT MOUSE; FIBER TYPES; DEFICIENCY; EXPRESSION; WOMEN; PROTEINS AB A common null polymorphism (R577X) in ACTN3 causes alpha-actinin-3 deficiency in similar to 18% of the global population. There is no associated disease phenotype, but alpha-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of alpha-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of alpha-actinin-3 expression level by comparing the muscle phenotypes of Actn(3+/-) (HET) mice to Actn(3+/+) [wild-type (WT)] and Actn3(-/-) [knockout (KO)] littermates. We show reduction in alpha-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of alpha-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations. C1 [Hogarth, Marshall W.; Garton, Fleur C.; Houweling, Peter J.; Quinlan, Kate G. R.; Yang, Nan; North, Kathryn N.] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia. [Hogarth, Marshall W.; Garton, Fleur C.; Houweling, Peter J.; Quinlan, Kate G. R.; North, Kathryn N.] Univ Sydney, Discipline Paediat & Child Hlth, Fac Med, Sydney, NSW 2006, Australia. [Garton, Fleur C.; Houweling, Peter J.; Seto, Jane T.; North, Kathryn N.] Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia. [Garton, Fleur C.; Houweling, Peter J.; Seto, Jane T.; North, Kathryn N.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Head, Stewart I.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. RP North, KN (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM kathryn.north@mcri.edu.au RI Garton, Fleur/H-7713-2016; North, Kathryn/K-6476-2012; Houweling, Peter/B-4157-2016 OI Garton, Fleur/0000-0002-1490-5930; North, Kathryn/0000-0003-0841-8009; Houweling, Peter/0000-0001-6132-2554 FU National Health and Medical Research Council of Australia [1002033, 1062500]; Common Fund of the Office of the Director of the National Institutes of Health; GTEx Laboratory, Data Analysis, and Coordinating Center (LDACC) [HHSN268201000029C]; National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health [R01GM104371] FX This project was funded by grants from the National Health and Medical Research Council of Australia (1002033 and 1062500). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. The work by TT and DGM was partially funded by the GTEx Laboratory, Data Analysis, and Coordinating Center (LDACC) contract (HHSN268201000029C) to The Broad Institute, Inc. The work by M.L. and D.G.M. was partially funded by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health, under award R01GM104371. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 39 TC 2 Z9 2 U1 6 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2016 VL 25 IS 5 BP 866 EP 877 DI 10.1093/hmg/ddv613 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5XA UT WOS:000372152400003 PM 26681802 ER PT J AU Richards, AL Leonenko, G Walters, JT Kavanagh, DH Rees, EG Evans, A Chambert, KD Moran, JL Goldstein, J Neale, BM McCarroll, SA Pocklington, AJ Holmans, PA Owen, MJ O'Donovan, MC AF Richards, A. L. Leonenko, G. Walters, J. T. Kavanagh, D. H. Rees, E. G. Evans, A. Chambert, K. D. Moran, J. L. Goldstein, J. Neale, B. M. McCarroll, S. A. Pocklington, A. J. Holmans, P. A. Owen, M. J. O'Donovan, M. C. TI Exome arrays capture polygenic rare variant contributions to schizophrenia SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; GENE ONTOLOGY; LOCI; HERITABILITY; DATABASE; DISEASE; BIOLOGY; LINKAGE; PANTHER AB Schizophrenia is a highly heritable disorder. Genome-wide association studies based largely on commonalleles have identified over 100 schizophrenia risk loci, but it is also evident from studies of copy number variants (CNVs) and from exome-sequencing studies that rare alleles are also involved. Full characterization of the contribution of rare alleles to the disorder awaits the deployment of sequencing technology in very large sample sizes, meanwhile, as an interim measure, exome arrays allow rare non-synonymous variants to be sampled at a fraction of the cost. In an analysis of exome array data from 13 688 individuals (5585 cases and 8103 controls) from the UK, we found that rare (minor allele frequency <0.1%) variant association signal was enriched among genes that map to autosomal loci that are genome-wide significant (GWS) in common variant studies of schizophrenia genome-wide association study (P-GWAS = 0.01) as well as gene sets known to be enriched for rare variants in sequencing studies (P-RARE = 0.026). We also identified the gene-wise equivalent of GWS support for WDR88 (WD repeat-containing protein 88), a gene of unknown function (P = 6.5 x 10(-7)). Rare alleles represented on exome chip arrays contribute to the genetic architecture of schizophrenia, but as is the case for GWAS, very large studies are required to reveal additional susceptibility alleles for the disorder. C1 [Richards, A. L.; Leonenko, G.; Walters, J. T.; Kavanagh, D. H.; Rees, E. G.; Evans, A.; Pocklington, A. J.; Holmans, P. A.; Owen, M. J.; O'Donovan, M. C.] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC,Ctr Neuropsychiat Genet & Genom, Hadyn Ellis Bldg, Cardiff CF24 4HQ, S Glam, Wales. [Kavanagh, D. H.] Icahn Sch Med Mt Sinai, 1468 Madison Ave, New York, NY 10029 USA. [Chambert, K. D.; Moran, J. L.; Goldstein, J.; Neale, B. M.; McCarroll, S. A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Neale, B. M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP O'Donovan, MC (reprint author), Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC,Ctr Neuropsychiat Genet & Genom, Hadyn Ellis Bldg, Cardiff CF24 4HQ, S Glam, Wales. EM odonovanmc@cardiff.ac.uk OI Moran, Jennifer/0000-0002-5664-4716; Walters, James/0000-0002-6980-4053; Holmans, Peter/0000-0003-0870-9412 FU Medical Research Council (MRC) [G0800509, G0801418]; European Community [HEALTH-F2-2010-241909]; philanthropic gift; Cardiff University for RCUK FX The work at Cardiff University was funded by Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418), the European Community's Seventh Framework Programme [HEALTH-F2-2010-241909 (Project EU-GEI)]. Genotyping at the Broad Institute was funded by a philanthropic gift to the Stanley Center for Psychiatric Research. Funding to pay the Open Access publication charges for this article was provided by funds held within Cardiff University for RCUK funded projects. NR 44 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2016 VL 25 IS 5 BP 1001 EP 1007 DI 10.1093/hmg/ddv620 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5XA UT WOS:000372152400014 PM 26740555 ER PT J AU Nyholm, AM Palm, H Malchau, H Troelsen, A Gromov, K AF Nyholm, Anne Marie Palm, Henrik Malchau, Henrik Troelsen, Anders Gromov, Kirill TI Lacking evidence for performance of implants used for proximal femoral fractures - A systematic review SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Review DE Hip fracture; Proximal femoral fracture; Trochanteric fracture; Implant survival; Implant failure; Reoperation ID DYNAMIC HIP SCREW; UNSTABLE INTERTROCHANTERIC FRACTURES; QUALITY-OF-LIFE; PERCUTANEOUS COMPRESSION PLATE; GAMMA LOCKING NAIL; TROCHANTERIC FRACTURES; INTRAMEDULLARY NAIL; INTERNAL-FIXATION; NECK FRACTURES; PERTROCHANTERIC FRACTURES AB Introduction: Evaluation of the long-term performance of implants used in trauma surgery relies on post-marked clinical studies since no registry based implant assessment exists. The purpose of this study was to evaluate the evidence of performance of implants currently used for treating proximal femoral fractures (PFF) in Denmark. Method: PubMed was searched for clinical studies on primary PFF with follow-up >= 12 months, reporting implant-related failure and evaluating one of following: DHS, CHS, HipLoc, Gamma3, IMHS, InterTan, PFN, PFNA or PTN. Limits: English language and publication date after 1st of January 1990. Results: All studies were evidence level II or III. 30 publications for SHS were found: 13 of CHS, 15 of DHS and 2 of HipLoc. In total CHS was evaluated in 1110 patients (900 prospectively), DHS in 2486 (567 prospectively) and HipLoc in 251 (all prospectively). Fifty-four publications for nails were found: 13 of Gamma3, 7 of IMHS, 5 of InterTan, 10 of PFN, 24 of PFNA and 0 of PTN. In total Gamma3 was evaluated in 1088 patients (829 prospectively), IMHS in 1543 (210 prospectively), InterTan in 595 (585 prospectively), PFN in 716 (557 prospectively), PFNA in 1762 (1018 prospectively) and PTN in 0. Conclusions: The clinical evidence behind the current implants used for proximal femoral fractures is weak considering the number of implants used worldwide. Sporadic evaluation is not sufficient to identify long term problems. A systematic post market surveillance of implants used for fracture treatment, preferable by a national register, is necessary in the future. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Nyholm, Anne Marie; Palm, Henrik; Troelsen, Anders; Gromov, Kirill] Univ Copenhagen, Hvidovre Hosp, Dept Orthopaed, Clin Orthopaed Res Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. [Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthoped, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. RP Nyholm, AM (reprint author), Univ Copenhagen, Hvidovre Hosp, Dept Orthopaed, Clin Orthopaed Res Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM rienyholm@gmail.com NR 96 TC 0 Z9 0 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD MAR PY 2016 VL 47 IS 3 BP 586 EP 594 DI 10.1016/j.injury.2016.01.001 PG 9 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DG3RV UT WOS:000371988400011 PM 26803696 ER PT J AU Gill, A Mellema, JJ Menendez, ME Ring, D AF Gill, Aditya Mellema, Jos J. Menendez, Mariano E. Ring, David TI Articular osteotomy of the distal humerus and excision of extensive heterotopic ossification SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Distal humeral fracture; Elbow; Intra-articular malunion; Heterotopic ossification; Ankylosis; Osteotomy ID RISK-FACTORS; ELBOW; RELEASE; FRACTURES; ANKYLOSIS AB Prior case series of corrective osteotomy of substantial intra-articular malunion after a fracture of the distal humerus described concomitant heterotopic ossification in a subset of patient, but only in mild forms. We present our experience in treating two patients with malunited articular fractures of the distal humerus with extensive heterotopic ossification and near ankylosis where the lateral articular fragments were encased in heterotopic bone. Although osteotomy of articular malunion after distal humeral fracture along with excision of extensive HO is challenging and risky due to potential devitalization of the fragments, articular deterioration during the delay to osteotomy, and recurrence of heterotopic bone among other concerns, restoring articular congruity in these patients using articular fracture fragments extracted from heterotopic ossification can lead to improved function of the elbow. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Gill, Aditya; Mellema, Jos J.; Menendez, Mariano E.] Harvard Univ, Sch Med, Hand & Upper Extrem Serv, Dept Orthopaed Surg,Massachusetts Gen Hosp,Yawkey, Suite 2100,55 Fruit St, Boston, MA 02114 USA. [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Chief Hand Surg,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Chief Hand Surg,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM agill2@mgh.harvard.edu; jmellema@mgh.harvard.edu; memenendez@partners.org; dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 NR 14 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD MAR PY 2016 VL 47 IS 3 BP 776 EP 779 DI 10.1016/j.injury.2015.12.030 PG 4 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DG3RV UT WOS:000371988400044 PM 26854073 ER PT J AU Liu, XD Li, JS Hosseini, A Gill, TJ Li, GA AF Liu, Xudong Li, Jing-Sheng Hosseini, Ali Gill, Thomas J. Li, Guoan TI Anteromedial and posterolateral graft kinematics of a double-bundle ACL reconstruction: a 3D computer simulation SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE ACL; double-bundle ACL reconstruction; anatomical ACL reconstruction ID ANTERIOR CRUCIATE LIGAMENT; ARTHROSCOPIC EVALUATION; SINGLE-BUNDLE; JOINT; LENGTH; TUNNEL AB BackgroundThe posterolateral graft has been reported to fail more frequently than the anteromedial graft in double-bundle ACL reconstructions. This study investigated the graft kinematics using a 3D modelling technique. MethodsTwenty subjects performed a stair-ascending activity under dual fluoroscopy surveillance. A double-bundle ACL reconstruction was simulated on those healthy knees using an anteromedial portal technique. The graft-tunnel interaction was described using the graft-tunnel angle and the range of the graft-tunnel edge contact (GTEC). ResultsThe femoral graft-tunnel angle of the anteromedial/posterolateral graft was 97.6 7.5/100.7 +/- 7.7 degrees and the tibial graft-tunnel angle was 158.8 +/- 6.5/146.5 +/- 8.9 degrees at knee extension. The femoral GTEC ranges were 23.2 +/- 5.3-28.1 +/- 7.6 degrees for both grafts and the tibial GTEC ranges were 27.3 +/- 2.2-34.5 +/- 2.1 degrees during stair-ascending. ConclusionThe femoral graft-tunnel angle was larger than on the tibial side and the GTEC angles influenced the PL graft more, implying that grafts may experience a less optimal biomechanical environment at the femoral tunnels. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Liu, Xudong; Li, Jing-Sheng; Hosseini, Ali; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Liu, Xudong] Shanghai Jiao Tong Univ, Dept Orthopaed, Shanghai Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Sch Med, Bioengn Lab, Dept Orthopaed Surg,Massachusetts Gen Hosp, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@mgh.harvard.edu FU National Institutes of Health (NIH) [R01 AR0055612] FX The authors gratefully acknowledge financial support from the National Institutes of Health (NIH; Grant No. R01 AR0055612). NR 25 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-5951 EI 1478-596X J9 INT J MED ROBOT COMP JI Int. J. Med. Robot. Comput. Assist. Surg. PD MAR PY 2016 VL 12 IS 1 BP 96 EP 101 DI 10.1002/rcs.1645 PG 6 WC Surgery SC Surgery GA DG8KW UT WOS:000372333700009 PM 25644175 ER PT J AU McGinley, KF Sun, XZ Howard, LE Aronson, WJ Terris, MK Kane, CJ Amling, CL Cooperberg, MR Freedland, SJ AF McGinley, Kathleen F. Sun, Xizi Howard, Lauren E. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Cooperberg, Matthew R. Freedland, Stephen J. TI Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE lymph node excision; prostatectomy; prostatic neoplasms; quality of health care; robotic surgical procedures ID MEN; UPDATE AB ObjectiveTo evaluate performance of pelvic lymph node dissection during radical prostatectomy within an equal access care setting over a period of time, and stratified by prostate cancer risk group and surgical technique. MethodsWe identified men in the Shared Equal Access Regional Cancer Hospital database who had open or robotic-assisted radical prostatectomy from 2006 to 2013. Univariable logistic regression was used to test the association between age, race, body mass index, total biopsy cores, number of positive biopsy cores, risk group, year, center, surgical volume and surgical technique on pelvic lymph node dissection use. Multivariable logistic analysis was used to examine surgical technique and pelvic lymph node dissection performance. Spearman's correlation examined temporal changes in pelvic lymph node dissection utilization stratified by risk group and surgical technique. ResultsA total of 1425 men met inclusion criteria; 67% of them underwent pelvic lymph node dissection. On multivariable analysis, robotic-assisted radical prostatectomy was associated with an 92% decreased use of pelvic lymph node dissection in low-risk, 84% decreased in intermediate-risk and 91% decreased in high-risk men (all P < 0.001). In robotic-assisted radical prostatectomy, there was a trend for increased pelvic lymph node dissection utilization over time in high-risk men (Spearman; P = 0.077) reaching similar to 85% in 2012-2013, which was accompanied by increased use in low-risk men (P = 0.016). For open radical prostatectomy, fewer pelvic lymph node dissections were carried out in low-risk men over time, decreasing to similar to 35% (P = 0.047) in 2012-2013, whereas rates remained high for high-risk men throughout (similar to 95%; P = 0.621). ConclusionRegardless of risk group, pelvic lymph node dissection is carried out significantly less during robotic-assisted radical prostatectomy. For robotic-assisted radical prostatectomy, pelvic lymph node dissection utilization increased over time for high-risk men, but rates also increased for low-risk men. Further attention to the discrepancy between provided and guideline recommended pelvic lymph node dissection performance is required to improve prostate cancer care. C1 [McGinley, Kathleen F.] Duke Univ, Dept Surg, Div Urol, Durham, NC USA. [McGinley, Kathleen F.; Sun, Xizi; Howard, Lauren E.; Freedland, Stephen J.] Vet Affairs Med Ctr, Dept Surg, Div Urol, Durham, NC USA. [Sun, Xizi; Howard, Lauren E.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Georgia Regents Univ, Dept Urol, Augusta, GA USA. [Kane, Christopher J.] Univ Calif San Diego Hlth Syst, Dept Urol, San Diego, CA USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97201 USA. [Cooperberg, Matthew R.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA USA. [Freedland, Stephen J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, Dept Surg, Div Urol, Los Angeles, CA 90048 USA. RP Freedland, SJ (reprint author), Cedars Sinai Med Ctr, 8635 West 3rd St,Suite 1070W, Los Angeles, CA 90048 USA. EM stephen.freedland@cshs.org NR 21 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD MAR PY 2016 VL 23 IS 3 BP 241 EP 246 DI 10.1111/iju.13027 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DG5YH UT WOS:000372157100011 PM 26667212 ER PT J AU Hadlock, T AF Hadlock, Tessa TI Standard Outcome Measures in Facial Paralysis Getting on the Same Page SO JAMA FACIAL PLASTIC SURGERY LA English DT Editorial Material ID MANAGEMENT C1 [Hadlock, Tessa] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAR-APR PY 2016 VL 18 IS 2 BP 85 EP 86 DI 10.1001/jamafacial.2015.2095 PG 2 WC Surgery SC Surgery GA DG5XF UT WOS:000372153100001 PM 26746124 ER PT J AU Tjoa, T Manuel, CT Leary, RP Harb, R Protsenko, DE Wong, BJF AF Tjoa, Tjoson Manuel, Cyrus T. Leary, Ryan P. Harb, Rani Protsenko, Dmitriy E. Wong, Brian J. F. TI A Finite Element Model to Simulate Formation of the Inverted-V Deformity SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID COMPUTATIONAL FLUID-DYNAMICS; NASAL TIP SUPPORT; REVISION RHINOPLASTY; CARTILAGE; EAR; BIOMECHANICS; MANAGEMENT; REDUCTION; SURGERY; SEPTUM AB IMPORTANCE Computational modeling can be used to mimic the forces acting on the nasal framework that lead to the inverted-V deformity (IVD) after surgery and potentially determine long-range outcomes. OBJECTIVE To demonstrate the use of the finite element method (FEM) to predict the formation of the IVD after separation of the upper lateral cartilages (ULCs) from the nasal septum. DESIGN, SETTING, AND PARTICIPANTS A computer model of a nose was derived from human computed tomographic data. The septum and upper and lower lateral cartilages were designed to fit within the soft-tissue envelope using computer-aided design software. Mechanical properties were obtained from the literature. The 3 simulations created included (1) partial fusion of the ULCs to the septum, (2) separation of the ULCs from the septum, and (3) a fully connected model to serve as a control. Forces caused by wound healing were prescribed at the junction of the disarticulated ULCs and septum. Using FEM software, equilibrium stress and strain were calculated. Displacement of the soft tissue along the nasal dorsum was measured and evaluated for evidence of morphologic change consistent with the IVD. MAIN OUTCOME AND MEASURES Morphologic changes on the computer models in response to each simulation. RESULTS When a posteroinferior force vector was applied along the nasal dorsum, the areas of highest stress were along the medial edge of the ULCs and at the junction of the ULCs and the nasal bones. With full detachment of ULCs and the dorsal septum, the characteristic IVD was observed. Both separation FEMs produced a peak depression of 0.3mm along the nasal dorsum. CONCLUSIONS AND RELEVANCE The FEM can be used to simulate the long-term structural complications of a surgical maneuver in rhinoplasty, such as the IVD. When applied to other rhinoplasty maneuvers, the use of FEMs may be useful to simulate the long-term outcomes, particularly when long-term clinical results are not available. In the future, use of FEMs may simulate rhinoplasty results beyond simply morphing the outer contours of the nose and allow estimation of potentially long-term clinical outcomes that may not be readily apparent. C1 [Tjoa, Tjoson] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Manuel, Cyrus T.; Leary, Ryan P.; Harb, Rani; Protsenko, Dmitriy E.; Wong, Brian J. F.] Univ Calif Irvine, Beckman Laser Inst, 101 City Dr S,Bldg 56, Orange, CA 92868 USA. [Wong, Brian J. F.] Univ Calif Irvine, Dept Otolaryngol, Orange, CA 92868 USA. RP Wong, BJF (reprint author), Univ Calif Irvine, Beckman Laser Inst, 101 City Dr S,Bldg 56, Orange, CA 92868 USA. EM bjwong@uci.edu FU National Institutes of Health [R21DE019026-01A2]; US Department of Defense [DR090349]; National Center for Advancing Translational Sciences [UL1 TR000153] FX This study was supported by grant R21DE019026-01A2 from the National Institutes of Health; by grant DR090349 from the US Department of Defense; and by grant UL1 TR000153 from the National Center for Advancing Translational Sciences. NR 34 TC 1 Z9 1 U1 10 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAR-APR PY 2016 VL 18 IS 2 BP 136 EP 143 DI 10.1001/jamafacial.2015.1954 PG 8 WC Surgery SC Surgery GA DG5XF UT WOS:000372153100013 PM 26720757 ER PT J AU Yee, CS Massaad, MJ Bainter, W Ohsumi, TK Foger, N Chan, AC Akarsu, NA Aytekin, C Ayvaz, DC Tezcan, I Sanal, O Geha, RS Chou, J AF Yee, Christina S. Massaad, Michel J. Bainter, Wayne Ohsumi, Toshiro K. Foeger, Niko Chan, Andrew C. Akarsu, Nurten A. Aytekin, Caner Ayvaz, Deniz Cagdas Tezcan, Ilhan Sanal, Ozden Geha, Raif S. Chou, Janet TI Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Coronin-1A; immunodeficiency; T-cell lymphopenia ID SEVERE COMBINED IMMUNODEFICIENCY; HEALTHY-CHILDREN; CORONIN 1A; ACTIN; PROTEIN; DEFICIENCY; ACTIVATION; SURVIVAL; SERUM; MYCOBACTERIA AB Background: Coronin-1A (CORO1A) is a regulator of actin dynamics important for T-cell homeostasis. CORO1A deficiency causes T-B+ natural killer-positive severe combined immunodeficiency or T-cell lymphopenia with severe viral infections. However, because all known human mutations in CORO1A abrogate protein expression, the role of the protein's functional domains in host immunity is unknown. Objective: We sought to identify the cause of the primary immunodeficiency in 2 young adult siblings with a history of disseminated varicella, cutaneous warts, and CD4(+) T-cell lymphopenia. Methods: We performed immunologic, genetic, and biochemical studies in the patients, family members, and healthy control subjects. Results: Both patients had CD4(+) T-cell lymphopenia and decreased lymphocyte proliferation to mitogens. IgG, IgM, IgA, and specific antibody responses were normal. Whole-genome sequencing identified a homozygous frameshift mutation in CORO1A disrupting the last 2 C-terminal domains by replacing 61 amino acids with a novel 91-amino-acid sequence. The CORO1A(S401fs) mutant was expressed in the patients' lymphocytes at a level comparable with that of wild-type CORO1A in normal lymphocytes but did not oligomerize and had impaired cytoskeletal association. CORO1A(S401fs) was associated with increased filamentous actin accumulation in T cells, severely defective thymic output, and impaired T-cell survival but normal calcium flux and cytotoxicity, demonstrating the importance of CORO1A oligomerization and subcellular localization in T-cell homeostasis. Conclusions: We describe a truncating mutation in CORO1A that permits protein expression and survival into young adulthood. Our studies demonstrate the importance of intact CORO1A C-terminal domains in thymic egress and T-cell survival, as well as in defense against viral pathogens. C1 [Yee, Christina S.; Massaad, Michel J.; Bainter, Wayne; Geha, Raif S.; Chou, Janet] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Yee, Christina S.; Massaad, Michel J.; Bainter, Wayne; Geha, Raif S.; Chou, Janet] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ohsumi, Toshiro K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ohsumi, Toshiro K.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Chan, Andrew C.] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA. [Akarsu, Nurten A.] Hacettepe Univ, Fac Med, Dept Med Genet, TR-06100 Ankara, Turkey. [Aytekin, Caner] Dr Sami Ulus Childrens Hlth & Dis Training & Res, Ankara, Turkey. [Ayvaz, Deniz Cagdas; Tezcan, Ilhan; Sanal, Ozden] Hacettepe Univ, Ankara, Turkey. [Ayvaz, Deniz Cagdas; Tezcan, Ilhan; Sanal, Ozden] Ihsan Dogramaci Childrens Hosp, Ankara, Turkey. RP Geha, RS (reprint author), Boston Childrens Hosp, Div Immunol, Boston, MA USA.; Geha, RS (reprint author), Childrens Hosp, Div Immunol, Karp Bldg,10th Floor,1 Blackfan Circle, Boston, MA 02115 USA. EM Raif.Geha@childrens.harvard.edu RI Bayram, Cem/D-7403-2013 OI Bayram, Cem/0000-0001-8717-4668 FU National Institutes of Health [P01AI-076210, AI-094017, T32 AI-007512-26]; Dubai-Harvard Foundation for Medical Research; Perkins Fund; Jeffrey Modell Foundation; Hacettepe Scientific Research Projects Unit (BAP) [010-01-101-010] FX Supported by National Institutes of Health grants P01AI-076210 (to R.S.G.), AI-094017 (to R.S.G.), and T32 AI-007512-26 (to C.S.Y.); the Dubai-Harvard Foundation for Medical Research (to R.S.G.); the Perkins Fund (to R.S.G); a Jeffrey Modell Foundation Translational Research Program Grant Award (to J.C.); and the Hacettepe Scientific Research Projects Unit (BAP) Project 010-01-101-010 (to N.A.A., D.C.A., I.T., and O.S.). NR 35 TC 1 Z9 1 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2016 VL 137 IS 3 BP 879 EP + DI 10.1016/j.jaci.2015.08.020 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA DG2LB UT WOS:000371897500032 PM 26476480 ER PT J AU Tahhan, AS Vaduganathan, M Kelkar, A Georgiopoulou, VV Kalogeropoulos, AP Greene, SJ Fonarow, GC Gheorghiade, M Butler, J AF Tahhan, Ayman Samman Vaduganathan, Muthiah Kelkar, Anita Georgiopoulou, Vasiliki V. Kalogeropoulos, Andreas P. Greene, Stephen J. Fonarow, Gregg C. Gheorghiade, Mihai Butler, Javed TI Trends in Heart Failure Clinical Trials From 2001-2012 SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Clinical trials; heart failure; outcomes; temporal trends ID DRUG TRIALS; RECRUITMENT; OUTCOMES; CLINICALTRIALS.GOV; GLOBALIZATION; RETENTION; INSIGHTS AB Background: A systematic assessment of the temporal trends in heart failure (HF) clinical trials is lacking. Methods and Results: A total of 154 phase II-IV HF trials including 162,725 patients published from 2001 to 2012 in 8 high-impact-factor journals were reviewed. The median number of participants and sites per trial were 367 (interquartile range [IQR] 133-1450) and 38 (5-101), respectively. Median enrollment duration was 2.2 (1.5-3.3) years. The majority of studies investigated treatment for chronic HF (82.5%) and investigated HF with reduced ejection fraction (EF) (71.4%), whereas 27 trials (17.5%) enrolled patients with mixed EF and 9 (5.8%) enrolled HF with preserved EF patients alone. Enrollment rates did not significantly change over time (median 0.49 patients site(-1) month(-1), IQR 0.34-0.98; P = .53). Trials meeting their primary end point decreased over time from 73.5% in 2001-2003 to 52.5% in 2010-2012 (P = .08) and were more often smaller and used nonmortality end points. Industry trials were larger with shorter enrollment duration, more concentrated in North America, and more likely to be positive. Trials conducted exclusively outside North America and Western Europe had the highest enrollment rates (median 1.95 patients site(-1) month(-1), IQR 1.34-4.11). Conclusions: Contemporary HF clinical trials display slow enrollment rates and decreased rates of positive outcomes over time. Positive trials tended to be smaller size with a higher proportion of surrogate end points. C1 [Tahhan, Ayman Samman; Kelkar, Anita; Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA. RP Butler, J (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Div Cardiol, T-16,Room 080, Stony Brook, NY 11794 USA. EM javed.butler@stonybrookmedicine.edu FU National Heart, Lung, and Blood Institute; National Institutes of Health; European Union; Agency for Healthcare Research and Quality FX Dr Fonarow reports significant research grants from the National Heart, Lung, and Blood Institute and Agency for Healthcare Research and Quality, significant consultancy support from Novartis and Takeda, and modest consultancy support from Bayer, Gambro, Janssen, The Medicines Company, and Medtronic. Dr Gheorghiade reports relationships with Abbott, Astellas, Astrazeneca, Bayer, Cardiorentis, Corthera, Cytokinetics, Cytopherx, Debiopharm, Errekappa Terapeutici, Glaxosmithkline, Ikaria, Intersection Medical, Johnson and Johnson, Medtronic, Merck, Novartis, Ono Pharma, Otsuka, Palatin Technologies, Pericor Therapeutics, Protein Design, Sanofi-Aventis, Sigma Tau, Solvay, Sticares Interact, Takeda, and Trevena. Dr Butler reports research support from the National Institutes of Health and European Union and is a consultant to Amgen, Bayer, BG Medicine, Celladon, Gambro, GE Healthcare, Harvest, Medtronic, Ono Pharma, Stemedica, and Trevena. The other authors report no relevant conflicts of interest. NR 27 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2016 VL 22 IS 3 BP 171 EP 179 DI 10.1016/j.cardfail.2015.06.014 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG6QN UT WOS:000372211300002 ER PT J AU Talab, SS Elmi, A Sarma, J Barrisford, GW Tabatabaei, S AF Talab, Saman S. Elmi, Azadeh Sarma, Jaydev Barrisford, Glen W. Tabatabaei, Shahin TI Safety and Effectiveness of SAF-R, a Novel Patient Positioning Device for Robot-Assisted Pelvic Surgery in Trendelenburg Position SO JOURNAL OF ENDOUROLOGY LA English DT Article ID INJURIES C1 [Talab, Saman S.; Elmi, Azadeh; Barrisford, Glen W.; Tabatabaei, Shahin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,15 Parkman St, Boston, MA 02114 USA. [Sarma, Jaydev] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02115 USA. RP Tabatabaei, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,15 Parkman St, Boston, MA 02114 USA. EM stabatabaei@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 EI 1557-900X J9 J ENDOUROL JI J. Endourol. PD MAR 1 PY 2016 VL 30 IS 3 BP 286 EP 292 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DG2AZ UT WOS:000371869900010 PM 26531773 ER PT J AU Rivlin, M Fernandez, DL Nagy, L Grana, GL Jupiter, J AF Rivlin, Michael Fernandez, Diego L. Nagy, Ladislav Lopez Grana, Gabriel Jupiter, Jesse TI Extensor Pollicis Longus Ruptures Following Distal Radius Osteotomy Through a Volar Approach SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Malunion; reconstruction of the wrist; surgical risks; tendon rupture; wrist deformity ID FRACTURES; TENDON; FIXATION AB Purpose To investigate the cause and pathological process of extensor pollicis longus (EPL) ruptures after correction of distal radius malunion through a volar approach. Methods We included patients with EPL ruptures who underwent distal radius osteotomies performed through a volar approach. Data were pooled from members of the International Wrist Investigators Workshop. Patient demographics, initial injury parameters, imaging studies, preoperative and postoperative examination, intraoperative findings, surgical technique, and outcomes were compared and analyzed. Preoperative and postoperative radiographic images were evaluated and compared. Results We evaluated 6 cases from 5 surgeons in 4 institutions. Length of follow-up ranged from 1 to 5 years. On initial radiographic evaluation all malunions were healed with dorsal angulation (20 degrees to 60 degrees) and with positive ulnar variance. Deformity correction in the sagittal plane was 25 degrees to 55 degrees. Osteotomies were fixed with volar locking plates with autologous bone graft except for one patient who received calcium phosphate-based bone void filler. Postoperative x-rays suggested prominent osteotomy resection edges, osteophytes, or dorsal bony prominence resulting from healed callus. Average time from osteotomy to EPL rupture was 10 weeks (range, 2-17 weeks). Two patients initially refused to undergo tendon transfers. One was pleased with the outcome despite the ruptured EPL. The other patient ruptured 2 more tendons and chose to have tendon transfers. One patient also ruptured the transferred tendon after 2 months and underwent successful tendon grafting. Conclusions In the absence of screw prominence and technical flaws, it is likely that dorsal callus, prominent osteotomy resection edges, and osteophytes may contribute to attritional rupture of the EPL tendon after a corrective osteotomy through a volar approach. Exposure and debridement of excessive callus, dorsal ridge, or a prominent Lister tubercle performed during the osteotomy may reduce subsequent EPL rupture. (Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Rivlin, Michael] Thomas Jefferson Univ, Rothman Inst, Dept Hand & Orthopaed Surg, 925 Chestnut St,5th Floor, Philadelphia, PA 19107 USA. [Fernandez, Diego L.] Lindenhof Hosp, Dept Orthopaed Surg, Bern, Switzerland. [Nagy, Ladislav] Balgrist Univ Clin, Dept Hand Surg, Zurich, Switzerland. [Lopez Grana, Gabriel] Ibermutuamur Clin, Madrid, Spain. [Jupiter, Jesse] Harvard Univ, Massachusetts Gen Hosp, Dept Hand & Upper Extrem Surg, Boston, MA USA. RP Rivlin, M (reprint author), Thomas Jefferson Univ, Rothman Inst, Dept Hand & Orthopaed Surg, 925 Chestnut St,5th Floor, Philadelphia, PA 19107 USA. EM Michael.Rivlin@rothmaninstitute.com OI Rivlin, Michael/0000-0003-1290-3410 NR 13 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2016 VL 41 IS 3 BP 395 EP 398 DI 10.1016/j.jhsa.2015.10.029 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DG4CS UT WOS:000372018800011 PM 26794125 ER PT J AU Wilkens, SC Claessen, FMAP Ogink, PT Moradi, A Ring, D AF Wilkens, Suzanne C. Claessen, Femke M. A. P. Ogink, Paul T. Moradi, Ali Ring, David TI Reoperation After Combined Injury of the Index Finger: Repair Versus Immediate Amputation SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Amputation; combined injury; index finger; reoperation; repair ID DIGITAL REPLANTATION; REVASCULARIZATION; HAND; RAY; FIXATION; SURGERY AB Purpose To identify factors associated with unplanned reoperation of severely injured index fingers and to address the number of amputations after initial repair. Methods In this retrospective study, we included all patients older than 18 years of age who had repair or immediate amputation for combined index finger injury at 2 level I trauma centers and 1 community hospital tied to a level I trauma center between January 2004 and February 2014. Twelve patients were excluded because of inadequate follow-up. Bivariate and multivariable analyses sought factors associated with unplanned reoperation after repair and immediate amputation. Results Among 114 patients with combined injury, 75 were treated with repair and 39 with immediate amputation. A total of 41 patients had an unplanned reoperation, 33 after repair (44%) and 8 after immediate amputation (21%). In multivariable analysis, patients who had a reoperation for fingers other than the index finger were at risk for unplanned reoperation after repair. Women were more likely to have an unplanned reoperation than men, and patients who had a ray amputation were at risk for unplanned reoperation after immediate amputation. Six patients (18%) had amputation after initial repair. Conclusions Surgeons may counsel patients that they are twice as likely to have an unplanned reoperation after a repair for combined injury of the index finger compared with an immediate amputation. Unplanned reoperations were more common among patients with injuries involving multiple fingers. Effective shared decision making is particularly important in this setting given that 1 in 5 repaired index fingers were eventually amputated. (Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Wilkens, Suzanne C.; Claessen, Femke M. A. P.; Ogink, Paul T.; Moradi, Ali; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Dept Hand Surg,Massachusetts Gen Hosp, Dept Orthopaed Surg,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 NR 38 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2016 VL 41 IS 3 BP 436 EP + DI 10.1016/j.jhsa.2015.12.013 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DG4CS UT WOS:000372018800018 PM 26794123 ER PT J AU Deng, W Wickham, T McMullin, D Feeney, K Buonanno, FS Lo, EH Ning, M AF Deng, W. Wickham, T. McMullin, D. Feeney, K. Buonanno, F. S. Lo, E. H. Ning, M. TI IMPORTANT ROLE OF PROTHROMBIN TIME (PT) AND PARTIAL THROMBOPLASTIN TIME (PTT) IN PREDICTING TPA-RELATED HEMORRHAGIC TRANSFORMATION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 13, 2016 CL Washington, DC SP Amer Federat Med Res C1 [Deng, W.; Wickham, T.; McMullin, D.; Feeney, K.; Buonanno, F. S.; Lo, E. H.; Ning, M.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2016 VL 64 IS 3 MA MP13 BP 810 EP 810 DI 10.1136/jim-2016-000080.25 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DG6GE UT WOS:000372180700032 ER PT J AU Deng, W McMullin, D Wickham, T Feeney, K Inglessis, I Palacios, I Buonanno, FS Lo, EH Ning, M AF Deng, W. McMullin, D. Wickham, T. Feeney, K. Inglessis, I. Palacios, I. Buonanno, F. S. Lo, E. H. Ning, M. TI PFO CLOSURE REDUCES PLASMA LEVELS OF SEROTONIN IN A LONG TERM FOLLOWUP OF STROKE PATIENTS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 13, 2016 CL Washington, DC SP Amer Federat Med Res C1 [Deng, W.; McMullin, D.; Wickham, T.; Feeney, K.; Inglessis, I.; Palacios, I.; Buonanno, F. S.; Lo, E. H.; Ning, M.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2016 VL 64 IS 3 MA 15 BP 812 EP U105 DI 10.1136/jim-2016-000080.31 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DG6GE UT WOS:000372180700036 ER PT J AU Deng, W Wickham, T McMullin, D Feeney, K Silverman, S Inglessis, I Palacios, I Lo, EH Buonanno, FS Ning, M AF Deng, W. Wickham, T. McMullin, D. Feeney, K. Silverman, S. Inglessis, I. Palacios, I. Lo, E. H. Buonanno, F. S. Ning, M. TI HOMOCYSTEINE LEVEL IN PFO RELATED STROKE PATIENTS WITH RESPECT TO MEDICAL THERAPY VS PFO CLOSURE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 13, 2016 CL Washington, DC SP Amer Federat Med Res C1 [Deng, W.; Wickham, T.; McMullin, D.; Feeney, K.; Silverman, S.; Inglessis, I.; Palacios, I.; Lo, E. H.; Buonanno, F. S.; Ning, M.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2016 VL 64 IS 3 MA MP6 DI 10.1136/jim-2016-000080.18 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DG6GE UT WOS:000372180700024 ER PT J AU Harwood, NMK Golden-Mason, L Cheng, LL Rosen, HR Mengshol, JA AF Harwood, Noah M. K. Golden-Mason, Lucy Cheng, Linling Rosen, Hugo R. Mengshol, John A. TI HCV-infected cells and differentiation increase monocyte immunoregulatory galectin-9 production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE JFH-1; non-classical monocyte; exosome ID HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; IN-VITRO; HEPATOCELLULAR-CARCINOMA; GLYCAN INTERACTIONS; SIGNALING PATHWAY; TIM-3 EXPRESSION; STRANDED-RNA; IMMUNITY; REPLICATION AB The lectin galectin-9 may help establish and maintain chronic hepatitis C virus infection. Galectin-9 is elevated in the liver and sera of hepatitis C virus patients, induces apoptosis of hepatitis C virus-specific T cells, and increases inhibitory regulatory T cells. Kupffer cells stain strongly for galectin-9 protein in hepatitis C virus patients. In the current study, we determined stimuli that induce galectin-9 production by monocytes and macrophages in hepatitis C virus infection. With the use of real-time PCR and flow cytometry, we analyzed galectin-9 mRNA and protein from human monocytes cocultured with hepatitis C virus-infected cells or noninfectious hepatitis C virus subgenomic replicon cells. We focused on finding the stimuli for galectin-9 production. Additionally, we measured galectin-9 during monocyte-to-macrophage maturation. Finally, we examined galectin-9 in peripheral monocytes from hepatitis C virus patients using flow cytometry. Galectin-9 mRNA increased 8-fold when primary monocytes were exposed to hepatitis C virus-infected cells. Maximum induction required proximity or contact and did not require IFN-gamma or hepatitis C virus virions. Coculture of monocytes with subgenomic replicon cells increased galectin-9 5-fold, and purified exosomes from infected cells stimulated galectin-9 production. Stimulation of monocyte TLR3, -7, and -8 increased galectin-9 production. Differentiation of monocytes to macrophages increased galectin-9, and nonclassic monocytes from hepatitis C virus patients had the highest levels of galectin-9. Hepatitis C virus-infected cells stimulated monocytes to produce galectin-9 in close proximity, possibly, in part, as a result of exosomes and endosomal TLRs. Differentiation of monocytes to macrophages increased galectin-9. Nonclassic monocytes from hepatitis C virus patients express the highest galectin-9 levels, suggesting they may contribute to elevated galectin-9 and adaptive immune inhibition in hepatitis C virus infection. C1 [Harwood, Noah M. K.; Golden-Mason, Lucy; Cheng, Linling; Rosen, Hugo R.; Mengshol, John A.] Univ Colorado, Sch Med, Denver VA Med Ctr, Div Gastroenterol & Hepatol, Denver, CO 80220 USA. RP Mengshol, JA (reprint author), Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, 1055 Clermont St,Box 111E, Denver, CO 80220 USA. EM andy.mengshol@ucdenver.edu FU Denver Research Institute; Liver Scholar Award from American Association for the Study of Liver Disease; U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases [R21-AI103361]; American Liver Foundation; VA Merit Review Grant FX J.A.M. is supported by the Denver Research Institute and a Liver Scholar Award from the American Association for the Study of Liver Disease and the American Liver Foundation. H.R.R. is funded by U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases Grant R21-AI103361 and a VA Merit Review Grant. The authors thank our leukocyte donors for their generous contribution and Diana Ir and Katelyn Leahy for tissue-culture work. Additionally, the authors thank Harsh Pratap for flow cytometry assistance and Ron Bouchard for immunofluorescence guidance. Amy Stone provided valuable advice regarding TLR stimulation. NR 52 TC 1 Z9 1 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2016 VL 99 IS 3 BP 495 EP 503 DI 10.1189/jlb.5A1214-582R PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA DG2IO UT WOS:000371890800012 PM 26475932 ER PT J AU Bernier, UR Clark, GG Gurman, P Elman, NM AF Bernier, Ulrich R. Clark, Gary G. Gurman, Pablo Elman, Noel M. TI The Use of Microdispensers with Spatial Repellents for Personal Protection Against Mosquito Biting SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE vector-borne disease; drug delivery; human landing collection; spatial repellent ID MUCOSAL CELLS; DEET; TRANSFLUTHRIN; FORMULATION; SAFETY AB Mosquito-borne pathogens affect millions of people worldwide. This work describes a new method to deliver spatial repellents. Functional microdispensers (FMDs) were designed to deliver spatial repellents against mosquitoes. In vivo trials showed that FMDs protect human subjects against mosquitoes by reducing 70-90% of bites received, with a protection that lasted up to 4 weeks. FMDs can be cost-effectively implemented as wearable or field-dispensed devices for local area protection, defined as a confined geographical region. C1 [Bernier, Ulrich R.; Clark, Gary G.] USDA ARS, Ctr Med Agr & Vet Entomol, 1600 SW 23rd Dr, Gainesville, FL 32608 USA. [Gurman, Pablo] Univ Texas Dallas, Dept Mat Sci & Engn, 800W Campbell Rd, Richardson, TX 75080 USA. [Elman, Noel M.] MIT, Inst Soldier Nanotechnol, 500 Technol Sq,NE47-525, Cambridge, MA 02139 USA. [Elman, Noel M.] Charles Stark Draper Labs, Div Mat, Bio Grp, 555 Technol Sq, Cambridge, MA 02139 USA. [Elman, Noel M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, 275 Cambridge St, Boston, MA 02114 USA. RP Elman, NM (reprint author), MIT, Inst Soldier Nanotechnol, 500 Technol Sq,NE47-525, Cambridge, MA 02139 USA.; Elman, NM (reprint author), Charles Stark Draper Labs, Div Mat, Bio Grp, 555 Technol Sq, Cambridge, MA 02139 USA.; Elman, NM (reprint author), Massachusetts Gen Hosp, Ctr Innovat Care Delivery, 275 Cambridge St, Boston, MA 02114 USA. EM uli.bernier@ars.usda.gov; roofus209@yahoo.com; pablogurman@gmail.com; noel.elman@gmail.com FU Department of Defense Deployed Warfighter Protection Program [W911QY-12-1-0005] FX We acknowledge Gregory M. Allen of United States Department of Agriculture-Agriculture Research Service-Center for Medical, Agricultural and Veterinary Entomology (USDA-ARS-CMAVE) for conducting the study with the FMDs against laboratory mosquitoes. This research work was partially supported by the Department of Defense Deployed Warfighter Protection Program (contract: W911QY-12-1-0005). NR 11 TC 0 Z9 0 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-2585 EI 1938-2928 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAR PY 2016 VL 53 IS 2 BP 470 EP 472 DI 10.1093/jme/tjv190 PG 3 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA DG2PA UT WOS:000371908500027 PM 26637385 ER PT J AU Tang, Y Chang, CCH Lave, JR Gellad, WF Huskamp, HA Donohue, JM AF Tang, Yan Chang, Chung-Chou H. Lave, Judith R. Gellad, Walid F. Huskamp, Haiden A. Donohue, Julie M. TI Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Article ID CARE; RECOMMENDATIONS; ANTIDEPRESSANT; SCHIZOPHRENIA; INFORMATION; PERFORMANCE; MORTALITY; DIFFUSION; OUTCOMES; IMPACT AB Background: Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the Study: To assess variation. in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods: Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOS (TM) database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to >= 10 patients. We constructed three physician level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results: There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion: Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties regularly prescribing a therapeutic category, some physicians rely heavily on a small number of agents. Implications for Health Policies, Health Care Provision and Use: Health systems may need to offer educational interventions to clinicians in order to improve their ability to tailor treatment decisions to the needs of individual patients. Implications for Future Research: Future studies should examine the impact of the diversity of antipsychotic prescribing to determine whether more diversified prescribing improves patient adherence and outcomes. C1 [Tang, Yan; Gellad, Walid F.; Donohue, Julie M.] Univ Pittsburgh, Hlth Policy Inst, Ctr Pharmaceut Policy & Prescribing CP3, Pittsburgh, PA 15261 USA. [Tang, Yan; Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,Crabtree Hall A645, Pittsburgh, PA 15261 USA. [Chang, Chung-Chou H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Lave, Judith R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Div Gen Med, Pittsburgh, PA 15261 USA. [Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. RP Tang, Y (reprint author), Univ Pittsburgh, Hlth Policy Inst, Ctr Pharmaceut Policy & Prescribing CP3, Pittsburgh, PA 15261 USA.; Tang, Y (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,Crabtree Hall A645, Pittsburgh, PA 15261 USA. EM yan.tang@pitt.edu FU National Institute of Mental Health [R01MH093359]; Pennsylvania Department of Human Services; University of Pittsburgh FX This work was supported in part by grant R01MH093359 from the National Institute of Mental Health (Drs. Donohue and Huskamp), and by an inter -governmental agreement between the Pennsylvania Department of Human Services and the University of Pittsburgh. Dr. Huskamp serves on the Academic Advisory Committee for the Health Services Research Network at IMS Health Inc. (uncompensated). The other authors report no conflict of interest. Some of the findings were presented at the International Society of Pharmacoeconomics and Outcomes Research 20th Annual International Meeting, May 16-20, 2015, Philadelphia, PA, USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2016 VL 19 IS 1 BP 45 EP 59 PG 15 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA DG6QP UT WOS:000372211500005 PM 27084793 ER PT J AU Bunpin, JJD Chapman, S Blegen, M Spetz, J AF Bunpin, Jose J. Dy, III Chapman, Susan Blegen, Mary Spetz, Joanne TI Differences in Innovative Behavior Among Hospital-Based Registered Nurses SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID CARE; EMPOWERMENT; AUTONOMY AB BACKGROUND: The 2010 Institute of Medicine report, 'The Future of Nursing: Leading Change, Advancing Health', advocated for nurses to innovate in their practice, research, and education. However, little is known about the innovative behavior of registered nurses or whether there are differences in innovative behavior among registered nurses. OBJECTIVE: The purpose of this article is to describe the innovative behavior of hospital-based registered nurses and understand the differences in innovative behavior when registered nurses are categorized into various demographic groups. METHODS: A survey of 251 hospital-based registered nurses from 9 hospitals in California was administered to assess demographic characteristics and innovative behavior, measured through Scott and Bruce's Individual Innovative Behavior Scale. RESULTS: Hospital-based registered nurses, on average, reported moderate levels of innovative behavior. There were statistically significant differences in innovative behavior when registered nurses were categorized according to specialty certification, role, level of education, hospital size, and hospital innovativeness. CONCLUSIONS: To support innovative behavior, organizations should provide opportunities for specialty certification and increasing levels of education. C1 [Bunpin, Jose J. Dy, III] San Francisco VA Med Ctr, Surg & Procedural Care, San Francisco, CA 94121 USA. [Chapman, Susan] Univ Calif San Francisco, Sch Nursing, Dept Social & Behav Sci, San Francisco, CA 94143 USA. [Blegen, Mary] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Spetz, Joanne] Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Bunpin, JJD (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM jose.dybunpin@va.gov NR 33 TC 0 Z9 0 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 2016 VL 46 IS 3 BP 122 EP 127 DI 10.1097/NNA.0000000000000310 PG 6 WC Nursing SC Nursing GA DF8BZ UT WOS:000371583200006 ER PT J AU Ikizler, HO Zelnick, L Ruzinski, J Curtin, L Utzschneider, KM Kestenbaum, B Himmelfarb, J de Boer, IH AF Ikizler, Halil O. Zelnick, Leila Ruzinski, John Curtin, Laura Utzschneider, Kristina M. Kestenbaum, Bryan Himmelfarb, Jonathan de Boer, Ian H. TI Dietary Acid Load is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease SO JOURNAL OF RENAL NUTRITION LA English DT Article ID GLOMERULAR-FILTRATION-RATE; METABOLIC-ACIDOSIS; AFRICAN-AMERICANS; HYPERTENSIVE NEPHROPATHY; UNITED-STATES; OLDER-ADULTS; RESISTANCE; RISK; PROGRESSION; HUMANS AB Objective: In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. Design: In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet's acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Subjects: Forty-two patients with CKD Stages 3 to 5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (estimated glomerular filtration rate [eGFR] >= 60 mL/minute/1.73 m(2)). Main Outcome Measures: Serum bicarbonate and insulin sensitivity (SIclamp). Results: Mean age was 60.8 +/- 13.6 years, and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4 +/- 13.1 mL/minute/1.73 m(2) and 24.1 +/- 2.9 mEq/L for participants with CKD and 88.6 +/- 14.5 mL/minute/1.73 m(2) and 26.3 +/- 1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2 +/- 24.3, 9.7 +/- 18.4, and 32.1 +/- 19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, gender, race, eGFR, body mass index, and diuretic use: -1.2 mEq/L per standard deviation (SD) NEAP (95% confidence interval [CI] -1.8 to -0.6, P<.0001); -0.9 mEq/L bicarbonate per SD PRAL (95% CI -1.5 to -0.4, P=.0005); -0.7 mEq/L bicarbonate per SD NAE (95% CI -1.2 to -0.1, P=.01). These associations were similar in participants with and without CKD. However, neither NEAP and PRAL nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. Conclusions: In CKD, dietary acid load is associated with serum bicarbonate, suggesting that acidosis may be improved by dietary changes, but not with insulin sensitivity. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 [Ikizler, Halil O.] Univ Vermont, Coll Med, Burlington, VT USA. [Ikizler, Halil O.; Zelnick, Leila; Ruzinski, John; Curtin, Laura; Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Box 359606,325 9th Ave, Seattle, WA 98104 USA. [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Utzschneider, Kristina M.] Univ Washington, Seattle, WA 98195 USA. [Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP de Boer, IH (reprint author), Univ Washington, Kidney Res Inst, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32DK007247]; NIDDK [DK087726, DK007247, DK017047]; University of Washington Diabetes Research Center [P30 DK01704]; University of Washington Institute of Translational Health Sciences [UL1TR000423]; Department of Veterans Affairs FX H.O.I. was supported by grant T32DK007247 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The SUGAR study was supported by NIDDK grants DK087726, DK007247, and DK017047. Support was also provided by the University of Washington Diabetes Research Center (P30 DK01704), the University of Washington Institute of Translational Health Sciences (UL1TR000423), and the Department of Veterans Affairs. The funding sources had no role in study design, analysis or interpretation of data, writing of the report, or the decision to submit this article for publication. NR 44 TC 4 Z9 4 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD MAR PY 2016 VL 26 IS 2 BP 93 EP 102 DI 10.1053/j.jrn.2015.08.008 PG 10 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA DG4AA UT WOS:000372011100007 PM 26508542 ER PT J AU Molfino, A Kaysen, GA Chertow, GM Doyle, J Delgado, C Dwyer, T Laviano, A Fanelli, FR Johansen, KL AF Molfino, Alessio Kaysen, George A. Chertow, Glenn M. Doyle, Julie Delgado, Cynthia Dwyer, Tjien Laviano, Alessandro Fanelli, Filippo Rossi Johansen, Kirsten L. TI Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis SO JOURNAL OF RENAL NUTRITION LA English DT Article ID CHRONIC KIDNEY-DISEASE; HOSPITALIZED-PATIENTS; NUTRITIONAL-STATUS; ANOREXIA; LEPTIN; INFLAMMATION; ADIPONECTIN; MORTALITY; CACHEXIA; DEATH AB Objective: To test the performance of appetite assessment tools among patients receiving hemodialysis (HD). Design: Cross-sectional. Subjects: Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California. Intervention: We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]). Main Outcome Measures: Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake. Results: Fifty-eight (26%) patients reported food intake <= 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake <= 50% (P<.001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake <= 50% (C-statistic 0.80 and 0.76). Patients with food intake <= 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 +/- 0.3 vs 1.2 +/- 0.3, P=.03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03). Conclusions: Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well. (C) 2016 by the National Kidney Foundation, Inc. All rights reserved. C1 [Molfino, Alessio; Kaysen, George A.; Dwyer, Tjien] Univ Calif Davis, Dept Internal Med, Div Nephrol, Davis, CA 95616 USA. [Molfino, Alessio; Laviano, Alessandro; Fanelli, Filippo Rossi] Univ Roma La Sapienza, Dept Clin Med, Viale Univ 37, I-00185 Rome, Italy. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Div Nephrol, Palo Alto, CA 94304 USA. [Doyle, Julie; Delgado, Cynthia; Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Doyle, Julie; Delgado, Cynthia; Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Molfino, A (reprint author), Univ Roma La Sapienza, Dept Clin Med, Viale Univ 37, I-00185 Rome, Italy. EM alessio.molfino@uniroma1.it FU National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-7-005, N01-DK-7-5004]; NIDDK [K24DK085153]; Department of Veterans Affairs, Clinical Science Research and Development Program [1IK2CX000527-01A2]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant [UL1 RR024131] FX This work was supported by contracts N01-DK-7-005 and N01-DK-7-5004 from the National Institute of Diabetes and Digestive and Kidney Diseases. K.L.J.'s effort was supported in part by K24DK085153 from NIDDK. C.D.'s work was supported by the Department of Veterans Affairs, Clinical Science Research and Development Program under Career Development Award 1IK2CX000527-01A2. Her contribution is the result of work supported with the resources and the use of facilities at the San Francisco VA Medical Center. This publication was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant number UL1 RR024131. NR 28 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD MAR PY 2016 VL 26 IS 2 BP 103 EP 110 DI 10.1053/j.jrn.2015.09.002 PG 8 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA DG4AA UT WOS:000372011100008 PM 26522141 ER PT J AU Howard, J Etz, RS Crocker, JB Skinner, D Kelleher, KJ Hahn, KA Miller, WL Crabtree, BF AF Howard, Jenna Etz, Rebecca S. Crocker, J. Benjamin Skinner, Daniel Kelleher, Kelly J. Hahn, Karissa A. Miller, William L. Crabtree, Benjamin F. TI Maximizing the Patient-Centered Medical Home (PCMH) by Choosing Words Wisely SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Health Care Systems; Patient-Centered Care; Primary Health Care; Qualitative Research ID PRIMARY-CARE PRACTICES; MENTAL MODELS; TRANSFORMATION; QUALITY; PROJECT AB Background: Culture is transmitted through language and reflects a group's values, yet much of the current language used to describe the new patient-centered medical home (PCMH) is a carryover from the traditional, physician-centric model of care. This language creates a subtle yet powerful force that can perpetuate the status quo, despite transformation efforts. This article describes new terminology that some innovative primary care practices are using to support the transformational culture of the PCMH. Methods: Data come from the Agency for Healthcare Research and Quality-funded Working Conference for PCMH Innovation 2013, which convened 10 innovative practices and interdisciplinary content experts to discuss innovative practice redesign. Session and interview transcripts were analyzed using a grounded theory approach to identify patterns and explore their significance. Results: Language innovations are used by 5 practices. Carefully selected terms facilitate creative reimagining of traditional roles and spaces through connotations that highlight practice goals. Participants felt that the language used was important for reinforcing substantive changes. Conclusions: Reworking well-established vernacular requires openness to change. True transformation does not, however, occur through a simple relabeling of old concepts. New terminology must represent values to which practices genuinely aspire, although caution is advised when using language to support cultural and clinical change. C1 [Howard, Jenna; Crabtree, Benjamin F.] Rutgers Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, 1 Worlds Fair Dr, Somerset, NJ 08873 USA. [Etz, Rebecca S.] Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, Richmond, VA 23284 USA. [Crocker, J. Benjamin] Massachusetts Gen Hosp, Dept Gen Med, Ambulatory Practice Future, Boston, MA 02114 USA. [Skinner, Daniel] Ohio Univ, Heritage Coll Osteopath Med, Dept Social Med, Dublin, Ireland. [Kelleher, Kelly J.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. [Miller, William L.] Lehigh Valley Hlth Network, Dept Family Med, Allentown, PA USA. RP Howard, J (reprint author), Rutgers Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, 1 Worlds Fair Dr, Somerset, NJ 08873 USA. EM jenna.howard@rutgers.edu FU Agency for Healthcare Research and Quality [R13HS021287] FX This project was supported by grant no. R13HS021287 from the Agency for Healthcare Research and Quality. NR 30 TC 1 Z9 1 U1 3 U2 7 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAR-APR PY 2016 VL 29 IS 2 BP 248 EP 253 DI 10.3122/jabfm.2016.02.150199 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA DG3WJ UT WOS:000372000900011 PM 26957382 ER PT J AU Shah, PV Kozin, ED Kaplan, AB Lee, DJ AF Shah, Parth V. Kozin, Elliott D. Kaplan, Alyson B. Lee, Daniel J. TI Pediatric Auditory Brainstem Implant Surgery: A New Option for Auditory Habilitation in Congenital Deafness? SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Auditory Brain Stem Implants; Deafness; Cochlear Implants; Cochlear Nucleus; Hearing Loss; Pediatrics ID OUTCOMES AB Introduction: The auditory brainstem implant (ABI) is a neuroprosthetic device that provides sound sensations to individuals with profound hearing loss who are not candidates for a cochlear implant (CI) because of anatomic constraints. Herein we describe the ABI for family physicians. Methods: PubMed was searched to identify articles relevant to the ABI, as well as articles that contain outcomes data for pediatric patients (age <18 years) who have undergone ABI surgery. Results: The ABI was originally developed for patients with neurofibromatosis type 2 (NF2) who become deaf from bilateral vestibular schwannomas. Over the past decade, indications for an ABI have expanded to adult patients without tumors (without NF2) who cannot receive a CI and children with no cochlea or cochlear nerve. Outcomes among NF2 ABI users are modest compared to cochlear implant patients, but recent studies from Europe suggest that some non-tumor adult and pediatric ABI users achieve speech perception. Conclusion: The ABI is a reasonable surgical option for children with profound hearing loss due to severe cochlear or cochlear nerve deformities. Continued prospective data collection from several clinical trials in the U.S. will provide greater understanding on long term outcomes that focus on speech intelligibility. C1 [Shah, Parth V.; Kozin, Elliott D.; Kaplan, Alyson B.; Lee, Daniel J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. RP Kozin, ED (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM elliott_kozin@meei.harvard.edu NR 5 TC 1 Z9 1 U1 1 U2 2 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAR-APR PY 2016 VL 29 IS 2 BP 286 EP 288 DI 10.3122/jabfm.2016.02.150258 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA DG3WJ UT WOS:000372000900017 PM 26957388 ER PT J AU Klauschen, F Blaker, H Stenzinger, A AF Klauschen, Frederick Blaeker, Hendrik Stenzinger, Albrecht TI Re: "Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course" SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Letter C1 [Klauschen, Frederick; Blaeker, Hendrik] Charite, Inst Pathol, D-13353 Berlin, Germany. [Stenzinger, Albrecht] Heidelberg Univ, Sch Med, Inst Pathol, Heidelberg, Germany. [Stenzinger, Albrecht] Harvard Univ, Sch Med, Dept Pathol, Ctr Integrated Diagnost,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Klauschen, F (reprint author), Charite, Inst Pathol, D-13353 Berlin, Germany. NR 7 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2016 VL 14 IS 3 BP LXVI EP LXVIII PG 2 WC Oncology SC Oncology GA DG3VF UT WOS:000371997900001 PM 26957621 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Somatostatin Analogues in Neuroendocrine Tumors SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID MALIGNANT CARCINOID-SYNDROME; FORMULATION; LANREOTIDE C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. [Kulke, Matthew H.] Harvard Univ, Sch Med, Med, Cambridge, MA 02138 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA.; Kulke, MH (reprint author), Harvard Univ, Sch Med, Med, Cambridge, MA 02138 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2016 VL 14 IS 3 BP 241 EP 242 PG 2 WC Oncology SC Oncology GA DG3VF UT WOS:000371997900004 PM 26957610 ER PT J AU Ettinger, DS Wood, DE Akerley, W Bazhenova, LA Borghaei, H Camidge, DR Cheney, RT Chirieac, LR D'Amico, TA Dilling, TJ Dobelbower, MC Govindan, R Hennon, M Horn, L Jahan, TM Komaki, R Lackner, RP Lanuti, M Lilenbaum, R Lin, J Loo, BW Martins, R Otterson, GA Patel, JD Pisters, KM Reckamp, K Riely, GJ Schild, SE Shapiro, TA Sharma, N Stevenson, J Swanson, SJ Tauer, K Yang, SC Gregory, K Hughes, M AF Ettinger, David S. Wood, Douglas E. Akerley, Wallace Bazhenova, Lyudmila A. Borghaei, Hossein Camidge, David Ross Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Dilling, Thomas J. Dobelbower, M. Chris Govindan, Ramaswamy Hennon, Mark Horn, Leora Jahan, Thierry M. Komaki, Ritsuko Lackner, Rudy P. Lanuti, Michael Lilenbaum, Rogerio Lin, Jules Loo, Billy W., Jr. Martins, Renato Otterson, Gregory A. Patel, Jyoti D. Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Schild, Steven E. Shapiro, Theresa A. Sharma, Neelesh Stevenson, James Swanson, Scott J. Tauer, Kurt Yang, Stephen C. Gregory, Kristina Hughes, Miranda TI NCCN Guidelines (R) Insights: Non-Small Cell Lung Cancer, Version 4.2016 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID NIVOLUMAB; IMMUNOTHERAPY; PEMBROLIZUMAB; DOCETAXEL; SAFETY AB These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy. C1 [Ettinger, David S.; Shapiro, Theresa A.; Yang, Stephen C.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [Wood, Douglas E.; Martins, Renato] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bazhenova, Lyudmila A.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA. [Camidge, David Ross] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Cheney, Richard T.; Hennon, Mark] Roswell Pk Canc Inst, Buffalo, NY USA. [Chirieac, Lucian R.; Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [D'Amico, Thomas A.] Duke Canc Inst, Durham, NC USA. [Dilling, Thomas J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Dobelbower, M. Chris] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry M.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Komaki, Ritsuko; Pisters, Katherine M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Lackner, Rudy P.] Fred & Pamela Buffett Canc Ctr, Durham, NC USA. [Lanuti, Michael] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lilenbaum, Rogerio] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Lin, Jules] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Palo Alto, CA USA. [Otterson, Gregory A.] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Otterson, Gregory A.] Solove Res Inst, Columbus, OH USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Schild, Steven E.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Sharma, Neelesh; Stevenson, James] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Sharma, Neelesh; Stevenson, James] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [Tauer, Kurt] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Gregory, Kristina; Hughes, Miranda] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Ettinger, DS (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. FU AstraZeneca; Bayer Healthcare Pharmaceuticals Inc.; Bristol-Myers Squibb; Clovis Oncology; Genentech; Novartis Oncology; Otsuka America Pharmaceutical, Inc.; Seattle Genetics, Inc.; Takeda Oncology; Actelion Pharmaceuticals US, Inc.; Astellas and Medivation, Inc. FX This activity is supported by educational grants from AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Clovis Oncology, Genentech, Novartis Oncology, Otsuka America Pharmaceutical, Inc., Seattle Genetics, Inc., and Takeda Oncology; support provided by Actelion Pharmaceuticals US, Inc.; and by an independent educational grant from Astellas and Medivation, Inc. NR 23 TC 30 Z9 31 U1 4 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2016 VL 14 IS 3 BP 255 EP 264 PG 10 WC Oncology SC Oncology GA DG3VF UT WOS:000371997900006 PM 26957612 ER PT J AU Gradishar, WJ Anderson, BO Balassanian, R Blair, SL Burstein, HJ Cyr, A Elias, AD Farrar, WB Forero, A Giordano, SH Goetz, M Goldstein, LJ Hudis, CA Isakoff, SJ Marcom, PK Mayer, IA McCormick, B Moran, M Patel, SA Pierce, LJ Reed, EC Salerno, KE Schwartzberg, LS Smith, KL Smith, ML Soliman, H Somlo, G Telli, M Ward, JH Shead, DA Kumar, R AF Gradishar, William J. Anderson, Benjamin O. Balassanian, Ron Blair, Sarah L. Burstein, Harold J. Cyr, Amy Elias, Anthony D. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goetz, Matthew Goldstein, Lori J. Hudis, Clifford A. Isakoff, Steven J. Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Moran, Meena Patel, Sameer A. Pierce, Lori J. Reed, Elizabeth C. Salerno, Kilian E. Schwartzberg, Lee S. Smith, Karen Lisa Smith, Mary Lou Soliman, Hatem Somlo, George Telli, Melinda Ward, John H. Shead, Dorothy A. Kumar, Rashmi TI Invasive Breast Cancer Version 1.2016 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SKIN-SPARING MASTECTOMY; CONTRALATERAL PROPHYLACTIC MASTECTOMY; RANDOMIZED CONTROLLED-TRIAL; SENTINEL-NODE BIOPSY; 20-YEAR FOLLOW-UP; POSTMASTECTOMY RADIATION IMPROVES; LUMPECTOMY PLUS TAMOXIFEN; CARCINOMA IN-SITU; FERTILITY PRESERVATION; CONSERVING THERAPY AB Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org. C1 [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Anderson, Benjamin O.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Balassanian, Ron] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Blair, Sarah L.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Burstein, Harold J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cyr, Amy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Cyr, Amy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Elias, Anthony D.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Solove Res Inst, Columbus, OH USA. [Forero, Andres] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Goetz, Matthew] Mayo Clin, Ctr Canc, Rochester, MN USA. [Goldstein, Lori J.; Patel, Sameer A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moran, Meena] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Reed, Elizabeth C.] Fred & Pamela Buffett Canc Ctr, Durham, NC USA. [Salerno, Kilian E.] Roswell Pk Canc Inst, Buffalo, NY USA. [Schwartzberg, Lee S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Smith, Karen Lisa] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Smith, Mary Lou] Res Advocacy Network, New York, NY USA. [Soliman, Hatem] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Telli, Melinda] Stanford Canc Inst, Palo Alto, CA USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. NR 178 TC 26 Z9 30 U1 6 U2 10 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2016 VL 14 IS 3 BP 324 EP 354 PG 31 WC Oncology SC Oncology GA DG3VF UT WOS:000371997900012 PM 26957618 ER PT J AU Waks, AG Partridge, AH AF Waks, Adrienne G. Partridge, Ann H. TI Fertility Preservation in Patients With Breast Cancer: Necessity, Methods, and Safety SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID OVARIAN-FUNCTION; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; EMBRYO CRYOPRESERVATION; ANTIMULLERIAN HORMONE; PROGNOSTIC IMPACT; AMERICAN-SOCIETY; PREGNANCY; STIMULATION; TAMOXIFEN AB As treatment paradigms improve and young women live longer after a breast cancer diagnosis, there is an increasing need to define the fertility-related problems that premenopausal women with breast cancer face, and, more importantly, to find solutions. This article discusses what is known regarding fertility risks associated with standard breast cancer treatment regimens and limitations of that information. We outline established and emerging techniques for fertility preservation, including recent developments surrounding the controversial utility of gonadotropin-releasing hormone agonists through chemotherapy, and review available data on the safety of pregnancy in breast cancer survivors. We highlight opportunities for further investigation, and contextualize fertility-related concerns in the modern treatment landscape. Above all, we stress the importance of this topic in a patient-centered approach to breast cancer care for young women. C1 [Waks, Adrienne G.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Waks, Adrienne G.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu NR 50 TC 3 Z9 3 U1 1 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2016 VL 14 IS 3 BP 355 EP 363 PG 9 WC Oncology SC Oncology GA DG3VF UT WOS:000371997900013 PM 26957619 ER PT J AU Auchincloss, HG Wright, CD AF Auchincloss, Hugh G. Wright, Cameron D. TI Complications after tracheal resection and reconstruction: prevention and treatment SO JOURNAL OF THORACIC DISEASE LA English DT Review DE Airway obstruction; laryngeal edema; tracheal stenosis; tracheoesophageal fistula (TEF); tracheostomy ID HYPERBARIC-OXYGEN THERAPY; ANASTOMOTIC COMPLICATIONS; STENOSIS; SURGERY AB Tracheal resection and reconstruction (TRR) and laryngotracheal resection and reconstruction (LTRR) is commonly performed for post-intubation tracheal stenosis, tracheal tumor, idiopathic laryngotracheal stenosis (ILTS), and tracheoesophageal fistula (TEF). Ninety-five percent of patients have a good result from surgery. Complications occur in similar to 20% of patients, of which half are anastomotic complications. Complications include granulation tissue formation, restenosis of the trachea, anastomotic separation, TEF and tracheoinnominate fistula (TIF), wound infection, laryngeal edema, and glottic dysfunction. Risk factors for anastomotic complication include diabetes, reoperation, previous tracheal appliance, and long-segment tracheal resection. Bronchoscopy should be part of the diagnostic workup when a complication is suspected. Anastomotic separation-the most feared complication of tracheal surgery-may present subtly with stridor and wound infection, or with respiratory distress and extremis. Prompt management is required to prevent devastating consequences. The airway should be secured, bronchoscopy should be performed to address the degree of separation, and the anastomosis should be revised if needed, usually with the addition of t-tube or tracheostomy. Anastomotic complications that are managed aggressively typically yield good results. More than half of such patients will eventually have a satisfactory airway. However, an anastomotic complication is associated with a thirteen-fold increase in the risk of death following tracheal resection. C1 [Auchincloss, Hugh G.] Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02114 USA. [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570, Boston, MA 02114 USA. EM Wright.Cameron@mgh.harvard.edu NR 17 TC 3 Z9 3 U1 2 U2 5 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 EI 2077-6624 J9 J THORAC DIS JI J. Thorac. Dis. PD MAR PY 2016 VL 8 SU 2 BP S160 EP S167 DI 10.3978/j.issn.2072-1439.2016.01.86 PG 8 WC Respiratory System SC Respiratory System GA DG5EZ UT WOS:000372099900008 PM 26981267 ER PT J AU Costantino, CL Mathisen, DJ AF Costantino, Christina L. Mathisen, Douglas J. TI Idiopathic laryngotracheal stenosis SO JOURNAL OF THORACIC DISEASE LA English DT Article DE Trachea; larynx; stenosis; idiopathic AB Idiopathic laryngotracheal stenosis (ILTS) is a rare inflammatory disease of unknown etiology. Infectious, traumatic and immunologic processes must first be excluded. The majority of patients affected are female who present with progressive symptoms of upper airway obstruction, which can extend over a number of years. ILTS is characterized by short segment, circumferential stenotic lesions, located particularly at the level of the cricoid. Bronchoscopic evaluation is essential for establishing the diagnosis and operative planning. Various temporizing interventions have historically been utilized, including dilation and laser ablation, for symptomatic management. However these interventions have demonstrated diminishing returns and poor long-term outcomes. Patients with ILTS should be considered early for definitive surgical intervention to minimize complications and optimize outcomes. Laryngotracheal resection and reconstruction is a viable intervention, which has demonstrated good long-term results and low recurrence rates for this patient population. C1 [Costantino, Christina L.; Mathisen, Douglas J.] Massachusetts Gen Hosp, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 10 TC 0 Z9 0 U1 1 U2 2 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 EI 2077-6624 J9 J THORAC DIS JI J. Thorac. Dis. PD MAR PY 2016 VL 8 SU 2 BP S204 EP S209 DI 10.3978/j.issn.2072-1439.2016.01.71 PG 6 WC Respiratory System SC Respiratory System GA DG5EZ UT WOS:000372099900013 PM 26981272 ER PT J AU Madariaga, ML Gaissert, HA AF Madariaga, Maria Lucia Gaissert, Henning A. TI Reresection for recurrent stenosis after primary tracheal repair SO JOURNAL OF THORACIC DISEASE LA English DT Review DE Trachea; restenosis; reoperation ID RESECTION; RECONSTRUCTION; COMPLICATIONS; ANASTOMOSIS; AIRWAY AB Failure of the anastomosis after primary tracheal reconstruction for benign disease is uncommon. Here we review the available evidence on tracheal restenosis and the results of second reconstructions. Factors associated with failed primary anastomosis are examined. Temporizing immediate and alternative long-term management with T-tube or tracheostomy is described, emphasizing the role of tracheal stenting in abating the urgency for reoperation. From available evidence, elective reoperative treatment of failed tracheal reconstruction should be considered in selected patients after careful review and reversal of patient-and operation-specific factors that initiated failure. Referral to a high-volume center with a deep bench of nursing, anesthesiologic and surgical expertise is recommended for reoperation. C1 [Madariaga, Maria Lucia; Gaissert, Henning A.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org NR 16 TC 1 Z9 1 U1 1 U2 1 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 EI 2077-6624 J9 J THORAC DIS JI J. Thorac. Dis. PD MAR PY 2016 VL 8 SU 2 BP S153 EP S159 DI 10.3978/j.issn.2072-1439.2016.01.66 PG 7 WC Respiratory System SC Respiratory System GA DG5EZ UT WOS:000372099900007 PM 26981266 ER PT J AU Mysore, VS Szablowski, J Dervan, PB Frost, PJ AF Mysore, Veena S. Szablowski, Jerzy Dervan, Peter B. Frost, Patrick J. TI A DNA-binding Molecule Targeting the Adaptive Hypoxic Response in Multiple Myeloma Has Potent Antitumor Activity SO MOLECULAR CANCER RESEARCH LA English DT Article ID BONE-MARROW ANGIOGENESIS; IN-VIVO; ACTIVATED PRODRUG; INDUCIBLE FACTOR; CELLS; CANCER; TUMOR; EXPRESSION; TRANSLATION; INHIBITION AB Multiple myeloma is incurable and invariably becomes resistant to chemotherapy. Although the mechanisms remain unclear, hypoxic conditions in the bone marrow have been implicated in contributing to multiple myeloma progression, angiogenesis, and resistance to chemotherapy. These effects occur via adaptive cellular responses mediated by hypoxia-inducible transcription factors (HIF), and targeting HIFs can have anticancer effects in both solid and hematologic malignancies. Here, it was found that in most myeloma cell lines tested, HIF1 alpha, but not HIF2 alpha expression was oxygen dependent, and this could be explained by the differential expression of the regulatory prolyl hydroxylase isoforms. The anti-multiple myeloma effects of a sequence-specific DNA-binding pyrrole-imidazole (Py-Im) polyamide (HIF-PA), which disrupts the HIF heterodimer from binding to its cognate DNA sequences, were also investigated. HIF-PA is cell permeable, localizes to the nuclei, and binds specific regions of DNA with an affinity comparable with that of HIFs. Most of the multiple myeloma cells were resistant to hypoxia-mediated apoptosis, and HIF-PA treatment could overcome this resistance in vitro. Using xenograft models, it was determined that HIF-PA significantly decreased tumor volume and increased hypoxic and apoptotic regions within solid tumor nodules and the growth of myeloma cells engrafted in the bone marrow. This provides a rationale for targeting the adaptive cellular hypoxic response of the O-2-dependent activation of HIF alpha using polyamides. C1 [Mysore, Veena S.; Frost, Patrick J.] Greater Los Angeles Vet Adm Healthcare Syst, 11301Wilshire Blvd,Bldg 114,Room 113, Los Angeles, CA 90073 USA. [Mysore, Veena S.; Frost, Patrick J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Szablowski, Jerzy; Dervan, Peter B.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. RP Frost, PJ (reprint author), Greater Los Angeles Vet Adm Healthcare Syst, 11301Wilshire Blvd,Bldg 114,Room 113, Los Angeles, CA 90073 USA. EM pfrost@ucla.edu FU MERIT from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service [1I01BX001532]; NIH [GM051747] FX This work was supported by a MERIT grant 1I01BX001532 (to P.J. Frost) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service and a NIH GM051747 grant (to P.B. Dervan). NR 50 TC 0 Z9 0 U1 4 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2016 VL 14 IS 3 BP 253 EP 266 DI 10.1158/1541-7786.MCR-15-0361 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DG3XM UT WOS:000372004400002 PM 26801054 ER PT J AU Li, H Wheeler, S Park, Y Ju, ZL Thomas, SM Fichera, M Egloff, AM Lui, VW Duvvuri, U Bauman, JE Mills, GB Grandis, JR AF Li, Hua Wheeler, Sarah Park, Yongseok Ju, Zhenlin Thomas, Sufi M. Fichera, Michele Egloff, Ann M. Lui, Vivian W. Duvvuri, Umamaheswar Bauman, Julie E. Mills, Gordon B. Grandis, Jennifer R. TI Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts SO MOLECULAR CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PHASE PROTEIN ARRAY; DRUG DEVELOPMENT; PANCREATIC-CANCER; GENOMIC CHARACTERIZATION; PREDICTIVE BIOMARKERS; TUMOR XENOGRAFTS; IN-VITRO; MODELS; MOUSE AB Despite advances in treatment approaches for head and neck squamous cell carcinoma (HNSCC), survival rates have remained stagnant due to the paucity of preclinical models that accurately reflect the human tumor. Patient-derived xeno-grafts (PDX) are an emerging model system where patient tumors are implanted directly into mice. Increased understanding of the application and limitations of PDXs will facilitate their rational use. Studies to date have not reported protein profiles of PDXs. Therefore, we developed a large cohort of HNSCC PDXs and found that tumor take rate was not influenced by the clinical, pathologic, or processing features. Protein expression profiles, from a subset of the PDXs, were characterized by reverse-phase protein array and the data was compared with The Cancer Genome Atlas HNSCC data. Cluster analysis revealed that HNSCC PDXs were more similar to primary HNSCC than to any other tumor type. Interestingly, while a significant fraction of proteins were expressed similarly in both primary HNSCC and PDXs, a subset of proteins/phosphoproteins were expressed at higher (or lower) levels in PDXs compared with primary HNSCC. These findings indicate that the proteome is generally conserved in PDXs, but mechanisms for both positive and negative model selection and/or differences in the stromal components exist. C1 [Li, Hua; Egloff, Ann M.; Duvvuri, Umamaheswar; Grandis, Jennifer R.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Wheeler, Sarah; Fichera, Michele; Grandis, Jennifer R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Park, Yongseok] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Ju, Zhenlin; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Thomas, Sufi M.] Univ Kansas, Med Ctr, Dept Otolaryngol, Kansas City, KS 66103 USA. [Thomas, Sufi M.] Univ Kansas, Med Ctr, Dept Canc Biol, Kansas City, KS 66103 USA. [Lui, Vivian W.] Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Healthcare Syst, Univ Dr Campus, Pittsburgh, PA USA. [Bauman, Julie E.] Univ Pittsburgh, Dept Internal Med Hematol Oncol, Pittsburgh, PA USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Grandis, Jennifer R.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94158 USA. RP Grandis, JR (reprint author), Univ Calif San Francisco, 1450 3rd St,Room HD200, San Francisco, CA 94158 USA. EM jennifer.grandis@ucsf.edu RI Lui, Vivian/I-5458-2016 FU NIH [P50CA097190, K07 CA137140]; American Cancer Society; Department of Veterans Affairs BLRD; NCI [CA16672] FX This work was supported by grants NIH P50CA097190 and the American Cancer Society (to J.R. Grandis), NIH K07 CA137140 (to A.M. Egloff), Department of Veterans Affairs BLR&D (to U. Duvvuri). RPPA work was performed in the MDACC CCSG supported core NCI CA16672. NR 40 TC 4 Z9 5 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2016 VL 14 IS 3 BP 278 EP 286 DI 10.1158/1541-7786.MCR-15-0354 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DG3XM UT WOS:000372004400004 PM 26685214 ER PT J AU Videnovic, A Willis, GL AF Videnovic, Aleksandar Willis, Gregory L. TI Circadian system A novel diagnostic and therapeutic target in Parkinson's disease? SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's; circadian; sleep; clock genes; chronobiology ID EXCESSIVE DAYTIME SLEEPINESS; AUTONOMIC NERVOUS-SYSTEM; SUPRACHIASMATIC NUCLEUS; SECRETION PATTERN; BRIGHT LIGHT; MOUSE MODEL; DE-NOVO; MELATONIN SECRETION; METABOLIC RHYTHMS; WAKE REGULATION AB The circadian system regulates biological rhythmicity in the human body. The role of the circadian system in neurological disorders is a theme that is attracting an increasing amount of interest from the scientific community. This has arisen, in part, from emerging evidence that disorders such as Parkinson's disease (PD) are multifactorial with many features exhibiting diurnal fluctuations, thereby suggestive of circadian involvement. Although the importance of fluctuating motor and nonmotor manifestations in PD have been well acknowledged, the role of the circadian system has received little attention until recently. It is proposed that intervening with circadian function provides a novel research avenue down which new strategies for improving symptomatic treatment and slowing of the progressive degenerative process can be approached to lessen the burden of PD. In this article we review the literature describing existing circadian research in PD and its experimental models. (c) 2016 International Parkinson and Movement Disorder Society C1 [Videnovic, Aleksandar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Movement Disorders Unit,Div Sleep Med, Boston, MA 02114 USA. [Willis, Gregory L.] Bronowski Inst Behav Neurosci, Kyneton, Vic, Australia. RP Videnovic, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 165 Cambridge St,Suite 600, Boston, MA 02114 USA. EM avidenovic@mgh.harvard.edu FU NIH/NINDS [K23 NS072283]; Bronowski Institute of Behavioural Neuroscience FX Dr. Videnovic - NIH/NINDS, K23 NS072283; Dr. Willis - The Bronowski Institute of Behavioural Neuroscience. NR 83 TC 4 Z9 4 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2016 VL 31 IS 3 BP 260 EP 269 DI 10.1002/mds.26509 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DG7SR UT WOS:000372284500002 PM 26826022 ER PT J AU Martinez-Martin, P Leentjens, AFG de Pedro-Cuesta, J Chaudhuri, KR Schrag, AE Weintraub, D AF Martinez-Martin, Pablo Leentjens, Albert F. G. de Pedro-Cuesta, Jesus Chaudhuri, Kallol Ray Schrag, Anette E. Weintraub, Daniel TI Accuracy of screening instruments for detection of neuropsychiatric syndromes in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; neuropsychiatric symptoms; screening; instruments; accuracy ID GERIATRIC DEPRESSION SCALE; IMPULSIVE-COMPULSIVE DISORDERS; DRUG-INDUCED PSYCHOSIS; ANXIETY RATING-SCALES; QUALITY-OF-LIFE; NONMOTOR SYMPTOMS; HOSPITAL ANXIETY; RECOGNIZING DEPRESSION; COGNITIVE IMPAIRMENT; REPETITIVE BEHAVIORS AB Parkinson's disease includes neuropsychiatric manifestations, such as depression, anxiety, apathy, psychosis, and impulse control disorders, which often are unreported by patients and caregivers or undetected by doctors. Given their substantial impact on patients and caregivers as well as the existence of effective therapies for some of these disorders, screening for neuropsychiatric symptoms is important. Instruments for screening have a particular methodology for validation, and their performance is expressed in terms of accuracy compared with formal diagnostic criteria. The present study reviews the attributes of the screening instruments applied for detection of the aforementioned major neuropsychiatric symptoms in Parkinson's disease. A quasi-systematic review (including predefined selection criteria, but not evaluating the quality of the reviewed studies) was carried out on the basis of previous systematic reviews (commissioned by the American Academy of Neurology and the Movement Disorder Society) and made current by conducting a literature search (2005-2014). For depression, 11 scales and questionnaires were shown to be valid for Parkinson's disease screening. The recently developed Parkinson Anxiety Scale and the Geriatric Anxiety Inventory demonstrate satisfactory properties as screening instruments for anxiety, and the Lille Apathy Rating Scale for detection of apathy. No scale adequately screens for psychosis, so a specific psychosis instrument should be developed. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (Questionnaire and Rating Scale) are valid for comprehensive screening of impulse control disorders, and the Parkinson's Disease-Sexual Addiction Screening Test for hypersexuality specifically. (c) 2015 International Parkinson and Movement Disorder Society C1 [Martinez-Martin, Pablo; de Pedro-Cuesta, Jesus] Carlos III Inst Hlth, Natl Ctr Epidemiol, Avda Monforte de Lemos 5, Madrid 28029, Spain. [Martinez-Martin, Pablo; de Pedro-Cuesta, Jesus] Carlos III Inst Hlth, CIBERNED, Madrid 28029, Spain. [Leentjens, Albert F. G.] Maastricht Univ, Med Ctr, Dept Psychiat, NL-6200 MD Maastricht, Netherlands. [Chaudhuri, Kallol Ray] Kings Coll London, Natl Parkinson Fdn Int Ctr Excellence, London WC2R 2LS, England. [Chaudhuri, Kallol Ray] South London & Maudsley NHS Fdn Trust, Natl Inst Hlth Res, Mental Hlth Biomed Res Ctr, London, England. [Chaudhuri, Kallol Ray] South London & Maudsley NHS Fdn Trust, Dementia Unit, London, England. [Chaudhuri, Kallol Ray] Kings Coll London, London WC2R 2LS, England. [Schrag, Anette E.] UCL, Inst Neurol, Royal Free Campus, London, England. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Martinez-Martin, P (reprint author), Carlos III Inst Hlth, Natl Ctr Epidemiol, Avda Monforte de Lemos 5, Madrid 28029, Spain. EM pmartinez@isciii.es NR 97 TC 6 Z9 6 U1 5 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2016 VL 31 IS 3 BP 270 EP 279 DI 10.1002/mds.26522 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DG7SR UT WOS:000372284500003 PM 26695691 ER PT J AU Moelter, ST Weintraub, D Mace, L Cary, M Sullo, E Xie, SX Karlawish, J AF Moelter, Stephen T. Weintraub, Daniel Mace, Lauren Cary, Mark Sullo, Elizabeth Xie, Sharon X. Karlawish, Jason TI Research consent capacity varies with executive function and memory in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; decision making; capacity; cognitive impairment; informed consent ID MILD COGNITIVE IMPAIRMENT; DEMENTIA; TRIAL AB BackgroundWe examined the association between cognitive domains and research consent capacity in PD. Our hypothesis was that research consent capacity is best predicted by executive function. MethodsA cohort of 90 PD patients and 30 healthy older adults were administered the MacArthur Competence Assessment Tool for Clinical Research, Dementia Rating Scale-2, and the MoCA. Experts classified patients as either capable or not capable of providing informed consent to participate in two clinical trials. ResultsMacArthur Competence Assessment Tool for Clinical Research Reasoning scores for both clinical trial types were most associated with executive functions and delayed recall. As scores on these domains improved, the odds of an expert rating of capable of consent increased. ConclusionsThese results extend our previous findings by demonstrating that memory and executive abilities appear closely associated with capacity when evaluated using either a structured interview or expert judgment of that interview. (c) 2016 International Parkinson and Movement Disorder Society C1 [Moelter, Stephen T.; Mace, Lauren] Univ Sci, Dept Behav & Social Sci, 600 South 43rd St, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Geriatr Psychiat Sect, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cary, Mark; Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sullo, Elizabeth; Karlawish, Jason] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Leonard Davis Inst Hlth Econ, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Alzheimers Dis Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Moelter, ST (reprint author), Univ Sci, Dept Behav & Social Sci, 600 South 43rd St, Philadelphia, PA 19104 USA. EM s.moelte@usciences.edu FU National Institute of Neurological Disorders and Stroke [R01NS65087]; Morris K. Udall Center for Parkinson's Disease Research [P50 NS053488, NS062684]; National Institute on Aging [AG10124] FX This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS65087), Morris K. Udall Center for Parkinson's Disease Research (P50 NS053488 and NS062684), and the National Institute on Aging (AG10124). NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2016 VL 31 IS 3 BP 414 EP 417 DI 10.1002/mds.26469 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA DG7SR UT WOS:000372284500026 PM 26861463 ER PT J AU Bhattacharyya, S Bakshi, R Logan, R Ascherio, A Macklin, EA Schwarzschild, MA AF Bhattacharyya, Shamik Bakshi, Rachit Logan, Robert Ascherio, Alberto Macklin, Eric A. Schwarzschild, Michael A. TI Oral Inosine Persistently Elevates Plasma antioxidant capacity in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; antioxidant; uric acid; urate; inosine ID OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; CEREBROSPINAL-FLUID; MEDITERRANEAN DIET; URIC-ACID; URATE; RISK; PROGRESSION; SERUM; SUPPLEMENTATION AB IntroductionHigher serum urate predicts slower progression in PD. The aim of this work was to assess whether oral inosine alters antioxidant capacity of plasma or CSF or urinary markers of oxidative injury in early PD. MethodsWe assayed plasma and CSF antioxidant capacity by ferric-reducing antioxidant power and measured DNA oxidation adduct 8-hydroxydeoxyguanosine from urine in Safety of URate Elevation in PD, a randomized, placebo-controlled trial of oral inosine assessing safety of elevating serum urate from <6 mg/dL to 6.1-7.0 or 7.1-8.0 mg/dL in patients with early PD. ResultsAt 6 months, antioxidant capacity was 29% higher among mild and 43% higher among moderate group participants compared to placebo and correlated with change in serum urate (r = 0.86) and inversely with rate of clinical decline (r=-0.26). CSF antioxidant capacity and urine 8-hydroxydeoxyguanosine did not differ. ConclusionsThe findings demonstrate a dose-dependent, persistent elevation of plasma antioxidant capacity from oral inosine of potential therapeutic relevance. (c) 2016 International Parkinson and Movement Disorder Society C1 [Bhattacharyya, Shamik; Bakshi, Rachit; Logan, Robert; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. [Bhattacharyya, Shamik] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Bhattacharyya, Shamik; Bakshi, Rachit; Ascherio, Alberto; Macklin, Eric A.; Schwarzschild, Michael A.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhattacharyya, S (reprint author), MassGeneral Inst Neurodegenerat Dis, Bldg 114,Charlestown Navy Yard,16th St, Charlestown, MA 02129 USA. EM sbhattacharyya3@partners.org OI Bhattacharyya, Shamik/0000-0001-8047-3622; Macklin, Eric/0000-0003-1618-3502 FU Michael J. Fox Foundation for Parkinson's Research; Department of Defense [W81XWH-11-1-0150]; Granite State Development; Harvard NeuroDiscovery Center FX The authors were supported by a grant from the Michael J. Fox Foundation for Parkinson's Research, Department of Defense W81XWH-11-1-0150 and Granite State Development, and the Harvard NeuroDiscovery Center. NR 28 TC 4 Z9 4 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2016 VL 31 IS 3 BP 417 EP 421 DI 10.1002/mds.26483 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DG7SR UT WOS:000372284500027 PM 26805433 ER PT J AU Adamala, KP Engelhart, AE Szostak, JW AF Adamala, Katarzyna P. Engelhart, Aaron E. Szostak, Jack W. TI Collaboration between primitive cell membranes and soluble catalysts SO NATURE COMMUNICATIONS LA English DT Article ID VITRO SELECTED RIBOZYMES; RNA WORLD; MODEL PROTOCELLS; BOND FORMATION; METAL-IONS; LIFE; CHEMISTRY; LIPOSOMES; RIBOSOME; ORIGINS AB One widely held model of early life suggests primitive cells consisted of simple RNA-based catalysts within lipid compartments. One possible selective advantage conferred by an encapsulated catalyst is stabilization of the compartment, resulting from catalyst-promoted synthesis of key membrane components. Here we show model protocell vesicles containing an encapsulated enzyme that promotes the synthesis of simple fatty acid derivatives become stabilized to Mg2+, which is required for ribozyme activity and RNA synthesis. Thus, protocells capable of such catalytic transformations would have enjoyed a selective advantage over other protocells in high Mg2+ environments. The synthetic transformation requires both the catalyst and vesicles that solubilize the water-insoluble precursor lipid. We suggest that similar modified lipids could have played a key role in early life, and that primitive lipid membranes and encapsulated catalysts, such as ribozymes, may have acted in conjunction with each other, enabling otherwise-impossible chemical transformations within primordial cells. C1 [Adamala, Katarzyna P.; Engelhart, Aaron E.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. [Adamala, Katarzyna P.; Engelhart, Aaron E.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. [Adamala, Katarzyna P.; Engelhart, Aaron E.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Adamala, Kate/0000-0003-1066-7207 FU NASA Exobiology grant [NNX07AJ09G]; Simons Foundation [290363]; NASA; Massachusetts General Hospital Executive Committee on Research FX We thank Mr Tony Jia, Dr Neha Kamat, Ms Lin Jin, and Dr Christian Hentrich for helpful discussions. This work was supported in part by NASA Exobiology grant NNX07AJ09G to J.W.S. and a grant (290363) from the Simons Foundation to J.W.S. A.E.E. was supported by an appointment to the NASA Postdoctoral Program, administered by Oak Ridge Associated Universities through a contract with NASA and a Tosteson Fellowship from the Massachusetts General Hospital Executive Committee on Research. J.W.S. is an investigator of the Howard Hughes Medical Institute. NR 33 TC 2 Z9 3 U1 15 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 11041 DI 10.1038/ncomms11041 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DH0UK UT WOS:000372499400001 PM 26996603 ER PT J AU Du, Z Sun, T Hacisuleyman, E Fei, T Wang, XD Brown, M Rinn, JL Lee, MGS Chen, YW Kantoff, PW Liu, XS AF Du, Zhou Sun, Tong Hacisuleyman, Ezgi Fei, Teng Wang, Xiaodong Brown, Myles Rinn, John L. Lee, Mary Gwo-Shu Chen, Yiwen Kantoff, Philip W. Liu, X. Shirley TI Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer SO NATURE COMMUNICATIONS LA English DT Article ID TUMOR-SUPPRESSOR PTEN; IN-SITU HYBRIDIZATION; INTRAEPITHELIAL NEOPLASIA; MICRORNA SPONGES; DOWN-REGULATION; MESSENGER-RNAS; CELL-SURVIVAL; GENE; EXPRESSION; BIOLOGY AB Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA. C1 [Du, Zhou] Shanghai Pulm Hosp, Shanghai Key Lab TB, Shanghai 200433, Peoples R China. [Du, Zhou] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Sun, Tong; Fei, Teng; Wang, Xiaodong; Brown, Myles; Lee, Mary Gwo-Shu; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sun, Tong; Fei, Teng; Wang, Xiaodong; Brown, Myles; Lee, Mary Gwo-Shu; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sun, Tong] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. [Hacisuleyman, Ezgi] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Hacisuleyman, Ezgi; Rinn, John L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hacisuleyman, Ezgi; Rinn, John L.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Fei, Teng; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Rinn, John L.] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. [Chen, Yiwen] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Div Quantitat Sci, Houston, TX 77030 USA. [Kantoff, Philip W.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Kantoff, PW (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.; Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.; Chen, YW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Div Quantitat Sci, Houston, TX 77030 USA.; Kantoff, PW (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA.; Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.; Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. EM ychen26@mdanderson.org; kantoff@mskcc.org; xsliu@jimmy.harvard.edu FU National Natural Science Foundation of China [31329003, 2012M520923]; University of Texas Rising STARs award; University of Texas at MD Anderson Cancer Center start-up fund; Texas CPRIT grant [RR140071]; US National Cancer Institute (NCI; MD Anderson TCGA Genome Data Analysis Center) [CA143883]; Cancer Prevention Research Institute of Texas (CPRIT) [RP130397]; Mary K. Chapman Foundation; Michael and Susan Dell Foundation; MD Anderson Cancer Center Support Grant [P30 CA016672]; NIH/NIEHS [R01ES020260]; NIH/NCI [U01CA180980, R00CA175290] FX We thank Dr Bert Vogelstein for sharing the wild-type HCT116 and HCT116 Dicerex5 cells, Dr Marc Beal for his help with RNA-FISH probe-design and, Dr Xuerui Yang and Dr Andrea Califano for sharing the luciferase-PTEN-3'UTR reporter construct. This work was partially funded by National Natural Science Foundation of China 31329003 to X.S.L., 2012M520923 to D.Z., NIH/NCI U01CA180980 to X.S.L., NIH/NCI R00CA175290, University of Texas Rising STARs award, University of Texas at MD Anderson Cancer Center start-up fund and Texas CPRIT grant RR140071 to Y.C. This work was also supported in part by US National Cancer Institute (NCI; MD Anderson TCGA Genome Data Analysis Center) grant number CA143883, the Cancer Prevention Research Institute of Texas (CPRIT) grant number RP130397, the Mary K. Chapman Foundation, the Michael and Susan Dell Foundation (honoring Lorraine Dell) and MD Anderson Cancer Center Support Grant P30 CA016672 (the Bioinformatics Shared Resource). J.L.R. is the Alvin and Esta Star Associate Professor and is supported by NIH/NIEHS R01ES020260. NR 45 TC 15 Z9 15 U1 7 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10982 DI 10.1038/ncomms10982 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DG6IW UT WOS:000372188800001 PM 26975529 ER PT J AU Ke, YG Meyer, T Shih, WM Bellot, G AF Ke, Yonggang Meyer, Travis Shih, William M. Bellot, Gaetan TI Regulation at a distance of biomolecular interactions using a DNA origami nanoactuator SO NATURE COMMUNICATIONS LA English DT Article ID NANOSCALE SHAPES; FOLDING DNA; NANOSTRUCTURES; PATTERNS; BINDING; ARRAYS; BOX AB The creation of nanometre-sized structures that exhibit controllable motions and functions is a critical step towards building nanomachines. Recent developments in the field of DNA nanotechnology have begun to address these goals, demonstrating complex static or dynamic nanostructures made of DNA. Here we have designed and constructed a rhombus-shaped DNA origami 'nanoactuator' that uses mechanical linkages to copy distance changes induced on one half ('the driver') to be propagated to the other half ('the mirror'). By combining this nanoactuator with split enhanced green fluorescent protein (eGFP), we have constructed a DNA-protein hybrid nanostructure that demonstrates tunable fluorescent behaviours via long-range allosteric regulation. In addition, the nanoactuator can be used as a sensor that responds to specific stimuli, including changes in buffer composition and the presence of restriction enzymes or specific nucleic acids. C1 [Ke, Yonggang; Meyer, Travis] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA. [Ke, Yonggang; Meyer, Travis] Emory Univ, Atlanta, GA 30322 USA. [Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bellot, Gaetan] CNRS, CNRS Unite Mixte Rech UMR 5203, Inst Natl Sante & Rech Med, Dept Neurosci,Inst Genom Fonct,INSERM U1191, 141 Rue Cardonille, F-34000 Montpellier, France. [Bellot, Gaetan] Univ Montpellier, F-34000 Montpellier, France. RP Ke, YG (reprint author), Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA.; Ke, YG (reprint author), Emory Univ, Atlanta, GA 30322 USA.; Bellot, G (reprint author), CNRS, CNRS Unite Mixte Rech UMR 5203, Inst Natl Sante & Rech Med, Dept Neurosci,Inst Genom Fonct,INSERM U1191, 141 Rue Cardonille, F-34000 Montpellier, France.; Bellot, G (reprint author), Univ Montpellier, F-34000 Montpellier, France. EM yonggang.ke@emory.edu; gaetan.bellot@inserm.fr OI Meyer, Travis/0000-0002-8047-4649 FU Emory Department of Biomedical Engineering startup fund; Emory Billi and Bernie Marcus Research Award; Wyss Institute Faculty Grant; ARO MURI grant [W911NF1210420]; ONR Grants [N000014091118, N000141010241]; NIH [1DP2OD004641]; National Science Foundation [DGE-1148903] FX This work is supported by an Emory Department of Biomedical Engineering startup fund and an Emory 2014 Billi and Bernie Marcus Research Award to Y.K., a Wyss Institute Faculty Grant, ARO MURI grant W911NF1210420, ONR Grants N000014091118 and N000141010241, and an NIH Director New Innovator Award 1DP2OD004641 to W.M.S. T.M. is supported by a National Science Foundation Graduate Research Fellowship under grant number DGE-1148903. NR 42 TC 4 Z9 4 U1 18 U2 63 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10935 DI 10.1038/ncomms10935 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DG9MW UT WOS:000372408100001 PM 26988942 ER PT J AU Kantor, ED Rehm, CD Haas, JS Chan, AT Giovannucci, EL AF Kantor, Elizabeth D. Rehm, Colin D. Haas, Jennifer S. Chan, Andrew T. Giovannucci, Edward L. TI Trends in Prescription Drug Use Among Adults in the United States From 1999-2012 SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Obstet Gynecol Surv 2016;71(3):131-133 Prescription drug usage is a major expenditure in the United States, and evidence indicates that this usage is increasing. Because practice patterns are continually evolving, an updated comprehensive assessment of prescription drug use is important to reflect the changing health needs, advances in treatment, new clinical guidelines, the entrance or exit of drugs from the market, and shifts in policies regarding drug marketing and promotion. C1 [Kantor, Elizabeth D.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kantor, Elizabeth D.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Rehm, Colin D.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Rehm, Colin D.] Montefiore Med Ctr, Off Community & Populat Hlth, 111 E 210th St, Bronx, NY 10467 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Haas, Jennifer S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Kantor, ED (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.; Kantor, ED (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAR PY 2016 VL 71 IS 3 BP 131 EP 133 DI 10.1097/OGX.0000000000000306 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DG4JN UT WOS:000372038600001 ER PT J AU Jena, AB Schoemaker, L Bhattacharya, J Seabury, SA AF Jena, Anupam B. Schoemaker, Lena Bhattacharya, Jay Seabury, Seth A. TI Physician Spending and Subsequent Risk of Malpractice Claims: Observational Study SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material ID CESAREAN DELIVERY AB Obstet Gynecol Surv 2016;71(3):139-141 This study explores whether greater resource use (defensively motivated or not) is associated with reduced malpractice claims. Data were obtained from Florida Agency for Health Care Administration on all hospital discharges (from all nonstate, nonfederal Florida acute care hospitals) during 2000-2009, from the Florida Office of Insurance Regulation on all closed malpractice claims against Florida physicians with active medical licenses reported during the study period and on physician specialty from publicly available practitioner profiles maintained by the Florida Agency for Health Care Administration. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.; Bhattacharya, Jay; Seabury, Seth A.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Schoemaker, Lena; Bhattacharya, Jay] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.; Jena, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Jena, AB (reprint author), Natl Bur Econ Res, Cambridge, MA 02138 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAR PY 2016 VL 71 IS 3 BP 139 EP 141 DI 10.1097/01.ogx.0000481018.20322.1f PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DG4JN UT WOS:000372038600005 ER PT J AU Oeffinger, KC Fontham, ETH Etzioni, R Herzig, A Michaelson, JS Shih, YCT Walter, LC Church, TR Flowers, CR LaMonte, SJ Wolf, AMD DeSantis, C Lortet-Tieulent, J Andrews, K Manassaram-Baptiste, D Saslow, D Smith, RA Brawley, OW Wender, R AF Oeffinger, Kevin C. Fontham, Elizabeth T. H. Etzioni, Ruth Herzig, Abbe Michaelson, James S. Shih, Ya-Chen Tina Walter, Louise C. Church, Timothy R. Flowers, Christopher R. LaMonte, Samuel J. Wolf, Andrew M. D. DeSantis, Carol Lortet-Tieulent, Joannie Andrews, Kimberly Manassaram-Baptiste, Deana Saslow, Debbie Smith, Robert A. Brawley, Otis W. Wender, Richard TI Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Obstet Gynecol Surv 2016;71(3):153-155 The aim of this updated American Cancer Society (ACS) guideline was to provide guidance and flexibility for women at average risk for breast cancer about when to start and stop screening mammography and how frequently screening should be performed. Since the last ACS update on breast cancer screening in 2003, new evidence has accumulated showing the need for greater emphasis on harms associated with screening and for balance of benefits and harms. C1 [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Etzioni, Ruth] Univ Washington, Seattle, WA 98195 USA. [Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Michaelson, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michaelson, James S.] Harvard Univ, Sch Med, Boston, MA USA. [Shih, Ya-Chen Tina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Church, Timothy R.] Masonic Canc Ctr, Minneapolis, MN USA. [Church, Timothy R.] Univ Minnesota, Minneapolis, MN USA. [Flowers, Christopher R.] Emory Univ, Sch Med, Atlanta, GA USA. [Flowers, Christopher R.] Winship Canc Inst, Atlanta, GA USA. [Wolf, Andrew M. D.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [DeSantis, Carol; Lortet-Tieulent, Joannie; Andrews, Kimberly; Manassaram-Baptiste, Deana; Saslow, Debbie; Smith, Robert A.; Brawley, Otis W.; Wender, Richard] Amer Canc Soc, Atlanta, GA 30329 USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 NR 3 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAR PY 2016 VL 71 IS 3 BP 153 EP 155 DI 10.1097/01.ogx.0000480954.49941.b5 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DG4JN UT WOS:000372038600012 ER PT J AU Scalia-Wilbur, J Colins, BL Penson, RT Dizon, DS AF Scalia-Wilbur, Jennifer Colins, Bradley L. Penson, Richard T. Dizon, Don S. TI Breast Cancer Risk Assessment: Moving Beyond BRCA1 and 2 SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Obstet Gynecol Surv 2016;71(3):156-157 Women carrying germ line mutations of the BRCA gene are at high risk of developing breast and ovarian cancer. Since the discovery of the BRCA1 gene in 1994 and the BRCA2 gene 1 year later, efforts have been made to develop effective screening methods for detection of breast cancer. C1 [Scalia-Wilbur, Jennifer] Brown Univ, Women & Infants Hosp, Program Womens Oncol, Canc Risk & Prevent Program, Providence, RI USA. [Colins, Bradley L.] Harvard Univ, Sch Med, Boston, MA USA. [Penson, Richard T.; Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Gynecol Oncol Program, Boston, MA USA. [Penson, Richard T.; Dizon, Don S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Scalia-Wilbur, J (reprint author), Brown Univ, Women & Infants Hosp, Program Womens Oncol, Canc Risk & Prevent Program, Providence, RI USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAR PY 2016 VL 71 IS 3 BP 156 EP 157 DI 10.1097/OGX.0000000000000297 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DG4JN UT WOS:000372038600013 ER PT J AU Jakobiec, FA Stagner, AM Freitag, SK Yoon, MK AF Jakobiec, Frederick A. Stagner, Anna M. Freitag, Suzanne K. Yoon, Michael K. TI Unusual Eyelid Dermal Keratinous Cysts of Pilosebaceous Origin SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID VELLUS HAIR CYSTS; STEATOCYSTOMA MULTIPLEX; PALPEBRAL CONJUNCTIVA; HYBRID CYSTS; DACRYOPS; SIMPLEX AB Purpose: To describe 2 types of previously unrecognized dermal keratinous cysts of the eyelids2 single sebaceous duct cysts derived from the glands of Zeis and 2 cases of multiple eruptive vellus hair cysts, both types associated with the pilosebaceous apparatus. Methods: Clinical records and paraffin sections subjected to hematoxylin and eosin and acid-fast staining were critically reviewed from each case, and additional sections were immunoreacted for cytokeratins (CKs) 7, 14, and 17. Results: Two patients had a slowly enlarging solitary sebaceous duct keratinous cyst at the eyelid margin where the glands of Zeis are located. The squamous cell lining displayed a corrugated squamous membrane manifesting an eosinophilic, refractile, surface cuticle. Either a sebaceous gland or a hair was proximate to the cyst. The squamous lining was CK7(-), CK14(+), and CK17(+). Two other patients developed over 2 and 10 years a different condition consisting of unilateral or bilateral clusters, respectively, of small papules of the upper eyelids. These were lined by keratinizing squamous epithelium without a cuticular membrane. Numerous small vellus hairs along with keratin in the lumens were discovered with acid-fast staining. The epithelium was also CK7(-), CK14(+), and CK17(+). Conclusions: Histopathologic and immunohistochemical studies can separate these 2 disparate new eyelid entities from the more common keratinous epidermoid cyst of the surface epidermis or the upper hair follicle (CK7(-), CK14(+), and CK17(-)). Simple local excision of the anterior lamella of the eyelid is appropriate for the sebaceous duct keratinous cysts of Zeis, but the multiple vellus hair cysts are comparatively refractory to treatment. Both superficial types of cysts are totally unrelated to the deeper Meibomian keratinous cyst, which is not associated with a hair structure and is situated in the tarsus rather than the dermis of the eyelids. C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Freitag, Suzanne K.; Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Surg Serv, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 26 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2016 VL 32 IS 2 BP 93 EP 97 DI 10.1097/IOP.0000000000000423 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DG4RN UT WOS:000372060200003 PM 25719379 ER PT J AU Jakobiec, FA Rashid, A Massoud, V Fay, A AF Jakobiec, Frederick A. Rashid, Alia Massoud, Vicky Fay, Aaron TI Pseudoadenomatous Hyperplasia of the Inferior Forniceal Conjunctiva Due To Prosthetic Irritation in an Anophthalmic Socket SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CARCINOMA AB Secondary complications in an anophthalmic socket can include late appearing shrinkage due to scarring and squamous cell carcinoma. This article reports a 51-year-old man who 27 years after an enucleation developed an inability to retain his ocular prosthesis due to an acquired multilobular fleshy mass in his inferior fornix. The patient had worn his prosthesis without removal for years at a time. Microscopic evaluation of the excised lesion disclosed a pseudoadenomatous (pseudoglandular) hyperplasia of the conjunctival epithelium with myriad goblet cells and accompanying chronic inflammation. In cross section, these structures microscopically resembled an adenoma but were found to display multifocal origins from the surface epithelium resembling exaggerated pseudoglands of Henle. Simple excision without recurrence 6 months later has permitted a new prosthesis to be comfortably worn with stability. C1 [Jakobiec, Frederick A.; Rashid, Alia] David G Cogan Lab Ophthalm Pathol, Boston, MA USA. [Jakobiec, Frederick A.; Rashid, Alia; Massoud, Vicky; Fay, Aaron] Harvard Univ, Sch Med, Boston, MA USA. [Massoud, Vicky; Fay, Aaron] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2016 VL 32 IS 2 BP E32 EP E34 DI 10.1097/IOP.0000000000000208 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DG4RT UT WOS:000372060900004 PM 24911539 ER PT J AU Brawner, BM Alexander, KA Fannin, EF Baker, JL Davis, ZM AF Brawner, Bridgette M. Alexander, Kamila A. Fannin, Ehriel F. Baker, Jillian L. Davis, Zupenda M. TI The Role of Sexual Health Professionals in Developing a Shared Concept of Risky Sexual Behavior as it Relates to HIV Transmission SO PUBLIC HEALTH NURSING LA English DT Article DE disease prevention; diversity; health promotion; HIV; AIDS; patient education; prevention; programme planning; public health systems; sexual behavior ID INTIMATE PARTNER VIOLENCE; YOUNG-ADULTS; RELATIONSHIP POWER; DOMESTIC VIOLENCE; ADOLESCENT GIRLS; UNITED-STATES; SELF-EFFICACY; SOUTH-AFRICA; CONDOM USE; PREVENTION AB Risky sexual behavior accounts for the majority of new HIV infections regardless of gender, age, geographic location, or ethnicity. The phrase, however, refers to a relatively nebulous concept that hampers development of effective sexual health communication strategies. The purpose of this paper was to propose development of a shared conceptual understanding of risky sexual behavior. We reviewed multidisciplinary HIV/AIDS literature to identify definitions of risky sexual behavior. Both the linguistic components and the social mechanisms that contribute to the concept of risky sexual behaviors were noted. Risky sexual behavior was often defined in a subjective manner in the literature, even in the scientific research. We urge a paradigm shift to focus on explicit behaviors and the social context of those behaviors in determining HIV risk. We also propose a new definition that reduces individual biases and promotes a broader discussion of the degree of sexual risk across a diversity of behavioral contexts. Sexual health professionals can strengthen practice and research initiatives by operating from a concise working definition of risky sexual behavior that is broadly transferable and expands beyond a traditional focus on identity-based groups. C1 [Brawner, Bridgette M.] Univ Penn, Sch Nursing, Dept Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Brawner, Bridgette M.; Fannin, Ehriel F.] Univ Penn, Sch Nursing, Ctr Global Womens Hlth, 418 Curie Blvd,Room 419, Philadelphia, PA 19036 USA. [Alexander, Kamila A.] Johns Hopkins Sch Nursing, Dept Community Publ Hlth, Baltimore, MD USA. [Fannin, Ehriel F.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, 418 Curie Blvd,Room 419, Philadelphia, PA 19036 USA. [Baker, Jillian L.; Davis, Zupenda M.] La Salle Univ, Sch Nursing & Hlth Sci, Dept Urban Publ Hlth & Nutr, Philadelphia, PA 19141 USA. RP Brawner, BM (reprint author), Univ Penn, Sch Nursing, Ctr Global Womens Hlth, 418 Curie Blvd,Room 419, Philadelphia, PA 19036 USA.; Brawner, BM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, 418 Curie Blvd,Room 419, Philadelphia, PA 19036 USA. EM brawnerb@nursing.upenn.edu FU Centers for Disease Control and Prevention [CDC U01PS003304]; National Institute of Mental Health [NIH/NIMH R25MH087217]; Substance Abuse and Mental Health Services Administration at American Nurses Association Minority Fellowship Program [5SM058566-02]; Hampton-Penn Center for Health Disparities Research [NINR P20NR008361]; Distinguished Postdoctoral Fellowship; Fontaine Society Fellowship at University of Pennsylvania; Individual Ruth L. Kirschstein NRSA Predoctoral Fellowship [F31NR013121]; Ruth L. Kirschstein NRSA Postdoctoral Fellowship; Ruth L. Kirschstein NRSA Predoctoral Fellowship [5T32NR007100-13]; National Institute of Child Health & Human Development Diversity Research Supplement Award [5R01HD061061-03] FX This article was supported by funding to Dr. Brawner from the Centers for Disease Control and Prevention (CDC U01PS003304), the National Institute of Mental Health (NIH/NIMH R25MH087217; PI: B. Guthrie, J.), the Substance Abuse and Mental Health Services Administration at the American Nurses Association Minority Fellowship Program (5SM058566-02), the Hampton-Penn Center for Health Disparities Research (NINR P20NR008361), and the Distinguished Postdoctoral Fellowship and the Fontaine Society Fellowship at the University of Pennsylvania. The article was also supported by the Individual Ruth L. Kirschstein NRSA Predoctoral Fellowship (F31NR013121) and the Ruth L. Kirschstein NRSA Postdoctoral Fellowship (T32HDO64428; PI: Campbell) awarded to Dr. Alexander; the Ruth L. Kirschstein NRSA Predoctoral Fellowship (5T32NR007100-13; PI: Sommers) awarded to Ms. Ehriel Fannin; and funding from a National Institute of Child Health & Human Development Diversity Research Supplement Award (5R01HD061061-03; PI: Jemmott) to Dr. Baker. NR 74 TC 0 Z9 0 U1 5 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0737-1209 EI 1525-1446 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD MAR-APR PY 2016 VL 33 IS 2 BP 139 EP 150 DI 10.1111/phn.12216 PG 12 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA DG2PW UT WOS:000371910700007 PM 26184496 ER PT J AU Pang, CE Sarraf, D Freund, KB AF Pang, Claudine E. Sarraf, David Freund, K. Bailey TI An Atypical Presentation of Bartonella Neuroretinitis Reply SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Letter ID MYOPIA C1 [Pang, Claudine E.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY USA. [Pang, Claudine E.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA. RP Pang, CE (reprint author), Vitreous Retina Macula Consultants New York, New York, NY USA.; Pang, CE (reprint author), Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAR PY 2016 VL 36 IS 3 BP e24 EP e24 DI 10.1097/IAE.0000000000000990 PG 1 WC Ophthalmology SC Ophthalmology GA DG1MX UT WOS:000371833300008 PM 26849457 ER PT J AU Chen, SS Unruh, M Williams, M AF Chen, Shan Shan Unruh, Mark Williams, Mark TI In Quality We Trust; but Quality of Life or Quality of Care? SO SEMINARS IN DIALYSIS LA English DT Article ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; SERUM-ALBUMIN; HEALTH-CARE; MAINTENANCE HEMODIALYSIS; PERFORMANCE-MEASUREMENT; PRACTICE PATTERNS; VASCULAR ACCESS; MEMBRANE FLUX AB The ESRD program provides medical care to a diverse and medically complex patient population. The care for the ESRD patient population has become increasingly benchmarked with process of care measures. These measures include dialysis adequacy, anemia, nutrition, and vascular access outcomes. These process-related dialysis measures may not improve the care of the individual patient as care relates to the individual's goals and values. There is also evidence that these process measures may not be causally related to quality of life, hospitalization, and survival. The adoption of patient-reported outcomes may shift the balance toward more patient-centered care. However, the extent to which mandated measures of health-related quality of life and patient satisfaction result in improved outcomes remains unclear. C1 [Chen, Shan Shan; Unruh, Mark] Univ New Mexico, Dept Internal Med, Sch Med, Div Nephrol, Albuquerque, NM 87131 USA. [Unruh, Mark] Univ New Mexico, Raymond G Murphy VA Med Ctr, Sch Med, Renal Sect,Med Serv,Dept Med, Albuquerque, NM 87131 USA. [Williams, Mark] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. RP Williams, M (reprint author), Harvard Univ, Sch Med, Med, One Joslin Pl, Boston, MA 02215 USA.; Williams, M (reprint author), Beth Israel Deaconess Med Ctr, Dialysis Operat, One Joslin Pl, Boston, MA 02215 USA.; Williams, M (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 57 TC 0 Z9 0 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR PY 2016 VL 29 IS 2 BP 103 EP 110 DI 10.1111/sdi.12470 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DG7SC UT WOS:000372283000003 PM 26860436 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Patient-Centered Dialysis Care: Depression, Pain, and Quality of Life SO SEMINARS IN DIALYSIS LA English DT Article ID STAGE RENAL-DISEASE; RECEIVING CHRONIC-HEMODIALYSIS; MAINTENANCE HEMODIALYSIS; PSYCHOSOCIAL FACTORS; TRANSPLANT PATIENTS; MORTALITY RISK; SYMPTOMS; PREVALENCE; ADHERENCE; HOSPITALIZATION AB Remarkable advancements have been made in the provision of chronic dialysis therapy since its inception decades ago. A series of studies inform current dialysis dosing recommendations, while advancements in strategies to treat mineral and bone disease, acid-base and electrolyte disturbances, and anemia have facilitated the management of these well-recognized complications of ESRD. The collective result has been a model of chronic dialysis care focused principally on the achievement of metabolic and dialysis-related targets. In fact, guidelines such as the Kidney Disease Outcomes Quality Initiative put forth by the National Kidney Foundation recommend metrics that characterize successful dialysis care, including the attainment of specific solute clearance targets; maintenance of hemoglobin, calcium, phosphorous, and parathyroid hormone levels within target ranges; and the preferred use of primary arteriovenous fistulae for vascular access. This focus on serologic and dialysis-specific outcomes has helped renal providers manage the biochemical effects related to the loss of kidney function and has reduced ESRD-related morbidity and mortality. Yet, absent from this model of care is an emphasis on the treatment of bothersome symptoms and the impact of such treatment on quality of life (QOL). Among the many symptoms that affect patients on chronic dialysis, depression and pain are particularly common, strongly associated with decrements in QOL, and potentially treatable. This review discusses key research findings and unanswered questions pertaining to the prevalence, significance, and treatment of depression and pain and the effect of such treatment on QOL in patients dependent on chronic dialysis, with the broad goal of incorporating symptom management strategies into a paradigm of patient-centered dialysis care. C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Med Serv Line, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, 7E Room 120,111F U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 47 TC 2 Z9 2 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR PY 2016 VL 29 IS 2 BP 158 EP 164 DI 10.1111/sdi.12464 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DG7SC UT WOS:000372283000010 PM 26748494 ER PT J AU Saby, A Miller, LS AF Saby, Adam Miller, Lawrence S. TI Functional Assessment in End-Stage Renal Disease: Enhancing Quality of Life SO SEMINARS IN DIALYSIS LA English DT Article ID DIALYSIS PATIENTS; HEMODIALYSIS; MORTALITY; HEALTH; FACILITIES; DISABILITY; CAPACITY; OUTCOMES; FALLS; RISK AB Why do functional assessments in patients with end-stage renal disease (ESRD) matter? Multiple studies show that new dialysis patients undergo a substantial decline among activities of daily living. Moreover, poor functional status in ESRD patients is associated with early morality. That is why CMS has developed new criteria to assess ESRD patients in regards to their functional, psychologic, and cognitive capabilities. Functional assessments by health providers have been used in field of Rehabilitation Medicine for over 50 years; rehabilitation physicians have found them effective in establishing goals and monitoring improvement. Assessments can provide guidance by identifying the needs and types of intervention most suited for patients. Impairments can be addressed with referrals to physical therapy for gross motor issues, occupational therapy for self-care problems, psychiatry for mental disorders, and neurology for cognitive deficits. The more accurate the assessments over time, the more targeted and effective the therapies become. We believe that the new CMS goals to assess functionality will improve ESRD patient's quality of life, longevity, and long-term healthcare costs. C1 [Saby, Adam] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Adm Hlth Care Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90095 USA. [Miller, Lawrence S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Saby, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Adm Hlth Care Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90095 USA.; Saby, A (reprint author), Dept Phys Med & Rehabil 117, 11301 Wilshire blvd, Los Angeles, CA 90073 USA. EM asaby@ucla.edu NR 21 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR PY 2016 VL 29 IS 2 BP 170 EP 172 DI 10.1111/sdi.12466 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA DG7SC UT WOS:000372283000012 PM 26756940 ER PT J AU Sarmiento, K Rossettie, J Stepnowsky, C Atwood, C Calvitti, A AF Sarmiento, Kathleen Rossettie, John Stepnowsky, Carl Atwood, Charles Calvitti, Alan CA VA Sleep Network TI The state of Veterans Affairs sleep medicine programs: 2012 inventory results SO SLEEP AND BREATHING LA English DT Article DE Access to health care; Health services; Sleep disorders; Veterans AB The Veterans Health Administration (VHA) represents one of the largest integrated health-care systems in the country. In 2012, the Veterans Affairs Sleep Network (VASN) sought to identify available sleep resources at VA medical centers (VAMCs) across the country through a national sleep inventory. The sleep inventory was administered at the annual 2012 VA Sleep Practitioners meeting and by email to sleep contacts at each VAMC. National prosthetics contacts were used to identify personnel at VAMCs without established sleep programs. Follow-up emails and telephone calls were made through March 2013. One hundred eleven VA medical centers were included for analysis. Thirty-nine programs did not respond, and 10 were considered "satellites," referring all sleep services to a larger neighboring VAMC. Sleep programs were stratified based on extent of services offered (i.e., in-lab and home testing, sleep specialty clinics, cognitive behavioral therapy for insomnia (CBT-i)): 28 % were complex sleep programs (CSPs), 46 % were intermediate (ISPs), 9 % were standard (SSPs), and 17 % offered no formal sleep services. Overall, 138,175 clinic visits and 90,904 sleep testing encounters were provided in fiscal year 2011 by 112.1 physicians and clinical psychologists, 100.4 sleep technologists, and 115.3 respiratory therapists. More than half of all programs had home testing and CBT-i programs, and 26 % utilized sleep telehealth. The 2012 VA sleep inventory suggests considerable variability in sleep services within the VA. Demand for sleep services is high, with programs using home testing, sleep telehealth, and a growing number of mid-level providers to improve access to care. C1 [Sarmiento, Kathleen; Rossettie, John; Stepnowsky, Carl; Calvitti, Alan] VA San Diego Healthcare Syst, 3350 Jolla Village Dr,111J, San Diego, CA 92161 USA. [Sarmiento, Kathleen] Univ Calif San Diego, Dept Pulm & Crit Care Med, La Jolla, CA 92093 USA. [Rossettie, John; Stepnowsky, Carl] Univ Calif San Diego, Dept Med, La Jolla, CA 92103 USA. [Atwood, Charles] VA Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. [Atwood, Charles] UPMC Montefiore, PACCM, Pittsburgh, PA 15213 USA. RP Sarmiento, K (reprint author), VA San Diego Healthcare Syst, 3350 Jolla Village Dr,111J, San Diego, CA 92161 USA.; Sarmiento, K (reprint author), Univ Calif San Diego, Dept Pulm & Crit Care Med, La Jolla, CA 92093 USA. EM kfsarmiento@ucsd.edu NR 1 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1520-9512 EI 1522-1709 J9 SLEEP BREATH JI Sleep Breath. PD MAR PY 2016 VL 20 IS 1 BP 379 EP 382 DI 10.1007/s11325-015-1184-0 PG 4 WC Clinical Neurology; Respiratory System SC Neurosciences & Neurology; Respiratory System GA DG5ZJ UT WOS:000372160800058 PM 25924933 ER PT J AU Dzik, WS Ziman, A Cohen, C Pai, M Lozano, M Kaufman, RM Delaney, M Selleng, K Murphy, MF Hervig, T Yazer, M AF Dzik, Walter Sunny Ziman, Alyssa Cohen, Claudia Pai, Menaka Lozano, Miguel Kaufman, Richard M. Delaney, Meghan Selleng, Kathleen Murphy, Michael F. Hervig, Tor Yazer, Mark CA Biomed Excellence Safer Transfusio TI Survival after ultramassive transfusion: a review of 1360 cases SO TRANSFUSION LA English DT Review ID MASSIVE BLOOD-TRANSFUSION; TRAUMA; STATE AB BACKGROUNDInformation about patient survival after transfusion of multiple blood volumes is limited, and most reports have focused on trauma patients. STUDY DESIGN AND METHODSRetrospective study of blood use and survival at 11 hospitals in six nations between 2009 and 2013. Ultramassive transfusion (UMT) was defined as transfusion of 20 or more red blood cell (RBC) units over the course of any 2 consecutive calendar days. RESULTSA total of 1975 patients received UMT and a representative sample of 1360 patients was studied in detail. Patients were grouped into seven diagnostic categories: solid organ transplantation (n=411), cardiac or major vascular surgery (n=317), general surgery (n=228), trauma (n=221), general medicine (n=124), obstetrics (n=23), and other (n=36). During the 7 days after initiation of UMT, these patients used more than 120,000 blood components. The median (interquartile range) blood use was 35 (26-50) RBC units, 30 (20-47) plasma units, and 7 (4-13) platelet doses. Five- and 30-day survival significantly declined with increasing RBC use. Overall survivals of patients receiving UMT were 71% (5 day) and 60% (30 day), and in the subset of 165 patients receiving 60 or more RBC units over 2 consecutive days, 5-day survival was 54% ranging from 17% (trauma) to 75% (solid organ transplant). The decline in survival with increasing RBC transfusions was minimal for patients undergoing solid organ transplantation and was most pronounced for trauma and nonsurgical bleeding patients. CONCLUSIONTrauma was not the leading cause of UMT. Increasing RBC requirements were significantly associated with decreasing survival. However, survival was more strongly associated with diagnostic category than total RBCs transfused, with highest survival rates in solid organ transplant surgery. C1 [Dzik, Walter Sunny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ziman, Alyssa] Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Div Transfus Med, Los Angeles, CA 90024 USA. [Cohen, Claudia] Univ Minnesota, Med Ctr, Lab Med & Pathol, Minneapolis, MN 55455 USA. [Pai, Menaka] McMaster Univ, Med, Hamilton, ON, Canada. [Pai, Menaka] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Lozano, Miguel] Univ Clin Hosp, Hemotherapy & Hemostasis, Barcelona, Spain. [Kaufman, Richard M.] Brigham & Womens Hosp, Pathol, 75 Francis St, Boston, MA 02115 USA. [Delaney, Meghan] Univ Washington, Lab Med, Seattle, WA 98195 USA. [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Selleng, Kathleen] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany. [Murphy, Michael F.] John Radcliffe Hosp, NHS Blood & Transplant, Oxford OX3 9DU, England. [Hervig, Tor] Haukeland Hosp, Transfus Med, N-5021 Bergen, Norway. [Yazer, Mark] Inst Transfus Med, Pittsburgh, PA USA. RP Dzik, WS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224, Boston, MA 02114 USA. EM sdzik@mgh.harvard.edu NR 16 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2016 VL 56 IS 3 BP 558 EP 563 DI 10.1111/trf.13370 PG 6 WC Hematology SC Hematology GA DG7SH UT WOS:000372283500005 PM 26450364 ER PT J AU Becker, WC Gordon, K Edelman, EJ Kerns, RD Crystal, S Dziura, JD Fiellin, LE Gordon, AJ Goulet, JL Justice, AC Fiellin, DA AF Becker, William C. Gordon, Kirsha Edelman, E. Jennifer Kerns, Robert D. Crystal, Stephen Dziura, James D. Fiellin, Lynn E. Gordon, Adam J. Goulet, Joseph L. Justice, Amy C. Fiellin, David A. TI Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV SO AIDS AND BEHAVIOR LA English DT Article DE Analgesics; Opioids; Aging; Pain; Chronic; Human immunodeficiency virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; CORONARY-HEART-DISEASE; CHRONIC NONCANCER PAIN; HEALTH-CARE-SYSTEM; UNINFECTED PATIENTS; INFECTED ADULTS; DRUG-DEPENDENCE; UNITED-STATES; RISK-FACTORS; BACK-PAIN AB Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (a parts per thousand yen120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age. C1 [Becker, William C.; Gordon, Kirsha; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven VA Med Ctr, Internal Med, Mail Stop 151B,950 Campbell Ave, West Haven, CT 06516 USA. [Kerns, Robert D.; Goulet, Joseph L.] VA Connecticut Healthcare Syst, Psychol, West Haven, CT 06516 USA. [Becker, William C.; Edelman, E. Jennifer; Dziura, James D.; Fiellin, Lynn E.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Internal Med, New Haven, CT USA. [Kerns, Robert D.; Goulet, Joseph L.] Yale Univ, Sch Med, Psychol, New Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, Ctr Hlth Serv Res, New Brunswick, NJ 08903 USA. [Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Becker, WC (reprint author), VA Connecticut Healthcare Syst, West Haven VA Med Ctr, Internal Med, Mail Stop 151B,950 Campbell Ave, West Haven, CT 06516 USA.; Becker, WC (reprint author), Yale Univ, Sch Med, Internal Med, New Haven, CT USA. EM william.becker@yale.edu OI Edelman, E. Jennifer/0000-0002-9375-0489; Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502; Goulet, Joseph/0000-0002-0842-804X FU Veterans Health Administration Health Services Research & Development Career Development Award [08-276]; VA Health Services Research and Development Center of Innovation [CIN 13-047]; Society of General Internal Medicine's Lawrence Linn Award; Robert Wood Johnson Foundation Clinical Scholars Program; Veterans Aging Cohort study; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566] FX This work was supported by a Veterans Health Administration Health Services Research & Development Career Development Award (08-276); other VA support came from VA Health Services Research and Development Center of Innovation (CIN 13-047). This work was also supported by the Society of General Internal Medicine's Lawrence Linn Award, the Robert Wood Johnson Foundation Clinical Scholars Program, and the Veterans Aging Cohort study, funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566). This work was presented at the Northeast Regional Society of General Internal Medicine Meeting, New Haven, CT, March 8, 2013 and the Society of General Internal Medicine National Meeting, Denver, CO, April 25, 2013. The authors would like to thank Dr. Eugenia Buta for input on statistical analyses. NR 60 TC 2 Z9 2 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD MAR PY 2016 VL 20 IS 3 BP 679 EP 686 DI 10.1007/s10461-015-1197-5 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DF8JA UT WOS:000371602700020 PM 26384973 ER PT J AU Merlin, JS Tamhane, A Starrels, JL Kertesz, S Saag, M Cropsey, K AF Merlin, Jessica S. Tamhane, Ashutosh Starrels, Joanna L. Kertesz, Stefan Saag, Michael Cropsey, Karen TI Factors Associated with Prescription of Opioids and Co-prescription of Sedating Medications in Individuals with HIV SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Chronic pain; Opioid; Benzodiazepine; Muscle relaxant ID QUALITY-OF-LIFE; OVERDOSE DEATHS; UNITED-STATES; PRESCRIBING PRACTICES; NONMALIGNANT PAIN; INFECTED PATIENTS; SCREENING-TEST; MENTAL-HEALTH; BENZODIAZEPINES; DISORDERS AB Opioids are often prescribed for chronic pain, and opioid risks such as overdose and death are heightened when opioids are co-prescribed with other sedating medications. We investigated factors associated with chronic opioid prescription, alone and in combination with benzodiazepines and muscle relaxants, in a clinical cohort of individuals with HIV. We used multivariable logistic regression models to determine participant clinical and demographic characteristics that are associated with chronic prescription of opioids or chronic co-prescription of opioids with sedating medications. Among 1474 participants, chronic prescription of opioids occurred in 253 individuals (17.2 %), and chronic co-prescription occurred in 90 individuals (6.1 %). Age > 50, public insurance as compared to private insurance, and symptoms of depression and anxiety were significantly associated with chronic opioid prescription and chronic co-prescription. Our findings raise concern that opioid prescription and co-prescription of sedating medications occurs disproportionately in patients for whom use is riskier. C1 [Merlin, Jessica S.; Tamhane, Ashutosh; Saag, Michael] Univ Alabama Birmingham, Dept Med, Div Infect Dis, BBRB 222,1530 3rd Ave S, Birmingham, AL 35294 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Starrels, Joanna L.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, Stefan] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Cropsey, Karen] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL 35294 USA. RP Merlin, JS (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, BBRB 222,1530 3rd Ave S, Birmingham, AL 35294 USA.; Merlin, JS (reprint author), Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. EM jmerlin@uab.edu OI Tamhane, Ashutosh/0000-0002-4475-2760; Kertesz, Stefan/0000-0001-6101-8421 FU University of Alabama at Birmingham (UAB) Center for AIDS Research, an NIH [P30 A1027767]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; FIC; OAR; AHRQ [1K12HS02169401]; NIDA [K23DA027719]; Mary Fisher CARE Fund at UAB FX This research was supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research, an NIH funded program (P30 A1027767) that was made possible by the following institutes: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. JSM was supported by 1K12HS02169401 (AHRQ). JLS was supported by K23DA027719 (NIDA). Funding was also provided by the Mary Fisher CARE Fund at UAB. NR 52 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD MAR PY 2016 VL 20 IS 3 BP 687 EP 698 DI 10.1007/s10461-015-1178-8 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DF8JA UT WOS:000371602700021 PM 26487298 ER PT J AU Hou, JB Xing, L Jia, HB Vergallo, R Soeda, T Minami, Y Hu, SN Yang, S Zhang, SS Lee, H Yu, B Jang, IK AF Hou, Jingbo Xing, Lei Jia, Haibo Vergallo, Rocco Soeda, Tsunerari Minami, Yoshiyasu Hu, Sining Yang, Shuang Zhang, Shaosong Lee, Hang Yu, Bo Jang, Ik-Kyung TI Comparison of Intensive Versus Moderate Lipid-Lowering Therapy on Fibrous Cap and Atheroma Volume of Coronary Lipid-Rich Plaque Using Serial Optical Coherence Tomography and Intravascular Ultrasound Imaging SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; STATIN THERAPY; ATHEROSCLEROTIC PLAQUE; ARTERY-DISEASE; RUPTURE; PROGRESSION; THICKNESS; EVENTS; ATORVASTATIN; SIMVASTATIN AB Despite marked clinical benefit, reduction in atheroma volume with statin therapy is minimal. Changes in plaque composition may explain this discrepancy. We aimed in the present study to assess the effect of statin therapy on coronary plaque composition and plaque volume using serial multimodality imaging. From an open-label, single-blinded study, patients with angiographically mild-to-moderate lesion were randomized to receive atorvastatin 60 (AT 60) mg or atorvastatin 20 (AT 20) mg for 12 months. Optical coherence tomography was used to assess fibrous cap thickness (FCT) and intravascular ultrasound to assess atheroma burden at 3 time points: baseline, at 6 months, and at 12 months. Thirty-six lipid-rich plaques in 27 patients with AT 60 mg and 30 lipid-rich plaques in 19 patients with AT 20 mg were enrolled in this study. Low-density lipoprotein cholesterol level was significantly decreased at 6 months without further reduction at 12 months. AT 60 mg induced greater reduction in low-density lipoprotein cholesterol compared with AT 20 mg. Optical coherence tomography revealed continuous increase in FCT from baseline to 6 months and to 12 months in both groups. AT 60 mg induced greater increase in FCT compared with AT 20 mg at both follow-up points. The prevalence of thin-cap fibroatheroma and the presence of macrophage at 6 months were significantly lower in AT 60 mg compared with AT 20 mg. Plaque burden did not change significantly in both groups. In conclusion, both intensive and moderate statin therapy stabilizes coronary plaques, with a greater benefit in the intensive statin group. However, no significant changes in plaque volume were observed over time regardless of the intensity of statin therapy. (C) 2016 Elsevier Inc. All rights reserved. C1 [Hou, Jingbo; Xing, Lei; Jia, Haibo; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. [Xing, Lei; Vergallo, Rocco; Soeda, Tsunerari; Minami, Yoshiyasu; Hu, Sining; Yang, Shuang; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Zhang, Shaosong] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lee, Hang] Harvard Univ, Sch Med, Boston, MA USA. [Jang, Ik-Kyung] Kyung Hee Univ, Sch Med, Div Cardiol, Seoul, South Korea. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. EM yubodr@163.com OI minami, yoshiyasu/0000-0003-2745-9682 FU National Natural Science Foundation, China [81330033]; St. Jude Medical FX Dr. Yu has received research grants from National Natural Science Foundation, China, grant 81330033. Dr. Ik-Kyung Jang has received grants and consulting fees from St. Jude Medical. And Dr. Ik-Kyung Jang's research was supported by "Mr. and Mrs. Michael and Kathryn Park" and by "Mrs. and Mr. Gill and Allan Gray." The other authors have no conflicts of interest to disclose. NR 30 TC 11 Z9 11 U1 2 U2 8 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2016 VL 117 IS 5 BP 800 EP 806 DI 10.1016/j.amjcard.2015.11.062 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG0JA UT WOS:000371749900016 PM 26778524 ER PT J AU Graff, RE Pettersson, A Lis, RT Ahearn, TU Markt, SC Wilson, KM Rider, JR Fiorentino, M Finn, S Kenfield, SA Loda, M Giovannucci, EL Rosner, B Mucci, LA AF Graff, Rebecca E. Pettersson, Andreas Lis, Rosina T. Ahearn, Thomas U. Markt, Sarah C. Wilson, Kathryn M. Rider, Jennifer R. Fiorentino, Michelangelo Finn, Stephen Kenfield, Stacey A. Loda, Massimo Giovannucci, Edward L. Rosner, Bernard Mucci, Lorelei A. TI Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ERG protein expression; TMPRSS2:ERG; lycopene; prostate cancer; tomato sauce ID DOUBLE-STRAND BREAKS; FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; OXIDATIVE STRESS; CHROMOSOMAL TRANSLOCATIONS; GENE REARRANGEMENTS; CAROTENOID DATABASE; FRUIT CONSUMPTION; EPITHELIAL-CELLS; COMPETING RISKS AB Background: There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion trans membrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG). Objective: We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. Design: Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases. Results: During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (>= 2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results. Conclusions: Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease. C1 [Graff, Rebecca E.; Pettersson, Andreas; Ahearn, Thomas U.; Markt, Sarah C.; Wilson, Kathryn M.; Rider, Jennifer R.; Fiorentino, Michelangelo; Kenfield, Stacey A.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Graff, Rebecca E.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Kenfield, Stacey A.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Pettersson, Andreas] Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden. [Lis, Rosina T.; Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wilson, Kathryn M.; Rider, Jennifer R.; Kenfield, Stacey A.; Giovannucci, Edward L.; Rosner, Bernard; Mucci, Lorelei A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div,Network Med, Boston, MA 02115 USA. [Lis, Rosina T.; Fiorentino, Michelangelo; Finn, Stephen; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Finn, Stephen] Univ Dublin Trinity Coll, Dept Histopathol, Dublin 2, Ireland. RP Graff, RE (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.; Graff, RE (reprint author), Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. EM rebecca.graff@ucsf.edu OI Finn, Stephen/0000-0002-8628-5814 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer [5P50CA090381]; National Cancer Institute at the NIH [R25 CA098566, R25 CA112355, T32 CA09001, R25 CA136578, CA141298, CA40360, CA097193, PO1 CA055075, UM1CA167552, U01CA098233]; American Cancer Society Ellison Foundation Postdoctoral Fellowship [PF-14-140-01-CCE]; Swedish Research Council [2009-7309]; Royal Physiographic Society in Lund FX Supported by the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer (5P50CA090381); the National Cancer Institute at the NIH (R25 CA098566 to REG and SCM, R25 CA112355 to REG, T32 CA09001 to TUA and SCM, R25 CA136578, CA141298, CA40360, CA097193, PO1 CA055075, UM1CA167552, U01CA098233); the American Cancer Society Ellison Foundation Postdoctoral Fellowship (PF-14-140-01-CCE to TUA); the Swedish Research Council (registration number 2009-7309 to AP); and the Royal Physiographic Society in Lund (to AP). LAM and JRR are Prostate Cancer Foundation Young Investigators. NR 84 TC 4 Z9 4 U1 7 U2 15 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2016 VL 103 IS 3 BP 851 EP 860 DI 10.3945/ajcn.115.118703 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DF8ZO UT WOS:000371650200022 PM 26817504 ER PT J AU Korom-Djakovic, D Canamucio, A Lempa, M Yano, EM Long, JA AF Korom-Djakovic, Danijela Canamucio, Anne Lempa, Michele Yano, Elizabeth M. Long, Judith A. TI Organization Complexity and Primary Care Providers' Perceptions of Quality Improvement Culture Within the Veterans Health Administration SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE quality improvement; culture; organizational complexity; primary care; Veterans Affairs ID MEDICAL GROUP PRACTICES; IMPLEMENTATION; DELIVERY; STAFF; HOME AB This study examined how aspects of quality improvement (QI) culture changed during the introduction of the Veterans Health Administration (VHA) patient-centered medical home initiative and how they were influenced by existing organizational factors, including VHA facility complexity and practice location. A voluntary survey, measuring primary care providers' (PCPs') perspectives on QI culture at their primary care clinics, was administered in 2010 and 2012. Participants were 320 PCPs from hospital- and community-based primary care practices in Pennsylvania, West Virginia, Delaware, New Jersey, New York, and Ohio. PCPs in community-based outpatient clinics reported an improvement in established processes for QI, and communication and cooperation from 2010 to 2012. However, their peers in hospital-based clinics did not report any significant improvements in QI culture. In both years, compared with high-complexity facilities, medium- and low-complexity facilities had better scores on the scales assessing established processes for QI, and communication and cooperation. C1 [Korom-Djakovic, Danijela; Canamucio, Anne; Lempa, Michele; Long, Judith A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Korom-Djakovic, Danijela; Long, Judith A.] Univ Penn, Philadelphia, PA 19104 USA. [Yano, Elizabeth M.] VA Greater Angeles Healthcare Syst, Sepulveda, CA USA. [Yano, Elizabeth M.] UCLA Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Long, JA (reprint author), Univ Penn, Perelman Sch Med, 1201 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu FU VA Office of Patient Care Services FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was undertaken as part of the Veterans Affairs (VA) Patient Aligned Care Team (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. NR 25 TC 2 Z9 2 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2016 VL 31 IS 2 BP 139 EP 146 DI 10.1177/1062860614559743 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DF8VL UT WOS:000371638300007 PM 25414376 ER PT J AU Chen, Q Shin, MH Chan, JA Sullivan, JL Borzecki, AM Shwartz, M Rivard, PE Hatoun, J Rosen, AK AF Chen, Qi Shin, Marlena H. Chan, Jeffrey A. Sullivan, Jennifer L. Borzecki, Ann M. Shwartz, Michael Rivard, Peter E. Hatoun, Jonathan Rosen, Amy K. TI Partnering With VA Stakeholders to Develop a Comprehensive Patient Safety Data Display: Lessons Learned From the Field SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE engage frontline stakeholders; patient safety; quality improvement; tool development ID DETECTING ADVERSE EVENTS; IMPLEMENTATION; INNOVATIONS AB Health care systems are increasingly burdened by the large numbers of safety measures currently being reported. Within the Veterans Administration (VA), most safety reporting occurs within organizational silos, with little involvement by the frontline users of these measures. To provide a more integrated picture of patient safety, the study team partnered with multiple VA stakeholders and engaged potential frontline users at 2 hospitals to develop a Guiding Patient Safety (GPS) tool. The GPS is currently in its fourth generation; once approval is obtained from senior leadership, implementation will begin. Stakeholders were enthusiastic about the GPS's user-friendly format, comprehensive content, and potential utility for improving safety. These findings suggest that stakeholder engagement is a critical first step in the development of tools that will more likely be used by frontline users. Policy makers and researchers may consider adopting this innovative partnered-research model in developing future national initiatives to deliver meaningful programs to frontline users. C1 [Chen, Qi; Shin, Marlena H.; Chan, Jeffrey A.; Sullivan, Jennifer L.; Shwartz, Michael; Rivard, Peter E.; Rosen, Amy K.] VA Boston Healthcare Syst, Boston, MA USA. [Borzecki, Ann M.] Bedford VAMC, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Shwartz, Michael] Boston Univ, Sch Management, Boston, MA 02215 USA. [Rivard, Peter E.] Suffolk Univ, Sawyer Business Sch, Boston, MA 02114 USA. [Hatoun, Jonathan] Boston Med Ctr, Boston, MA USA. RP Chen, Q (reprint author), CHOIR, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM qc2112@bu.edu FU Department of Veterans Affairs, Veterans Health Administration, National Center for Patient Safety, the Patient Safety Center of Inquiry on Measurement to Advance Patient Safety [XVA 68-023] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Department of Veterans Affairs, Veterans Health Administration, National Center for Patient Safety, the Patient Safety Center of Inquiry on Measurement to Advance Patient Safety, #XVA 68-023. NR 13 TC 0 Z9 0 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2016 VL 31 IS 2 BP 178 EP 186 DI 10.1177/1062860614560214 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DF8VL UT WOS:000371638300012 PM 25500716 ER PT J AU Castillo, ER Hsu, C Mair, RW Lieberman, DE AF Castillo, Eric R. Hsu, Connie Mair, Ross W. Lieberman, Daniel E. TI Testing biomechanical models for lumbar lordosis variation in hominins SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 85th Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 13-16, 2016 CL Atlanta, GA SP Amer Assoc Phys Anthropologists C1 [Castillo, Eric R.; Hsu, Connie; Lieberman, Daniel E.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA. [Mair, Ross W.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Mair, Ross W.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 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 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 2016 VL 159 SU 62 BP 111 EP 111 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA DF3OW UT WOS:000371255201011 ER PT J AU Green, DR Colman, AS Green, GM Bidlack, FB Tafforeau, P Smith, TM AF Green, Daniel R. Colman, Albert S. Green, Gregory M. Bidlack, Felicitas B. Tafforeau, Paul Smith, Tanya M. TI Experimental water switch in sheep improves models for seasonal climate reconstruction SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 85th Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 13-16, 2016 CL Atlanta, GA SP Amer Assoc Phys Anthropologists C1 [Green, Daniel R.; Smith, Tanya M.] Harvard Univ, Human Evolutionary Biol, Cambridge, MA 02138 USA. [Colman, Albert S.] Univ Chicago, Geophys Sci, Chicago, IL 60637 USA. [Green, Gregory M.] Harvard Univ, Ctr Astrophys, Cambridge, MA 02138 USA. [Bidlack, Felicitas B.] Forsyth Inst, Mineralized Tissue Biol, Cambridge, MA USA. [Tafforeau, Paul] European Synchrotron Radiat Facil, Paleontol, Grenoble, France. 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 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 2016 VL 159 SU 62 BP 160 EP 160 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA DF3OW UT WOS:000371255201208 ER PT J AU Tanner, NT Kanodra, NM Gebregziabher, M Payne, E Halbert, CH Warren, GW Egede, LE Silvestri, GA AF Tanner, Nichole T. Kanodra, Neeti M. Gebregziabher, Mulugeta Payne, Elizabeth Halbert, Chanita Hughes Warren, Graham W. Egede, Leonard E. Silvestri, Gerard A. TI The Association between Smoking Abstinence and Mortality in the National Lung Screening Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE smoking cessation; lung neoplasms; early detection of cancer; tobacco ID UNITED-STATES; COST-EFFECTIVENESS; CLINICAL-PRACTICE; CANCER-PATIENTS; PUBLIC-HEALTH; TOBACCO USE; CESSATION; PARTICIPANTS; GUIDELINE; DIAGNOSIS AB Rationale: Smoking is the largest contributor to lung cancer risk, and those who continue to smoke after diagnosis have a worse survival. Screening for lung cancer with low-dose computed tomography (LDCT) reduces mortality in high-risk individuals. Smoking cessation is an essential component of a high-quality screening program. Objectives: To quantify the effects of smoking history and abstinence on mortality in high-risk individuals who participated in the NLST (National Lung Screening Trial). Methods: This is a secondary analysis of a randomized controlled trial (NLST). Measurements and Main Results: Measurements included self-reported demographics, medical and smoking history, and lung cancer-specific and all-cause mortality. Cox regression was used to study the association of mortality with smoking status and pack-years. Kaplan-Meier survival curves were examined for differences in survival based on trial arm and smoking status. Current smokers had an increased lung cancer-specific (hazard ratio [HR], 2.14-2.29) and all-cause mortality (HR, 1.79-1.85) compared with former smokers irrespective of screening arm. Former smokers in the control arm abstinent for 7 years had a 20% mortality reduction comparable with the benefit reported with LDCT screening in the NLST. The maximum benefit was seen with the combination of smoking abstinence at 15 years and LDCT screening, which resulted in a 38% reduction in lung cancer-specific mortality (HR, 0.62; 95% confidence interval, 0.51-0.76). Conclusions: Seven years of smoking abstinence reduced lung cancer-specific mortality at a magnitude comparable with LDCT screening. This reduction was greater when abstinence was combined with screening, highlighting the importance of smoking cessation efforts-in screening programs. C1 [Tanner, Nichole T.; Kanodra, Neeti M.; Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm Crit Care & Sleep Med, Charleston, SC 29425 USA. [Tanner, Nichole T.; Gebregziabher, Mulugeta; Halbert, Chanita Hughes; Egede, Leonard E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Payne, Elizabeth] Med Univ S Carolina, Dept Psychiat & Behav Sci, Hollings Canc Ctr, 171 Ashley Ave, Charleston, SC 29425 USA. [Halbert, Chanita Hughes] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Warren, Graham W.] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA. [Warren, Graham W.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson Vet Affairs Hosp, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. RP Tanner, NT (reprint author), 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM tripici@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU OneBreath Foundation FX Supported by OneBreath Foundation. NR 33 TC 12 Z9 12 U1 2 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2016 VL 193 IS 5 BP 534 EP 541 DI 10.1164/rccm.201507-1420OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DG0KI UT WOS:000371753300014 PM 26502000 ER PT J AU Ramalingam, SS O'Byrne, K Boyer, M Mok, T Janne, PA Zhang, H Liang, J Taylor, I Sbar, EI Paz-Ares, L AF Ramalingam, S. S. O'Byrne, K. Boyer, M. Mok, T. Jaenne, P. A. Zhang, H. Liang, J. Taylor, I. Sbar, E. I. Paz-Ares, L. TI Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials SO ANNALS OF ONCOLOGY LA English DT Article DE dacomitinib; erlotinib; EGFR mutation; NSCLC; tyrosine kinase inhibitor ID CLINICAL-RESPONSE; OPEN-LABEL; MUTATIONS; INHIBITOR; GEFITINIB; ADENOCARCINOMA; PF-00299804; MULTICENTER; RESISTANT; AFATINIB AB The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067). C1 [Ramalingam, S. S.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, 1365 Clifton Rd NE,Suite C-3090, Atlanta, GA 30322 USA. [O'Byrne, K.] Princess Alexandra Hosp, Dept Oncol, Brisbane, Qld 4102, Australia. [Boyer, M.] Chris Brien Lifehouse, Dept Oncol, Sydney, NSW, Australia. [Mok, T.] Chinese Univ Hong Kong, Clin Oncol, Shatin, Hong Kong, Peoples R China. [Jaenne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, H.; Liang, J.; Taylor, I.; Sbar, E. I.] Pfizer Oncol, New York, NY USA. [Paz-Ares, L.] Doce Octubre Univ Hosp, Dept Oncol, Madrid, Spain. [Paz-Ares, L.] CNIO, Madrid, Spain. RP Ramalingam, SS (reprint author), Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, 1365 Clifton Rd NE,Suite C-3090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu FU Pfizer, Inc. FX This study was sponsored by Pfizer, Inc. No grant numbers apply. NR 16 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2016 VL 27 IS 3 BP 423 EP 429 DI 10.1093/annonc/mdv593 PG 7 WC Oncology SC Oncology GA DF9OU UT WOS:000371691600010 PM 26768165 ER PT J AU De Santis, M Wiechno, PJ Bellmunt, J Lucas, C Su, WC Albiges, L Lin, CC Senkus-Konefka, E Flechon, A Mourey, L Necchi, A Loidl, WC Retz, MM Vaissiere, N Culine, S AF De Santis, M. Wiechno, P. J. Bellmunt, J. Lucas, C. Su, W. -C. Albiges, L. Lin, C. -C. Senkus-Konefka, E. Flechon, A. Mourey, L. Necchi, A. Loidl, W. C. Retz, M. M. Vaissiere, N. Culine, S. TI Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1) SO ANNALS OF ONCOLOGY LA English DT Article DE vinflunine; urothelial carcinoma; bladder cancer; cisplatin-ineligible; renal impairment ID TRANSITIONAL-CELL CARCINOMA; CHEMONAIVE PATIENTS; IV VINFLUNINE; LUNG-CANCER; COMBINATION; PACLITAXEL; THERAPY; PLUS; GUIDELINES; DESIGN AB There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting. Patients with aUC a creatinine clearance (CrCl) of < 60 but a parts per thousand yen30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1). They received vinflunine 250 or 280 mg/m(2) (based on baseline CrCl) on day 1, plus either gemcitabine [750 mg/m(2) escalated to 1000 mg/m(2) in cycle 2 if no toxicity grade (G) a parts per thousand yen2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days]. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (alpha = 5%, beta = 20%). Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non-haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively. Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study. NCT 01599013. C1 [De Santis, M.] KFJ Spital, ACR VIEnna LB CTO ACR ITR VIEnna, Ludwig Boltzmann Inst, Vienna, Austria. [De Santis, M.] Univ Warwick, Canc Res Ctr, Gibbet Hill Campus,Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. [Wiechno, P. J.] Inst Sklodowskiej Curie, Inst Oncol, Warsaw, Poland. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Lucas, C.; Vaissiere, N.] Inst Rech Pierre Fabre, Boulogne, France. [Su, W. -C.] Natl Cheng Kung Univ Hosp, Dept Internal Med, Taipei, Taiwan. [Albiges, L.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Lin, C. -C.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Senkus-Konefka, E.] Med Univ Gdansk, Dept Oncol & Radiotherapy, Gdansk, Poland. [Flechon, A.] Ctr Leon Berard, Dept Med, F-69373 Lyon, France. [Mourey, L.] Inst Claudius Regaud, Dept Oncol, Toulouse, France. [Necchi, A.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy. [Loidl, W. C.] KH Barmherzige Schwestern Linz, Dept Urol, Linz, Austria. [Retz, M. M.] Univ Hosp Rechts Isar, Dept Urol, Munich, Germany. [Culine, S.] Paris Diderot Univ, Hop St Louis, AP HP, Dept Med Oncol, Paris, France. RP De Santis, M (reprint author), Univ Warwick, Canc Res Ctr, Gibbet Hill Campus,Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. EM maria@desantis.cc OI Necchi, Andrea/0000-0002-3007-2756 FU Pierre Fabre Research Institute, France FX This study was supported by Pierre Fabre Research Institute, France. No grant number is applicable. NR 23 TC 7 Z9 7 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2016 VL 27 IS 3 BP 449 EP 454 DI 10.1093/annonc/mdv609 PG 6 WC Oncology SC Oncology GA DF9OU UT WOS:000371691600014 PM 26673352 ER PT J AU Chi, KN Kheoh, T Ryan, CJ Molina, A Bellmunt, J Vogelzang, NJ Rathkopf, DE Fizazi, K Kantoff, PW Li, J Azad, AA Eigl, BJ Heng, DYC Joshua, AM de Bono, JS Scher, HI AF Chi, K. N. Kheoh, T. Ryan, C. J. Molina, A. Bellmunt, J. Vogelzang, N. J. Rathkopf, D. E. Fizazi, K. Kantoff, P. W. Li, J. Azad, A. A. Eigl, B. J. Heng, D. Y. C. Joshua, A. M. de Bono, J. S. Scher, H. I. TI A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel SO ANNALS OF ONCOLOGY LA English DT Article DE castration-resistant prostate cancer; abiraterone acetate; prognostic; risk; survival ID PLACEBO-CONTROLLED PHASE-3; 1ST-LINE CHEMOTHERAPY; PLUS PREDNISONE; DOUBLE-BLIND; MEN; ENZALUTAMIDE; MITOXANTRONE; MANAGEMENT; CARCINOMA; LYMPHOMA AB Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. Baseline data were available from 762 patients treated with abiraterone-prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin a parts per thousand currency sign4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment a parts per thousand currency sign36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 +/- 0.014. The model was validated by the external dataset (n = 286). This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. NCT00638690. C1 [Chi, K. N.; Azad, A. A.; Eigl, B. J.] BC Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Kheoh, T.] Janssen Res & Dev, San Diego, CA USA. [Ryan, C. J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Molina, A.] Janssen Res & Dev, Menlo Pk, CA USA. [Bellmunt, J.; Kantoff, P. W.] Dana Farber Canc Inst, Dept Solid Tumor Oncol, Boston, MA 02115 USA. [Bellmunt, J.; Kantoff, P. W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Vogelzang, N. J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Rathkopf, D. E.] Mem Sloan Kettering Canc Ctr, Dept Oncol & Internal Med, 1275 York Ave, New York, NY 10021 USA. [Rathkopf, D. E.; Scher, H. I.] Weill Cornell Med Coll, New York, NY USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Grp Urogenitol, Villejuif, France. [Li, J.] Johnson & Johnson Med China, Shanghai, Peoples R China. [Heng, D. Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. [Heng, D. Y. C.] Univ Calgary, Calgary, AB, Canada. [Joshua, A. M.] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [Joshua, A. M.] Univ Toronto, Toronto, ON, Canada. [de Bono, J. S.] Inst Canc Res, Div Canc Therapeut Clin Studies, Drug Dev Unit, Sutton, Surrey, England. [de Bono, J. S.] Royal Marsden Hosp, Sutton, Surrey, England. [Scher, H. I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10021 USA. RP Chi, KN (reprint author), BC Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. EM kchi@bccancer.bc.ca FU Janssen Research Development FX This work was supported by Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology (now Janssen Research & Development). No grant number is applicable. NR 34 TC 6 Z9 7 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2016 VL 27 IS 3 BP 454 EP 460 DI 10.1093/annonc/mdv594 PG 7 WC Oncology SC Oncology GA DF9OU UT WOS:000371691600015 PM 26685010 ER PT J AU Clark, DJ Neptune, RR Behrman, AL Kautz, SA AF Clark, David J. Neptune, Richard R. Behrman, Andrea L. Kautz, Steven A. TI Locomotor Adaptability Task Promotes Intense and Task-Appropriate Output From the Paretic Leg During Walking SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Electromyography; Rehabilitation; Stroke; Walking ID COORDINATION; HEMIPARESIS; PERFORMANCE; POSTSTROKE; LENGTH; STROKE AB Objective: To test the hypothesis that participants with stroke will exhibit appropriate increase in muscle activation of the paretic leg when taking a long step with the nonparetic leg compared to during steady-state walking, with a consequent increase in biomechanical output and symmetry during the stance phase of the modified gait cycle. Design: Single-session observational study. Setting: Clinical research center in an outpatient hospital setting. Participants: Adults with chronic poststroke hemiparesis (N=15). Interventions: Participants walked on an instrumented treadmill while kinetic, kinematic, and electromyogram data were recorded. Participants performed steady-state walking and a separate trial of the long-step adaptability task in which they were instructed to intermittently take a longer step with the nonparetic leg. Main Outcome Measures: Forward progression, propulsive force, and neuromuscular activation during walking. Results: Participants performed the adaptability task successfully and demonstrated greater neuromuscular activation in appropriate paretic leg muscles, particularly increased activity in paretic plantarflexor muscles. Propulsion and forward progression by the paretic leg were also increased. Conclusions: These findings support the assertion that the nonparetic long-step task may be effective for use in poststroke locomotor rehabilitation to engage the paretic leg and promote recovery of walking. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Clark, David J.] Malcom Randall Vet Affairs Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL 32608 USA. [Clark, David J.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Behrman, Andrea L.] Univ Louisville, Dept Neurol Surg, Louisville, KY 40292 USA. [Kautz, Steven A.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. RP Clark, DJ (reprint author), Malcom Randall Vet Affairs Med Ctr, Brain Rehabil Res Ctr 151A, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM davidclark@ufl.edu FU National Institutes of Health [HD-46820, GM-109040]; U.S. Department of Veterans Affairs Rehabilitation Research and Development Service [B3983R, B4888M, B7176W] FX Supported by the National Institutes of Health (grant nos. HD-46820 and GM-109040) and the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service (Merit Review B3983R and Career Development Awards B4888M and B7176W). The contents do not represent the views of the U.S Department of Veterans Affairs or the U.S. government. NR 10 TC 2 Z9 2 U1 5 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2016 VL 97 IS 3 BP 493 EP 496 DI 10.1016/j.apmr.2015.10.081 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DG1TJ UT WOS:000371850100018 PM 26525528 ER PT J AU Vopat, BG Lee, BJ DeStefano, S Waryasz, GR Kane, PM Gallacher, SE Fava, J Green, AG AF Vopat, Bryan G. Lee, Bea J. DeStefano, Sherilyn Waryasz, Gregory R. Kane, Patrick M. Gallacher, Stacey E. Fava, Joseph Green, Andrew G. TI Risk Factors for Infection After Rotator Cuff Repair SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID 2-YEAR FOLLOW-UP; MINI-OPEN; PROPIONIBACTERIUM-ACNES; DEEP INFECTION; CLINICAL-OUTCOMES; SHOULDER SURGERY; TEARS; MANAGEMENT; TRIAL AB Purpose: To identify risk factors for infection after rotator cuff repair. We hypothesized that patient characteristics and surgical technique would affect the rate of infection. Methods: The records of 1,824 rotator cuff repairs performed by a single surgeon from 1995 to 2010 were reviewed retrospectively. Fourteen patients had an early deep postoperative wound infection that was treated with surgical irrigation and debridement. One hundred eighty-five control patients who were treated with rotator cuff repair and did not develop an infection were selected randomly for comparison and statistical analysis. Data regarding preoperative and intraoperative risk factors for infection were recorded, and a multiple logistic regression was conducted to investigate predictors of infection. Results: The infection rate was 0.77% (14/1,822). On average 2.1 (range 1 to 4) surgical debridements were performed in addition to treatment with intravenous antibiotics. Patients who had open or miniopen rotator cuff repair had a significantly greater risk of acute postoperative infection (odds ratio [OR] = 8.63, P = .002). Seventy-nine percent of the patients in the infection group had an open or miniopen repair, whereas only 28% of the control group had an open or miniopen repair. Male patients also had a significantly greater risk of acute postoperative infection (OR = 9.52, P = .042). A total of 92% of the infection patients were male compared with 58% of the control group. In addition, as body mass index increased there was a reduction in the odds of infection (OR = 0.81, P = .023). Conclusions: The results of this case control study demonstrate that open or miniopen surgical technique and male sex are significant risk factors for infection after rotator cuff repair. In our study, arthroscopic rotator cuff repair reduced the risk of infection compared with open techniques. C1 [Vopat, Bryan G.] Massachusetts Gen Hosp Harvard, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. [Waryasz, Gregory R.; Kane, Patrick M.; Fava, Joseph; Green, Andrew G.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA. [Lee, Bea J.] Irving Orthoped & Sports Med, Irving, TX USA. [DeStefano, Sherilyn] Univ Vermont, Sch Med, Burlington, VT 05405 USA. [Kane, Patrick M.] Philadelphia Hand Ctr South Jersey, Cherry Hill, NJ USA. [Gallacher, Stacey E.] St Lukes Univ Hlth Network, Bethlehem, PA USA. RP Vopat, BG (reprint author), Massachusetts Gen Hosp Harvard, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. EM bvopat@gmail.com FU Tornier; Orthopaedics; IlluminOss Medical; Pfizer FX The authors report the following potential conflict of interest or source of funding: A.G.G. receives support from Tornier, Orthopaedics, IlluminOss Medical, and Pfizer. NR 40 TC 1 Z9 1 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD MAR PY 2016 VL 32 IS 3 BP 428 EP 434 DI 10.1016/j.arthro.2015.08.021 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DG1MY UT WOS:000371833400008 PM 26483170 ER PT J AU Trahanas, JM Kolobow, MA Hardy, MA Berra, L Zapol, WM Bartlett, RH AF Trahanas, John M. Kolobow, Mary Anne Hardy, Mark A. Berra, Lorenzo Zapol, Warren M. Bartlett, Robert H. TI "Treating Lungs": The Scientific Contributions of Dr. Theodor Kolobow SO ASAIO JOURNAL LA English DT Article DE Kolobow; ECMO; Barotrauma; Extracorporeal life support; ECLS; ECC02R ID EXTRACORPOREAL MEMBRANE-OXYGENATION; POSITIVE-PRESSURE VENTILATION; RESPIRATORY-DISTRESS SYNDROME; ARTIFICIAL LUNG; CO2 REMOVAL; SUPPORT; FAILURE AB We are fortunate to live in an age in which biomedical technology has provided us with unprecedented ability to supplant the functions of organs and support the physiologic processes of the human body. Ingenious doctors, physiologists, and engineers helped create these advances with new and innovative ideas. One of these pioneers was Dr. Theodor Kolobow. He is best known for one of his earliest inventions, the spiral coil membrane lung. His contributions to medical innovation, however, are diverse, as he also contributed to advances in hemodialysis, improvements in extracorporeal life support technology/circuit components, and through his laboratory experiments helped shape our current understanding of cardiopulmonary pathophysiology. In retrospect, much of Kolobow's work was unified by the theme of preventing iatrogenic lung injury caused by mechanical ventilation. This tenet became more obvious as his later studies progressed to developing techniques and devices intended to limit ventilator pressures, and prevent bacterial colonization of the lungs. Although he formally retired from his research endeavors in 2009, the impact of his contributions remains prominent in our everyday use of techniques and equipment that he either originated or helped to develop. C1 [Trahanas, John M.; Bartlett, Robert H.] Univ Michigan, Dept Surg, Extracorporeal Life Support Lab, 1150 W Med Ctr Dr,B560 MSRBII SPC 5686, Ann Arbor, MI 48109 USA. [Trahanas, John M.; Hardy, Mark A.] Columbia Univ, Med Ctr, Dept Surg, New York, NY USA. [Berra, Lorenzo; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Trahanas, JM (reprint author), Univ Michigan, Dept Surg, Extracorporeal Life Support Lab, 1150 W Med Ctr Dr,B560 MSRBII SPC 5686, Ann Arbor, MI 48109 USA. EM jtrahana@med.umich.edu FU NIH [T32HL007854-20, 2R01 HD015434-29] FX This study was in part supported by NIH Grant T32HL007854-20 (MAH); and NIH Grant 2R01 HD015434-29 (RHB). NR 28 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1058-2916 EI 1538-943X J9 ASAIO J JI Asaio J. PD MAR-APR PY 2016 VL 62 IS 2 BP 203 EP 210 DI 10.1097/MAT.0000000000000323 PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA DG0IA UT WOS:000371747300016 PM 26720733 ER PT J AU Thorgeirsson, T Jordahl, KM Flavin, R Epstein, MM Fiorentino, M Andersson, SO Andren, O Rider, JR Mosquera, JM Ingoldsby, H Fall, K Tryggvadottir, L Mucci, LA AF Thorgeirsson, Tryggvi Jordahl, Kristina M. Flavin, Richard Epstein, Mara Meyer Fiorentino, Michelangelo Andersson, Swen-Olof Andren, Ove Rider, Jennifer R. Mosquera, Juan Miguel Ingoldsby, Helen Fall, Katja Tryggvadottir, Laufey Mucci, Lorelei A. CA Transdisciplinary Prostate Canc Pa TI Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort SO CARCINOGENESIS LA English DT Article ID MUTATION CARRIERS; LOCALIZATION AB We found association between prognosis of prostate cancer patients and positive staining for the BRCA2 protein in diagnostic cancer tissue. Positive staining at the cell membrane was associated with improved survival whereas staining in the cytoplasm predicted adverse outcome.Prostate cancer patients with inherited BRCA2 mutations have a survival disadvantage. However, it is unknown whether progression is associated with BRCA2 protein expression in diagnostic prostate cancer tissue, among men without inherited mutations. We conducted a nested case-control study within the Swedish Watchful Waiting cohort. The case group included all 71 patients who died from prostate cancer within 5 years from diagnosis and controls were all patients (n = 165) who lived at least 7 years after diagnosis. Tissue microarrays were stained using antibodies for C- and N-terminal domains of the BRCA2 protein. Location (nuclear, cytoplasmic and membranous) and magnitude (intensity and percentage) of expression were assessed. Logistic regression models produced odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, year of diagnosis and Gleason score. Positive BRCA2 staining at the cell membrane was associated with reduced risk of death within 5 years (N-terminal: OR = 0.47, 95% CI = 0.21-1.04, P = 0.06; C-terminal: OR = 0.41, 95% CI = 0.18-0.91, P = 0.03) and low Gleason scores (P = 0.006). Positive cytoplasmic C-terminal staining was associated with higher Gleason scores and increased lethality (OR = 3.61, 95% CI = 1.61-8.07, P = 0.002). BRCA2 protein expression at the cell membrane and lack of C-terminal expression in the cytoplasm were associated with a reduced risk of rapidly fatal prostate cancer. BRCA2 protein expression in prostate cancer tissue may have independent prognostic value. The potential biological significance of BRCA2 expression at the cell membrane warrants further investigation. C1 [Thorgeirsson, Tryggvi; Jordahl, Kristina M.; Fiorentino, Michelangelo; Rider, Jennifer R.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Thorgeirsson, Tryggvi; Mucci, Lorelei A.] Univ Iceland, Publ Hlth Sci, IS-101 Reykjavik, Iceland. [Flavin, Richard] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Flavin, Richard] St James Hosp, Dept Histopathol, Dublin 8, Ireland. [Flavin, Richard] Trinity Coll Dublin, Dublin, Ireland. [Epstein, Mara Meyer] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Epstein, Mara Meyer] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA 01605 USA. [Fiorentino, Michelangelo] Univ Bologna, S Orsola Malpighi Hosp, F Addarii Inst Oncol & Transplantat Pathol, I-40126 Bologna, Italy. [Andersson, Swen-Olof; Andren, Ove] Univ Orebro, Fac Med & Hlth, Dept Urol, SE-70182 Orebro, Sweden. [Mosquera, Juan Miguel] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Mosquera, Juan Miguel] Weill Cornell Med Coll, Inst Precis Med, New York, NY 10065 USA. [Mosquera, Juan Miguel] New York Presbyterian, New York, NY 10065 USA. [Ingoldsby, Helen] Nat Univ Ireland, Shantalla Rd, Galway, Ireland. [Fall, Katja] Univ Orebro, Fac Med & Hlth, Clin Epidemiol & Biostat, SE-70182 Orebro, Sweden. [Tryggvadottir, Laufey] Iceland Canc Registry, IS-105 Reykjavik, Iceland. [Tryggvadottir, Laufey] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. RP Tryggvadottir, L (reprint author), Iceland Canc Registry, IS-105 Reykjavik, Iceland.; Tryggvadottir, L (reprint author), Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. EM laufeyt@krabb.is OI Fall, Katja/0000-0002-3649-2639 FU Icelandic Prostate Cancer Group Framfor; Icelandic Cancer Society; Swedish Cancer Society, CAN; Dana Farber/Harvard Cancer Center SPORE in Prostate Cancer [P50 CA090381] FX Icelandic Prostate Cancer Group Framfor, the Dana Farber/Harvard Cancer Center SPORE in Prostate Cancer (P50 CA090381 to L.M.); Icelandic Cancer Society and the Swedish Cancer Society, CAN 2006. NR 21 TC 0 Z9 0 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2016 VL 37 IS 3 BP 262 EP 268 DI 10.1093/carcin/bgw001 PG 7 WC Oncology SC Oncology GA DF9QP UT WOS:000371696400004 PM 26775038 ER PT J AU Kang, XZ Liu, HL Onaitis, MW Liu, ZS Owzar, K Han, YH Su, L Wei, YY Hung, RJ Brhane, Y McLaughlin, J Brennan, P Bickeboller, H Rosenberger, A Houlston, RS Caporaso, N Landi, MT Heinrich, J Risch, A Wu, XF Ye, YQ Christiani, DC Amos, CI Wei, QY AF Kang, Xiaozheng Liu, Hongliang Onaitis, Mark W. Liu, Zhensheng Owzar, Kouros Han, Younghun Su, Li Wei, Yongyue Hung, Rayjean J. Brhane, Yonathan McLaughlin, John Brennan, Paul Bickeboeller, Heike Rosenberger, Albert Houlston, Richard S. Caporaso, Neil Landi, Maria Teresa Heinrich, Joachim Risch, Angela Wu, Xifeng Ye, Yuanqing Christiani, David C. Amos, Christopher I. Wei, Qingyi CA Transdisciplinary Res Canc Lung TI Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14 463 cases and 44 188 controls SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; DISEASE; AMPLIFICATION; ABNORMALITIES; VITILIGO; VARIANTS; CELLS; VISUALIZATION; INSTABILITY AB After combining the summary results of SNPs in 106 centrosomal genes from eight published lung cancer GWASs, we found that two potential functional SNPs (rs151606 and rs12212247) in FGFR1OP were significantly associated with lung cancer risk.Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12 160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26 380 controls). A total of 44 significant SNPs with false discovery rate (FDR) a parts per thousand currency sign 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P (combined) = 8.032x10(-6)) was with rs151606 within FGFR1OP. The rs151606 T > G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T > C (P (combined) = 9.589x10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P (trend) = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis. C1 [Kang, Xiaozheng; Liu, Hongliang; Onaitis, Mark W.; Liu, Zhensheng; Owzar, Kouros; Wei, Qingyi] Duke Univ, Med Ctr, Duke Canc Inst, 905 S LaSalle St, Durham, NC 27710 USA. [Kang, Xiaozheng; Onaitis, Mark W.] Duke Univ, Med Ctr, Div Cardiovasc & Thorac Surg, Dept Surg, 905 S LaSalle St, Durham, NC 27710 USA. [Kang, Xiaozheng] Peking Univ, Canc Hosp & Inst, Minist Educ,Dept Thorac Surg 1, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China. [Liu, Hongliang; Liu, Zhensheng; Wei, Qingyi] Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA. [Owzar, Kouros] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Han, Younghun; Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Community & Family Med, Hanover, NH 03755 USA. [Su, Li; Wei, Yongyue; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Su, Li; Wei, Yongyue; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Hung, Rayjean J.; Brhane, Yonathan] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [McLaughlin, John] Publ Hlth Ontario, Toronto, ON M5T 3L9, Canada. [Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon, France. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, D-37073 Gottingen, Germany. [Houlston, Richard S.] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Heinrich, Joachim] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol 1, D-85764 Neuherberg, Germany. [Risch, Angela] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria. [Wu, Xifeng; Ye, Yuanqing] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Wei, QY (reprint author), Duke Univ, Med Ctr, Duke Canc Inst, 905 S LaSalle St, Durham, NC 27710 USA.; Wei, QY (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA. EM qingyi.wei@duke.edu RI Hung, Rayjean/A-7439-2013; Risch, Angela/H-2669-2013; OI Risch, Angela/0000-0002-8026-5505; Houlston, Richard/0000-0002-5268-0242 FU Duke Cancer Institute as part of the P30 Cancer Center Support Grant [NIH CA014236]; Duke Cancer Institute, Duke University Medical Center FX As Duke Cancer Institute members, Q.W., M.W.O., and K.O. acknowledge support from the Duke Cancer Institute as part of the P30 Cancer Center Support Grant (NIH CA014236). Q.W. was also supported by a start-up fund from Duke Cancer Institute, Duke University Medical Center. NR 61 TC 1 Z9 1 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2016 VL 37 IS 3 BP 280 EP 289 DI 10.1093/carcin/bgw014 PG 10 WC Oncology SC Oncology GA DF9QP UT WOS:000371696400006 PM 26905588 ER PT J AU Ma, JF Yang, F Mahida, SN Zhao, L Chen, XM Zhang, ML Sun, ZJ Yao, Y Zhang, YX Zheng, GY Dong, J Feng, MJ Zhang, R Sun, J Li, S Wang, QS Cao, HQ Benjamin, EJ Ellinor, PT Li, YG Tian, XL AF Ma, Ji-Fang Yang, Fan Mahida, Saagar N. Zhao, Ling Chen, Xiaomin Zhang, Micheal L. Sun, Zhijun Yao, Yan Zhang, Yi-Xin Zheng, Gu-Yan Dong, Jie Feng, Ming-Jun Zhang, Rui Sun, Jian Li, Shuo Wang, Qun-Shan Cao, Huiqing Benjamin, Emelia J. Ellinor, Patrick T. Li, Yi-Gang Tian, Xiao-Li TI TBX5 mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians SO CARDIOVASCULAR RESEARCH LA English DT Article DE Atrial fibrillation; TBX5; ANP; Connexin; Mutation ID HOLT-ORAM-SYNDROME; CARDIAC CONDUCTION SYSTEM; TRANSCRIPTION FACTOR TBX5; NATRIURETIC-PEPTIDE; COMMON VARIANTS; RISK-FACTORS; PR INTERVAL; CONNEXIN40; GENE; POLYMORPHISMS AB Atrial fibrillation (AF) is a common arrhythmia with an important heritable aspect. The genetic factors underlying AF have not been fully elucidated. We screened six candidate genes (CAV1, KCNJ2, KCNQ1, NKX2.5, PITX2, and TBX5) for novel mutations in 139 patients of Chinese descent with early-onset AF and 576 controls. Four missense TBX5 mutations, p.R355C, p.Q376R, p.A428S, and p.S372L, were identified in evolutionarily conserved regions. We did not find any mutations in CAV1, KCNJ2, KCNQ1, NKX2.5, and PITX2. These mutations increased the expression of atrial natriuretic peptide (ANP) and connexin-40 (CX40) in the primarily cultured rat atrial myocytes but did not alter the expression of cardiac structural genes, atrial myosin heavy chain-alpha (MHC-alpha) and myosin light chain-2 alpha (MLC-2 alpha). Overexpression of p.R355C developed an atrial arrhythmia suggestive of paroxysmal AF in the zebrafish model. To replicate our findings, we screened TBX5 in 527 early-onset AF cases from the Massachusetts General Hospital AF study. A novel TBX5 deletion (Delta Asp118, p.D118del) was identified, while no TBX5 mutations were identified in 1176 control subjects. Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40. C1 [Ma, Ji-Fang; Zhang, Rui; Sun, Jian; Li, Shuo; Wang, Qun-Shan; Li, Yi-Gang] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Cardiol, Shanghai 200092, Peoples R China. [Yang, Fan; Zhao, Ling; Zhang, Yi-Xin; Zheng, Gu-Yan; Dong, Jie; Cao, Huiqing; Tian, Xiao-Li] Peking Univ, Dept Human Populat Genet, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. [Yang, Fan; Zhao, Ling; Zhang, Yi-Xin; Zheng, Gu-Yan; Dong, Jie; Cao, Huiqing; Tian, Xiao-Li] Peking Univ, Beijing Key Lab Cardiometabol Mol Med, IMM, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. [Mahida, Saagar N.; Zhang, Micheal L.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Chen, Xiaomin; Feng, Ming-Jun] Ningbo Univ, Ningbo Hosp 1, Key Lab, 59 Liuting St, Ningbo 315010, Peoples R China. [Chen, Xiaomin; Feng, Ming-Jun] Ningbo Univ, Ningbo Hosp 1, Ctr Cardiovasc, 59 Liuting St, Ningbo 315010, Peoples R China. [Sun, Zhijun] Peoples Liberat Army Gen Hosp, Cardiovasc Dept, 28 Fuxing Rd, Beijing 100853, Peoples R China. [Yao, Yan] Capital Med Univ, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Li, YG (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Cardiol, Shanghai 200092, Peoples R China.; Tian, XL (reprint author), Peking Univ, Dept Human Populat Genet, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.; Tian, XL (reprint author), Peking Univ, Beijing Key Lab Cardiometabol Mol Med, IMM, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. EM drliyigang@outlook.com; tianxiaoli@pku.edu.cn FU National Basic Research Program of China (973 program) [2013CB530700, 2007CB512100]; National Science Foundation of China [31221002, 81070154, 81270258]; Shanghai Excellent Academic Leaders Project [10xd1402800]; National Institutes of Health [1RO1HL104156, 1K24HL105780, 1RO1HL092577]; American Heart Association [13EIA14220013] FX This study was supported by grants from the National Basic Research Program of China (973 program) (2013CB530700 and 2007CB512100 to X.L.T.), the National Science Foundation of China (31221002 to X.L.T., no. 81070154 and No. 81270258 to Y.G.L.), the Shanghai Excellent Academic Leaders Project (grant number 10xd1402800 to Y.G.L.), the National Institutes of Health to P.T.E. (1RO1HL104156 and 1K24HL105780 to P.T.E., 1RO1HL092577 to P.T.E. and E.J.B.), and the American Heart Association (13EIA14220013 to P.T.E.). NR 50 TC 4 Z9 4 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR 1 PY 2016 VL 109 IS 3 BP 442 EP 450 DI 10.1093/cvr/cvw003 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DF7ER UT WOS:000371521100013 PM 26762269 ER PT J AU Fjell, AM Sneve, MH Storsve, AB Grydeland, H Yendiki, A Walhovd, KB AF Fjell, Anders M. Sneve, Markus H. Storsve, Andreas B. Grydeland, Hakon Yendiki, Anastasia Walhovd, Kristine B. TI Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity SO CEREBRAL CORTEX LA English DT Article DE aging; longitudinal; memory; resting-state functional connectivity; structural connectivity ID RESTING-STATE FMRI; HUMAN CEREBRAL-CORTEX; DEFAULT-MODE NETWORK; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; ALZHEIMERS-DISEASE; BASAL GANGLIA; HEALTHY-ADULTS; WHITE-MATTER; HYPOTHETICAL MODEL AB Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. C1 [Fjell, Anders M.; Sneve, Markus H.; Storsve, Andreas B.; Grydeland, Hakon; Walhovd, Kristine B.] Univ Oslo, Dept Psychol, Res Grp Lifespan Changes Brain & Cognit, N-0373 Oslo, Norway. [Fjell, Anders M.; Walhovd, Kristine B.] Oslo Univ Hosp, Unit Neuropsychol, Dept Phys Med & Rehabil, N-0424 Oslo, Norway. [Yendiki, Anastasia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA USA. RP Fjell, AM (reprint author), Dept Psychol, Pb 1094 Blindern, N-0317 Oslo, Norway. EM andersmf@psykologi.uio.no OI Storsve, Andreas B/0000-0001-6807-8638 FU Department of Psychology, University of Oslo; Norwegian Research Council; European Research Council's Starting Grant scheme (ERC) [313440, 283634]; US-Norway Fulbright Foundation; National Institute for Biomedical Imaging and Bioengineering [R00-EB008129, R01-EB006758]; National Institutes of Health Blueprint for Neuroscience Research [5U01-MH093765]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health; NIH [S10RR023401, S10RR019307, S10RR019254, S10RR023043] FX This work was supported by the Department of Psychology, University of Oslo (A.B.S., K.B.W. and A.M.F.), the Norwegian Research Council (to K.B.W. and A.M.F.), the European Research Council's Starting Grant scheme (ERC grant agreement 313440 to K.B.W. and 283634 to A.M.F.), the US-Norway Fulbright Foundation (to A.B.S.), the National Institute for Biomedical Imaging and Bioengineering (R00-EB008129, R01-EB006758) (to A.Y.), and the National Institutes of Health Blueprint for Neuroscience Research (5U01-MH093765) (to A.Y.), part of the multi-institutional Human Connectome Project. Additional resources were provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (to A.Y.). This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grants S10RR023401, S10RR019307, S10RR019254, S10RR023043. NR 94 TC 8 Z9 8 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2016 VL 26 IS 3 BP 1272 EP 1286 DI 10.1093/cercor/bhv102 PG 15 WC Neurosciences SC Neurosciences & Neurology GA DF7FP UT WOS:000371523600033 PM 25994960 ER PT J AU Kheirkhah, A Saboo, US Marmalidou, A Dana, R AF Kheirkhah, Ahmad Saboo, Ujwala S. Marmalidou, Anna Dana, Reza TI Overestimation of Corneal Endothelial Cell Density in Smaller Frame Sizes in In Vivo Confocal Microscopy SO CORNEA LA English DT Article DE in vivo confocal microscopy; cornea; endothelial cells ID NONCONTACT SPECULAR MICROSCOPE; IMAGES; TRANSPLANTATION; RELIABILITY; DYSTROPHY; NERVES AB Purpose: To evaluate the effect of frame size on the calculated corneal endothelial cell density (CECD) in images of laser scanning in vivo confocal microscopy (IVCM). Methods: Forty-nine corneal endothelial images acquired by laser scanning IVCM (Heidelberg Retina Tomograph 3 with Rostock Corneal Module) with different endothelial cell densities were analyzed. In each image (160,000 mu m(2)), the CECD was calculated using the fixed-frame method by counting cells in the following frame sizes: 80,000 mu m(2), 40,000 mu m(2), 20,000 mu m(2), 10,000 mu m(2), 5000 mu m(2), and 2500 mu m(2). The calculated CECD was then compared with that of the variable-frame method as the reference value. Results: There was no significant difference in the calculated CECD between the variable-frame method (2004 +/- 832 cells/mm(2)), and the fixed-frame method using a 40,000-mu m(2) frame (2023 +/- 810 cells/mm(2)). On the other hand, the calculated CECD showed significant overestimations in frame sizes of 20,000 mu m(2) (2066 +/- 820 cells/mm(2)), 10,000 mu m(2) (2156 +/- 785 cells/mm(2)), 5000 mu m(2) (2352 +/- 783 cells/mm(2)), and 2500 mu m(2) (2715 +/- 754 cells/mm(2)), with P < 0.001 in all. This resulted in overestimations of 4.8 +/- 9.8%, 11.9 +/- 16.2%, 24.9 +/- 23.1%, and 49.1 +/- 38.8% for these frame sizes, respectively. Images with lower CECD demonstrated higher overestimations of cell density in smaller frame sizes. Conclusions: In laser scanning IVCM images, there is significant overestimation of CECD if the cells are counted in frames smaller than 25% of the image. Similar frame sizes should be used when monitoring CECD over time. C1 [Kheirkhah, Ahmad; Saboo, Ujwala S.; Marmalidou, Anna; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu NR 30 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD MAR PY 2016 VL 35 IS 3 BP 363 EP 369 DI 10.1097/ICO.0000000000000698 PG 7 WC Ophthalmology SC Ophthalmology GA DF5IY UT WOS:000371386400014 PM 26606299 ER PT J AU Smith, HAB Gangopadhyay, M Goben, CM Jacobowski, NL Chestnut, MH Savage, S Rutherford, MT Denton, D Thompson, JL Chandrasekhar, R Acton, M Newman, J Noori, HP Terrell, MK Williams, SR Griffith, K Cooper, TJ Ely, EW Fuchs, DC Pandharipande, PP AF Smith, Heidi A. B. Gangopadhyay, Maalobeeka Goben, Christina M. Jacobowski, Natalie L. Chestnut, Mary Hamilton Savage, Shane Rutherford, Michael T. Denton, Danica Thompson, Jennifer L. Chandrasekhar, Rameela Acton, Michelle Newman, Jessica Noori, Hannah P. Terrell, Michelle K. Williams, Stacey R. Griffith, Katherine Cooper, Timothy J. Ely, E. Wesley Fuchs, D. Catherine Pandharipande, Pratik P. TI The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children* SO CRITICAL CARE MEDICINE LA English DT Article DE encephalopathy; agitation; sedation; pediatric; critical care ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; PEDIATRIC DELIRIUM; CRITICAL ILLNESS; COGNITIVE IMPAIRMENT; CAM-ICU; SEDATION; SCALE; TOOL; RELIABILITY AB Objectives: Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children and to determine delirium prevalence. Design and Setting: Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU in a tertiary medical center PICU. Patients: Participants aged 6 months to 5 years and admitted to the PICU regardless of admission diagnosis were enrolled. Measurements and Main Results: An interdisciplinary team created the PreSchool Confusion Assessment Method for the ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the PreSchool Confusion Assessment Method for the ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent PreSchool Confusion Assessment Method for the ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (interquartile range, 11-37) and 43% requiring mechanical ventilation. The PreSchool Confusion Assessment Method for the ICU demonstrated a specificity of 91% (95% CI, 90-93), sensitivity of 75% (95% CI, 72-78), negative predictive value of 86% (95% CI, 84-88), positive predictive value of 84% (95% CI, 81-87), and a reliability kappa-statistic of 0.79 (0.76-0.83). Delirium prevalence was 44% using the PreSchool Confusion Assessment Method for the ICU and 47% by the reference rater. The rates of delirium were 53% versus 56% in patients younger than 2 years old and 33% versus 35% in patients 2-5 years old using the PreSchool Confusion Assessment Method for the ICU and reference rater, respectively. The short-form PreSchool Confusion Assessment Method for the ICU maintained a high specificity (87%) and sensitivity (78%) in post hoc analysis. Conclusions: The PreSchool Confusion Assessment Method for the ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent. C1 [Smith, Heidi A. B.; Chestnut, Mary Hamilton; Pandharipande, Pratik P.] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Smith, Heidi A. B.; Goben, Christina M.; Acton, Michelle; Newman, Jessica; Noori, Hannah P.; Terrell, Michelle K.; Williams, Stacey R.; Griffith, Katherine] Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat, Nashville, TN USA. [Gangopadhyay, Maalobeeka] New York Presbyterian Morgan Stanley Childrens Ho, Dept Psychiat, New York, NY USA. [Jacobowski, Natalie L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Savage, Shane] Georgia Regents Univ, Dept Psychiat, Augusta, GA USA. [Rutherford, Michael T.] Kalispell Reg Healthcare, Dept Psychiat, Kalispell, MT USA. [Denton, Danica; Fuchs, D. Catherine] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. [Thompson, Jennifer L.; Chandrasekhar, Rameela] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Cooper, Timothy J.] Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Dev Med, Nashville, TN USA. [Ely, E. Wesley] Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Dept Internal Med, Nashville, TN USA. [Ely, E. Wesley] Vanderbilt Univ, Med Ctr, Div Pulm & Crit Care Med, Nashville, TN USA. [Ely, E. Wesley] Tennessee Valley VA GRECC, Nashville, TN USA. RP Smith, HAB (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA.; Smith, HAB (reprint author), Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat, Nashville, TN USA. EM heidi.smith@vanderbilt.edu FU Foundation for Anesthesia Education and Research; Vanderbilt Clinical and Translational Science Awards (CTSA) grant from National Center for Research Resources (NCRR)/National Institutes of Health (NIH) [UL1 TR000445]; Vanderbilt CTSA grant from NCRR/NIH [UL1 TR000445]; NIH [HL111111, AG027472, AG035117]; Hospira Inc.; Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center; VA Clinical Science Research and Development Service; Abbott Laboratories; Orion; Hospira FX Dr. Smith is supported by the Foundation for Anesthesia Education and Research and supported in part by the Vanderbilt Clinical and Translational Science Awards (CTSA) grant UL1 TR000445 from the National Center for Research Resources (NCRR)/National Institutes of Health (NIH). Dr. Gangopadhyay and Dr. Fuchs are supported in part by the Vanderbilt CTSA grant UL1 TR000445 from NCRR/NIH. Dr. Pandharipande is supported by the NIH (HL111111, AG027472, and AG035117); and his institute receives research funding from Hospira Inc. Dr. Ely is supported by the Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center, the VA Clinical Science Research and Development Service, and the NIH (AG027472, AG035117, and HL111111). He has received funding from Abbott Laboratories, Orion, and Hospira. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 30 TC 10 Z9 10 U1 6 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2016 VL 44 IS 3 BP 592 EP 600 DI 10.1097/CCM.0000000000001428 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA DF7HM UT WOS:000371528700017 PM 26565631 ER PT J AU Muralidhar, V Nipp, RD Ryan, DP Hong, TS Nguyen, PL Wo, JY AF Muralidhar, Vinayak Nipp, Ryan D. Ryan, David P. Hong, Theodore S. Nguyen, Paul L. Wo, Jennifer Y. TI Association Between Very Small Tumor Size and Increased Cancer-Specific Mortality in Node-Positive Colon Cancer SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Lymph node metastasis; Personalized medicine; Colon cancer; Tumor size ID COLORECTAL-CANCER; HEPATIC METASTASES; SURVIVAL; DISSECTION; EXPRESSION; INVASION; INSIGHTS; BREAST; CELLS AB BACKGROUND: Larger tumor size and lymph node involvement are traditionally associated with increased colon cancer-specific mortality. OBJECTIVE: We sought to determine whether patients with very small tumors associated with lymph node involvement are at paradoxically increased risk of colon cancer-specific mortality in comparison with those who have larger tumors and lymph node involvement. DESIGN: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. SETTING: Geographic areas included in one of the 18 Surveillance, Epidemiology, and End Results registries were used. PATIENTS: We identified 99,594 patients with nonmetastatic colon adenocarcinoma treated with surgery between 1988 and 2001. MAIN OUTCOME MEASURES: The primary predictor variables were regional lymph node involvement and primary tumor size by longest dimension, grouped into the following predetermined strata: < 5 mm, 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, >= 60 mm. We used competing risks regression to determine differences in the risk of colon cancer-specific mortality between strata after controlling for T stage, tumor grade, age, year of diagnosis, race, and number of dissected lymph nodes. RESULTS: Median follow-up among censored patients was 12.9 years. We found a significant interaction between lymph node involvement and tumor size (p < 0.05). Among those with node-negative disease, colon cancer-specific mortality increased monotonically with tumor size. In contrast, among those with node-positive disease, patients with the smallest tumors (< 5 mm) were at increased risk of 10-year colon cancer-specific mortality compared with those with tumors sized 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, and >= 60 mm (53.3% vs 30.1%, 37.5%, 39.2%, and 39.7%; adjusted hazard ratios, 1.63-2.24; p < 0.05 in all cases). LIMITATIONS: The main limitations are the retrospective design and information available in the study database. CONCLUSION: In the setting of lymph node involvement, very small tumor size may predict for increased colon cancer-specific mortality compared with larger tumors. Smaller tumors associated with lymph node involvement may represent more aggressive malignancies with a distinct biology that merits further investigation. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Nipp, Ryan D.; Ryan, David P.] Massachusetts Gen Hosp, Div Hematol & Med Oncol, Boston, MA 02114 USA. [Hong, Theodore S.; Wo, Jennifer Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Wo, JY (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM jwo@mgh.harvard.edu NR 29 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD MAR PY 2016 VL 59 IS 3 BP 187 EP 193 DI 10.1097/DCR.0000000000000532 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DF5GW UT WOS:000371380800005 PM 26855392 ER PT J AU Yoder, KK Albrecht, DS Dzemidzic, M Normandin, MD Federici, LM Graves, T Herring, CM Hile, KL Walters, JW Liang, TB Plawecki, MH O'Connor, S Kareken, DA AF Yoder, Karmen K. Albrecht, Daniel S. Dzemidzic, Mario Normandin, Marc D. Federici, Lauren M. Graves, Tammy Herring, Christine M. Hile, Karen L. Walters, James W. Liang, Tiebing Plawecki, Martin H. O'Connor, Sean Kareken, David A. TI Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Dopamine; Raclopride; Alcohol; Positron emission tomography; Ventral striatum ID POSITRON-EMISSION-TOMOGRAPHY; NUCLEUS-ACCUMBENS DOPAMINE; RECEPTOR AVAILABILITY; SUBJECTIVE RESPONSES; FAMILY-HISTORY; ORAL ALCOHOL; DEPENDENCE; ETHANOL; REWARD; RELIABILITY AB Background: Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). Methods: Twenty-four SD and twenty-one NTS received two [C-11]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then "clamped." The alcohol clamp was started 5 min after scan start, with a linear increase in BrAC over 15 min to the target of 80 mg%, the legal threshold for intoxication. Target BrAC was maintained for 30 min. Voxel-wise binding potential (BPND) was estimated with MRTM2. Results: IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. Conclusions: Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Yoder, Karmen K.; Albrecht, Daniel S.; Dzemidzic, Mario; Normandin, Marc D.; Federici, Lauren M.; Graves, Tammy; Herring, Christine M.; Hile, Karen L.; Walters, James W.; Kareken, David A.] IUSM, Dept Radiol & Imaging Sci, R2-E124,950 W Walnut St, Indianapolis, IN 46202 USA. [Yoder, Karmen K.; Albrecht, Daniel S.; Dzemidzic, Mario; Federici, Lauren M.; Herring, Christine M.; Hile, Karen L.; Walters, James W.; Kareken, David A.] IUSM, Ctr Neuroimaging, GH Ste 4100,355 W 16th St, Indianapolis, IN 46202 USA. [Yoder, Karmen K.; Albrecht, Daniel S.] IUSM, Stark Neurosci Res Inst, NB Ste 414,320 W 16th St, Indianapolis, IN 46202 USA. [Yoder, Karmen K.] Indiana Univ Purdue Univ, Dept Psychol, 402 N Blackford St, Indianapolis, IN 46202 USA. [Dzemidzic, Mario; Kareken, David A.] IUSM, Dept Neurol, GH Ste 4700,355 W 16th St, Indianapolis, IN 46202 USA. [Graves, Tammy; Liang, Tiebing] IUSM, Dept Med, 340 W 10th St,Ste 6200, Indianapolis, IN 46202 USA. [Plawecki, Martin H.; O'Connor, Sean; Kareken, David A.] IUSM, Dept Psychiat, GH Ste 4800,355 W 16th St, Indianapolis, IN 46202 USA. [O'Connor, Sean] Richard L Roudebush Vet Adm Med Ctr, 1481 W 10th St, Indianapolis, IN 46202 USA. [Albrecht, Daniel S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 Thirteenth St,Room 2301, Charlestown, MA 02129 USA. [Normandin, Marc D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gordon Ctr Med Imaging,Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. RP Yoder, KK (reprint author), Indiana Univ Sch Med, Radiol & Imaging Sci, Ctr Neuroimaging, Goodman Hall Ste 4100,355 W 16th St, Indianapolis, IN 46202 USA. EM kkyoder@iupui.edu FU National Institute on Alcoholism and Alcohol Abuse [R01AA018354]; ABMRF/The Foundation for Alcohol Research; NIAAA [P60 AA007611]; Genomics and Bioinformatics Core; Indiana Clinical and Translational Sciences Institute (from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award) [UL RR025761] FX National Institute on Alcoholism and Alcohol Abuse R01AA018354 (KKY), ABMRF/The Foundation for Alcohol Research (KKY), NIAAA (SOC, MP; Pilot 50 to KKY) and Genomics and Bioinformatics Core (TL), and the Indiana Clinical and Translational Sciences Institute (from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award, grant #UL RR025761). NR 50 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2016 VL 160 BP 163 EP 169 DI 10.1016/j.drugalcdep.2016.01.001 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DG1OK UT WOS:000371837200021 PM 26832934 ER PT J AU West, JS Low, JCM Stankovic, KM AF West, Jessica S. Low, Jacob C. M. Stankovic, Konstantina M. TI Revealing Hearing Loss: A Survey of How People Verbally Disclose Their Hearing Loss SO EAR AND HEARING LA English DT Article DE Hearing loss; Public health; Self-disclosure ID QUALITATIVE CONTENT-ANALYSIS; NORMAL AUDIOGRAM; BEAVER DAM; HIV STATUS; PREVALENCE; STIGMA; TINNITUS; NOISE; IMPAIRMENT; STRATEGIES AB Objective: Hearing loss is the most common sensory deficit and congenital anomaly, yet the decision-making processes involved in disclosing hearing loss have been little studied. To address this issue, we have explored the phrases that adults with hearing loss use to disclose their hearing loss. Design: Since self-disclosure research has not focused on hearing loss-specific issues, we created a 15-question survey about verbally disclosing hearing loss. English speaking adults (> 18 years old) with hearing loss of any etiology were recruited from otology clinics in a major referral hospital. Three hundred and thirty-seven participants completed the survey instrument. Participants' phrase(s) used to tell people they have hearing loss were compared across objective characteristics (age; sex; type, degree, and laterality of hearing loss; word recognition scores) and self-reported characteristics (degree of hearing loss; age of onset and years lived with hearing loss; use of technology; hearing handicap score). Results: Participants' responses revealed three strategies to address hearing loss: Multipurpose disclosure (phrases that disclose hearing loss and provide information to facilitate communication), Basic disclosure (phrases that disclose hearing loss through the term, a label, or details about the condition), or nondisclosure (phrases that do not disclose hearing loss). Variables were compared between patients who used and who did not use each disclosure strategy using chi(2) or Wilcoxon rank sum tests. Multipurpose disclosers were mostly female (p = 0.002); had experienced reactions of help, support, and accommodation after disclosing (p = 0.008); and had experienced reactions of being overly helpful after disclosing (p=0.039). Basic disclosers were predominantly male (p = 0.004); reported feeling somewhat more comfortable disclosing their hearing loss over time (p = 0.009); had not experienced reactions of being treated unfairly or discriminated against (p = 0.021); and were diagnosed with mixed hearing loss (p = 0.004). Nondisclosers tended not to disclose in a group setting (p = 0.002) and were diagnosed with bilateral hearing loss (p = 0.005). In addition, all of the variables were examined to build logistic regression models to predict the use of each disclosure strategy. Conclusions: Our results reveal three simple strategies for verbally addressing hearing loss that can be used in a variety of contexts. We recommend educating people with hearing loss about these strategies-this could improve the experience of disclosing hearing loss, and could educate society at large about how to interact with those who have a hearing loss. C1 [West, Jessica S.; Low, Jacob C. M.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [West, Jessica S.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [West, Jessica S.] Duke Univ, Dept Sociol, 276 Sociol Psychol Bldg,417 Chapel Dr, Durham, NC 27708 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.; West, JS (reprint author), Duke Univ, Dept Sociol, 276 Sociol Psychol Bldg,417 Chapel Dr, Durham, NC 27708 USA. EM jessie.west@duke.edu; Konstantina_Stankovic@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders NIH-NIDCD [K08 DC010419]; Bertarelli Foundation; Nancy Sayles Day Foundation FX Dr. Stankovic is a board member of the American Auditory Society. No other conflicts of interest were declared. Dr. Stankovic's research is supported by the National Institute on Deafness and Other Communication Disorders NIH-NIDCD K08 DC010419, the Bertarelli Foundation, and the Nancy Sayles Day Foundation. NR 99 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD MAR-APR PY 2016 VL 37 IS 2 BP 194 EP 205 DI 10.1097/AUD.0000000000000238 PG 12 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA DG0IK UT WOS:000371748300008 PM 26513208 ER PT J AU Farahmand, RB Merchant, GR Lookabaugh, SA Roosli, C Ulku, CH McKenna, MJ de Venecia, RK Halpin, CF Rosowski, JJ Nakajima, HH AF Farahmand, Rosemary B. Merchant, Gabrielle R. Lookabaugh, Sarah A. Roeoesli, Christof Ulku, Cagatay H. McKenna, Michael J. de Venecia, Ronald K. Halpin, Christopher F. Rosowski, John J. Nakajima, Hideko H. TI The Audiometric and Mechanical Effects of Partial Ossicular Discontinuity SO EAR AND HEARING LA English DT Article DE Audiogram; Air-bone gap; Ossicular interruption; Wideband immittance; Ossicular discontinuity; Laser Doppler vibrometry; Ossicular disruption ID CONDUCTIVE HEARING-LOSS; EAR-CANAL REFLECTANCE; AIR-BONE GAPS; UMBO VELOCITY; ADULTS; CHAIN AB Objectives: Ossicular discontinuity may be complete, with no contact between the disconnected ends, or partial, where normal contact at an ossicular joint or along a continuous bony segment of an ossicle is replaced by soft tissue or simply by contact of opposing bones. Complete ossicular discontinuity typically results in an audiometric pattern of a large, flat conductive hearing loss. In contrast, in cases where otomicroscopy reveals a normal external ear canal and tympanic membrane, high-frequency conductive hearing loss has been proposed as an indicator of partial ossicular discontinuity. Nevertheless, the diagnostic utility of high-frequency conductive hearing loss has been limited due to gaps in previous research on the subject, and clinicians often assume that an audiogram showing high-frequency conductive hearing loss is flawed. This study aims to improve the diagnostic utility of high-frequency conductive hearing loss in cases of partial ossicular discontinuity by (1) making use of a control population against which to compare the audiometry of partial ossicular discontinuity patients and (2) examining the correlation between high-frequency conductive hearing loss and partial ossicular discontinuity under controlled experimental conditions on fresh cadaveric temporal bones. Furthermore, ear-canal measurements of umbo velocity and wideband acoustic immittance measurements were investigated to determine the usefulness regarding diagnosis of ossicular discontinuity. Design: The authors analyzed audiograms from 66 patients with either form of surgically confirmed ossicular discontinuity and no confounding pathologies. The authors also analyzed umbo velocity (n = 29) and power reflectance (n = 12) measurements from a subset of these patients. Finally, the authors performed experiments on six fresh temporal bone specimens to study the differing mechanical effects of complete and partial discontinuity. The mechanical effects of these lesions were assessed via laser Doppler measurements of stapes velocity. In a subset of the specimen (n = 4), wideband acoustic immittance measurements were also collected. Results: (1) Calculations comparing the air-bone gap (ABG) at high and low frequencies show that when high-frequency ABGs are larger than low-frequency ABGs, the surgeon usually reported soft-tissue bands at the point of discontinuity. However, in cases with larger low-frequency ABGs and flat ABGs across frequencies, some partial discontinuities as well as complete discontinuities were reported. (2) Analysis of umbo velocity and power reflectance (calculated from wideband acoustic immittance) in patients reveal no significant difference across frequencies between the two types of ossicular discontinuities. (3) Temporal bone experiments reveal that partial discontinuity results in a greater loss in stapes velocity at high frequencies when compared with low frequencies, whereas with complete discontinuity, large losses in stapes velocity occur at all frequencies. Conclusion: The clinical and experimental findings suggest that when encountering larger ABGs at high frequencies when compared with low frequencies, partial ossicular discontinuity should be considered in the differential diagnosis. C1 [Farahmand, Rosemary B.; Merchant, Gabrielle R.; Lookabaugh, Sarah A.; Rosowski, John J.; Nakajima, Hideko H.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Merchant, Gabrielle R.; Rosowski, John J.; Nakajima, Hideko H.] Harvard MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol, Cambridge, MA USA. [Roeoesli, Christof] Univ Zurich, Univ Zurich Hosp, Dept Otorhinolaryngol Head & Neck Surg, Zurich, Switzerland. [Ulku, Cagatay H.] Necmettin Erbakan Univ, Meram Med Fac, Dept Otolaryngol, Konya, Turkey. [McKenna, Michael J.; de Venecia, Ronald K.; Halpin, Christopher F.; Rosowski, John J.; Nakajima, Hideko H.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [McKenna, Michael J.; de Venecia, Ronald K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Halpin, Christopher F.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu OI Merchant, Gabrielle/0000-0001-7251-1879 FU Nachwuchsforderungskredit of the University of Zurich; TUBITAK [2011-1059B191100156]; National Institutes of Health/National Institute on Deafness and Other Communication [R01DC004798, R03DC011158] FX This research is supported by the Nachwuchsforderungskredit of the University of Zurich (C.R.), TUBITAK (2011-1059B191100156; C.H.U.), and the National Institutes of Health/National Institute on Deafness and Other Communication-R01DC004798 (J.J.R.) and R03DC011158 (H.H.N.). NR 15 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD MAR-APR PY 2016 VL 37 IS 2 BP 206 EP 215 DI 10.1097/AUD.0000000000000239 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA DG0IK UT WOS:000371748300009 PM 26510125 ER PT J AU Placzek, AN Molfese, DL Khatiwada, S Di Prisco, GV Huang, W Sidrauski, C Krnjevic, K Amos, CL Ray, R Dani, JA Walter, P Salas, R Costa-Mattioli, M AF Placzek, Andon N. Molfese, David L. Khatiwada, Sanjeev Di Prisco, Gonzalo Viana Huang, Wei Sidrauski, Carmela Krnjevic, Kresimir Amos, Christopher L. Ray, Russell Dani, John A. Walter, Peter Salas, Ramiro Costa-Mattioli, Mauro TI Translational control of nicotine -evoked synaptic potentiation in mice and neuronal responses in human smokers by elF2 alpha SO ELIFE LA English DT Article ID LONG-TERM POTENTIATION; DOPAMINE NEURONS; BINDING-PROTEIN; IN-VIVO; HOMEOSTASIS; EXPOSURE; SMOKING; REWARD; DEPRESSION; WITHDRAWAL AB Adolescents are particularly vulnerable to nicotine, the principal addictive component driving tobacco smoking. In a companion study, we found that reduced activity of the translation initiation factor eIF2 alpha underlies the hypersensitivity of adolescent mice to the effects of cocaine. Here we report that nicotine potentiates excitatory synaptic transmission in ventral tegmental area dopaminergic neurons more readily in adolescent mice compared to adults. Adult mice with genetic or pharmacological reduction in p-eIF2 alpha-mediated translation are more susceptible to nicotine's synaptic effects, like adolescents. When we investigated the influence of allelic variability of the Eif2s1 gene (encoding eIF2 alpha) on reward -related neuronal responses in human smokers, we found that a single nucleotide polymorphism in the Eif2s1 gene modulates mesolimbic neuronal reward responses in human smokers. These findings suggest that p-eIF2 alpha regulates synaptic actions of nicotine in both mice and humans, and that reduced p-eIF2 alpha may enhance susceptibility to nicotine (and other drugs of abuse) during adolescence. C1 [Placzek, Andon N.; Khatiwada, Sanjeev; Di Prisco, Gonzalo Viana; Huang, Wei; Ray, Russell; Salas, Ramiro; Costa-Mattioli, Mauro] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Placzek, Andon N.; Khatiwada, Sanjeev; Di Prisco, Gonzalo Viana; Huang, Wei; Ray, Russell; Costa-Mattioli, Mauro] Baylor Coll Med, Memory & Brain Res Ctr, Houston, TX 77030 USA. [Molfese, David L.; Salas, Ramiro] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Molfese, David L.; Salas, Ramiro] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Khatiwada, Sanjeev] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Sidrauski, Carmela; Walter, Peter] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA USA. [Krnjevic, Kresimir] McGill Univ, Dept Physiol, Montreal, PQ, Canada. [Amos, Christopher L.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Ctr Genom Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Dani, John A.] Perelman Sch Med, Mahoney Inst Neurosci, Dept Neurosci, Philadelphia, PA USA. [Placzek, Andon N.] Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. [Sidrauski, Carmela] Calico LLC, San Francisco, CA USA. RP Costa-Mattioli, M (reprint author), Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.; Costa-Mattioli, M (reprint author), Baylor Coll Med, Memory & Brain Res Ctr, Houston, TX 77030 USA. EM costamat@bcm.edu FU National Institute of Mental Health [MH096816]; National Institute of Neurological Disorders and Stroke [NS076708, NS21229]; National Institute on Drug Abuse [DA09411, DA026539, DA09167]; Howard Hughes Medical Institute; U.S. Department of Veterans Affairs [VHA5101CX000994] FX National Institute of Mental Health MH096816 Mauro Costa-Mattioli; National Institute of Neurological Disorders and Stroke NS076708, NS21229 John A Dani Mauro Costa-Mattioli; National Institute on Drug Abuse DA09411, DA026539, DA09167 John A Dani Ramiro Salas; Howard Hughes Medical Institute PW Peter Walter; U.S. Department of Veterans Affairs VHA5101CX000994 Ramiro Salas NR 32 TC 3 Z9 3 U1 1 U2 2 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD MAR 1 PY 2016 VL 5 AR e12056 DI 10.7554/eLife.12056 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DG2IA UT WOS:000371889400001 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Academic-industrial collaboration in the development of the first angiotensin receptor blocker: neprilysin inhibitor in the treatment of heart failure SO EUROPEAN HEART JOURNAL LA English DT Article ID CONVERTING ENZYME; NEUTRAL ENDOPEPTIDASE; HYPERTENSION; DESIGN C1 [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp,Dept Med, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp,Dept Med, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM ebraunwald@partners.org FU AstraZeneca; Bristol-Myers Squibb; Daiichi Sankyo; Duke University; Johnson Johnson; Merck; Sanofi Aventis FX Research grant to institution: AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Duke University, Johnson & Johnson, Merck, and Sanofi Aventis; honoraria: Bayer, Daiichi-Sankyo, Medscape, and Menarini International; consultancy: Sanofi Aventis, and The Medicines Company. NR 19 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAR 1 PY 2016 VL 37 IS 9 BP 745 EP 746 DI 10.1093/eurheartj/ehw055 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG1IO UT WOS:000371820200010 PM 26933120 ER PT J AU Strasser-Weippl, K Horick, N Smith, IE O'Shaughnessy, J Ejlertsen, B Boyle, F Buzdar, AU Fumoleau, P Gradishar, W Martin, M Moy, B Piccart-Gebhart, M Pritchard, KI Lindquist, D Rappold, E Finkelstein, DM Goss, PE AF Strasser-Weippl, Kathrin Horick, Nora Smith, Ian E. O'Shaughnessy, Joyce Ejlertsen, Bent Boyle, Frances Buzdar, Aman U. Fumoleau, Pierre Gradishar, William Martin, Miguel Moy, Beverly Piccart-Gebhart, Martine Pritchard, Kathleen I. Lindquist, Deborah Rappold, Erica Finkelstein, Dianne M. Goss, Paul E. TI Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Lapatinib; Early breast cancer; Adjuvant; Hormone receptor ID PLUS ADJUVANT CHEMOTHERAPY; HORMONE-RECEPTOR STATUS; NEOADJUVANT CHEMOTHERAPY; ESTROGEN-RECEPTOR; OVARIAN-CANCER; PHASE-3 TRIAL; TRASTUZUMAB; EXPRESSION; HER-2/NEU; HER2 AB In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib <1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol & Hematol, Vienna, Austria. [Horick, Nora; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. [O'Shaughnessy, Joyce] US Oncol, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. [Ejlertsen, Bent] DBCG Secretariat, Rigshosp, Copenhagen, Denmark. [Boyle, Frances] Mater Hosp, Sydney, NSW, Australia. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fumoleau, Pierre] Ctr GF Leclerc, Dijon, France. [Gradishar, William] Northwestern Univ, Chicago, IL 60611 USA. [Martin, Miguel] Univ Complutense, Hosp Univ Gregorio Maranon, E-28040 Madrid, Spain. [Moy, Beverly; Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piccart-Gebhart, Martine] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lindquist, Deborah] US Oncol, Arizona Oncol, Sedona, AZ USA. [Rappold, Erica] GlaxoSmithKline, Collegeville, PA USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM kathrin.strasserweippl@gmail.com; nhorick@partners.org; ian.smith@rmh.nhs.uk; Joyce.OShaughnessy@usoncology.com; ejlertsen@dadlnet.dk; franb@bigpond.net.au; abuzdar@mdanderson.org; pfumoleau@cgfl.fr; WGradishar@nmff.org; mmartin@geicam.org; bmoy@partners.org; martine.piccart@bordet.be; kathy.pritchard@sunnybrook.ca; deborah.lindquist@usoncology.com; mprcer@gmail.com; dfinkelstein@partners.org; pgoss@partners.org FU GlaxoSmithKline [EGF105485]; Avon Foundation, NY [02-2010-083] FX The sponsor, GlaxoSmithKline (EGF105485) provided funding for the study. Part of the academic effort and time for this analysis was funded by a grant from the Avon Foundation, NY (02-2010-083). The corresponding author had full access to all the data and had final responsibility for the decision to submit the results for publication. NR 31 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2016 VL 56 BP 85 EP 92 DI 10.1016/j.ejca.2015.12.024 PG 8 WC Oncology SC Oncology GA DG0TK UT WOS:000371778400011 PM 26829011 ER PT J AU Yang, M Hu, FB Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS Wu, K Bao, Y AF Yang, M. Hu, F. B. Giovannucci, E. L. Stampfer, M. J. Willett, W. C. Fuchs, C. S. Wu, K. Bao, Y. TI Nut consumption and risk of colorectal cancer in women SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID COLON-CANCER; INFLAMMATORY MARKERS; METABOLIC SYNDROME; DIET; QUESTIONNAIRE; WALNUTS; OBESITY; FAT AB BACKGROUND/OBJECTIVES: Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. SUBJECTS/METHODS: We prospectively followed 75 680 women who were free of cancer at baseline in the Nurses' Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2-4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: During 2 103 037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, >= 56 g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72-1.05; P-trend: 0.06). No association was observed for peanut butter. CONCLUSIONS: In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors. C1 [Yang, M.; Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.; Fuchs, C. S.; Wu, K.; Bao, Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. [Yang, M.; Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.; Wu, K.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bao, Y (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.ed FU National Institutes of Health [P01 CA87969, P50 CA127003, 1U54CA155626]; International Tree Nut Council Nutrition Research & Education Foundation FX This study is supported by the Grants P01 CA87969, P50 CA127003 and 1U54CA155626 from the National Institutes of Health, and by the grant from the International Tree Nut Council Nutrition Research & Education Foundation. We thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. The authors assume full responsibility for analyses and interpretation of these data. NR 29 TC 1 Z9 1 U1 6 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 EI 1476-5640 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD MAR PY 2016 VL 70 IS 3 BP 333 EP 337 DI 10.1038/ejcn.2015.66 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DF9FZ UT WOS:000371667700008 PM 25944181 ER PT J AU Liu, M Blanco-Centurion, C Konadhode, RR Luan, LJ Shiromani, PJ AF Liu, Meng Blanco-Centurion, Carlos Konadhode, Roda Rani Luan, Liju Shiromani, Priyattam J. TI Orexin gene transfer into the amygdala suppresses both spontaneous and emotion-induced cataplexy in orexin-knockout mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; emotion; narcolepsy; orexin; predator odour; sleep ID HUMAN NARCOLEPSY; NEURONS; SLEEP; RAT; MUTATION; BEHAVIOR; RECEPTOR; MODELS; BRAIN; ONSET AB Narcolepsy is a chronic sleep disorder linked to the loss of orexin-producing neurons in the hypothalamus. Cataplexy, a sudden loss of muscle tone during waking, is an important distinguishing symptom of narcolepsy and it is often triggered by strong emotions. The neural circuit underlying cataplexy attacks is not known, but is likely to involve the amygdala, a region implicated in regulating emotions. In mice models of narcolepsy, transfer of the orexin gene into surrogate neurons has been successful in ameliorating narcoleptic symptoms. However, it is not known whether this method also blocks cataplexy triggered by strong emotions. To examine this possibility, the gene encoding mouse prepro-orexin was transferred into amygdala neurons of orexin-knockout (KO) mice (rAAV-orexin; n=8). Orexin-KO mice that did not receive gene transfer (no-rAAV; n=7) or received only the reporter gene (rAAV-GFP; n=7) served as controls. Three weeks later, the animal's sleep and behaviour were recorded at night (no-odour control night), followed by another recording at night in the presence of predator odour (odour night). Orexin-KO mice given the orexin gene transfer into surrogate amygdala neurons had significantly less spontaneous bouts of cataplexy, and predator odour did not induce cataplexy compared with control mice. Moreover, the mice with orexin gene transfer were awake more during the odour night. These results demonstrate that orexin gene transfer into amygdala neurons can suppress both spontaneous and emotion-induced cataplexy attacks in narcoleptic mice. It suggests that manipulating amygdala pathways is a potential strategy for treating cataplexy in narcolepsy. C1 [Liu, Meng; Blanco-Centurion, Carlos; Konadhode, Roda Rani; Luan, Liju; Shiromani, Priyattam J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. [Shiromani, Priyattam J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Liu, M (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA.; Shiromani, PJ (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM liumen@musc.edu; shiroman@musc.edu FU Medical Research Service of the Department of Veterans Affairs [I01 BX000798]; NIH [1K01AG041520, NS052287, NS084477, NS079940, HL091363] FX This study was supported by Medical Research Service of the Department of Veterans Affairs (I01 BX000798) and NIH grants 1K01AG041520, NS052287, NS084477, NS079940 and HL091363. We thank Dr Patrick K. Randall for support with the SPSS statistical analysis program. NR 34 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2016 VL 43 IS 5 BP 681 EP 688 DI 10.1111/ejn.13158 PG 8 WC Neurosciences SC Neurosciences & Neurology GA DG2PN UT WOS:000371909800009 PM 26741960 ER PT J AU Modestino, EJ AF Modestino, Edward J. TI NEUROPHENOMENOLOGY OF AN ALTERED STATE OF CONSCIOUSNESS: AN FMRI CASE STUDY SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Article DE Neurophenomenology; Kundalini; meditation; fMRI; physio-Kundalini syndrome ID KUNDALINI-YOGA MEDITATION; MINDFULNESS MEDITATION; BRAIN; ACTIVATION; DISORDERS; ATTENTION; MOTION AB A research participant came to our lab with self-proclaimed, ecstatic, Kundalini meditative experiences. Using neurophenomenology and functional magnetic resonance imaging (fMRI), we were able to identify brain activation in the left prefrontal cortex [primarily in left Brodmann's areas (BAs) 46 and 10, but also extending into BAs 11, 47, and 45] associated with this experience. The Phenomenology of Consciousness Inventory provided evidence that this was a perceived altered state of consciousness. Additionally, the Physio-Kundalini Syndrome Index strongly suggested that what he was experiencing was indeed Kundalini. The feelings of joy, happiness and the left prefrontal brain region found in this study are consistent with many published neuroimaging and electrophysiological studies of meditation. This case study suggests that using first-person subjective experience within a phenomenological reduction process can be combined with neuroimaging to divulge objective brain regions associated with such experiences. Furthermore, this provides evidence that at least in this participant, the Kundalini experience is associated with brain activation in the left prefrontal cortex. Future research is needed to confirm these results in a large group study, perhaps contrasting brain activation of those who experience spontaneously emerging Kundalini with trained Kundalini practitioners. C1 [Modestino, Edward J.] Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Modestino, EJ (reprint author), Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02118 USA. EM edward.modestino@gmail.com NR 46 TC 0 Z9 0 U1 7 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 EI 1878-7541 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD MAR-APR PY 2016 VL 12 IS 2 BP 128 EP 135 DI 10.1016/j.explore.2015.12.004 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DG0KS UT WOS:000371754300010 PM 26775225 ER PT J AU Greiner, JV AF Greiner, Jack V. TI Long-Term (3 Year) Effects of a Single Thermal Pulsation System Treatment on Meibomian Gland Function and Dry Eye Symptoms SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Dry eye disease; Meibomian gland dysfunction; Thermal pulsation system treatment; Long-term treatment ID LIPID LAYER THICKNESS; INTERNATIONAL WORKSHOP; TEAR FILM; THERMODYNAMIC TREATMENT; DYSFUNCTION; SUBCOMMITTEE; FLUORESCEIN; IMPROVEMENT AB Purpose: The present study examined the long-term (3 years) effects of a single (12 min) thermal pulsation system (TPS) treatment on symptomatic patients with evaporative dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). Methods: In this prospective, cohort, observational, single-center study design, signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT]) and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes) with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS treatment using LipiFlow. Results: Meibomian gland secretion scores increased from BL (4.5 +/- 0.8) to 1 month (12.0 +/- 1.1, P <= 0.001). Improvement persisted at 3 years (18.4 +/- 1.4) relative to BL (P <= 0.001). Meibomian gland secretion scores in all regions of the lower eyelid were improved over BL at 1 month (nasal [P <= 0.001], central [P <= 0.001], temporal [P <= 0.01]) and 3 years (nasal [P <= 0.001], central [P <= 0.001], temporal [P <= 0.001]). TBUT increased from BL (4.1 +/- 0.4) to 1 month (7.9 +/- 1.4, P <= 0.05) but was not significantly different than BL at 3 years (4.5 +/- 0.6, P>0.05). The OSDI scores decreased from BL (26.0 +/- 4.6) to 1 month (14.7 +/- 4.3, P <= 0.001) but returned to BL levels at 3 years (22.5 +/- 5.4, P>0.05). The SPEED scores decreased from BL (13.4 +/- 1.0) to 1 month (6.5 +/- 1.3, P <= 0.001), and this improvement persisted at 3 years (9.5 +/- 1.6, P <= 0.001). Conclusions: Thermal pulsation may be a uniquely efficacious treatment option for DED secondary to MGD in that a single 12-min procedure is associated with significant improvement in MGS and SPEED scores for up to 3 years. C1 [Greiner, Jack V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Greiner, Jack V.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Greiner, Jack V.] Boston Ocular Surface Ctr, Boston, MA USA. [Greiner, Jack V.] Boston Ocular Surface Ctr, Winchester, MA USA. RP Greiner, JV (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM jack_greiner@meei.harvard.edu FU Valerie and Walter Winchester Grant; Schepens Eye Research Institute, Boston, MA; Boston Ocular Surface Center, Boston and Winchester, MA; TearScience, Inc., Morrisville, NC FX Supported by Valerie and Walter Winchester Grant, Schepens Eye Research Institute, Boston, MA, Boston Ocular Surface Center, Boston and Winchester, MA, and TearScience, Inc., Morrisville, NC. NR 34 TC 3 Z9 3 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1542-2321 EI 1542-233X J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD MAR PY 2016 VL 42 IS 2 BP 99 EP 107 DI 10.1097/ICL.0000000000000166 PG 9 WC Ophthalmology SC Ophthalmology GA DG0IG UT WOS:000371747900003 PM 26222095 ER PT J AU Cheesman, HK Feinbaum, RL Thekkiniath, J Dowen, RH Conery, AL Pukkila-Worley, R AF Cheesman, Hilary K. Feinbaum, Rhonda L. Thekkiniath, Jose Dowen, Robert H. Conery, Annie L. Pukkila-Worley, Read TI Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans SO G3-GENES GENOMES GENETICS LA English DT Article DE innate immunity; immune regulation; C. elegans genetics; host-pathogen interactions; genetics of immunity ID INFLAMMATORY-BOWEL-DISEASE; PROTEIN-KINASE; HOST-DEFENSE; C. ELEGANS; PATHOGENESIS; RESISTANCE; TOLERANCE; PATHWAYS; STRESS; PHOSPHATASE AB Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk-1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy-1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans. C1 [Cheesman, Hilary K.; Feinbaum, Rhonda L.; Thekkiniath, Jose; Pukkila-Worley, Read] Univ Massachusetts, Div Infect Dis & Immunol, Program Innate Immun, Sch Med, Worcester, MA 01605 USA. [Dowen, Robert H.; Conery, Annie L.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Pukkila-Worley, R (reprint author), Univ Massachusetts, Sch Med, 364 Plantat St,Lazare Res Bldg 325, Worcester, MA 01605 USA. EM Pukkila-Worley@umassmed.edu FU National Institute of Allergy and Infectious Diseases [K08 AI081747, R01 AI085581, P01 AI083214] FX We thank Neal Silverman and Amy Walker for helpful discussions and Richa Chhaya for technical assistance. This study was supported by National Institute of Allergy and Infectious Diseases Award K08 AI081747 (to R.P.W.). R.L.F. and A.L.C. were supported by National Institute of Allergy and Infectious Diseases Awards R01 AI085581 and P01 AI083214. NR 37 TC 8 Z9 8 U1 3 U2 7 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD MAR 1 PY 2016 VL 6 IS 3 BP 541 EP 549 DI 10.1534/g3.115.025650 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DG1MA UT WOS:000371831000005 PM 26818074 ER PT J AU Zhang, DF Schumacher, C Harris, MB Bono, CM AF Zhang, Dafang Schumacher, Charles Harris, Mitchel B. Bono, Christopher M. TI The Quality and Readability of Information Available on the Internet Regarding Lumbar Fusion SO GLOBAL SPINE JOURNAL LA English DT Article DE lumbar fusion; Internet; patient education; quality; readability ID PATIENT EDUCATION MATERIALS; DISC HERNIATION; SURGERY; DEVICE; SITES AB Study DesignAn Internet-based evaluation of Web sites regarding lumbar fusion. ObjectiveThe Internet has become a major resource for patients; however, the quality and readability of Internet information regarding lumbar fusion is unclear. The objective of this study is to evaluate the quality and readability of Internet information regarding lumbar fusion and to determine whether these measures changed with Web site modality, complexity of the search term, or Health on the Net Code of Conduct certification. MethodsUsing five search engines and three different search terms of varying complexity (low back fusion, lumbar fusion, and lumbar arthrodesis), we identified and reviewed 153 unique Web site hits for information quality and readability. Web sites were specifically analyzed by search term and Web site modality. Information quality was evaluated on a 5-point scale. Information readability was assessed using the Flesch-Kincaid score for reading grade level. ResultsThe average quality score was low. The average reading grade level was nearly six grade levels above that recommended by National Work Group on Literacy and Health. The quality and readability of Internet information was significantly dependent on Web site modality. The use of more complex search terms yielded information of higher reading grade level but not higher quality. ConclusionsHigher-quality information about lumbar fusion conveyed using language that is more readable by the general public is needed on the Internet. It is important for health care providers to be aware of the information accessible to patients, as it likely influences their decision making regarding care. C1 [Zhang, Dafang; Schumacher, Charles] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Zhang, Dafang; Schumacher, Charles; Harris, Mitchel B.; Bono, Christopher M.] Harvard Univ, Dept Orthopaed Surg, Sch Med, Boston, MA USA. [Harris, Mitchel B.; Bono, Christopher M.] Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. RP Bono, CM (reprint author), Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM cmbono@partners.org NR 26 TC 0 Z9 0 U1 4 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 2192-5682 EI 2192-5690 J9 GLOB SPINE J JI Glob. Spine J. PD MAR PY 2016 VL 6 IS 2 BP 133 EP 138 DI 10.1055/s-0035-1557145 PG 6 WC Orthopedics SC Orthopedics GA DF8JE UT WOS:000371603100006 PM 26933614 ER PT J AU Burke, RE Johnson-Koenke, R Nowels, C Silveira, MJ Jones, J Bekelman, DB AF Burke, Robert E. Johnson-Koenke, Rachel Nowels, Carolyn Silveira, Maria J. Jones, Jacqueline Bekelman, David B. TI Can we engage caregiver spouses of patients with heart failure with a low-intensity, symptom-guided intervention? SO HEART & LUNG LA English DT Article DE Symptom management; Heart failure; Caregiver; Palliative care; Quality of life ID QUALITY-OF-LIFE; INFORMAL CAREGIVERS; PALLIATIVE CARE; TRANSITIONAL CARE; FAMILY CAREGIVERS; SELF-MANAGEMENT; OLDER-ADULTS; TRIAL; SUPPORT; METAANALYSIS AB Objective: Evaluate a pilot intervention to engage caregivers in management of heart failure (HF) patient symptoms. Background: HF impairs quality of life; caregivers provide an important role in HF management. Methods: We developed modules to help patients report and caregivers alleviate symptoms of depression, pain, dyspnea, and fatigue. Semi-structured interviews followed by a mixed inductive and deductive, team based analysis were used to evaluate acceptability and feasibility in patients with HF and their caregivers. Results: Participants (n = 22) expressed significant interest but few used the modules in follow-up. We identified three barriers to acceptability and feasibility: the quality of dyadic relationship, the timing and structure of the intervention, and the patient's perceived control over their illness. Conclusions: Future interventions should evaluate dyadic relationship dynamics, match the timing and content of the intervention to the patient population, and enroll patients with perceived control over their illness to maximize intervention acceptability and feasibility. Published by Elsevier Inc. C1 [Burke, Robert E.; Johnson-Koenke, Rachel; Bekelman, David B.] Denver VA Med Ctr, Dept Med, Denver, CO USA. [Burke, Robert E.; Nowels, Carolyn; Bekelman, David B.] Univ Colorado, Denver Sch Med, Dept Med, Div Gen Internal Med, Anschutz Med Campus, Aurora, CO USA. [Silveira, Maria J.] Ann Arbor Vet Affairs Med Ctr, Ctr Clin Management Res, Ann Arbor, MI USA. [Silveira, Maria J.] Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA. [Jones, Jacqueline] Univ Colorado, Coll Nursing, Aurora, CO USA. RP Burke, RE (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM Robert.Burke5@va.gov FU VA Chronic Heart Failure Quality Enhancement Research Initiative (QUERI) Locally Initiated Project award; VA [IIR 08-0309]; VA Career Development Award [08-022] FX The study was supported by a VA Chronic Heart Failure Quality Enhancement Research Initiative (QUERI) Locally Initiated Project award to Drs. Burke and Bekelman. Dr. Silveira was supported by VA IIR 08-0309. Dr. Bekelman was supported by a VA Career Development Award (08-022). These funding sources had no role in the design, interpretation, or presentation of results. This report represents the views of the authors and not necessarily those of the U.S. Department of Veterans Affairs. NR 57 TC 0 Z9 0 U1 6 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 EI 1527-3288 J9 HEART LUNG JI Heart Lung PD MAR-APR PY 2016 VL 45 IS 2 BP 114 EP 120 DI 10.1016/j.hrtlng.2015.12.006 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA DG1SL UT WOS:000371847700006 PM 26831372 ER PT J AU Choi, J Tate, JA Rogers, MA Donahoe, MP Hoffman, LA AF Choi, JiYeon Tate, Judith A. Rogers, Mary Alana Donahoe, Michael P. Hoffman, Leslie A. TI Depressive symptoms and anxiety in intensive care unit (ICU) survivors after ICU discharge SO HEART & LUNG LA English DT Article DE Post intensive care unit; Intensive care unit survivors; Depressive symptoms; Anxiety; Recovery ID QUALITY-OF-LIFE; PROLONGED MECHANICAL VENTILATION; RESPIRATORY-DISTRESS-SYNDROME; LONG-TERM OUTCOMES; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; ACUTE LUNG INJURY; CRITICAL ILLNESS; POSTTRAUMATIC-STRESS; HEALTH AB Background: The association between intensive care unit (ICU) survivors' psychological sequelae, individual care needs, and discharge disposition has not been evaluated. Objective: To describe depressive symptoms and anxiety in ICU survivors and explore these symptoms based on individual care needs and discharge disposition for 4 months post-ICU discharge. Methods: We analyzed data from 39 ICU survivors who self-reported measures of depressive symptoms (Center for Epidemiologic Studies-Depression 10 items [CESD-10]) and anxiety (Shortened Profile of Mood States-Anxiety subscale [POMS-A]). Results: A majority of patients reported CESD-10 scores above the cut off (>= 8) indicating risk for clinical depression. POMS-A scores were highest within 2 weeks post-ICU discharge and decreased subsequently. Data trends suggest worse depressive symptoms and anxiety when patients had moderate to high care needs and/or were unable to return home. Conclusion: ICU survivors who need caregiver assistance and extended institutional care reported trends of worse depressive symptoms and anxiety. (C) 2016 Elsevier Inc. All rights reserved. C1 [Choi, JiYeon; Hoffman, Leslie A.] Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA. [Donahoe, Michael P.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Tate, Judith A.] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Rogers, Mary Alana] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hoffman, Leslie A.] Clin & Translat Sci Inst, San Francisco, CA USA. RP Choi, J (reprint author), Univ Pittsburgh, Sch Nursing, 336 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. EM jic11@pitt.edu FU NIH, National Institute of Nursing Research, U.S. Public Health Service [F32 NR 011271, T32 NR 008857]; Rehabilitation Nursing Foundation [FEL-0905]; Undergraduate Research Mentorship Program, University of Pittsburgh School of Nursing FX Funding was provided by the NIH, National Institute of Nursing Research, U.S. Public Health Service (F32 NR 011271 and T32 NR 008857) and Rehabilitation Nursing Foundation, Fellow Research Award (FEL-0905). Work from Ms. Mary Alana Rogers was supported by the Undergraduate Research Mentorship Program, University of Pittsburgh School of Nursing. The authors declare no conflicts of interest. NR 54 TC 1 Z9 1 U1 3 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 EI 1527-3288 J9 HEART LUNG JI Heart Lung PD MAR-APR PY 2016 VL 45 IS 2 BP 140 EP 146 DI 10.1016/j.hrtlng.2015.12.002 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA DG1SL UT WOS:000371847700010 PM 26791248 ER PT J AU Nasioudis, D Tsilimigras, D Economopoulos, KP AF Nasioudis, Dimitrios Tsilimigras, Diamantis Economopoulos, Konstantinos P. TI Laparoscopic cholecystectomy during pregnancy: A systematic review of 590 patients SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Pregnancy; Laparoscopy; Cholecystectomy ID BILIARY-TRACT DISEASE; SURGICAL-MANAGEMENT; GALLSTONE DISEASE; INCREASES MORBIDITY; ACUTE-PANCREATITIS; CENTER EXPERIENCE; ABDOMINAL-WALL; 3RD TRIMESTER; SURGERY; COMPLICATIONS AB Background: The incidence of symptomatic biliary disease during pregnancy ranges from 0.05 to 8%. Cholecystectomy is one of the common operations performed during pregnancy and laparoscopic approach has gained popularity as an attractive alternative to open surgery. Methods: In order to evaluate the safety, feasibility, outcomes and technical aspects of laparoscopic cholecystectomy during pregnancy a comprehensive search of Medline and Cohrane Library databases was conducted. Results: Fifty-one studies were deemed eligible, in which laparoscopic cholecystectomy was attempted in 590 patients. The majority of the procedures (70.7%) were performed during the second trimester. Intraoperative and postoperative complications were observed in 3.5% and 4% of the study population. Conversion rate to open surgery was 2.2%. Fetal loss rate and preterm delivery rate were 0.4% and 5.7% respectively. Conclusion: Laparoscopic cholecystectomy seems to be a safe alternative to open surgery during pregnancy. (C) 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved. C1 [Nasioudis, Dimitrios; Tsilimigras, Diamantis; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Nasioudis, Dimitrios] Weill Cornell Med, Dept Obstet & Gynecol, New York, NY USA. [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 101 Merrimac St, Boston, MA 02114 USA. RP Economopoulos, KP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 101 Merrimac St, Boston, MA 02114 USA. NR 85 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD MAR PY 2016 VL 27 BP 165 EP 175 DI 10.1016/j.ijsu.2016.01.070 PG 11 WC Surgery SC Surgery GA DG0VI UT WOS:000371783400029 PM 26826612 ER PT J AU Gandhi, RT Kwon, DS Macklin, EA Shopis, JR McLean, AP McBrine, N Flynn, T Peter, L Sbrolla, A Kaufmann, DE Porichis, F Walker, BD Bhardwaj, N Barouch, DH Kavanagh, DG AF Gandhi, Rajesh T. Kwon, Douglas S. Macklin, Eric A. Shopis, Janet R. McLean, Anna P. McBrine, Nicole Flynn, Theresa Peter, Lauren Sbrolla, Amy Kaufmann, Daniel E. Porichis, Filippos Walker, Bruce D. Bhardwaj, Nina Barouch, Dan H. Kavanagh, Daniel G. TI Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE randomized controlled trial; immunization; mRNA-transfected dendritic cell; HIV-1; therapeutic vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; II COMPARTMENT; IN-VITRO; INFECTION; RESPONSES; CD8(+); ANTIGEN; IMMUNOTHERAPY AB Background: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. Methods: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. Results: After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine. C1 [Gandhi, Rajesh T.; Kwon, Douglas S.; Shopis, Janet R.; Flynn, Theresa; Sbrolla, Amy; Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Gandhi, Rajesh T.; Kwon, Douglas S.; McLean, Anna P.; McBrine, Nicole; Kaufmann, Daniel E.; Porichis, Filippos; Walker, Bruce D.; Barouch, Dan H.; Kavanagh, Daniel G.] Massachusetts Gen Hosp, MIT, Ragon Inst, Cambridge, MA USA. [Gandhi, Rajesh T.; Kwon, Douglas S.; McLean, Anna P.; McBrine, Nicole; Kaufmann, Daniel E.; Porichis, Filippos; Walker, Bruce D.; Barouch, Dan H.; Kavanagh, Daniel G.] Harvard, Cambridge, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. [Kaufmann, Daniel E.] Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ, Canada. [Kaufmann, Daniel E.] Univ Montreal, Montreal, PQ, Canada. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Bhardwaj, Nina] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Barouch, Dan H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rgandhi@mgh.harvard.edu OI Macklin, Eric/0000-0003-1618-3502 FU National Institutes of Health [R01 AI066992-01A1, AI078526, AI096040, HL092565]; Center of AIDS Research [NIAID 5P30AI060354-08]; Ragon Institute of MGH, MIT, and Harvard; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University FX Supported by National Institutes of Health (R01 AI066992-01A1, AI078526, AI096040, HL092565), by the Center of AIDS Research (NIAID 5P30AI060354-08), and by the Ragon Institute of MGH, MIT, and Harvard. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. NR 33 TC 3 Z9 3 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2016 VL 71 IS 3 BP 246 EP 253 DI 10.1097/QAI.0000000000000852 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DF7FB UT WOS:000371522100002 PM 26379068 ER PT J AU Blosnich, JR Bossarte, RM AF Blosnich, John R. Bossarte, Robert M. TI Childhood Abuse and Military Experience-Important Information to Better Serve Those Who Have Served SO JAMA PSYCHIATRY LA English DT Editorial Material C1 [Blosnich, John R.] US Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Bossarte, Robert M.] US Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. [Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Bossarte, Robert M.] Univ Rochester, Dept Publ Hlth Sci, Rochester, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAR PY 2016 VL 73 IS 3 BP 195 EP 196 DI 10.1001/jamapsychiatry.2015.2736 PG 2 WC Psychiatry SC Psychiatry GA DF8NC UT WOS:000371613500005 PM 26817448 ER PT J AU Volkow, ND Swanson, JM Evins, AE DeLisi, LE Meier, MH Gonzalez, R Bloomfield, MAP Curran, HV Baler, R AF Volkow, Nora D. Swanson, James M. Evins, A. Eden DeLisi, Lynn E. Meier, Madeline H. Gonzalez, Raul Bloomfield, Michael A. P. Curran, H. Valerie Baler, Ruben TI Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review SO JAMA PSYCHIATRY LA English DT Review ID HIGH-POTENCY CANNABIS; SWEDISH CONSCRIPTS; MEMORY IMPAIRMENT; GENETIC-VARIATION; ADULT PSYCHOSIS; SEX-DIFFERENCES; SCHIZOPHRENIA; RISK; ADOLESCENT; MARIJUANA AB With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis. C1 [Volkow, Nora D.; Baler, Ruben] NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. [Swanson, James M.] Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. [Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Meier, Madeline H.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Gonzalez, Raul] Florida Int Univ, Dept Psychol, Ctr Children & Families, Miami, FL 33199 USA. [Bloomfield, Michael A. P.] UCL, Div Psychiat, London, England. [Bloomfield, Michael A. P.] Hammersmith Hosp, MRC, Ctr Clin Sci, Psychiat Imaging Grp, London, England. [Curran, H. Valerie] UCL, Clin Psychopharmacol Unit, Clin Hlth Psychol, London, England. RP Volkow, ND (reprint author), NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Forum Pharmaceuticals from the National Institute of Drug Abuse [R01 DA030992]; Pfizer from the National Institute of Drug Abuse [R01 DA021245]; National Institutes of Health Intramural Research Program (National Institute on Alcohol Abuse and Alcoholism) [DE-AC02-98CH10886]; National Institute of Drug Abuse [R01 DA021576]; United Kingdom Medical Research Council; National Institute of Health Research; British Medical Association; United Kingdom National Institute of Health Research Biomedical Research Council; United Kingdom Medical Research Council grant FX This work was financed in part by support from the following: Forum Pharmaceuticals to support grant R01 DA030992 from the National Institute of Drug Abuse and Pfizer to support grant R01 DA021245 from the National Institute of Drug Abuse (Dr Evins); National Institutes of Health Intramural Research Program (National Institute on Alcohol Abuse and Alcoholism) using the infrastructure of the Brookhaven National Laboratory under contract DE-AC02-98CH10886 (Dr Volkow); grant R01 DA021576 from the National Institute of Drug Abuse (Dr DeLisi); United Kingdom Medical Research Council, National Institute of Health Research, and British Medical Association (Dr Bloomfield); and a grant from the United Kingdom National Institute of Health Research Biomedical Research Council to King's College London and a United Kingdom Medical Research Council grant (Dr Curran). NR 84 TC 32 Z9 32 U1 54 U2 119 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAR PY 2016 VL 73 IS 3 BP 292 EP 297 DI 10.1001/jamapsychiatry.2015.3278 PG 6 WC Psychiatry SC Psychiatry GA DF8NC UT WOS:000371613500017 PM 26842658 ER PT J AU Carter, SP DiMauro, J Renshaw, KD Curby, TW Babson, KA Bonn-Miller, MO AF Carter, Sarah P. DiMauro, Jennifer Renshaw, Keith D. Curby, Timothy W. Babson, Kimberly A. Bonn-Miller, Marcel O. TI Longitudinal associations of friend-based social support and PTSD symptomatology during a cannabis cessation attempt SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Social support; Substance use; Longitudinal study; Military ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; PSYCHOLOGICAL DISTRESS; CAREGIVER BURDEN; MENTAL-ILLNESS; VETERANS; SYMPTOMS; PARTNERS; ABUSE; METAANALYSIS AB Research supports bidirectional associations between social support and posttraumatic stress disorder (PTSD), whereby social support may buffer against PTSD, and individuals with PTSD may experience decreasing support over time. Research examining contexts that may affect these relations is needed. This study examined the longitudinal associations between PTSD and social support from friends over a 6-month period in 116 veterans with cannabis dependence who had recently initiated an attempt to quit cannabis use. A cross-lagged autoregressive model revealed a significant, negative relation between earlier PTSD symptoms and later support. An exploratory multigroup analysis comparing those with and without a relapse in the first month after their quit attempt revealed that the significant negative association between PTSD and future support was present only in those who relapsed. Although this analysis was limited by a small sample size, results suggest that substance use may be an influential contextual variable that impacts the longitudinal associations between PTSD and support. (c) 2016 Elsevier Ltd. All rights reserved. C1 [Carter, Sarah P.; DiMauro, Jennifer; Renshaw, Keith D.; Curby, Timothy W.] George Mason Univ, Dept Psychol, 4400 Univ Dr,3F5, Fairfax, VA 22030 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd, Menlo Pk, CA 94025 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, 3900 Woodland Ave, Philadelphia, PA 19104 USA. [Bonn-Miller, Marcel O.] Univ Penn, Perelman Sch Med, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. RP Carter, SP (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,3F5, Fairfax, VA 22030 USA. EM scarte18@gmu.edu FU VA Clinical Science Research and Development (CSR&D) Career Development Award [CDA-2, 1IK2CX1023-01A1] FX This work was supported, in part, by a VA Clinical Science Research and Development (CSR&D) Career Development Award (CDA-2; 1IK2CX1023-01A1) awarded to Dr. Babson. Data for the parent study were collected as part of VA CSR&D CDA-2 awarded to Dr. Bonn-Miller. NR 43 TC 0 Z9 0 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAR PY 2016 VL 38 BP 62 EP 67 DI 10.1016/j.janxdis.2016.01.008 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DF6EQ UT WOS:000371449100008 PM 26836369 ER PT J AU Korte, KJ Allan, NP Gros, DF Acierno, R AF Korte, Kristina J. Allan, Nicholas P. Gros, Daniel F. Acierno, Ron TI Differential treatment response trajectories in individuals with subclinical and clinical PTSD SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Posttraumatic stress disorder; Subclinical; Subthreshold; Military; Veterans; Growth curve modeling ID POSTTRAUMATIC-STRESS-DISORDER; COVARIANCE STRUCTURE-ANALYSIS; COGNITIVE PROCESSING THERAPY; CONFIRMATORY FACTOR-ANALYSIS; RANDOMIZED CONTROLLED-TRIAL; SUBTHRESHOLD PTSD; PRIMARY-CARE; BEHAVIORAL ACTIVATION; PROLONGED EXPOSURE; MILITARY VETERANS AB Subclinical presentations of posttraumatic stress disorder (PTSD), wherein patients are one or two symptom criteria short of the full disorder, are prevalent and associated with levels of distress and impaired functioning approximating that of full PTSD. Nonetheless, research examining treatment efficacy for this group is in the nascent stage. The purpose of the present study was to examine whether the sub clinical PTSD group would: (1) show a greater reduction in PTSD symptoms at pre and post treatment in response to an exposure based treatment and (2) show a greater rate of change over the course of treatment, when compared to the full criteria PTSD group. We also examined whether differences would emerge when examining PTSD symptom clusters. Consistent with predictions, the subclinical PTSD group demonstrated a greater reduction in PTSD symptoms at post-treatment (29%) than those with a PTSD diagnosis (14%). Further, the groups had different treatment trajectories, with the subclinical PTSD group showing a marginally greater rate of change during the course of treatment. Findings also varied by symptom cluster with the subclinical group showing a greater rate of change in the intrusions, hyper vigilance, and avoidance symptom clusters. There was not a significant between group difference in the numbing symptom cluster. This study provides preliminary evidence that treating PTSD symptoms at the subclinical level may result in a larger, and more rapid symptom reduction, and thus has implications supporting treatment earlier in the developmental trajectory of the disorder. Published by Elsevier Ltd. C1 [Korte, Kristina J.; Allan, Nicholas P.; Gros, Daniel F.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Korte, Kristina J.; Allan, Nicholas P.; Gros, Daniel F.; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM kortek@musc.edu; grosd@musc.edu FU CSRD VA [IK2 CX000845]; NIAAA NIH HHS [T32 AA007474] NR 49 TC 0 Z9 0 U1 4 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAR PY 2016 VL 38 BP 95 EP 101 DI 10.1016/j.janxdis.2016.01.006 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DF6EQ UT WOS:000371449100012 PM 26874291 ER PT J AU Pellino, G Nicolai, E Catalano, OA Campione, S D'Armiento, FP Salvatore, M Cuocolo, A Selvaggi, F AF Pellino, Gianluca Nicolai, Emanuele Catalano, Onofrio A. Campione, Severo D'Armiento, Francesco P. Salvatore, Marco Cuocolo, Alberto Selvaggi, Francesco TI PET/MR Versus PET/CT Imaging: Impact on the Clinical Management of Small-Bowel Crohn's Disease SO JOURNAL OF CROHNS & COLITIS LA English DT Article DE Crohn's disease; diagnosis; surgery; magnetic resonance imaging; fibrosis; inflammation; pathology ID COMPUTED-TOMOGRAPHY ENTEROGRAPHY; 4TH SCIENTIFIC WORKSHOP; INTESTINAL FIBROSIS; NONINVASIVE ASSESSMENT; ULCERATIVE-COLITIS; MR ENTEROGRAPHY; F-18-FDG PET/CT; INFLAMMATION; STRICTURES; ECCO AB Background and Aims: The aim of this study was to compare the accuracy and clinical impact of hybrid positron emission tomography [PET]/magnetic resonance-enterography [MR-E] and PET/computed tomography-enterography [CT-E] in patients with Crohn's disease [CD]. Methods: A total of 35 patients with symptomatic small-bowel CD who were scheduled to undergo operation were evaluated before operation by same-day PET/CT-E and PET/MR-E. PET/MR-E was also compared with MR-E alone. Imaging accuracy for detecting pathological sites and discriminating between fibrotic and inflammatory strictures was assessed. Treatment was adjusted according to imaging findings and change in medical/surgical strategy was also evaluated. Results: PET/CT-E, PET/MR-E, and MR-E were equally accurate in detecting CD sites. PET/MR-E was more accurate in assessing extra-luminal disease [p = 0.002], which was associated with higher need for stoma [p = 0.022] and distant localisation [p = 0.002]. When the latter was observed, laparoscopy was started with hand-assisted device, reducing operative time [p = 0.022]. PET/MR-E was also more accurate in detecting a fibrotic component compared with PET/CT-E [p = 0.043] and with MR-E [p = 0.024]. Fibrosis was more frequently classified as inflammation with MR-E compared with PET/MR-E [p = 0.019]. Out of 8 patients with predominantly inflammatory CD who received medical treatment, 6 [75%] remained surgery free. Overall, 29 patients received surgery. At median follow-up of 9 [6-22] months, no recurrences occurred in either the medical or the surgical group. Conclusions: Preoperative PET/MR-E imaging is highly accurate for assessing CD lesions before operation and contributed to clinical management of patients with small-bowel CD more often than PET/CT-E. C1 [Pellino, Gianluca; Selvaggi, Francesco] Univ Naples 2, Dept Med Surg Neurol Metab & Geriatr Sci, Unit Colorectal Surg, Piazza Miraglia 2, I-80138 Naples, Italy. [Nicolai, Emanuele; Salvatore, Marco] IRCCS SDN, Naples, Italy. [Catalano, Onofrio A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Campione, Severo; D'Armiento, Francesco P.; Cuocolo, Alberto] Univ Naples Federico II, Dept Adv Biomed Sci, Naples, Italy. RP Selvaggi, F (reprint author), Univ Naples 2, Dept Med Surg Neurol Metab & Geriatr Sci, Unit Colorectal Surg, Piazza Miraglia 2, I-80138 Naples, Italy. EM fselvaggi@hotmail.com RI Nicolai, Emanuele/K-6678-2016; OI Nicolai, Emanuele/0000-0003-3171-368X; Cuocolo, Alberto/0000-0003-3431-7658; Pellino, Gianluca/0000-0002-8322-6421 NR 44 TC 3 Z9 3 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD MAR PY 2016 VL 10 IS 3 BP 277 EP 285 DI 10.1093/ecco-jcc/jjv207 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DG1HS UT WOS:000371817600006 PM 26574490 ER PT J AU Sedaghat, G Ghafoori, E Waks, JW Kabir, MM Shvilkin, A Josephson, ME Tereshchenko, LG AF Sedaghat, Golriz Ghafoori, Elyar Waks, Jonathan W. Kabir, Muammar M. Shvilkin, Alexei Josephson, Mark E. Tereshchenko, Larisa G. TI Quantitative Assessment of Vectorcardiographic Loop Morphology SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Vectorcardiography; Planarity; Ventricular tachycardia ID MYOCARDIAL-INFARCTION; HEART-RATE; QRS LOOP; SYSTEM; ELECTROCARDIOGRAM; MORTALITY AB Vectorcardiography (VCG), developed 100 years ago, characterizes clinically important electrophysiological properties of the heart. In this study, VCG QRS loop roundness, planarity, thickness, rotational angle, and dihedral angle were measured in 81 healthy control subjects (39.0 +/- 14.2y; 51.8% male; 94% white), and 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (68.0 +/- 7.8y, 37.5% male). The angle between two consecutive QRS vectors was defined as the rotational angle, while dihedral angle quantified planar alteration over the QRS loop. In VT subjects, planarity index decreased (0.63 +/- 0.22 vs. 0.88 +/- 0.10; P = 0.014), and dihedral angle was significantly more variable (variance of dihedral angle, median (IQR): 897(575-1450) vs. 542(343-773); P = 0.029; rMSSD: 47.7 +/- 12.7 vs. 35.1 +/- 13.1; P = 0.027). Abnormal electrophysiological substrate in VT patients is characterized by the appearance of QRS loop folding, likely due to local conduction block. The presence of fragmented QRS complexes on the 12-lead ECG had low sensitivity (31%) for detecting QRS loop folding on the VCG. (C) 2016 Elsevier Inc. All rights reserved. C1 [Sedaghat, Golriz; Ghafoori, Elyar; Kabir, Muammar M.; Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Waks, Jonathan W.; Shvilkin, Alexei; Josephson, Mark E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA. [Sedaghat, Golriz] Portland State Univ, Portland, OR 97207 USA. [Ghafoori, Elyar] Univ Utah, Salt Lake City, UT USA. RP Tereshchenko, LG (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Shvilkin, Alexei/0000-0003-3662-9938; Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institute of Health [1R01HL118277] FX The authors would like to thank the National Institute of Health #1R01HL118277 (LGT and MEJ) for its support. NR 17 TC 1 Z9 1 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAR-APR PY 2016 VL 49 IS 2 BP 154 EP 163 DI 10.1016/j.jelectrocard.2015.12.014 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG1TH UT WOS:000371849900008 PM 26826894 ER PT J AU Karadeli, HH Giurgiutiu, DV Cloonan, L Fitzpatrick, K Kanakis, A Ozcan, ME Schwamm, LH Rost, NS AF Karadeli, Hasan H. Giurgiutiu, Dan-Victor Cloonan, Lisa Fitzpatrick, Kaitlin Kanakis, Allison Ozcan, Muhammed E. Schwamm, Lee H. Rost, Natalia S. TI FLAIR Vascular Hyperintensity is a Surrogate of Collateral Flow and Leukoaraiosis in Patients With Acute Stroke Due to Proximal Artery Occlusion SO JOURNAL OF NEUROIMAGING LA English DT Article DE Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH); acute ischemic stroke (AIS); white matter disease; leukoaraiosis; collateral ID ACUTE ISCHEMIC-STROKE; WHITE-MATTER LESIONS; CEREBRAL AMYLOID ANGIOPATHY; MR-ANGIOGRAPHY; INFARCTION; SEVERITY; PROGRESSION; VESSELS; DISEASE AB BACKGROUNDFluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is a novel radiographic marker detected in acute ischemic stroke (AIS) patients, which is linked to slow blood flow and potentially salvageable brain tissue. Poor leptomeningeal collateral status in AIS patients with proximal artery occlusion (PAO) is associated with larger final infarct and worse clinical outcomes, which are also affected by severity of white matter hyperintensity (WMH). We sought to evaluate FVH utility as a marker of acute collateral vessel status and its association with WMH burden in AIS patients. METHODSConsecutive AIS patients with PAO on baseline CT angiography (CTA) were retrospectively selected from a prospectively derived database. FVH was graded by its location, degree, and score on admission MRI obtained immediately after intravenous tissue plasminogen activator administration. Leptomeningeal collateral flow grade was ranked on admission CTA. WMH volume (WMHV) was assessed using a validated volumetric protocol. Relationship between FVH, collateral flow grade, and WMHV were analyzed. RESULTSAmong 39 patients (mean age 70.5 12.7 years; 56% women, mean National Institutes of Health Stroke Scale score 17.2 (+/- 4.4)), median WMHV was 6.0cm(3). FVH score and collateral flow grade were significantly correlated (Spearman's = .41, P = .009). In a univariate regression model, FVH degree was inversely associated with WMHV ( = -.33, P = .04). CONCLUSIONSFVH score detected on acute MRI can be used as a surrogate of collateral flow grade in AIS patients. FVH degree is inversely associated with WMHV, possibly signifying diffuse disease of cerebral vasculature in patients with severe leukoaraiosis. C1 [Karadeli, Hasan H.; Giurgiutiu, Dan-Victor; Cloonan, Lisa; Fitzpatrick, Kaitlin; Kanakis, Allison; Schwamm, Lee H.; Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. [Karadeli, Hasan H.; Ozcan, Muhammed E.] BezmialemVakif Univ, Dept Neurol, Istanbul, Turkey. [Giurgiutiu, Dan-Victor; Kanakis, Allison] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU NIH-NINDS [K23NS064052, R01NS082285-01A1]; TUBITAK [1059B191400176] FX This work is supported by the NIH-NINDS (K23NS064052 and R01NS082285-01A1, N. S. R) and the TUBITAK (1059B191400176, H. H. K.) awards. NR 26 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 EI 1552-6569 J9 J NEUROIMAGING JI J. Neuroimaging PD MAR-APR PY 2016 VL 26 IS 2 BP 219 EP 223 DI 10.1111/jon.12274 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DG0DW UT WOS:000371734400011 PM 26250448 ER PT J AU Krigbaum, H Takemoto, S Kim, HT Kuo, AC AF Krigbaum, Henry Takemoto, Steven Kim, Hubert T. Kuo, Alfred C. TI Costs and Complications of Short Versus Long Cephalomedullary Nailing of OTA 31-A2 Proximal Femur Fractures in U.S. Veterans SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE cephalomedullary nail; intertrochanteric femur fracture ID INTERTROCHANTERIC HIP-FRACTURES; INTRAMEDULLARY NAILS; GAMMA-NAIL; A2 AB Objectives: In fractures without subtrochanteric extension, the indications for the use of short versus long cephalomedullary nails (CMNs) for intertrochanteric femur fractures are unclear. We hypothesized that long nails would be associated with higher costs and similar complication rates. Design: Retrospective comparative study. Setting: United States Department of Veterans Affairs Medical Centers. Participants: Patients receiving CMNs for OTA 31-A2 pertrochanteric fractures from 2001 to 2010. Interventions: Short versus long cephalomedullary nailing. Main Outcome Measurements: Costs, perioperative complications, readmissions, surgical failures, and mortality. Results: We identified 262 patients with OTA 31-A2 pertrochanteric fractures (125 treated with short CMNs and 137 treated with long CMNs). The 2 cohorts had similar demographic and medical characteristics. There were no significant differences in perioperative complications, readmissions within 30 days, surgical failures within one year, or death within 30 days or one year. The average cost of hospitalization was significantly higher for the cohort treated with long nails (greater than $7000 in actual costs, and greater than $3000 when statistically adjusted for differences in postoperative lengths of stay). Multivariable analyses showed no significant differences in the rates of development of at least one complication, readmission, or death. Conclusions: In a cohort of patients with similar characteristics and fracture patterns, the use of long CMNs was associated with similar rates of complications, readmission, and reoperations, but significantly higher costs than with the use of short nails. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. C1 [Kuo, Alfred C.] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kuo, AC (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM kuoac@orthosurg.ucsf.edu FU James O. Johnston resident research grant FX Supported by the James O. Johnston resident research grant to H. Krigbaum. NR 14 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAR PY 2016 VL 30 IS 3 BP 125 EP 129 DI 10.1097/BOT.0000000000000521 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA DF5IK UT WOS:000371384900005 PM 26894639 ER PT J AU Sidhu, MS Lumish, H Uthamalingam, S Engel, LC Abbara, S Brady, TJ Hoffmann, U Ghoshhajra, BB AF Sidhu, Manavjot S. Lumish, Heidi Uthamalingam, Shanmugam Engel, Leif-Christopher Abbara, Suhny Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian B. TI Adherence to the 2010 American College of Cardiology Foundation Appropriate Use Criteria for Cardiac Computed Tomography: Quality Analysis at a Tertiary Referral Center SO JOURNAL OF PATIENT SAFETY LA English DT Article DE appropriate use criteria; cardiac computed tomography; quality improvement ID ECHOCARDIOGRAPHY; ASSOCIATION; PROGRESS; DISEASE AB Background In November 2010, the American College of Cardiology Foundation published revised appropriateness criteria (AC) for cardiac computed tomography (CT). We evaluated adherence to these criteria by providers of different subspecialties at a tertiary referral center. Methods Reports of 383 consecutive patients who underwent clinically indicated cardiac CT from December 1, 2010, to July 31, 2011, were reviewed by physicians with appropriate training in cardiac CT. Scans were classified as appropriate, inappropriate, or uncertain based on the revised 2010 AC. Studies that did not fall under any of the specified indications were labeled as unclassified. Adherence to the AC was also analyzed as a function of provider type. Research scans were excluded from this analysis. Results Three hundred eight exams (80%) were classified as appropriate; 26 (7%), as inappropriate; 30 (8%), as uncertain; and 19 (5%), as unclassified. Of the 19 (5%) unclassified cardiac CT exams, the most common indication was for evaluation of suspected aortic dissection. Three hundred five exams (80%) were referred by cardiologists; 73 (19%), by internists; and 5 (1%), by neurologists. Of the 305 cardiology-referred studies, 221 (73%) were ordered by general cardiologists; 28 (9%), by interventional cardiologists; and 56 (19%), by electrophysiologists. There was no significant difference in adherence to the criteria between provider specialties or between cardiology subspecialties (P > 0.05). Conclusions high across provider specialties. C1 [Sidhu, Manavjot S.] Massachusetts Gen Hosp, Dept Radiol, Dept Cardiovasc Imaging, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. [Sidhu, Manavjot S.] Massachusetts Gen Hosp, Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. [Sidhu, Manavjot S.] Harvard Univ, Sch Med, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Dept Cardiovasc Imaging, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.; Sidhu, MS (reprint author), Massachusetts Gen Hosp, Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.; Sidhu, MS (reprint author), Harvard Univ, Sch Med, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM manavsidhu83@gmail.com NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD MAR PY 2016 VL 12 IS 1 BP 40 EP 43 DI 10.1097/PTS.0000000000000124 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DF8AJ UT WOS:000371578700006 PM 25136850 ER PT J AU Norton, EK Singer, SJ Sparks, W Ozonoff, A Baxter, J Rangel, S AF Norton, Elizabeth K. Singer, Sara J. Sparks, William Ozonoff, Al Baxter, Jessica Rangel, Shawn TI Operating Room Clinicians' Attitudes and Perceptions of a Pediatric Surgical Safety Checklist at 1 Institution SO JOURNAL OF PATIENT SAFETY LA English DT Article DE pediatric surgical safety checklist; attitudes; survey; teamwork; operating room; communication; perceptions ID IMPLEMENTATION; MORTALITY AB Background Despite mounting evidence that use of surgical checklists improves patient morbidity and mortality, compliance among surgical teams in executing required elements of checklists has been low. Recognizing that clinicians' receptivity is a major determinant of checklist use, we conducted a survey to investigate how mandated use of a surgical checklist impacts its operating room clinicians' attitudes about and perceptions of operating room safety, efficiency, teamwork, and prevention of medical errors. Methods Operating room clinicians at 1 pediatric hospital were surveyed on their attitudes and perception of the novel Pediatric Surgical Safety Checklist and the impact the checklist had on efficiency, teamwork, and prevention of medical errors 1 year after its implementation. The survey responses were compared and classified by multidisciplinary perioperative clinical staff. Results Most responses reflected positive attitudes toward checklist use. The respondents felt that the checklist reduced complications and errors and improved patient safety, communication among team members, teamwork in complex procedures, and efficiency in the operating room. Many operating room staff also reported that checklist use had prevented or averted an error or a complication. Perceptions varied according to perioperative clinical discipline, reflecting differences in perspectives. For example, the nurses perceived a higher rate of consent-related errors and site marking errors than did the physicians; the surgeons reported more antibiotic timing and equipment errors than did others. Conclusions The surgical staff at 1 pediatric hospital who responded viewed the novel Pediatric Surgical Safety Checklist as potentially beneficial to operative patient safety by improving teamwork and communication, reducing errors, and improving efficiency. Responses varied by discipline, indicating that team members view the checklist from different perspectives. C1 [Norton, Elizabeth K.; Baxter, Jessica] Boston Childrens Hosp, Dept Nursing, Boston, MA 02115 USA. [Rangel, Shawn] Boston Childrens Hosp, Dept Gen Surg, Boston, MA 02115 USA. [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Mongan Inst Hlth Policy, Boston, MA USA. [Sparks, William] Boston Childrens Hosp, Dept Anesthesiol & Perioperat Pain Management, Clin Res Ctr, Boston, MA 02115 USA. [Ozonoff, Al] Boston Childrens Hosp, Dept Design & Anal Core, Clin Res Ctr, Boston, MA 02115 USA. [Ozonoff, Al] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Norton, EK (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM elizabeth.norton@childrens.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD MAR PY 2016 VL 12 IS 1 BP 44 EP 50 DI 10.1097/PTS.0000000000000120 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DF8AJ UT WOS:000371578700007 PM 25010191 ER PT J AU Schuler, M Wu, YL Hirsh, V O'Byrne, K Yamamoto, N Mok, T Popat, S Sequist, LV Massey, D Zazulina, V Yang, JCH AF Schuler, Martin Wu, Yi-Long Hirsh, Vera O'Byrne, Kenneth Yamamoto, Nobuyuki Mok, Tony Popat, Sanjay Sequist, Lecia V. Massey, Dan Zazulina, Victoria Yang, James C. -H. TI First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Afatinib; NSCLC; Brain metastases; Epidermal growth factor receptor ID TYROSINE KINASE INHIBITORS; ERBB FAMILY BLOCKER; HIGH-DOSE ERLOTINIB; EGFR MUTATIONS; PHASE-III; ADENOCARCINOMA; MANAGEMENT; SURVIVAL; RADIOTHERAPY; GEFITINIB AB Introduction: Metastatic spread to the brain is common in patients with non-small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. Methods: For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). Results: In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3:11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6:8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. Conclusions: These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases. (C) 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. C1 [Schuler, Martin] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Schuler, Martin] German Canc Consortium DKTK, Heidelberg, Germany. [Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Hirsh, Vera] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [O'Byrne, Kenneth] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [O'Byrne, Kenneth] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Yamamoto, Nobuyuki] Wakayama Med Univ, Wakayama, Japan. [Mok, Tony] Chinese Univ Hong Kong, Hong Kong Canc Inst, State Key Lab South China, Hong Kong, Hong Kong, Peoples R China. [Popat, Sanjay] Royal Marsden Hosp, London SW3 6JJ, England. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Massey, Dan; Zazulina, Victoria] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Yang, James C. -H.] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Yang, James C. -H.] Natl Taiwan Univ, Taipei 10764, Taiwan. RP Schuler, M (reprint author), Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Hufelandstr 55, D-45147 Essen, Germany. EM Martin.Schuler@uk-essen.de NR 33 TC 24 Z9 25 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2016 VL 11 IS 3 BP 380 EP 390 DI 10.1016/j.jtho.2015.11.014 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DF6DP UT WOS:000371446400011 PM 26823294 ER PT J AU Suhasini, AN Wang, L Holder, KN Lin, AP Bhatnagar, H Kim, SW Moritz, AW Aguiar, RCT AF Suhasini, A. N. Wang, L. Holder, K. N. Lin, A-P Bhatnagar, H. Kim, S-W Moritz, A. W. Aguiar, R. C. T. TI A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma SO LEUKEMIA LA English DT Article ID NON-HODGKIN-LYMPHOMA; MICROVESSEL DENSITY; GENE-EXPRESSION; CYCLIC-AMP; MURINE LYMPHOMAS; PDE4 INHIBITORS; PROLIFERATION; CANCER; VEGF; CHEMOTHERAPY AB Angiogenesis associates with poor outcome in diffuse large B-cell lymphoma (DLBCL), but the contribution of the lymphoma cells to this process remains unclear. Addressing this knowledge gap may uncover unsuspecting proangiogenic signaling nodes and highlight alternative antiangiogenic therapies. Here, we identify the second messenger cyclic-AMP (cAMP) and the enzyme that terminates its activity, phosphodiesterase 4B (PDE4B), as regulators of B-cell lymphoma angiogenesis. We first show that cAMP, in a PDE4B-dependent manner, suppresses PI3K/AKT signals to downmodulate vascular endothelial growth factor (VEGF) secretion and vessel formation in vitro. Next, we create a novel mouse model that combines the lymphomagenic Myc transgene with germline deletion of Pde4b. We show that lymphomas developing in a Pde4b-null background display significantly lower microvessel density (MVD) in association with lower VEGF levels and PI3K/AKT activity. We recapitulate these observations by treating lymphoma-bearing mice with the FDA-approved PDE4 inhibitor, Roflumilast. Lastly, we show that primary human DLBCLs with high PDE4B expression display significantly higher MVD. Here, we defined an unsuspected signaling circuitry in which the cAMP generated in lymphoma cells downmodulates PI3K/AKT and VEGF secretion to negatively influence vessel development in the microenvironment. These data identify PDE4 as an actionable antiangiogenic target in DLBCL. C1 [Suhasini, A. N.; Wang, L.; Lin, A-P; Bhatnagar, H.; Kim, S-W; Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Holder, K. N.; Moritz, A. W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Aguiar, R. C. T.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Aguiar, RCT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM aguiarr@uthscsa.edu FU CPRIT [RP110200, RP150277]; William and Ella Owens Medical Research Foundation; Cancer Center support grant [P30 CA054174] FX We thank the Cancer Therapy and Research Center at UTHSCSA Core Pathology Tissue Bank for procurement of the primary DLBCL samples. We acknowledge Patricia Dahia for insightful suggestions during the execution of this project. This work was supported by CPRIT awards RP110200 and RP150277 (to RCTA), a grant from the William and Ella Owens Medical Research Foundation (to RCTA), and a Cancer Center support grant P30 CA054174. NR 48 TC 3 Z9 3 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2016 VL 30 IS 3 BP 617 EP 626 DI 10.1038/leu.2015.302 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DF9NR UT WOS:000371688500011 PM 26503641 ER PT J AU Zeidan, AM Sekeres, MA Garcia-Manero, G Steensma, D Zell, K Barnard, J Ali, NA Zimmerman, C Roboz, G DeZern, A Nazha, A Jabbour, E Kantarjian, H Gore, SD Maciejewski, JP List, A Komrokji, R AF Zeidan, A. M. Sekeres, M. A. Garcia-Manero, G. Steensma, D. P. Zell, K. Barnard, J. Ali, N. A. Zimmerman, C. Roboz, G. DeZern, A. Nazha, A. Jabbour, E. Kantarjian, H. Gore, S. D. Maciejewski, J. P. List, A. Komrokji, R. CA MDS Clinical Res Consortium TI Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides SO LEUKEMIA LA English DT Article ID PROGNOSTIC SCORING SYSTEM; LEUKEMIA GROUP-B; CONVENTIONAL CARE REGIMENS; ACUTE MYELOID-LEUKEMIA; RANDOMIZED PHASE-III; HYPOMETHYLATING AGENTS; MOLECULAR MUTATIONS; ELDERLY-PATIENTS; GENETIC-BASIS; AZACITIDINE AB Established prognostic tools in patients with myelodysplastic syndromes (MDS) were largely derived from untreated patient cohorts. Although azanucleosides are standard therapies for higher-risk (HR)-MDS, the relative prognostic performance of existing prognostic tools among patients with HR-MDS receiving azanucleoside therapy is unknown. In the MDS Clinical Research Consortium database, we compared the prognostic utility of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Prognostic Scoring System (MDAPSS), World Health Organization-based Prognostic Scoring System (WPSS) and the French Prognostic Scoring System (FPSS) among 632 patients who presented with HR-MDS and were treated with azanucleosides as the first-line therapy. Median follow-up from diagnosis was 15.7 months. No prognostic tool predicted the probability of achieving an objective response. Nonetheless, all five tools were associated with overall survival (OS, P = 0.025 for the IPSS, P = 0.011 for WPSS and P<0.001 for the other three tools). The corrected Akaike Information Criteria, which were used to compare OS with the different prognostic scoring systems as covariates (lower is better) were 4138 (MDAPSS), 4156 (FPSS), 4196 (IPSS-R), 4186 (WPSS) and 4196 (IPSS). Patients in the highest-risk groups of the prognostic tools had a median OS from diagnosis of 11 - 16 months and should be considered for up-front transplantation or experimental approaches. C1 [Zeidan, A. M.; Gore, S. D.] Yale Univ, Sect Hematol, Dept Internal Med, Yale Comprehens Canc Ctr, 333 Cedar St,POB 208028, New Haven, CT 06520 USA. [Sekeres, M. A.; Zell, K.; Barnard, J.; Zimmerman, C.; Nazha, A.; Maciejewski, J. P.] Cleveland Clin, Dept Translat Hematol & Oncol Res, Leukemia Program, Cleveland, OH 44106 USA. [Garcia-Manero, G.; Jabbour, E.; Kantarjian, H.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Steensma, D. P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [List, A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA. [Roboz, G.] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. [DeZern, A.] Johns Hopkins Univ, Dept Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Zeidan, AM (reprint author), Yale Univ, Sect Hematol, Dept Internal Med, Yale Comprehens Canc Ctr, 333 Cedar St,POB 208028, New Haven, CT 06520 USA. EM amer.zeidan@yale.edu FU Evans Foundation; Aplastic Anemia and Myelodysplastic Syndromes Foundation; MDS Clinical Research Consortium; American Society of Oncology Young Investigator Award FX We would like to thank the patients who contributed to this large database and their families, as well the research coordinators in the six sites who worked to construct the database. The authors would also like to thank the Evans Foundation and the Aplastic Anemia and Myelodysplastic Syndromes Foundation for supporting the research activities of the MDS Clinical Research Consortium. This research was presented in part at the American Society of Hematology 56th Annual meeting in San Francisco, CA, USA in December 2014. AMZ received funding through MDS Clinical Research Consortium and the American Society of Oncology Young Investigator Award. NR 45 TC 6 Z9 6 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2016 VL 30 IS 3 BP 649 EP 657 DI 10.1038/leu.2015.283 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA DF9NR UT WOS:000371688500015 PM 26464171 ER PT J AU Wu, H Hu, C Wang, A Weisberg, EL Wang, W Chen, C Zhao, Z Yu, K Liu, J Wu, J Nonami, A Wang, L Wang, B Stone, RM Liu, S Griffin, JD Liu, J Liu, Q AF Wu, H. Hu, C. Wang, A. Weisberg, E. L. Wang, W. Chen, C. Zhao, Z. Yu, K. Liu, J. Wu, J. Nonami, A. Wang, L. Wang, B. Stone, R. M. Liu, S. Griffin, J. D. Liu, J. Liu, Q. TI Ibrutinib selectively targets FLT3-ITD in mutant FLT3-positive AML SO LEUKEMIA LA English DT Letter ID BRUTON TYROSINE KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; B-CELL MALIGNANCIES; BTK; INHIBITION; PCI-32765; ARTHRITIS C1 [Wu, H.; Hu, C.; Wang, A.; Wang, W.; Chen, C.; Zhao, Z.; Yu, K.; Liu, J.; Wu, J.; Wang, L.; Wang, B.; Liu, J.; Liu, Q.] Chinese Acad Sci, High Field Magnet Lab, Hefei, Anhui, Peoples R China. [Wu, H.; Wang, A.; Wu, J.; Liu, Q.] Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China. [Weisberg, E. L.; Nonami, A.; Stone, R. M.; Liu, S.; Griffin, J. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RP Liu, J; Liu, Q (reprint author), Chinese Acad Sci, High Field Magnet Lab, Hefei, Anhui, Peoples R China.; Liu, Q (reprint author), Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China. EM jingliu@hmfl.ac.cn; qsliu97@hmfl.ac.cn OI liu, jing/0000-0001-9513-3591 FU NCI NIH HHS [P01 CA066996] NR 18 TC 3 Z9 3 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2016 VL 30 IS 3 BP 754 EP 757 DI 10.1038/leu.2015.175 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DF9NR UT WOS:000371688500029 PM 26139428 ER PT J AU Touzeau, C Ryan, J Guerriero, J Moreau, P Chonghaile, TN Le Gouill, S Richardson, P Anderson, K Amiot, M Letai, A AF Touzeau, C. Ryan, J. Guerriero, J. Moreau, P. Chonghaile, T. N. Le Gouill, S. Richardson, P. Anderson, K. Amiot, M. Letai, A. TI BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics SO LEUKEMIA LA English DT Letter ID ABT-199; LEUKEMIA; CELLS; MCL-1; INHIBITION; ADDICTION; DEATH C1 [Touzeau, C.; Ryan, J.; Guerriero, J.; Richardson, P.; Anderson, K.; Letai, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Touzeau, C.; Moreau, P.; Le Gouill, S.] Univ Hosp, Dept Hematol, Nantes, France. [Touzeau, C.; Moreau, P.; Le Gouill, S.; Amiot, M.] Univ Nantes, CNRS UMR6299, INSERM UMR892, Nantes, France. [Chonghaile, T. N.] Conway Inst Biomol & Biomed Res, Dublin, Ireland. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU NCI NIH HHS [R01 CA129974, R01CA129974] NR 17 TC 12 Z9 12 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2016 VL 30 IS 3 BP 761 EP 764 DI 10.1038/leu.2015.184 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DF9NR UT WOS:000371688500031 PM 26174630 ER PT J AU Brown, RB Razzaque, MS AF Brown, Ronald B. Razzaque, Mohammed S. TI Phosphate toxicity: a stealth biochemical stress factor? SO MEDICAL MOLECULAR MORPHOLOGY LA English DT Editorial Material ID INORGANIC-PHOSPHATE; FGF23-KLOTHO AXIS; VITAMIN-D; HOMEOSTASIS; APOPTOSIS; CELLS; FGF23; RECEPTOR; KLOTHO; CKD C1 [Brown, Ronald B.] Kansas State Univ, Coll Human Ecol, Manhattan, KS 66506 USA. [Razzaque, Mohammed S.] Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. [Razzaque, Mohammed S.] VPS Hlth Care, Div Res & Dev, Abu Dhabi, U Arab Emirates. [Razzaque, Mohammed S.] Saba Univ, Dept Pathol, Devens, MA USA. RP Razzaque, MS (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA.; Razzaque, MS (reprint author), VPS Hlth Care, Div Res & Dev, Abu Dhabi, U Arab Emirates.; Razzaque, MS (reprint author), Saba Univ, Dept Pathol, Devens, MA USA. EM mrazzaque@forsyth.org NR 33 TC 1 Z9 1 U1 2 U2 4 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 1860-1480 EI 1860-1499 J9 MED MOL MORPHOL JI Med. Mol. Morphol. PD MAR PY 2016 VL 49 IS 1 BP 1 EP 4 DI 10.1007/s00795-015-0122-3 PG 4 WC Biology; Microscopy; Pathology SC Life Sciences & Biomedicine - Other Topics; Microscopy; Pathology GA DF7IC UT WOS:000371530300001 PM 26582553 ER PT J AU Logan, SM Tessier, SN Tye, J Storey, KB AF Logan, Samantha M. Tessier, Shannon N. Tye, Joann Storey, Kenneth B. TI Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE JAK-STAT signal transduction; Anti-apoptosis; Heart; Muscle; Ictidomys tridecemlineatus; Mammalian hibernation ID SKELETAL-MUSCLE; GENE-EXPRESSION; SERINE PHOSPHORYLATION; SIGNALING PATHWAY; GROWTH-HORMONE; REAL-TIME; TRANSCRIPTION; ACTIVATION; SURVIVAL; TORPOR AB Over the course of the torpor-arousal cycle, hibernators must make behavioral, physiological, and molecular rearrangements in order to keep a very low metabolic rate and retain organ viability. 13-lined ground squirrels (Ictidomys tridecemlineatus) remain immobile during hibernation, and although the mechanisms of skeletal muscle survival are largely unknown, studies have shown minimal muscle loss in hibernating organisms. Additionally, the ground squirrel heart undergoes cold-stress, reversible cardiac hypertrophy, and ischemia-reperfusion without experiencing fatal impairment. This study examines the role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway in the regulation of cell stress in cardiac and skeletal muscles, comparing euthermic and hibernating ground squirrels. Immunoblots showed a fivefold decrease in JAK3 expression during torpor in skeletal muscle, along with increases in STAT3 and 5 phosphorylation and suppressors of cytokine signaling-1 (SOCS1) protein levels. Immunoblots also showed coordinated increases in STAT1, 3 and 5 phosphorylation and STAT1 inhibitor protein expression in cardiac muscle during torpor. PCR analysis revealed that the activation of these pro-survival signaling cascades did not result in coordinate changes in downstream genes such as anti-apoptotic B-cell lymphoma-2 (Bcl-2) family gene expression. Overall, these results indicate activation of the JAK-STAT pathway in both cardiac and skeletal muscles, suggesting a response to cellular stress during hibernation. C1 [Logan, Samantha M.; Tessier, Shannon N.; Tye, Joann; Storey, Kenneth B.] Carleton Univ, Inst Biochem, 1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada. [Logan, Samantha M.; Tessier, Shannon N.; Tye, Joann; Storey, Kenneth B.] Carleton Univ, Dept Biol, 1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada. [Tessier, Shannon N.] Massachusetts Gen Hosp, Dept Surg, Bldg 114,16th St, Charlestown, MA 02129 USA. [Tessier, Shannon N.] Massachusetts Gen Hosp, Ctr Engn Med, Bldg 114,16th St, Charlestown, MA 02129 USA. [Tessier, Shannon N.] Harvard Univ, Sch Med, Bldg 114,16th St, Charlestown, MA 02129 USA. [Tye, Joann] New Beginnings Ob Gyn, 193 Mt Ave, Springfield, NJ 07081 USA. RP Storey, KB (reprint author), Carleton Univ, Inst Biochem, 1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada.; Storey, KB (reprint author), Carleton Univ, Dept Biol, 1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada. EM kenneth_storey@carleton.ca FU Natural Sciences and Engineering Research Council of Canada [6793]; Heart and Stroke Foundation of Canada [G-14-0005874]; NSERC FX We thank Dr. J. M. Hallenbeck at the NIH for providing ground squirrel tissues, Bryan E. Luu for advice and assistance with polymerase chain reaction and Luminex (R) assay preparation, and Jan Storey for editorial review of this manuscript. This work was supported by a Discovery Grant (#6793) from the Natural Sciences and Engineering Research Council of Canada and a grant from the Heart and Stroke Foundation of Canada (#G-14-0005874). KBS holds the Canada Research Chair in Molecular Physiology, SNT holds a NSERC Postdoctoral Fellowship, and SML held an NSERC Undergraduate Student Research Award. NR 55 TC 2 Z9 3 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2016 VL 414 IS 1-2 BP 115 EP 127 DI 10.1007/s11010-016-2665-6 PG 13 WC Cell Biology SC Cell Biology GA DF8TU UT WOS:000371633300012 PM 26885984 ER PT J AU Kvedar, JC Fogel, AL Elenko, E Zohar, D AF Kvedar, Joseph C. Fogel, Alexander L. Elenko, Eric Zohar, Daphne TI Digital medicine's march on chronic disease SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID UNITED-STATES; ADHERENCE; THERAPY; MEDICATION; TRIAL C1 [Kvedar, Joseph C.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kvedar, Joseph C.] Harvard Univ, Sch Med, Boston, MA USA. [Kvedar, Joseph C.] Partners Healthcare, Partners Connected Hlth, Boston, MA USA. [Fogel, Alexander L.] Stanford Univ, Grad Sch Business, Stanford, CA 94305 USA. [Fogel, Alexander L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Elenko, Eric; Zohar, Daphne] PureTech Hlth, Boston, MA USA. RP Zohar, D (reprint author), PureTech Hlth, Boston, MA USA. EM DaphneNB@puretechhealth.com NR 41 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2016 VL 34 IS 3 BP 239 EP 246 DI 10.1038/nbt.3495 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DG1CJ UT WOS:000371802600014 PM 26963544 ER PT J AU Amit, I Baker, D Barker, R Berger, B Bertozzi, C Bhatia, S Biffi, A Demichelis, F Doudna, J Dowdy, SF Endy, D Helmstaedter, M Junca, H June, C Kamb, S Khvorova, A Kim, DH Kim, JS Krishnan, Y Lakadamyali, M Lappalainen, T Lewin, S Liao, J Loman, N Lundberg, E Lynd, L Martin, C Mellman, I Miyawaki, A Mummery, C Nelson, K Paz, J Peralta-Yahya, P Picotti, P Polyak, K Prather, K Qin, J Quake, S Regev, A Rogers, JA Shetty, R Sommer, M Stevens, M Stolovitzky, G Takahashi, M Tang, F Teichmann, S Torres-Padilla, ME Tripathi, L Vemula, P Verdine, G Vollmer, F Wang, J Ying, JY Zhang, F Zhang, T AF Amit, Ido Baker, David Barker, Roger Berger, Bonnie Bertozzi, Carolyn Bhatia, Sangeeta Biffi, Alessandra Demichelis, Francesca Doudna, Jennifer Dowdy, Steven F. Endy, Drew Helmstaedter, Moritz Junca, Howard June, Carl Kamb, Sasha Khvorova, Anastasia Kim, Dae-Hyeong Kim, Jin-Soo Krishnan, Yamuna Lakadamyali, Melike Lappalainen, Tuuli Lewin, Sharon Liao, James Loman, Nick Lundberg, Emma Lynd, Lee Martin, Cathie Mellman, Ira Miyawaki, Atsushi Mummery, Christine Nelson, Karen Paz, Jeanne Peralta-Yahya, Pamela Picotti, Paola Polyak, Kornelia Prather, Kristala Qin, Jun Quake, Stephen Regev, Aviv Rogers, John A. Shetty, Reshma Sommer, Morten Stevens, Molly Stolovitzky, Gustavo Takahashi, Masayo Tang, Fuchou Teichmann, Sarah Torres-Padilla, Maria-Elena Tripathi, Leena Vemula, Praveen Verdine, Greg Vollmer, Frank Wang, Jun Ying, Jackie Y. Zhang, Feng Zhang, Tian TI Voices of biotech SO NATURE BIOTECHNOLOGY LA English DT Article C1 [Amit, Ido] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Baker, David] Univ Washington, Seattle, WA 98195 USA. [Barker, Roger] Univ Cambridge, Cambridge, England. MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Bertozzi, Carolyn; Endy, Drew; Quake, Stephen] Stanford Univ, Stanford, CA 94305 USA. [Biffi, Alessandra; Polyak, Kornelia] Dana Farber Canc Inst, Cambridge, MA USA. [Biffi, Alessandra; Polyak, Kornelia; Regev, Aviv; Verdine, Greg] Harvard Univ, Cambridge, MA 02138 USA. [Demichelis, Francesca] Univ Trento, Trento, Italy. [Doudna, Jennifer] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Dowdy, Steven F.] Univ Calif San Diego, San Diego, CA 92103 USA. [Helmstaedter, Moritz] Max Planck Inst Brain Res, Frankfurt, Germany. [Junca, Howard] Microbiomas Fdn, Chia, Colombia. [June, Carl] Univ Penn, Philadelphia, PA 19104 USA. [Kamb, Sasha] Amgen Inc, Thousand Oaks, CA USA. [Khvorova, Anastasia] Univ Massachusetts, Worcester, MA 01605 USA. [Kim, Dae-Hyeong; Kim, Jin-Soo] Seoul Natl Univ, Seoul, South Korea. [Krishnan, Yamuna] Univ Chicago, Chicago, IL 60637 USA. [Lakadamyali, Melike] Inst Photon Sci, Barcelona, Spain. [Lappalainen, Tuuli] New York Genome Ctr New York, New York, NY USA. [Lappalainen, Tuuli] Columbia Univ, New York, NY USA. [Lewin, Sharon] Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia. [Liao, James] Univ Calif Los Angeles, Los Angeles, CA USA. [Loman, Nick] Univ Birmingham, Birmingham, W Midlands, England. [Lundberg, Emma] KTH Royal Inst Technol, Stockholm, Sweden. [Lynd, Lee] Dartmouth Coll, Hanover, NH 03755 USA. [Martin, Cathie] John Innes Ctr, Norwich, Norfolk, England. [Mellman, Ira] Genentech Inc, San Francisco, CA 94080 USA. [Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Mummery, Christine] Leiden Univ, Med Ctr, Leiden, Netherlands. [Nelson, Karen] J Craig Venter Inst, La Jolla, CA USA. [Nelson, Karen] Human Longev, San Diego, CA USA. [Paz, Jeanne] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. [Peralta-Yahya, Pamela] Georgia Inst Technol, Atlanta, GA 30332 USA. [Picotti, Paola] Swiss Fed Inst Technol, Zurich, Switzerland. [Qin, Jun] Beijing Proteome Res Ctr, Beijing, Peoples R China. [Qin, Jun] Baylor Coll Med, Houston, TX 77030 USA. [Rogers, John A.] Univ Illinois, Champaign, IL USA. [Shetty, Reshma] Ginkgo Bioworks, Boston, MA USA. [Sommer, Morten; Zhang, Tian] Tech Univ Denmark, Horsholm, Denmark. [Stevens, Molly] Univ London Imperial Coll Sci Technol & Med, London, England. [Stolovitzky, Gustavo] IBM Res Corp, Yorktown Hts, NY USA. [Stolovitzky, Gustavo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Takahashi, Masayo] RIKEN, Ctr Dev Biol, Kobe, Hyogo, Japan. [Tang, Fuchou] Peking Univ, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China. [Teichmann, Sarah] Wellcome Trust Sanger Inst, Cambridge, England. [Torres-Padilla, Maria-Elena] Inst Genet & Biol Mol & Cellulaire, Strasbourg, France. [Torres-Padilla, Maria-Elena] Helmholtz Ctr, Inst Epigenet & Stem Cells, Munich, Germany. [Tripathi, Leena] Int Inst Trop Agr, Ibadan, Kenya. [Vemula, Praveen] Inst Stem Cell Biol & Regenerat Med, Bangalore, Karnataka, India. [Verdine, Greg] Warp Drive Bio, Cambridge, MA USA. [Verdine, Greg] FogPharma, Gloucester, MA USA. [Vollmer, Frank] Max Planck Inst Sci Light, Erlangen, Germany. [Wang, Jun] ICarbonX, Shenzhen, Peoples R China. [Ying, Jackie Y.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RP Amit, I (reprint author), Weizmann Inst Sci, IL-76100 Rehovot, Israel. RI Rogers, John /L-2798-2016; Junca, Howard/K-5525-2014; Miyawaki, Atsushi/K-3569-2014; Zhang, Tian/N-4696-2015 OI Junca, Howard/0000-0003-4546-6229; Miyawaki, Atsushi/0000-0002-2329-3235; Lappalainen, Tuuli/0000-0002-7746-8109; Vollmer, Frank/0000-0003-0565-4671; Zhang, Tian/0000-0003-3840-4839 FU Biotechnology and Biological Sciences Research Council [BBS/E/J/00000153]; Medical Research Council [MR/M501621/1]; NIGMS NIH HHS [R01 GM108803] NR 0 TC 0 Z9 0 U1 15 U2 55 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2016 VL 34 IS 3 BP 270 EP 275 DI 10.1038/nbt.3502 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DG1CJ UT WOS:000371802600019 PM 26963549 ER PT J AU Vegas, AJ Veiseh, O Doloff, JC Ma, ML Tam, HH Bratlie, K Li, J Bader, AR Langan, E Olejnik, K Fenton, P Kang, JW Hollister-Locke, J Bochenek, MA Chiu, A Siebert, S Tang, K Jhunjhunwala, S Aresta-Dasilva, S Dholakia, N Thakrar, R Vietti, T Chen, M Cohen, J Siniakowicz, K Qi, MRG McGarrigle, J Lyle, S Harlan, DM Greiner, DL Oberholzer, J Weir, GC Langer, R Anderson, DG AF Vegas, Arturo J. Veiseh, Omid Doloff, Joshua C. Ma, Minglin Tam, Hok Hei Bratlie, Kaitlin Li, Jie Bader, Andrew R. Langan, Erin Olejnik, Karsten Fenton, Patrick Kang, Jeon Woong Hollister-Locke, Jennifer Bochenek, Matthew A. Chiu, Alan Siebert, Sean Tang, Katherine Jhunjhunwala, Siddharth Aresta-Dasilva, Stephanie Dholakia, Nimit Thakrar, Raj Vietti, Thema Chen, Michael Cohen, Josh Siniakowicz, Karolina Qi, Meirigeng McGarrigle, James Lyle, Stephen Harlan, David M. Greiner, Dale L. Oberholzer, Jose Weir, Gordon C. Langer, Robert Anderson, Daniel G. TI Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates SO NATURE BIOTECHNOLOGY LA English DT Article ID ALGINATE-BASED MICROCAPSULES; L-LYSINE MICROCAPSULES; INFLAMMATORY RESPONSES; MECHANICAL-PROPERTIES; CONFOCAL RAMAN; ISLETS; BIOMATERIALS; MEMBRANE; BIOCOMPATIBILITY; ENCAPSULATION AB The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient(1-6). There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response. C1 [Vegas, Arturo J.; Veiseh, Omid; Doloff, Joshua C.; Ma, Minglin; Tam, Hok Hei; Bratlie, Kaitlin; Li, Jie; Bader, Andrew R.; Langan, Erin; Olejnik, Karsten; Fenton, Patrick; Chiu, Alan; Siebert, Sean; Tang, Katherine; Jhunjhunwala, Siddharth; Aresta-Dasilva, Stephanie; Dholakia, Nimit; Thakrar, Raj; Vietti, Thema; Chen, Michael; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Vegas, Arturo J.; Doloff, Joshua C.; Ma, Minglin; Li, Jie; Bader, Andrew R.; Langan, Erin; Olejnik, Karsten; Fenton, Patrick; Chiu, Alan; Siebert, Sean; Tang, Katherine; Jhunjhunwala, Siddharth; Aresta-Dasilva, Stephanie; Dholakia, Nimit; Thakrar, Raj; Vietti, Thema; Chen, Michael; Langer, Robert; Anderson, Daniel G.] Boston Childrens Hosp, Dept Anesthesiol, Boston, MA USA. [Veiseh, Omid; Tam, Hok Hei; Bratlie, Kaitlin; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Kang, Jeon Woong] MIT, Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Hollister-Locke, Jennifer; Cohen, Josh; Siniakowicz, Karolina; Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. [Bochenek, Matthew A.; Qi, Meirigeng; McGarrigle, James; Oberholzer, Jose] Univ Illinois, Dept Surg, Div Transplantat, Chicago, IL 60680 USA. [Lyle, Stephen] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Harlan, David M.; Greiner, Dale L.] Univ Massachusetts, Sch Med, Diabet Ctr Excellence, Worcester, MA USA. [Langer, Robert; Anderson, Daniel G.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Vegas, Arturo J.] Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA. [Ma, Minglin] Cornell Univ, Dept Biol & Environm Engn, Ithaca, NY USA. [Bratlie, Kaitlin] Iowa State Univ, Dept Mat Sci & Engn, Ames, IA USA. [Bratlie, Kaitlin] Iowa State Univ, Dept Chem & Biol Engn, Ames, IA USA. [Bader, Andrew R.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Anderson, DG (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Anderson, DG (reprint author), Boston Childrens Hosp, Dept Anesthesiol, Boston, MA USA.; Anderson, DG (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.; Anderson, DG (reprint author), MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Anderson, DG (reprint author), MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM dgander@mit.edu OI Bratlie, Kaitlin/0000-0002-5197-0176; Chen, Michael/0000-0002-1590-768X FU JDRF [3-SRA-2014-285-M-R]; Leona M. and the Harry B. Helmsley Charitable Trust [3-SRA-2014-285-M-R]; National Institutes of Health (NIH) [EB000244, EB000351, DE013023, CA151884, R01DK093909, P30DK036836]; NIH NIBIB [P41EB015871-27]; MIT SkolTech initiative; JDRF; Department of Defense/Congressionally Directed Medical Research Programs (DOD/CDMRP) [3-2013-178, W81XWH-13-1-0215]; National Institutes of Health (NIH, Joslin Diabetes Research Center and its Advanced Microscopy Core); Diabetes Research and Wellness Foundation; National Institutes of Health (NIH/NIDDK) [R01DK091526]; Chicago Diabetes Project; Koch Institute from the National Cancer Institute [P30-CA14051] FX This work was supported jointly by the JDRF and Leona M. and the Harry B. Helmsley Charitable Trust (grant 3-SRA-2014-285-M-R), National Institutes of Health (NIH grants EB000244, EB000351, DE013023 and CA151884), NIH NIBIB (P41EB015871-27), MIT SkolTech initiative (J.W.K.), JDRF and the Department of Defense/Congressionally Directed Medical Research Programs (DOD/CDMRP postdoctoral fellowships 3-2013-178 and W81XWH-13-1-0215 for O.V.) and through a generous gift from the Tayebati Family Foundation. G.C.W. is supported by National Institutes of Health (NIH grants R01DK093909 and P30DK036836, the Joslin Diabetes Research Center and its Advanced Microscopy Core), as well as the Diabetes Research and Wellness Foundation. J.O. is supported by the National Institutes of Health (NIH/NIDDK) R01DK091526 and the Chicago Diabetes Project. This work was also supported in part by the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute. We also thank the Koch Institute Swanson Biotechnology Center for technical support, specifically Tang Histology Facility, Microscopy, Flow Cytometry, Nanotechnology Materials, and Applied Therapeutics and Whole Animal Imaging. The authors would like to acknowledge the use of resources at W.M. Keck Biological Imaging Facility (Whitehead Institute). NR 56 TC 24 Z9 24 U1 34 U2 67 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2016 VL 34 IS 3 BP 345 EP + DI 10.1038/nbt.3462 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DG1CJ UT WOS:000371802600033 PM 26807527 ER PT J AU Cote, AJ McLeod, CM Farrell, MJ McClanahan, PD Dunagin, MC Raj, A Mauck, RL AF Cote, Allison J. McLeod, Claire M. Farrell, Megan J. McClanahan, Patrick D. Dunagin, Margaret C. Raj, Arjun Mauck, Robert L. TI Single-cell differences in matrix gene expression do not predict matrix deposition SO NATURE COMMUNICATIONS LA English DT Article ID MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; HUMAN ARTICULAR CHONDROCYTES; BONE-MARROW; IN-VITRO; CHONDROGENIC DIFFERENTIATION; ADIPOGENIC DIFFERENTIATION; LINEAGE COMMITMENT; HETEROGENEITY; CARTILAGE AB Mesenchymal stem cells (MSCs) display substantial cell-to-cell heterogeneity, complicating their use in regenerative medicine. However, conventional bulk assays mask this variability. Here we show that both chondrocytes and chondrogenically induced MSCs exhibit substantial mRNA expression heterogeneity. Single-molecule RNA FISH to measure mRNA expression of differentiation markers in single cells reveals that sister cell pairs have high levels of mRNA variability, suggesting that marker expression is not heritable. Surprisingly, this variability does not correlate with cell-to-cell differences in cartilage-like matrix production. Transcriptome-wide analysis suggests that no combination of markers can predict functional potential. De-differentiating chondrocytes also show a disconnect between mRNA expression of the cartilage marker aggrecan and cartilage-like matrix accumulation. Altogether, these quantitative analyses suggest that sorting subpopulations based on these markers would only marginally enrich the progenitor population for ' superior' MSCs. Our results suggest that instantaneous mRNA abundance of canonical markers is tenuously linked to the chondrogenic phenotype at the single-cell level. C1 [Cote, Allison J.; McLeod, Claire M.; Farrell, Megan J.; McClanahan, Patrick D.; Dunagin, Margaret C.; Raj, Arjun; Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [McLeod, Claire M.; Farrell, Megan J.; Mauck, Robert L.] Univ Penn, Perelman Sch Med, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [McLeod, Claire M.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. RP Raj, A; Mauck, RL (reprint author), Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.; Mauck, RL (reprint author), Univ Penn, Perelman Sch Med, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA.; Mauck, RL (reprint author), Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. EM arjunrajlab@gmail.com; lemauck@mail.med.upenn.edu OI Raj, Arjun/0000-0002-2915-6960 FU NSF CAREER award [1350601]; NIH New Innovator [1DP2OD008514]; Penn Center for Musculoskeletal Disorders [P30 AR050950]; NIH [R01 EB008722, R01 EB02425]; NIH training grant [T32 GM-07229, T32 HL007954]; NSF Graduate Research Fellowship [DGE-0822] FX A.R. acknowledges support from an NSF CAREER award (Grant Number 1350601), NIH New Innovator 1DP2OD008514, and a pilot grant from the Penn Center for Musculoskeletal Disorders P30 AR050950. R.L.M. acknowledges support from NIH grants R01 EB008722 and R01 EB02425. A.J.C. was supported by NIH training grant T32 GM-07229. C.M.M. was supported by NSF Graduate Research Fellowship DGE-0822 and by NIH training grant T32 HL007954. NR 70 TC 5 Z9 5 U1 5 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10865 DI 10.1038/ncomms10865 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF9WG UT WOS:000371712300001 PM 26936319 ER PT J AU Lane, JM Vlasac, I Anderson, SG Kyle, SD Dixon, WG Bechtold, DA Gill, S Little, MA Luik, A Loudon, A Emsley, R Scheer, FAJL Lawlor, DA Redline, S Ray, DW Rutter, MK Saxena, R AF Lane, Jacqueline M. Vlasac, Irma Anderson, Simon G. Kyle, Simon D. Dixon, William G. Bechtold, David A. Gill, Shubhroz Little, Max A. Luik, Annemarie Loudon, Andrew Emsley, Richard Scheer, Frank A. J. L. Lawlor, Deborah A. Redline, Susan Ray, David W. Rutter, Martin K. Saxena, Richa TI Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank SO NATURE COMMUNICATIONS LA English DT Article ID CIRCADIAN-RHYTHM DISRUPTION; SLEEP-PHASE SYNDROME; BODY-MASS INDEX; MORNINGNESS-EVENINGNESS; MENDELIAN RANDOMIZATION; GENETIC EPIDEMIOLOGY; CLOCK; INSIGHTS; SCHIZOPHRENIA; IMPUTATION AB Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n = 100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment. C1 [Lane, Jacqueline M.; Vlasac, Irma; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lane, Jacqueline M.; Saxena, Richa] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lane, Jacqueline M.; Saxena, Richa] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lane, Jacqueline M.; Vlasac, Irma; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Anderson, Simon G.] Univ Manchester, Inst Cardiovasc Sci, Cardiovasc Res Grp, Manchester M13 9PL, Lancs, England. [Kyle, Simon D.; Luik, Annemarie] Univ Oxford, Nuffield Dept Clin Neurosci, Sleep & Circadian Neurosci Inst, S Parks Rd, Oxford OX1 2JD, England. [Dixon, William G.] Univ Manchester, Ctr Musculoskeletal Res, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England. [Bechtold, David A.; Loudon, Andrew] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. [Gill, Shubhroz] Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA. [Little, Max A.] Aston Univ, Dept Math Engn & Appl Sci, Birmingham B4 7ET, W Midlands, England. [Emsley, Richard] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England. [Scheer, Frank A. J. L.; Redline, Susan; Saxena, Richa] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. [Scheer, Frank A. J. L.; Redline, Susan] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Lawlor, Deborah A.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England. [Lawlor, Deborah A.] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Ray, David W.; Rutter, Martin K.] Univ Manchester, Inst Human Dev, Ctr Endocrinol & Diabet, Manchester M13 9PL, Lancs, England. [Rutter, Martin K.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Diabet Ctr, Manchester M13 9PL, Lancs, England. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Saxena, R (reprint author), Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.; Saxena, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Saxena, R (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Saxena, R (reprint author), Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. EM rsaxena@partners.org RI Emsley, Richard/N-1342-2016; OI Emsley, Richard/0000-0002-1218-675X; Kyle, Simon/0000-0002-9581-5311; Ray, David/0000-0002-4739-6773; Anderson, Simon/0000-0002-8896-073X; Lawlor, Debbie A/0000-0002-6793-2262; Luik, Annemarie I/0000-0001-7517-197X; Dixon, William/0000-0001-5881-4857 FU NIH [R21HL121728-02, F32DK102323-01A1, R01HL113338-04]; University of Manchester (Research Infrastructure Fund); Wellcome Trust; UK Medical Research Council [MC_UU_12013/5] FX This work was supported by NIH grants R21HL121728-02 (R.S.), F32DK102323-01A1 (J.M.L.), R01HL113338-04 (J.M.L., S.R. and R.S.), the University of Manchester (Research Infrastructure Fund), the Wellcome Trust (salary support D.W.R. and A.L.) and UK Medical Research Council MC_UU_12013/5 (D.A.L.). Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on coronary artery disease/myocardial infarction have been contributed by CARDIo-GRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. NR 70 TC 11 Z9 11 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10889 DI 10.1038/ncomms10889 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DG0BZ UT WOS:000371728300001 PM 26955885 ER PT J AU Meyer, PA Socias, S Key, J Ransey, E Tjon, EC Buschiazzo, A Lei, M Botka, C Withrow, J Neau, D Rajashankar, K Anderson, KS Baxter, RH Blacklow, SC Boggon, TJ Bonvin, AMJJ Borek, D Brett, TJ Caflisch, A Chang, CI Chazin, WJ Corbett, KD Cosgrove, MS Crosson, S Dhe-Paganon, S Di Cera, E Drennan, CL Eck, MJ Eichman, BF Fan, QR Ferre-D'Amare, AR Fromme, JC Garcia, KC Gaudet, R Gong, P Harrison, SC Heldwein, EE Jia, ZC Keenan, RJ Kruse, AC Kvansakul, M McLellan, JS Modis, Y Nam, Y Otwinowski, Z Pai, EF Pereira, PJB Petosa, C Raman, S Rapoport, TA Roll-Mecak, A Rosen, MK Rudenko, G Schlessinger, J Schwartz, TU Shamoo, Y Sondermann, H Tao, YZJ Tolia, NH Tsodikov, OV Westover, KD Wu, H Foster, I Fraser, JS Maia, FRNC Gonen, T Kirchhausen, T Diederichs, K Crosas, M Sliz, P AF Meyer, Peter A. Socias, Stephanie Key, Jason Ransey, Elizabeth Tjon, Emily C. Buschiazzo, Alejandro Lei, Ming Botka, Chris Withrow, James Neau, David Rajashankar, Kanagalaghatta Anderson, Karen S. Baxter, Richard H. Blacklow, Stephen C. Boggon, Titus J. Bonvin, Alexandre M. J. J. Borek, Dominika Brett, Tom J. Caflisch, Amedeo Chang, Chung-I Chazin, Walter J. Corbett, Kevin D. Cosgrove, Michael S. Crosson, Sean Dhe-Paganon, Sirano Di Cera, Enrico Drennan, Catherine L. Eck, Michael J. Eichman, Brandt F. Fan, Qing R. Ferre-D'Amare, Adrian R. Fromme, J. Christopher Garcia, K. Christopher Gaudet, Rachelle Gong, Peng Harrison, Stephen C. Heldwein, Ekaterina E. Jia, Zongchao Keenan, Robert J. Kruse, Andrew C. Kvansakul, Marc McLellan, Jason S. Modis, Yorgo Nam, Yunsun Otwinowski, Zbyszek Pai, Emil F. Barbosa Pereira, Pedro Jose Petosa, Carlo Raman, S. Rapoport, Tom A. Roll-Mecak, Antonina Rosen, Michael K. Rudenko, Gabby Schlessinger, Joseph Schwartz, Thomas U. Shamoo, Yousif Sondermann, Holger Tao, Yizhi J. Tolia, Niraj H. Tsodikov, Oleg V. Westover, Kenneth D. Wu, Hao Foster, Ian Fraser, James S. Maia, Filipe R. N. C. Gonen, Tamir Kirchhausen, Tom Diederichs, Kay Crosas, Merce Sliz, Piotr TI Data publication with the structural biology data grid supports live analysis SO NATURE COMMUNICATIONS LA English DT Article ID X-RAY SCATTERING; PROTEIN DATA-BANK; MACROMOLECULAR CRYSTALLOGRAPHY; STRUCTURE MODELS; DATA QUALITY; SYNCHROTRON; SOFTWARE; SCIENCE; EXPERIENCES; RESOLUTION AB Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis. C1 [Meyer, Peter A.; Socias, Stephanie; Key, Jason; Ransey, Elizabeth; Tjon, Emily C.; Blacklow, Stephen C.; Eck, Michael J.; Harrison, Stephen C.; Kruse, Andrew C.; Wu, Hao; Sliz, Piotr] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Buschiazzo, Alejandro] Inst Pasteur Montevideo, Lab Mol & Struct Microbiol, Montevideo 11400, Uruguay. [Buschiazzo, Alejandro] Inst Pasteur, Dept Biol Struct & Chem, F-75015 Paris, France. [Lei, Ming] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. [Botka, Chris] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Withrow, James; Neau, David; Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, NE CAT, Bldg 436E,9700S Cass Ave, Argonne, IL 60439 USA. [Withrow, James; Neau, David; Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Bldg 436E,9700S Cass Ave, Argonne, IL 60439 USA. [Anderson, Karen S.; Boggon, Titus J.] Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA. [Anderson, Karen S.; Baxter, Richard H.; Boggon, Titus J.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA. [Baxter, Richard H.] Yale Univ, Dept Chem, 225 Prospect St, New Haven, CT 06520 USA. [Bonvin, Alexandre M. J. J.] Univ Utrecht, Bijvoet Ctr, Fac Sci, NL-3584 CH Utrecht, Netherlands. [Borek, Dominika; Otwinowski, Zbyszek] Univ Texas SW Med Ctr Dallas, Dept Biophys & Biochem, Dallas, TX 75390 USA. [Brett, Tom J.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Caflisch, Amedeo] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland. [Chang, Chung-I] Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan. [Chazin, Walter J.] Vanderbilt Univ, Dept Biochem, Struct Biol Ctr, Nashville, TN 37232 USA. [Chazin, Walter J.] Vanderbilt Univ, Dept Chem, Struct Biol Ctr, Nashville, TN 37232 USA. [Corbett, Kevin D.] Ludwig Inst Canc Res, San Diego Branch, La Jolla, CA 92093 USA. [Corbett, Kevin D.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Cosgrove, Michael S.] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA. [Crosson, Sean; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA. [Dhe-Paganon, Sirano; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Di Cera, Enrico] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. [Drennan, Catherine L.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Drennan, Catherine L.] MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Eichman, Brandt F.] Vanderbilt Univ, Dept Biol, Nashville, TN 37235 USA. [Eichman, Brandt F.] Vanderbilt Univ, Struct Biol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA. [Fan, Qing R.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. [Fan, Qing R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Ferre-D'Amare, Adrian R.] NHLBI, Lab RNA Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. [Fromme, J. Christopher] Cornell Univ, Dept Mol Biol & Genet, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA. [Garcia, K. Christopher] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA. [Garcia, K. Christopher] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA. [Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA. [Gaudet, Rachelle] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Gong, Peng] Chinese Acad Sci, Key Lab Special Pathogens & Biosafety, Wuhan Inst Virol, Wuhan 430071, Peoples R China. [Harrison, Stephen C.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Harrison, Stephen C.] Harvard Univ, Mol Med Lab, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Heldwein, Ekaterina E.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Jia, Zongchao] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7M 3G5, Canada. [Kvansakul, Marc] La Trobe Univ, Dept Biochem & Genet, Melbourne, Vic, Australia. [McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA. [Modis, Yorgo] Univ Cambridge, Dept Med, MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England. [Nam, Yunsun] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Pai, Emil F.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Pai, Emil F.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada. [Pai, Emil F.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Pai, Emil F.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2M9, Canada. [Barbosa Pereira, Pedro Jose] Univ Porto, Inst Biol Mol & Celular, P-4150 Oporto, Portugal. [Barbosa Pereira, Pedro Jose] Univ Porto, Inst Invest & Inovacao Saude, P-4150 Oporto, Portugal. [Petosa, Carlo] Univ Grenoble Alpes, CNRS, CFA, Inst Biol Struct, F-38027 Grenoble, France. [Raman, S.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Roll-Mecak, Antonina] Natl Inst Neurol Disorders & Stroke, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA. [Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA. [Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Rudenko, Gabby] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA. [Schlessinger, Joseph] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Schwartz, Thomas U.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Shamoo, Yousif; Tao, Yizhi J.] Rice Univ, Dept Biosci, Houston, TX 77005 USA. [Sondermann, Holger] Cornell Univ, Dept Mol Med, Coll Vet Med, Ithaca, NY 14853 USA. [Tolia, Niraj H.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Tsodikov, Oleg V.] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA. [Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. [Wu, Hao; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Foster, Ian] Argonne Natl Lab, Math & Comp Sci Div, 9700 S Cass Ave, Argonne, IL 60439 USA. [Foster, Ian] Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA. [Fraser, James S.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. [Maia, Filipe R. N. C.] Uppsala Univ, Lab Mol Biophys, Dept Cell & Mol Biol, Husargatan 3,Box 596, SE-75124 Uppsala, Sweden. [Maia, Filipe R. N. C.] Lawrence Berkeley Natl Lab, NERSC, Berkeley, CA 94720 USA. [Gonen, Tamir] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA. [Kirchhausen, Tom] Boston Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Diederichs, Kay] Univ Konstanz, Dept Biol, D-78457 Constance, Germany. [Crosas, Merce] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA. RP Sliz, P (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM sliz@hkl.hms.harvard.edu RI Bonvin, Alexandre/A-5420-2009; Borek, Dominika/D-2943-2011; Pereira, Pedro/F-8972-2011; OI Bonvin, Alexandre/0000-0001-7369-1322; Gaudet, Rachelle/0000-0002-9177-054X; Borek, Dominika/0000-0002-4321-6253; Pereira, Pedro/0000-0003-0969-5438; Corbett, Kevin/0000-0001-5854-2388; Modis, Yorgo/0000-0002-6084-0429; Fraser, James/0000-0002-5080-2859; Pai, Emil/0000-0002-1162-7242; Kvansakul, Marc/0000-0003-2639-2498 FU Leona M. and Harry B. Helmsley Charitable Trust [2016PG-BRI002]; NSF [1448069]; NIH [P41 GM103403, 1S10RR028832, 1U54EB020406-01]; DOE [DE-AC02-06CH11357]; NIST [60NANB15D077] FX Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357; NIH 1U54EB020406-01, Big Data for Discovery Science Center; and NIST 60NANB15D077 (Globus Project). AB acknowledges Ariel Chaparro for assistance with the DAA setup (Inst Pasteur Montevideo). Collections of pilot data sets were supported by various grants (see Supplementary Table 1). NR 52 TC 12 Z9 12 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10882 DI 10.1038/ncomms10882 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF9YS UT WOS:000371719200001 PM 26947396 ER PT J AU Soh, BS Ng, SY Wu, H Buac, K Park, JHC Lian, XJ Xu, JJ Foo, KS Felldin, U He, XB Nichane, M Yang, H Bu, L Li, RA Lim, B Chien, KR AF Soh, Boon-Seng Ng, Shi-Yan Wu, Hao Buac, Kristina Park, Joo-Hye C. Lian, Xiaojun Xu, Jiejia Foo, Kylie S. Felldin, Ulrika He, Xiaobing Nichane, Massimo Yang, Henry Bu, Lei Li, Ronald A. Lim, Bing Chien, Kenneth R. TI Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells SO NATURE COMMUNICATIONS LA English DT Article ID IN-VITRO EXPANSION; SMOOTH-MUSCLE; SELF-RENEWAL; HEART; DIFFERENTIATION; PERICYTES; MICE; REGENERATION; MAINTENANCE; POPULATION AB Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo. C1 [Soh, Boon-Seng; Wu, Hao; Buac, Kristina; Park, Joo-Hye C.; Bu, Lei] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. [Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C.; Bu, Lei; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA. [Soh, Boon-Seng; Bu, Lei; Li, Ronald A.] Univ Hong Kong, Li Dak Sum Res Ctr, HKU, Karolinska Inst Collaborat Regenerat Med, Hong Kong, Hong Kong, Peoples R China. [Soh, Boon-Seng; Bu, Lei; Li, Ronald A.] Karolinska Inst, Lau Ming Wai Ctr Regenerat Med, Hong Kong, Hong Kong, Peoples R China. [Soh, Boon-Seng; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S.; Felldin, Ulrika; He, Xiaobing; Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol & Med, S-17177 Stockholm, Sweden. [Buac, Kristina] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Nichane, Massimo; Lim, Bing] Genome Inst Singapore, Stem Cell & Dev Biol, Genome, 60 Biopolis St 02-01, Singapore 138672, Singapore. [Yang, Henry] Natl Univ Singapore, Canc Inst Singapore, 28 Med Dr, Singapore 117456, Singapore. [Soh, Boon-Seng] Proteos, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore. RP Chien, KR (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA.; Chien, KR (reprint author), Karolinska Inst, Dept Cell & Mol Biol & Med, S-17177 Stockholm, Sweden. EM kenneth.chien@ki.se OI Lian, Xiaojun/0000-0002-9161-1004 FU Research Grant Council of HKSAR [T13-706/11] FX This work was supported in part by the Research Grant Council of HKSAR (T13-706/11). NR 50 TC 3 Z9 3 U1 9 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2016 VL 7 AR 10774 DI 10.1038/ncomms10774 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DG0AB UT WOS:000371722900001 PM 26952167 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the legacy of kidney disease: focus on childhood SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; GLOBAL HEALTH; CHILDREN; EPIDEMIOLOGY AB Until recently, the WHO consensus statement on non-communicable diseases (NCD) included cardiovascular disease, cancer, diabetes and chronic respiratory disease, but not kidney disease. Fortunately, the Political Declaration on NCDs from the United Nations Summit in 2011 mentioned kidney disease under Item 19.35. C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, Franz] Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Int Federat Kidney Fdn, Int Soc Nephrol, World Kidney Day, Rues Fabriques 1B, B-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 2016 VL 31 IS 3 BP 327 EP 331 DI 10.1093/ndt/gfw003 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA DF7EU UT WOS:000371521400001 PM 26908830 ER PT J AU O'Hare, AM Rodriguez, RA Bowling, CB AF O'Hare, Ann M. Rodriguez, Rudolph A. Bowling, Christopher Barrett TI Caring for patients with kidney disease: shifting the paradigm from evidence-based medicine to patient-centered care SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Review DE evidence-based medicine; patient-centered care; kidney disease; older adults; paradigm ID MULTIPLE CHRONIC CONDITIONS; SHARED DECISION-MAKING; QUALITY-OF-CARE; CLINICAL-PRACTICE GUIDELINES; STAGE RENAL-DISEASE; OLDER-ADULTS; UNITED-STATES; HEALTH-CARE; BLOOD-PRESSURE; TRIALS AB The last several decades have witnessed the emergence of evidence-based medicine as the dominant paradigm for medical teaching, research and practice. Under an evidence-based approach, populations rather than individuals become the primary focus of investigation. Treatment priorities are largely shaped by the availability, relevance and quality of evidence and study outcomes and results are assumed to have more or less universal significance based on their implications at the population level. However, population-level treatment goals do not always align with what matters the most to individual patients-who may weigh the risks, benefits and harms of recommended treatments quite differently. In this article we describe the rise of evidence-based medicine in historical context. We discuss limitations of this approach for supporting real-world treatment decisions-especially in older adults with confluent comorbidity, functional impairment and/or limited life expectancy-and we describe the emergence of more patient-centered paradigms to address these limitations. We explain how the principles of evidence-based medicine have helped to shape contemporary approaches to defining, classifying and managing patients with chronic kidney disease. We discuss the limitations of this approach and the potential value of a more patient-centered paradigm, with a particular focus on the care of older adults with this condition. We conclude by outlining ways in which the evidence-base might be reconfigured to better support real-world treatment decisions in individual patients and summarize relevant ongoing initiatives. C1 [O'Hare, Ann M.; Rodriguez, Rudolph A.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA. [O'Hare, Ann M.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Innovat, Seattle, WA USA. [O'Hare, Ann M.; Rodriguez, Rudolph A.] Univ Washington, Dept Med, Seattle, WA USA. [Bowling, Christopher Barrett] Atlanta VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Decatur, GA USA. [Bowling, Christopher Barrett] Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP O'Hare, AM (reprint author), VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA.; O'Hare, AM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Innovat, Seattle, WA USA.; O'Hare, AM (reprint author), Univ Washington, Dept Med, Seattle, WA USA. EM ann.ohare@va.gov FU NIH [1U01DK102150-01]; US Department of Veterans Affairs [1I01HX000961-01, 1IK2CX000856-01A1]; CDC [IAA 14FED1405094-0001]; National Institute on Aging [R03AG042336-01]; T. Franklin Williams Scholarship Award (Atlantic Philanthropies, Inc.); T. Franklin Williams Scholarship Award (John A. Hartford Foundation); T. Franklin Williams Scholarship Award (Association of Specialty Professors); T. Franklin Williams Scholarship Award (American Society of Nephrology); T. Franklin Williams Scholarship Award (American Geriatrics Society) FX A.M.O. receives research funding from the NIH (1U01DK102150-01), the US Department of Veterans Affairs (1I01HX000961-01) and the CDC (IAA 14FED1405094-0001). She receives an honorarium from UpToDate. C.B.B. receives funding from the National Institute on Aging (R03AG042336-01) and the T. Franklin Williams Scholarship Award (funding provided by Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors, the American Society of Nephrology and the American Geriatrics Society) and the US Department of Veterans Affairs (1IK2CX000856-01A1). NR 89 TC 3 Z9 3 U1 5 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 2016 VL 31 IS 3 BP 368 EP 375 DI 10.1093/ndt/gfv003 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA DF7EU UT WOS:000371521400007 PM 25637639 ER PT J AU Bedlack, RS Vaughan, T Wicks, P Heywood, J Sinani, E Selsov, R Macklin, EA Schoenfeld, D Cudkowicz, M Sherman, A AF Bedlack, Richard S. Vaughan, Timothy Wicks, Paul Heywood, Jamie Sinani, Ervin Selsov, Roger Macklin, Eric A. Schoenfeld, David Cudkowicz, Merit Sherman, Alex TI How common are ALS plateaus and reversals? SO NEUROLOGY LA English DT Article ID FUNCTIONAL RATING-SCALE; CLINICAL-TRIALS AB Objective: To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. Methods: We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS-revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted. Results: Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months. Conclusion: ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study. C1 [Bedlack, Richard S.] Duke Univ, Dept Neurol, Durham, NC USA. [Bedlack, Richard S.] Durham VA Med Ctr, Durham, NC USA. [Vaughan, Timothy; Wicks, Paul; Heywood, Jamie] PatientsLikeMe, Cambridge, MA USA. [Sinani, Ervin; Selsov, Roger; Macklin, Eric A.; Schoenfeld, David; Cudkowicz, Merit; Sherman, Alex] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. RP Bedlack, RS (reprint author), Duke Univ, Dept Neurol, Durham, NC USA.; Bedlack, RS (reprint author), Durham VA Med Ctr, Durham, NC USA. EM Bedla001@mc.duke.edu OI Macklin, Eric/0000-0003-1618-3502 FU LVH ALS Foundation; Abbvie; Accorda; Actelion; Amgen; AstraZeneca; Avanir; Biogen; Boehringer Ingelheim; Genentech; Genzyme; Janssen; Johnson Johnson; Merck; Novartis; Sanofi; UCB; Kaiser Permanente; Robert Wood Johnson Foundation; Sage Bionetworks; AKU Society; University of Maryland FX Supported by the LVH ALS Foundation. The PatientsLikeMe Research Team has received research funding (including conference support and consulting fees) from Abbvie, Accorda, Actelion, Amgen, AstraZeneca, Avanir, Biogen, Boehringer Ingelheim, Genentech, Genzyme, Janssen, Johnson & Johnson, Merck, Novartis, Sanofi, and UCB. The PatientsLikeMe R&D team has received research grant funding from Kaiser Permanente, the Robert Wood Johnson Foundation, Sage Bionetworks, The AKU Society, and the University of Maryland. NR 8 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 1 PY 2016 VL 86 IS 9 BP 808 EP 812 DI 10.1212/WNL.0000000000002251 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DF4TA UT WOS:000371342400004 PM 26658909 ER PT J AU Barnett, PG Jeffers, A Smith, MW Chow, BK McFall, M Saxon, AJ AF Barnett, Paul G. Jeffers, Abra Smith, Mark W. Chow, Bruce K. McFall, Miles Saxon, Andrew J. TI Cost-Effectiveness of Integrating Tobacco Cessation Into Post-Traumatic Stress Disorder Treatment SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID QUALITY-OF-LIFE; SMOKING-CESSATION; VIETNAM VETERANS; ECONOMIC EVALUATIONS; CIGARETTE-SMOKING; MENTAL-ILLNESS; FORMER SMOKERS; HEALTH-CARE; MORTALITY; POPULATION AB We examined the cost-effectiveness of smoking cessation integrated with treatment for post-traumatic stress disorder (PTSD). Smoking veterans receiving care for PTSD (N = 943) were randomized to care integrated with smoking cessation versus referral to a smoking cessation clinic. Smoking cessation services, health care cost and utilization, quality of life, and biochemically-verified abstinence from cigarettes were assessed over 18-months of follow-up. Clinical outcomes were combined with literature on changes in smoking status and the effect of smoking on health care cost, mortality, and quality of life in a Markov model of cost-effectiveness over a lifetime horizon. We discounted cost and outcomes at 3% per year and report costs in 2010 US dollars. The mean of smoking cessation services cost was $1286 in those randomized to integrated care and $551 in those receiving standard care (P < .001). There were no significant differences in the cost of mental health services or other care. After 12 months, prolonged biochemically verified abstinence was observed in 8.9% of those randomized to integrated care and 4.5% of those randomized to standard care (P = .004). The model projected that Integrated Care added $836 in lifetime cost and generated 0.0259 quality adjusted life years (QALYs), an incremental cost-effectiveness ratio of $32 257 per QALY. It was 86.0% likely to be cost-effective compared to a threshold of $100 000/QALY. Smoking cessation integrated with treatment for PTSD was cost-effective, within a broad confidence region, but less cost-effective than most other smoking cessation programs reported in the literature. C1 [Barnett, Paul G.] Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. [Barnett, Paul G.] Univ Calif San Francisco, Dept Psychiat, Treatment Res Ctr, San Francisco, CA 94143 USA. [Jeffers, Abra] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Smith, Mark W.] Truven Hlth Analyt, Bethesda, MD USA. [Chow, Bruce K.] Vet Affairs Cooperat Studies Program Coordinating, Palo Alto, CA USA. [McFall, Miles; Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [McFall, Miles; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Barnett, PG (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. EM paul.barnett@va.gov FU Cooperative Studies Program; National Institute on Drug Abuse [P50 DA09253] FX This research was supported by the Cooperative Studies Program and grant P50 DA09253 from the National Institute on Drug Abuse. Trial registration: http://ClinicalTrials.gov identifier: NCT00118534. NR 49 TC 0 Z9 0 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAR PY 2016 VL 18 IS 3 BP 267 EP 274 DI 10.1093/ntr/ntv094 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DF8HP UT WOS:000371598600006 PM 25943761 ER PT J AU Kaufman, AR Koblitz, AR Persoskie, A Ferrer, RA Klein, WMP Dwyer, LA Park, ER AF Kaufman, Annette R. Koblitz, Amber R. Persoskie, Alexander Ferrer, Rebecca A. Klein, William M. P. Dwyer, Laura A. Park, Elyse R. TI Factor Structure and Stability of Smoking-Related Health Beliefs in the National Lung Screening Trial SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CANCER-RISK PERCEPTIONS; QUIT SMOKING; SMOKERS; SUSCEPTIBILITY; INTENTIONS; BEHAVIOR; WOMEN; WORRY; PARTICIPANTS; ASSOCIATION AB Absolute and comparative risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy are important theoretical determinants of tobacco use, but no measures have been validated to ensure the discriminant validity as well as test-retest reliability of these measures in the tobacco context. The purpose of the current study is to examine the reliability and factor structure of a measure assessing smoking-related health cognitions and emotions in a national sample of current and former heavy smokers in the National Lung Screening Trial. A sub-study of the National Lung Screening Trial assessed current and former smokers' (age 55-74; N = 4379) self-reported health cognitions and emotions at trial enrollment and at 12-month follow-up. Items were derived from the Health Belief Model and Self-Regulation Model. An exploratory factor analysis of baseline responses revealed a five-factor structure for former smokers (risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy) and a six-factor structure for current smokers, such that absolute risk and comparative risk perceptions emerged as separate factors. A confirmatory factor analysis of 12-month follow-up responses revealed a good fit for the five latent constructs for former smokers and six latent constructs for current smokers. Longitudinal stability of these constructs was also demonstrated. This is the first study to examine tobacco-related health cognition and emotional constructs over time in current and former heavy smokers undergoing lung screening. This study found that the theoretical constructs were stable across time and that the factor structure differed based on smoking status (current vs. former). C1 [Kaufman, Annette R.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Koblitz, Amber R.; Persoskie, Alexander; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Dwyer, Laura A.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kaufman, AR (reprint author), Natl Canc Inst, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,3-E-546, Rockville, MD 20850 USA. EM kaufmana@mail.nih.gov FU American Cancer Society Mentored Research Scholar Award [MRSG-005-05-CPPB]; National Cancer Institute [U01 CA079778, U01 CA080098] FX This work was funded by an American Cancer Society Mentored Research Scholar Award (MRSG-005-05-CPPB) to ERP, and the American College of Radiology Imaging Network (ACRIN) received funding from the National Cancer Institute through the grants U01 CA079778 and U01 CA080098. NR 50 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAR PY 2016 VL 18 IS 3 BP 321 EP 329 DI 10.1093/ntr/ntv091 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DF8HP UT WOS:000371598600013 PM 25964503 ER PT J AU Hartman, ML Goodson, JM Barake, R Alsmadi, O Al-Mutawa, S Ariga, J Soparkar, P Behbehani, J Behbehani, K AF Hartman, Mor-Li Goodson, J. Max Barake, Roula Alsmadi, Osama Al-Mutawa, Sabiha Ariga, Jitendra Soparkar, Pramod Behbehani, Jawad Behbehani, Kazem TI Salivary Biomarkers in Pediatric Metabolic Disease Research SO PEDIATRIC ENDOCRINOLOGY REVIEWS PER LA English DT Article DE Saliva; Biomarkers; Obesity; Type 2 Diabetes; Adolescence; Children; Metabolic disease; Hormones; Cytokines; Antioxidants ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; INSULIN-RESISTANCE; ADIPONECTIN LEVELS; OXIDATIVE STRESS; CORTISOL; CHILDREN; OBESITY; INFLAMMATION; DIAGNOSTICS AB The increasing prevalence of childhood obesity and obesity-related metabolic disorders is now considered a global pandemic. The main goal of the pediatric obesity research community is to identify children who are at risk of becoming obese before their body mass index rises above age norms. To do so, we must identify biomarkers of metabolic health and immunometabolism that can be used for large-scale; Screening and diagnosis initiatives among at-risk children. Because blood sampling is often unacceptable to both parents and children when there is no direct benefit to the child, as in a community-based research study, there is a clear need for a low-risk, non-invasive sampling strategy. Salivary analysis is now well recognized as a likely candidate for this purpose. In this review, we discuss the physiologic role of saliva and its strengths and limitations as a fluid for biomarker discovery, obesity screening, metabolic disease diagnosis, and response monitoring after interventions. We also describe the current state of the salivary biomarker field as it pertains to metabolic research, With a special emphasis on studies conducted in children and adolescents. Finally, we took forward to technological developments, such as salivary "omics" and point:of service diagnostic devices, which have the potential to accelerate the pace of research and discovery in this vitally important field. C1 [Hartman, Mor-Li; Goodson, J. Max; Soparkar, Pramod] Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. [Barake, Roula; Alsmadi, Osama; Behbehani, Kazem] Dasman Diabet Inst, Dasman, Kuwait. [Al-Mutawa, Sabiha; Ariga, Jitendra] Minist Hlth, Kuwait, Kuwait. [Behbehani, Jawad] Kuwait Univ, Fac Dent, Kuwait, Kuwait. RP Hartman, ML (reprint author), Forsyth Inst, 245 First St, Cambridge, MA 02142 USA. EM mhartman@forsyth.org FU Dasman Diabetes Institute, Kuwait FX The authors were supported in part by a grant from the Dasman Diabetes Institute, Kuwait. The authors confirm independence from the funding source. NR 74 TC 1 Z9 1 U1 1 U2 12 PU MEDICAL MEDIA PI NETANYA PA PO BOX 8214, NETANYA, 4250543, ISRAEL SN 1565-4753 J9 PEDIATR ENDOCR REV P JI Pediatr. Endocrinol. Rev. PER PD MAR PY 2016 VL 13 IS 3 BP 602 EP 611 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DF8ZQ UT WOS:000371650400005 PM 27116847 ER PT J AU Farvid, MS Eliassen, AH Cho, E Liao, XM Chen, WY Willett, WC AF Farvid, Maryam S. Eliassen, A. Heather Cho, Eunyoung Liao, Xiaomei Chen, Wendy Y. Willett, Walter C. TI Dietary Fiber Intake in Young Adults and Breast Cancer Risk SO PEDIATRICS LA English DT Article ID PROSPECTIVE COHORT; GLYCEMIC INDEX; PREMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; MEASUREMENT-ERROR; ADOLESCENT DIET; LIFE-STYLE; FAT; ESTROGEN AB OBJECTIVE: We evaluated fiber intake during adolescence and early adulthood in relation to breast cancer (BC) risk in the Nurses' Health Study II. METHODS: Among 90 534 premenopausal women who completed a dietary questionnaire in 1991, we documented 2833 invasive BC cases during 20 years of follow-up. In 1998, 44 263 of these women also completed a questionnaire about their diet during high school; among these women, we documented 1118 cases of BC by end of follow-up. Multivariable-adjusted Cox proportional hazards regression was used to model relative risks (RRs) and 95% confidence intervals (CIs) for BC across categories of dietary fiber. RESULTS: Among all women, early adulthood total dietary fiber intake was associated with significantly lower BC risk (RR for highest versus lowest quintile 0.81; 95% CI 0.72-0.91; P-trend = .002). Higher intakes of soluble fiber (RR for highest versus lowest quintile 0.86; 95% CI 0.77-0.97; P-trend = .02) and insoluble fiber (RR for highest versus lowest quintile 0.80; 95% CI 0.71-0.90; P-trend <. 001) were each associated with lower BC risk. Total dietary fiber intake in adolescence was also associated with lower BC risk (RR for highest versus lowest quintile 0.84; 95% CI 0.70-1.01; P-trend = .04). For the average of fiber intake during adolescence and early adult life, the RR comparing highest with lowest quintiles was 0.75 (95% CI 0.62-0.91, P(tren)d =.004). CONCLUSIONS: Our findings support the hypothesis that higher fiber intakes reduce BC risk and suggest that intake during adolescence and early adulthood may be particularly important. C1 [Farvid, Maryam S.; Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Eliassen, A. Heather; Liao, Xiaomei; Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liao, Xiaomei] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Eliassen, A. Heather; Cho, Eunyoung; Liao, Xiaomei; Chen, Wendy Y.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Eliassen, A. Heather; Cho, Eunyoung; Liao, Xiaomei; Chen, Wendy Y.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Farvid, MS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM mfarvid@hsph.harvard.edu FU NIH [R01 CA050385, UM1 CA176726]; Breast Cancer Research Foundation; Japan Pharmaceutical Manufacturers Association; National Institutes of Health (NIH) FX The study was supported by NIH grants (R01 CA050385, UM1 CA176726) and a grant from the Breast Cancer Research Foundation. Dr Farvid was supported by the Japan Pharmaceutical Manufacturers Association. Funded by the National Institutes of Health (NIH). NR 56 TC 7 Z9 7 U1 8 U2 12 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2016 VL 137 IS 3 AR e20151226 DI 10.1542/peds.2015-1226 PG 11 WC Pediatrics SC Pediatrics GA DF5MK UT WOS:000371395800011 PM 26908709 ER PT J AU Hillis, S Mercy, J Amobi, A Kress, H AF Hillis, Susan Mercy, James Amobi, Adaugo Kress, Howard TI Global Prevalence of Past-year Violence Against Children: A Systematic Review and Minimum Estimates SO PEDIATRICS LA English DT Review ID ADVERSE CHILDHOOD EXPERIENCES; SECONDARY-SCHOOL STUDENTS; INTIMATE PARTNER VIOLENCE; SEXUAL VIOLENCE; BULLYING VICTIMIZATION; CORPORAL PUNISHMENT; INCOME COUNTRIES; CONTROLLED-TRIAL; NATIONAL SAMPLE; UNITED-STATES AB CONTEXT: Evidence confirms associations between childhood violence and major causes of mortality in adulthood. A synthesis of data on past-year prevalence of violence against children will help advance the United Nations' call to end all violence against children. OBJECTIVES: Investigators systematically reviewed population-based surveys on the prevalence of past-year violence against children and synthesized the best available evidence to generate minimum regional and global estimates. DATA SOURCES: We searched Medline, PubMed, Global Health, NBASE, CINAHL, and the World Wide Web for reports of representative surveys estimating prevalences of violence against children. STUDY SELECTION: Two investigators independently assessed surveys against inclusion criteria and rated those included on indicators of quality. DATA EXTRACTION: Investigators extracted data on past-year prevalences of violent victimization by country, age group, and type (physical, sexual, emotional, or multiple types). We used a triangulation approach which synthesized data to generate minimum regional prevalences, derived from population-weighted averages of the country-specific prevalences. RESULTS: Thirty-eight reports provided quality data for 96 countries on past-year prevalences of violence against children. Base case estimates showed a minimum of 50% or more of children in Asia, Africa, and Northern America experienced past-year violence, and that globally over half of all children-1 billion children, ages 2-17 years-experienced such violence. LIMITATIONS: Due to variations in timing and types of violence reported, triangulation could only be used to generate minimum prevalence estimates. CONCLUSIONS: Expanded population-based surveillance of violence against children is essential to target prevention and drive the urgent investment in action endorsed in the United Nations 2030 Sustainable Development Agenda. C1 [Hillis, Susan] Ctr Dis Control & Prevent, Div Violence Prevent, Atlanta, GA 30333 USA. [Mercy, James; Kress, Howard] Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA 30333 USA. [Amobi, Adaugo] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Hillis, S (reprint author), Ctr Dis Control & Prevent, US Publ Hlth Serv, Natl Ctr Injury Prevent & Control, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM shillis@cdc.gov RI Figueroa Ossa, Ulda Omar/N-5821-2016 NR 92 TC 10 Z9 11 U1 6 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2016 VL 137 IS 3 AR e20154079 DI 10.1542/peds.2015-4079 PG 13 WC Pediatrics SC Pediatrics GA DF5MK UT WOS:000371395800062 PM 26810785 ER PT J AU Raffetto, JD AF Raffetto, Joseph D. TI Pathophysiology of wound healing and alterations in venous leg ulcers-review SO PHLEBOLOGY LA English DT Review DE Venous leg ulcer; wound; wound healing; fibroblasts; inflammation; endothelial cells; glycocalyx; leukocytes; macrophages; chemokines; cytokines; growth factors; collagen; extracellular matrix; matrix metalloproteinases; iron; free radical; oxidative stress ID MATRIX-METALLOPROTEINASE ACTIVITY; INFLAMMATORY PATHWAYS; COMPRESSION THERAPY; DISEASE; TISSUE; INSUFFICIENCY; ULCERATION; GLYCOSAMINOGLYCANS; GELATINASE; REPAIR AB Venous leg ulcer (VLU) is one of the most common lower extremity ulcerated wound, and is a significant healthcare problem with implications that affect social, economic, and the well-being of a patient. VLU can have debilitating related problems which require weekly medical care and may take months to years to heal. The pathophysiology of VLU is complex, and healing is delayed in many patients due to a persistent inflammatory condition. Patient genetic and environmental factors predispose individuals to chronic venous diseases including VLU. Changes in shear stress affecting the glycocalyx are likely initiating events, leading to activation of adhesion molecules on endothelial cells, and leukocyte activation with attachment and migration into vein wall, microcirculation, and in the interstitial space. Multiple chemokines, cytokines, growth factors, proteases and matrix metalloproteinases are produced. The pathology of VLU involves an imbalance of inflammation, inflammatory modulators, oxidative stress, and proteinase activity. Understanding the cellular and biochemical events that lead to the progression of VLU is critical. With further understanding of inflammatory pathways and potential mechanisms, certain biomarkers could be revealed and studied as both involvement in the pathophysiology of VLU but also as therapeutic targets for VLU healing. C1 [Raffetto, Joseph D.] Boston VA Hlth Care Syst, Vasc Surg, Boston, MA USA. [Raffetto, Joseph D.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Raffetto, Joseph D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Raffetto, JD (reprint author), VA Boston Hlth Care Syst, Surg 112,1400 VFW Pkwy, Boston, MA 02132 USA. EM joseph.raffetto@med.va.gov NR 24 TC 0 Z9 0 U1 7 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0268-3555 EI 1758-1125 J9 PHLEBOLOGY JI Phlebology PD MAR PY 2016 VL 31 SU 1 BP 56 EP 62 DI 10.1177/0268355516632998 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DF8HY UT WOS:000371599600010 PM 26916770 ER PT J AU Katzman, WB Vittinghoff, E Kado, DM Schafer, AL Wong, SS Gladin, A Lane, NE AF Katzman, Wendy B. Vittinghoff, Eric Kado, Deborah M. Schafer, Anne L. Wong, Shirley S. Gladin, Amy Lane, Nancy E. TI Study of Hyperkyphosis, Exercise and Function (SHEAF) Protocol of a Randomized Controlled Trial of Multimodal Spine-Strengthening Exercise in Older Adults With Hyperkyphosis SO PHYSICAL THERAPY LA English DT Article ID COMMUNITY-DWELLING MEN; OSTEOPOROTIC FRACTURES; PHYSICAL PERFORMANCE; RANCHO-BERNARDO; THORACIC KYPHOSIS; WOMEN; POSTURE; TRUNK; VALIDATION; GUIDELINES AB Background. Hyperkyphosis negatively affects health status, physical mobility, and quality of life, but there is no standard protocol for treating people with hyperkyphosis. Treatment options include targeted exercise. Objectives. This single-site randomized controlled trial (RCT) will determine the efficacy of a targeted multimodal spine-strengthening exercise program, compared with no exercise intervention, among community-dwelling men and women aged >= 60 years, with thoracic kyphosis >= 40 Design. The RCT is a parallel-group design, with 1:1 randomization to exercise and attentional control groups. Setting. The study will be conducted at one primary site (one academic medical center partnered with one local community medical center). Participants. One hundred men and women, aged years, with thoracic kyphosis degrees will be randomized. Intervention. The targeted multimodal spine-strengthening exercise intervention includes exercise and postural training delivered by a physical therapist in a group of 10 participants, 3 times a week for 6 months. Controls receive monthly health education meetings in a group of 10 participants and monthly calls from the study. coordinator to monitor physical activity and any adverse events. Measurements. The primary outcome is change in Cobb angle of kyphosis measured from lateral spine radiographs at baseline and 6 months. Secondary outcomes include change in physical function (assessed with the modified Physical Performance Test, Timed "Up & Go" Test, timed loaded standing, 4-m walk, and Six-Minute Walk Test) and health-related quality of life (assessed with the modified Scoliosis Research Society instrument [SRS-30] self-image domain and Patient Reported Outcomes Measurement Information System [PROMIS] global health and physical function indexes). Additional secondary outcomes include pain, physical activity level, spinal flexion and extension muscle strength, paraspinal extensor muscle density, and adverse events. Limitations. Blinding of the participants and instructors providing the intervention is not possible. Conclusions. The efficacy of a high-quality, adequately powered exercise intervention in men and women with kyphosis degrees will be evaluated to determine whether targeted multimodal spine-strengthening exercise reduces hyperkyphosis in older adults and improves important secondary outcomes of physical function and health-related quality of life. C1 [Katzman, Wendy B.; Wong, Shirley S.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, UCSF Box 0625, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Schafer, Anne L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kado, Deborah M.] Univ Calif San Diego, Dept Family Med, San Diego, CA 92103 USA. [Kado, Deborah M.] Univ Calif San Diego, Dept Publ Hlth, San Diego, CA 92103 USA. [Kado, Deborah M.] Univ Calif San Diego, Dept Internal Med, San Diego, CA 92103 USA. [Schafer, Anne L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Schafer, Anne L.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Gladin, Amy] Kaiser Permanente No Calif, San Francisco Med Ctr, San Francisco, CA USA. [Lane, Nancy E.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. RP Katzman, WB (reprint author), Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, UCSF Box 0625, San Francisco, CA 94143 USA. EM wendy.katzman@ucsf.edu FU National Institute of Aging [R01-AG028]; US Department of Veterans Affairs, Veterans Health Administration, Office of Clinical Science Research and Development [5 IK2 CX000549] FX The study was funded by National Institute of Aging grant R01-AG028. Additional support was provided by the US Department of Veterans Affairs, Veterans Health Administration, Office of Clinical Science Research and Development, under grant 5 IK2 CX000549 (to Dr Schafer). NR 36 TC 1 Z9 1 U1 4 U2 5 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD MAR PY 2016 VL 96 IS 3 BP 371 EP 381 DI 10.2522/ptj.20150171 PG 11 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA DF6FV UT WOS:000371452200013 PM 26251480 ER PT J AU Brune, KA Ferreira, F Mandke, P Chau, E Aggarwal, NR D'Alessio, FR Lambert, AA Kirk, G Blankson, J Drummond, MB Tsibris, AM Sidhaye, VK AF Brune, Kieran A. Ferreira, Fernanda Mandke, Pooja Chau, Eric Aggarwal, Neil R. D'Alessio, Franco R. Lambert, Allison A. Kirk, Gregory Blankson, Joel Drummond, M. Bradley Tsibris, Athe M. Sidhaye, Venkataramana K. TI HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BARRIER FUNCTION; E-CADHERIN; SUBTYPE-B; IN-VIVO; INFECTION; CELLS; ICAM-1; ACTIVATION; TROPISM AB Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air-liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway epithelial cells and alter their function by impairing cell-cell adhesion and increasing the expression of inflammatory mediators. These observed changes may contribute local inflammation, which can lead to lung function decline and increased susceptibility to COPD in HIV patients. C1 [Brune, Kieran A.; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R.; D'Alessio, Franco R.; Lambert, Allison A.; Drummond, M. Bradley; Sidhaye, Venkataramana K.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Ferreira, Fernanda; Tsibris, Athe M.] Mass Gen Hosp, Div Infect Dis, Boston, MA USA. [Kirk, Gregory] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kirk, Gregory; Blankson, Joel] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. RP Sidhaye, VK (reprint author), Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. EM vsidhay1@jhmi.edu FU Johns Hopkins University Center for AIDS Research (JHU CFAR), a center created through the NIH [P30AI094189] FX This work was funded by Johns Hopkins University Center for AIDS Research (JHU CFAR), a center created through the NIH P30AI094189. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 2 Z9 2 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 1 PY 2016 VL 11 IS 3 AR e0149679 DI 10.1371/journal.pone.0149679 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF5ZW UT WOS:000371434500041 PM 26930653 ER PT J AU Ho, CMK Donovan-Banfield, IZ Tan, L Zhang, TH Gray, NS Strang, BL AF Ho, Catherine M. K. Donovan-Banfield, I'ah Z. Tan, Li Zhang, Tinghu Gray, Nathanael S. Strang, Blair L. TI Inhibition of IKK alpha by BAY61-3606 Reveals IKK alpha-Dependent Histone H3 Phosphorylation in Human Cytomegalovirus Infected Cells SO PLOS ONE LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE UL97; EPSTEIN-BARR-VIRUS; GENE-EXPRESSION; BINDING-SITES; UL84 PROTEIN; IE2 86; REPLICATION; ACTIVATION; TRANSCRIPTION AB Protein kinase inhibitors can be used as tools to identify proteins and pathways required for virus replication. Using virus replication assays and western blotting we found that the widely used protein kinase inhibitor BAY61-3606 inhibits replication of human cytomegalovirus (HCMV) strain AD169 and the accumulation of HCMV immediate-early proteins in AD169 infected cells, but has no effect on replication of HCMV strain Merlin. Using in vitro kinase assays we found that BAY61-3606 is a potent inhibitor of the cellular kinase IKK alpha. Infection of cells treated with siRNA targeting IKK alpha indicated IKK alpha was required for efficient AD169 replication and immediate-early protein production. We hypothesized that IKK alpha was required for AD169 immediate-early protein production as part of the canonical NF-kappa B signaling pathway. However, although BAY61-3606 inhibited phosphorylation of the IKK alpha substrate I kappa B alpha, we found no canonical or non-canonical NF-kappa B signaling in AD169 infected cells. Rather, we observed that treatment of cells with BAY61-3606 or siRNA targeting IKK alpha decreased phosphorylation of histone H3 at serine 10 (H3S10p) in western blotting assays. Furthermore, we found treatment of cells with BAY61-3606, but not siRNA targeting IKK alpha, inhibited the accumulation of histone H3 acetylation (H3K9ac, H3K18ac and H3K27ac) and tri-methylation (H3K27me3 and H3K36me3) modifications. Therefore, the requirement for IKK alpha in HCMV replication was strain-dependent and during replication of an HCMV strain requiring IKK alpha, IKK alpha-dependent H3S10 phosphorylation was associated with efficient HCMV replication and immediate-early protein production. Plus, inhibition of HCMV replication by BAY61-3606 is associated with acetylation and tri-methylation modifications of histone H3 that do not involve IKK alpha. C1 [Ho, Catherine M. K.; Donovan-Banfield, I'ah Z.; Strang, Blair L.] Univ London, Inst Infect & Immun, Cranmer Terrace, London SW17 0RE, England. [Tan, Li; Zhang, Tinghu; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tan, Li; Zhang, Tinghu; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Longwood Ave, Boston, MA 02115 USA. RP Strang, BL (reprint author), Univ London, Inst Infect & Immun, Cranmer Terrace, London SW17 0RE, England. EM bstrang@sgul.ac.uk FU St George's, University of London; St George's Impact & Innovation Award; PARK/WestFocus Award FX New Investigator funds from St George's, University of London, a St George's Impact & Innovation Award and a PARK/WestFocus Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 1 Z9 1 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 MAR 1 PY 2016 VL 11 IS 3 AR e0150339 DI 10.1371/journal.pone.0150339 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF5ZW UT WOS:000371434500128 PM 26930276 ER PT J AU Lewis, NA Newell, J Burden, R Howatson, G Pedlar, CR AF Lewis, Nathan A. Newell, John Burden, Richard Howatson, Glyn Pedlar, Charles R. TI Critical Difference and Biological Variation in Biomarkers of Oxidative Stress and Nutritional Status in Athletes SO PLOS ONE LA English DT Article ID FREE OXYGEN RADICALS; C-REACTIVE PROTEIN; ALPHA-TOCOPHEROL; BETA-CAROTENE; VITAMIN-C; EXERCISE; MUSCLE; SUPPLEMENTATION; VARIABILITY; PERFORMANCE AB The longitudinal monitoring of oxidative stress (OS) in athletes may enable the identification of fatigued states and underperformance. The application of OS biomarker monitoring programs in sport are hindered by reliability and repeatability of in-the-field testing tools, the turnaround of results, and the understanding of biological variation (BV). Knowledge of BV and critical difference values (CDV) may assist with data interpretation in the individual athlete. Methods: We aimed firstly to assess the repeatability of the clinical point of care redox test, Free Oxygen Radical Test (FORT) and the Free Oxygen Radical Defence (FORD) in trained participants and elite athletes and secondly to calculate the analytical, BV, CDV and index of individuality (II) for FORT, FORD, red blood cell glutathione, lutein, alpha and gamma-tocopherol. Part 1: Fifteen elite athletes were sampled in duplicate for calculation of the repeatability of the FORT and FORD tests. Part 2: Twelve well-trained athletes had venous samples drawn every 2 hours from 0800 to 1800 for calculation of BV, CDV, II for FORT, FORD, RBC GSH, lutein, alpha-tocopherol and gamma-tocopherol. Results: Repeatability of the FORT and FORD assay was 3.9% and 3.7% respectively. Biomarker CDV ranged from 12.8% to 37%, with a circadian effect for FORT, alpha-tocopherol and gamma-tocopherol (p<0.01), with all biomarker indices of individuality < 0.8 arbitrary units. Conclusion: We report that the use of the novel redox test in athletes is practical, and the generation of BV and CDV for biomarkers of OS enhances the interpretation of physiologically meaningful changes in individuals above the use of clinical reference ranges alone. C1 [Lewis, Nathan A.; Burden, Richard] Univ Bath, English Inst Sport, Athletes Training Village, Bath BA2 7AY, Avon, England. [Lewis, Nathan A.; Burden, Richard; Pedlar, Charles R.] St Marys Univ, Sch Sport Hlth & Appl Sci, London, England. [Lewis, Nathan A.; Newell, John; Burden, Richard; Pedlar, Charles R.] Inst Technol, ORRECO, Sligo, Ireland. [Newell, John] Natl Univ Ireland, Sch Math Appl Stat & Math, Galway, Ireland. [Howatson, Glyn] Northumbria Univ, Dept Sport Exercise & Rehabil, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. [Howatson, Glyn] Northwest Univ, Sch Environm Sci & Dev, Water Res Grp, Potchefstroom, South Africa. [Pedlar, Charles R.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Lewis, NA (reprint author), Univ Bath, English Inst Sport, Athletes Training Village, Bath BA2 7AY, Avon, England.; Lewis, NA (reprint author), St Marys Univ, Sch Sport Hlth & Appl Sci, London, England.; Lewis, NA (reprint author), Inst Technol, ORRECO, Sligo, Ireland. EM nathan.lewis@eis2win.co.uk OI Newell, John/0000-0001-7685-6655 FU School of Sport, Health and Applied Science at St Mary's University, Twickenham; ORRECO Ltd. FX This study was financially supported by the research support fund in the School of Sport, Health and Applied Science at St Mary's University, Twickenham. The company ORRECO Ltd. had no role in funding the study, provided support in the form of salaries for authors N.A.L., C.A.P., and R.B., and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.N. is a scientific advisor to ORRECO Ltd. only. ORRECO Ltd. makes no contribution to his salary. NR 38 TC 3 Z9 3 U1 4 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 1 PY 2016 VL 11 IS 3 AR e0149927 DI 10.1371/journal.pone.0149927 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF5ZW UT WOS:000371434500074 PM 26930475 ER PT J AU Geng, CR Tang, XB Guan, FD Johns, J Vasudevan, L Gong, CH Shu, DY Chen, D AF Geng, Changran Tang, Xiaobin Guan, Fada Johns, Jesse Vasudevan, Latha Gong, Chunhui Shu, Diyun Chen, Da TI GEANT4 calculations of neutron dose in radiation protection using a homogeneous phantom and a Chinese hybrid male phantom SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID MONTE-CARLO; CONVERSION COEFFICIENTS; DOSIMETRY; THERAPY; MCNP AB The purpose of this study is to verify the feasibility of applying GEANT4 (version 10.01) in neutron dose calculations in radiation protection by comparing the calculation results with MCNP5. The depth dose distributions are investigated in a homogeneous phantom, and the fluence-to-dose conversion coefficients are calculated for different organs in the Chinese hybrid male phantom for neutrons with energy ranging from 1 x 10(-9) to 10 MeV. By comparing the simulation results between GEANT4 and MCNP5, it is shown that using the high-precision (HP) neutron physics list, GEANT4 produces the closest simulation results to MCNP5. However, differences could be observed when the neutron energy is lower than 1 x 10(-6) MeV. Activating the thermal scattering with an S matrix correction in GEANT4 with HP and MCNP5 in thermal energy range can reduce the difference between these two codes. C1 [Geng, Changran; Tang, Xiaobin; Gong, Chunhui; Shu, Diyun; Chen, Da] Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China. [Geng, Changran; Tang, Xiaobin; Gong, Chunhui; Shu, Diyun; Chen, Da] Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou, Peoples R China. [Geng, Changran] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Geng, Changran] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Guan, Fada] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Johns, Jesse] Nimbus Innovat LLC, Temple, TX 76501 USA. [Vasudevan, Latha] Texas A&M Univ, Environm Hlth & Safety, College Stn, TX 77843 USA. RP Tang, XB (reprint author), Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China.; Tang, XB (reprint author), Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou, Peoples R China. EM tangxiaobin@nuaa.edu.cn RI Tang, Xiaobin/I-7601-2014; OI Tang, Xiaobin/0000-0003-3308-0468; GUAN, FADA/0000-0001-8477-7391 FU National Natural Science Foundation of China [11475087]; Jiangsu Innovation Program for Graduate Education [KYLX_0265]; Fundamental Research Funds for the Central Universities [NS2014060]; Priority Academic Program Development of Jiangsu Higher Education Institutions FX This work was supported by National Natural Science Foundation of China (11475087), funding of Jiangsu Innovation Program for Graduate Education (KYLX_0265), the Fundamental Research Funds for the Central Universities (NS2014060) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. NR 21 TC 1 Z9 1 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD MAR PY 2016 VL 168 IS 4 BP 433 EP 440 DI 10.1093/rpd/ncv364 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA DF8LE UT WOS:000371608500001 PM 26156875 ER PT J AU Lewis, RC Hauser, R Wang, L Kavet, R Meeker, JD AF Lewis, Ryan C. Hauser, Russ Wang, Lu Kavet, Robert Meeker, John D. TI Personal power-frequency magnetic field exposure in women recruited at an infertility clinic: association with physical activity and temporal variability SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID PREGNANCY; RISK; MISCARRIAGE; MEN AB Current epidemiologic approaches for studying exposure to power-frequency magnetic fields and the risk of miscarriage are potentially biased due to lack of attention to the relationship of exposure with physical activity and within-individual variability in exposures over time. This analysis examines these two issues using data from a longitudinal pilot study of 40 women recruited from an infertility clinic that contributed data for up to three 24-h periods separated by a median of 3.6 weeks. Physical activity was positively associated with peak exposure metrics. Higher physical activity within environments did not necessarily lead to higher peak exposures, suggesting that movement between and not within environments increases one's probability of encountering a high field source. Peak compared with central tendency metrics were more variable over time. Future epidemiology studies associated with peak exposure metrics should adjust for physical activity and collect more than 1 d of exposure measurement to reduce bias. C1 [Lewis, Ryan C.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1835 SPH 1,1415Washington Hts, Ann Arbor, MI 48109 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Bldg 1,14th Floor,665 Huntington Ave, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, 55 Fruit St, Boston, MA 02114 USA. [Wang, Lu] Univ Michigan, Sch Publ Hlth, Dept Biostat, M4132 SPH 2,1415Washington Hts, Ann Arbor, MI 48109 USA. [Kavet, Robert] Elect Power Res Inst, 3420 Hillview Ave, Palo Alto, CA 94304 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1835 SPH 1,1415Washington Hts, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU Electric Power Research Institute; National Institute of Environmental Health Sciences of the National Institutes of Health [R01 ES009718, R01 ES016099] FX Work was supported by the Electric Power Research Institute and grants R01 ES009718 and R01 ES016099 from the National Institute of Environmental Health Sciences of the National Institutes of Health. NR 22 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD MAR PY 2016 VL 168 IS 4 BP 478 EP 488 DI 10.1093/rpd/ncv365 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA DF8LE UT WOS:000371608500007 PM 26152565 ER PT J AU Rai, SK Choi, HK Sayre, EC Avina-Zubieta, JA AF Rai, Sharan K. Choi, Hyon K. Sayre, Eric C. Avina-Zubieta, J. Antonio TI Risk of myocardial infarction and ischaemic stroke in adults with polymyositis and dermatomyositis: a general population-based study SO RHEUMATOLOGY LA English DT Article DE dermatomyositis; polymyositis; inflammatory myopathies; myocardial infarction; ischaemic stroke; cardiovascular disease ID BODY-MASS INDEX; RHEUMATOID-ARTHRITIS; CARDIOVASCULAR-DISEASE; ADMINISTRATIVE DATA; CARDIAC INVOLVEMENT; AUTOPSIED PATIENTS; 52 COUNTRIES; MORTALITY; METAANALYSIS; ACCURACY AB Objective. Limited data are available on the risk of cardiovascular disease in DM and PM. The purpose of this study was to estimate the risk of incident myocardial infarction (MI) and ischaemic stroke in adults with incident PM/DM at the general population level. Methods. We assembled a retrospective cohort of all adults with incident PM/DM in British Columbia, and we matched up to 10 adults randomly selected from the general population. We estimated the incidence rates (IRs) per 1000 person-years for MI and stroke. We calculated hazard ratios (HRs), adjusting for potential confounders. Results. Among 774 new cases of inflammatory myopathies, 424 had PM (59% female, mean age 60 years) and 350 had DM (65% female, mean age 56 years). IRs for MI and stroke in PM were 22.52 and 10.15 events per 1000 person-years, respectively, vs 5.50 and 5.58 events in the comparison cohort, respectively. Fully adjusted HRs (95% CI) were 3.89 (95% CI: 2.28, 6.65) for MI and 1.76 (95% CI: 0.91, 3.40) for stroke. The age-, sex- and entry time-matched HRs for MI and stroke were highest in the first year after PM diagnosis (6.51, [95% CI: 3.15, 13.47] and 3.48 [95% CI: 1.26, 9.62], respectively). Similar trends were seen for DM. Conclusion. Our study demonstrates that PM and DM are both associated with an increased risk of MI but not ischaemic stroke. Our findings support increased vigilance in cardiovascular prevention, surveillance and risk modification in adults with PM and DM. C1 [Rai, Sharan K.; Choi, Hyon K.; Sayre, Eric C.; Avina-Zubieta, J. Antonio] Arthrit Res Canada, Richmond, BC, Canada. [Rai, Sharan K.; Avina-Zubieta, J. Antonio] Univ British Columbia, Fac Med, Dept Expt Med, Vancouver, BC V5Z 1M9, Canada. [Choi, Hyon K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Avina-Zubieta, J. Antonio] Univ British Columbia, Dept Med, Div Rheumatol, Vancouver, BC V5Z 1M9, Canada. RP Avina-Zubieta, JA (reprint author), Univ British Columbia, Dept Med, Arthrit Res Canada, Div Rheumatol, 5591 3 Rd, Richmond, BC V6X 2C7, Canada. EM azubieta@arthritisresearch.ca FU Canadian Arthritis Network; Arthritis Society of Canada; British Columbia Lupus Society [10-SRP-IJD-01]; Canadian Institutes for Health Research [THC 135235] FX The work was supported by the Canadian Arthritis Network, The Arthritis Society of Canada, the British Columbia Lupus Society (Grant 10-SRP-IJD-01) and the Canadian Institutes for Health Research (THC 135235). NR 53 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD MAR PY 2016 VL 55 IS 3 BP 461 EP 469 DI 10.1093/rheumatology/kev336 PG 9 WC Rheumatology SC Rheumatology GA DF7SL UT WOS:000371557800011 PM 26424835 ER PT J AU Cassa, CA Smith, SE Docken, W Hoffman, E McLaughlin, H Chun, S Leshchiner, I Miraoui, H Raychaudhuri, S Frank, NY Wilson, BJ Sunyaev, SR Maas, RL Vuzman, D AF Cassa, Christopher A. Smith, Stacy E. Docken, William Hoffman, Erin McLaughlin, Heather Chun, Sung Leshchiner, Ignaty Miraoui, Hichem Raychaudhuri, Soumya Frank, Natasha Y. Wilson, Brian J. Sunyaev, Shamil R. Maas, Richard L. Vuzman, Dana CA Brigham Genomic Med TI An argument for early genomic sequencing in atypical cases: a WISP3 variant leads to diagnosis of progressive pseudorheumatoid arthropathy of childhood SO RHEUMATOLOGY LA English DT Letter ID DYSPLASIA; MUTATIONS; GENE C1 [Cassa, Christopher A.; Hoffman, Erin; Chun, Sung; Leshchiner, Ignaty; Miraoui, Hichem; Raychaudhuri, Soumya; Frank, Natasha Y.; Sunyaev, Shamil R.; Maas, Richard L.; Vuzman, Dana] Brigham & Womens Hosp, Div Genet, Harvard New Res Bldg,Room 0168B, Boston, MA 02115 USA. [Cassa, Christopher A.; Docken, William; Chun, Sung; Leshchiner, Ignaty; Miraoui, Hichem; Raychaudhuri, Soumya; Frank, Natasha Y.; Sunyaev, Shamil R.; Maas, Richard L.; Vuzman, Dana] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Smith, Stacy E.] Brigham & Womens Hosp, Div Musculoskeletal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. [Smith, Stacy E.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Docken, William] Brigham & Womens Hosp, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA. [McLaughlin, Heather] Partners Healthcare Ctr Personalized Med, Cambridge, MA USA. [McLaughlin, Heather] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Frank, Natasha Y.; Wilson, Brian J.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. RP Vuzman, D (reprint author), Brigham & Womens Hosp, Div Genet, Harvard New Res Bldg,Room 0168B, Boston, MA 02115 USA. EM dvuzman@broadinstitute.org OI Chun, Sung/0000-0003-3440-1913 FU NHGRI NIH HHS [K99 HG007229, K99-HG007229, U01 HG007690, U01-HG007690] NR 4 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD MAR PY 2016 VL 55 IS 3 BP 586 EP 589 DI 10.1093/rheumatology/kev367 PG 4 WC Rheumatology SC Rheumatology GA DF7SL UT WOS:000371557800026 PM 26493744 ER PT J AU Martin, CJ Carey, AF Fortune, SM AF Martin, Constance J. Carey, Allison F. Fortune, Sarah M. TI A bug's life in the granuloma SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Tuberculosis; Granuloma; Phenotypic heterogeneity; Macrophage ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; NITRIC-OXIDE SYNTHASE; CELL-WALL LIPIDS; IN-VITRO; STRINGENT RESPONSE; HUMAN MACROPHAGES; ISOCITRATE LYASE; FATTY-ACIDS; BOVIS BCG; EXPRESSION AB The granuloma is the defining feature of the host response to infection with Mycobacterium tuberculosis (Mtb). Despite knowing of its existence for centuries, much remains unclear regarding the host and bacterial factors that contribute to granuloma formation, heterogeneity of presentation, and the forces at play within. Mtb is highly adapted to life within the granuloma and employs many unique strategies to both create a niche within the host as well as survive the stresses imposed upon it. Adding to the complexity of the granuloma is the vast range of pathology observed, often within the same individual. Here, we explore some of the many ways in which Mtb crafts the immune response to its liking and builds a variety of granuloma features that contribute to its survival. We also consider the multitude of ways that Mtb is adapted to life in the granuloma and how variability in the deployment of these strategies may result in different fates for both the bacterium and the host. It is through better understanding of these complex interactions that we may begin to strategize novel approaches for tuberculosis treatments. C1 [Martin, Constance J.; Carey, Allison F.; Fortune, Sarah M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Martin, Constance J.; Fortune, Sarah M.] Ragon Inst Massachusetts Gen Hosp Harvard & Massa, Cambridge, MA USA. [Carey, Allison F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fortune, SM (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.; Fortune, SM (reprint author), Ragon Inst Massachusetts Gen Hosp Harvard & Massa, Cambridge, MA USA. EM sfortune@hsph.harvard.edu FU NIAID NIH HHS [P30 AI060354, R01 AI114674, R01 AI123286, T32 AI007061] NR 66 TC 6 Z9 6 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 EI 1863-2300 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD MAR PY 2016 VL 38 IS 2 BP 213 EP 220 DI 10.1007/s00281-015-0533-1 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA DF8UI UT WOS:000371634900007 PM 26577238 ER PT J AU Rutten-Jacobs, LCA Traylor, M Adib-Samii, P Thijs, V Sudlow, C Rothwell, PM Boncoraglio, G Dichgans, M Meschia, J Maguire, J Levi, C Rost, NS Rosand, J Hassan, A Bevan, S Markus, HS AF Rutten-Jacobs, Loes C. A. Traylor, Matthew Adib-Samii, Poneh Thijs, Vincent Sudlow, Cathie Rothwell, Peter M. Boncoraglio, Giorgio Dichgans, Martin Meschia, James Maguire, Jane Levi, Christopher Rost, Natalia S. Rosand, Jonathan Hassan, Ahamad Bevan, Steve Markus, Hugh S. TI Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype SO STROKE LA English DT Article DE lacunar stroke; homocysteine; hypertension; genetic association; MTHFR; cerebral small vessel disease ID SOUTH LONDON ETHNICITY; B-VITAMINS; FOLIC-ACID; HOMOCYSTEINE CONCENTRATIONS; MYOCARDIAL-INFARCTION; CONTROLLED-TRIAL; CLINICAL-TRIAL; RISK; POPULATION; CLASSIFICATION AB Background and Purpose- Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods- We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results- MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions- MTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. C1 [Rutten-Jacobs, Loes C. A.; Traylor, Matthew; Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QQ, England. [Traylor, Matthew] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Adib-Samii, Poneh] St Georges Univ London, Stroke & Dementia Res Ctr, Dept Clin Neurosci, London, England. [Thijs, Vincent] KULeuven, Dept Expt Neurol, Leuven, Belgium. [Thijs, Vincent] Univ Leuven, Leuven Res Inst Neurosci & Dis, Leuven, Belgium. [Thijs, Vincent] VIB, Neurobiol Lab, Vesalius Res Ctr, Leuven, Belgium. [Thijs, Vincent] Austin Hlth & Florey Inst Neurosci & Mental Hlth, Dept Neurol, Heidelberg, Vic, Australia. [Sudlow, Cathie] Univ Edinburgh, Neuroimaging Sci & Inst Genet & Mol Med, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Rothwell, Peter M.] Univ Oxford, Stroke Prevent Res Unit, Nuffield Dept Neurosci, Oxford OX1 2JD, England. [Boncoraglio, Giorgio] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] SyNergy, Munich Cluster Syst Neurol, Munich, Germany. [Meschia, James] Mayo Clin, Dept Neurol, Jacksonville, FL USA. [Meschia, James] Univ Newcastle, Sch Nursing & Midwifery, Callaghan, NSW 2308, Australia. [Meschia, James; Levi, Christopher] Univ Newcastle, Hunter Med Res Inst, Callaghan, NSW 2308, Australia. [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hassan, Ahamad] Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England. [Bevan, Steve] Lincoln Univ, Sch Life Sci, Lincoln, England. RP Rutten-Jacobs, LCA (reprint author), Univ Cambridge, Stroke Res Grp, Dept Neurosci, Cambridge CB2 0QQ, England. EM LR406@medschl.cam.ac.uk RI Boncoraglio, Giorgio/B-8647-2011; Thijs, Vincent/C-3647-2009; OI Thijs, Vincent/0000-0002-6614-8417; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Rutten-Jacobs, Loes/0000-0003-3223-885X FU Wellcome Trust [WT072952]; Stroke Association [TSA 2010/01, FSA 2013/00]; Wolfson Foundation; UK Stroke Association; British Heart Foundation; Dunhill Medical Trust; National Institute of Health Research (NIHR); Medical Research Council; NIHR Oxford Biomedical Research Centre; Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke; National Institute of Neurological Disorders and Stroke [U01 NS069208]; Stroke Association/British Heart Foundation programme grant [TSA BHF 2010/01]; Medical Research Council (United Kingdom); National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre; National Institute for Health Research Senior Investigator award; scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders; National Health and Medical Research Council (NHMRC Australia) Practitioner Fellowship; NHMRC [1010287]; National Institute of Neurological Disorders and Stroke grant [R01 NS082285-01] FX Collection of the UK Young Lacunar Stroke DNA Study (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples and Dr Traylor were supported by a Stroke Association Grant (FSA 2013/00). Genotyping of WTCCC2 ischemic stroke study was funded by the Wellcome Trust. The Oxford Vascular Study has been funded by Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre. Funding for the genotyping at Massachusetts General Hospital was provided by the Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke and the National Institute of Neurological Disorders and Stroke (U01 NS069208). Dr Rutten-Jacobs was supported by a Stroke Association/British Heart Foundation programme grant (TSA BHF 2010/01). Dr Adib-Samii was supported by a Medical Research Council (United Kingdom) training fellowship. Drs Markus and Bevan are supported by the National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre. Dr Markus is supported by a National Institute for Health Research Senior Investigator award. Dr Thijs is supported by a Clinical Investigator Grant from the scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders. Dr Levi is supported by a National Health and Medical Research Council (NHMRC Australia) Practitioner Fellowship and the Australian Stroke Genetics Collaboration has received Project Grant support from the NHMRC (App 1010287). Dr Rost was supported by a National Institute of Neurological Disorders and Stroke grant (R01 NS082285-01). Professor Rothwell is in receipt of an NIHR Senior Investigator Award and a Wellcome Trust Senior Investigator Award. We. also acknowledge the use of the facilities of the Acute Vascular Imaging Centre, Oxford, and the Cardiovascular Clinical Research Facility, Oxford. The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the article, or the decision to submit the article for publication. NR 26 TC 2 Z9 3 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP 646 EP 651 DI 10.1161/STROKEAHA.115.011545 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VT UT WOS:000371496200002 PM 26839351 ER PT J AU Dowlatshahi, D Brouwers, HB Demchuk, AM Hill, MD Aviv, RI Ufholz, LA Reaume, M Wintermark, M Hemphill, JC Murai, Y Wang, YJ Zhao, XQ Wang, YL Li, N Sorimachi, T Matsumae, M Steiner, T Rizos, T Greenberg, SM Romero, JM Rosand, J Goldstein, JN Sharma, M AF Dowlatshahi, Dar Brouwers, H. Bart Demchuk, Andrew M. Hill, Michael D. Aviv, Richard I. Ufholz, Lee-Anne Reaume, Michael Wintermark, Max Hemphill, J. Claude, III Murai, Yasuo Wang, Yongjun Zhao, Xingquan Wang, Yilong Li, Na Sorimachi, Takatoshi Matsumae, Mitsunori Steiner, Thorsten Rizos, Timolaos Greenberg, Steven M. Romero, Javier M. Rosand, Jonathan Goldstein, Joshua N. Sharma, Mukul TI Predicting Intracerebral Hemorrhage Growth With the Spot Sign The Effect of Onset-to-Scan Time SO STROKE LA English DT Article DE cerebral hemorrhage; hematoma expansion; CT angiography; spot sign; intracerebral hemorrhage ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; BLOOD-PRESSURE REDUCTION; ACTIVATED FACTOR-VII; HEMATOMA EXPANSION; CONTRAST EXTRAVASATION; CT ANGIOGRAPHY; CEREBRAL-HEMORRHAGE; MORTALITY; RISK; VOLUME AB Background and Purpose- Hematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign. Methods- We completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates. Results- Among 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P < 0.001). There was a significant decrease in hematoma expansion in spot-positive patients as onset-to-CTA time increased (P=0.004), with positive predictive values decreasing from 53% to 33%. Conclusions- The frequency of the CTA spot sign is inversely related to intracerebral hemorrhage onset-to-CTA time. Furthermore, the positive predictive value of the spot sign for significant hematoma expansion decreases as time-to-CTA increases. Our results offer more precise risk stratification for patients with acute intracerebral hemorrhage and will help refine clinical prediction rules for intracerebral hemorrhage expansion. C1 [Dowlatshahi, Dar; Reaume, Michael] Univ Ottawa, Dept Med, Ottawa, ON K1Y 4E9, Canada. [Dowlatshahi, Dar; Reaume, Michael] Ottawa Hosp Res Inst, Ottawa, ON K1Y 4E9, Canada. [Brouwers, H. Bart; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Sch Med, Boston, MA USA. [Brouwers, H. Bart] Univ Utrecht, Univ Med Ctr Utrecht, Dept Neurosurg, Utrecht, Netherlands. [Demchuk, Andrew M.; Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada. [Demchuk, Andrew M.; Hill, Michael D.] Univ Calgary, Calgary Stroke Program, Calgary, AB, Canada. [Aviv, Richard I.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON, Canada. [Ufholz, Lee-Anne] Univ Ottawa, Hlth Sci Lib, Ottawa, ON, Canada. [Wintermark, Max] Stanford Univ, Neuroradiol Div, Dept Radiol, Stanford, CA 94305 USA. [Hemphill, J. Claude, III] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Murai, Yasuo] Nippon Med Sch, Dept Neurol Surg, 1-1-5 Sendagi, Tokyo 113, Japan. [Wang, Yongjun; Zhao, Xingquan; Wang, Yilong; Li, Na] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. [Sorimachi, Takatoshi; Matsumae, Mitsunori] Tokai Univ, Dept Neurosurg, Hiratsuka, Kanagawa 25912, Japan. [Steiner, Thorsten; Rizos, Timolaos] Heidelberg Univ, Dept Neurol, Bergheimer Str 58, D-69115 Heidelberg, Germany. [Steiner, Thorsten] Klinikum Frankfurt Hochst, Frankfurt, Germany. [Sharma, Mukul] McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton, ON, Canada. RP Dowlatshahi, D (reprint author), Univ Ottawa, Ottawa Hosp Civ Campus Room C2102, Ottawa, ON K1Y 4E9, Canada.; Dowlatshahi, D (reprint author), Ottawa Hosp Res Inst, Ottawa Hosp Civ Campus Room C2102, Ottawa, ON K1Y 4E9, Canada. EM ddowlat@toh.on.ca RI Goldstein, Joshua/H-8953-2016 FU Heart & Stroke Foundation of Canada; University of Ottawa Department of Medicine; Heart & Stroke Foundation of Alberta/NWT/NU; Hotchkiss Brain Institute; Alberta Innovates Health Solutions; National Institutes of Health-National Institute of Neurological Disorders and Stroke FX Heart & Stroke Foundation of Canada (Dr Dowlatshahi), University of Ottawa Department of Medicine (Dr Dowlatshahi), Heart & Stroke Foundation of Alberta/NWT/NU (Dr Demchuk and Dr Hill), the Hotchkiss Brain Institute (Dr Demchuk and Dr Hill), Alberta Innovates Health Solutions (Dr Demchuk and Dr Hill), and National Institutes of Health-National Institute of Neurological Disorders and Stroke (Dr Brouwers, Dr Goldstein, and Dr Rosand). NR 41 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP 695 EP 700 DI 10.1161/STROKEAHA.115.012012 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VT UT WOS:000371496200009 PM 26846857 ER PT J AU Chua, MH Griessenauer, CJ Stapleton, CJ He, L Thomas, AJ Ogilvy, CS AF Chua, Michelle H. Griessenauer, Christoph J. Stapleton, Christopher J. He, Lucy Thomas, Ajith J. Ogilvy, Christopher S. TI Documentation of Improved Outcomes for Intracranial Aneurysm Management Over a 15-Year Interval SO STROKE LA English DT Article DE outcomes research; Glasgow Outcome Scale; surgical instruments; intracranial aneurysms; endovascular techniques ID UNRUPTURED CEREBRAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; ENDOVASCULAR TREATMENT; COIL EMBOLIZATION; MORTALITY; DATABASE; SYSTEM; TRENDS; TRIAL; AGE AB Background and Purpose- Despite rapid advancements in intracranial aneurysm management, there is no evidence as of yet that this has translated into improvement in overall prognosis. Methods- We compared 2 periods of aneurysm management, 1998 to 2003 (n=1023 aneurysms) and 2007 to 2013 (n=1499 aneurysms), at a single, high-volume neurovascular center. Our outcome of interest was low or moderate disability (Glasgow Outcome Scale score of 4 or 5) at 6 months or more post treatment. Results- There were significant improvements in outcome for surgical, endovascular, and overall treatment of unruptured (adjusted odds ratio [OR], 2.33; P=0.0091; adjusted OR, 4.40; P=0.0271; and adjusted OR, 2.58; P=0.0008, respectively) and ruptured (adjusted OR, 3.18; P=0.0004; adjusted OR, 3.54; P=0.0001; and adjusted OR, 3.11; P < 0.0001, respectively) aneurysms from the first to the second time period. In 2007 to 2013, the proportion of cases with low or moderate disability at 6 months post subarachnoid hemorrhage was 75.6% for surgical clipping and 76.6% for endovascular therapy. Conclusions- We report significantly improved outcomes over time for overall aneurysm management and for multiple patient subgroups, associated with increased usage of endovascular therapy. C1 [Chua, Michelle H.; Griessenauer, Christoph J.; He, Lucy; Thomas, Ajith J.; Ogilvy, Christopher S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Brain Aneurysm Inst, Neurosurg Serv,Med Sch, Boston, MA 02215 USA. [Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), 110 Francis St,Suite 3B, Boston, MA 02215 USA. EM cogilvy@bidmc.harvard.edu NR 23 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP 708 EP 712 DI 10.1161/STROKEAHA.115.011959 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VT UT WOS:000371496200011 PM 26839350 ER PT J AU Fonarow, GC Liang, L Thomas, L Xian, Y Saver, JL Smith, EE Schwamm, LH Peterson, ED Hernandez, AF Duncan, PW O'Brien, EC Bushnell, C Bettger, JP AF Fonarow, Gregg C. Liang, Li Thomas, Laine Xian, Ying Saver, Jeffrey L. Smith, Eric E. Schwamm, Lee H. Peterson, Eric D. Hernandez, Adrian F. Duncan, Pamela W. O'Brien, Emily C. Bushnell, Cheryl Bettger, Janet Prvu TI Assessment of Home-Time After Acute Ischemic Stroke in Medicare Beneficiaries SO STROKE LA English DT Article DE skilled nursing facilities; stroke; survivors; modified Rankin Scale; patient-centered outcomes research ID GUIDELINES-STROKE; PATIENTS PERSPECTIVE; UNCERTAINTY LIFE; CLINICAL-TRIALS; PATIENT; DISABILITY; OUTCOMES AB Background and Purpose- Stroke survivors have identified home-time as a meaningful outcome. We evaluated home-time as a patient-centered outcome in Medicare beneficiaries with ischemic stroke in comparison with modified Rankin Scale (mRS) score at 90 days and at 1 year post event. Methods- Patients enrolled in Get With The Guidelines-Stroke (GWTG-Stroke) and Adherence Evaluation After Ischemic Stroke-Longitudinal (AVAIL) registries were linked to Medicare claims to ascertain home-time, defined as time spent alive and out of a hospital, inpatient rehabilitation, or skilled nursing facilities, at 90 days and at 1 year after admission. The correlation of home-time with mRS at 90 days and at 1 year was evaluated by Pearson correlation coefficients, and the ability of home-time to discriminate mRS (0-2) was assessed by c-index. Results- There were 815 patients with ischemic stroke (age median, 76 years [interquartile range {IQR}, 70-82]; 46% women; National Institutes of Health Stroke Scale median, 4 [IQR, 2-7]) from 88 hospitals. The 90-day and 1-year median home-times were 79 (IQR, 52-86) days and 349 (IQR, 303-360) days and median mRS were 2 (IQR, 1-4) and 2 (IQR, 1-4). Greater home-time within 90 days was significantly correlated with lower 90-day mRS (Pearson correlation coefficient, -0.731; P < 0.0001) and showed strong ability to discriminate functional independence with mRS 0 to 2 (c-index, 0.837). Similar findings were observed at 1 year. Conclusions- In a population of older patients with ischemic stroke, home-time was readily available from administrative data and associated with mRS at 90 days and 1 year. Home-time represents a novel, easily measured, patient-centered, outcome measure for an episode of stroke care. C1 [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Dept Med, Los Angeles, CA 90095 USA. [Saver, Jeffrey L.] Ronald Reagan UCLA Med Ctr, Dept Neurol, Los Angeles, CA 90095 USA. [Liang, Li; Thomas, Laine; Xian, Ying; Peterson, Eric D.; Hernandez, Adrian F.; O'Brien, Emily C.; Bettger, Janet Prvu] Duke Clin Res Inst, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Duncan, Pamela W.; Bushnell, Cheryl] Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, 10833 Leconte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu FU Agency for Healthcare Research and Quality [U18HS016964, K12HS019479]; Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; Patient Centered Outcomes Research Institute [130]; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janssen Pharmaceutical Companies of Johnson Johnson; AHA Pharmaceutical Roundtable FX Adherence Evaluation After Ischemic Stroke-Longitudinal (AVAIL) was supported by the Agency for Healthcare Research and Quality (U18HS016964) and unrestricted funds from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. Medicare claims were obtained with funding from the Agency for Healthcare Research and Quality (K12HS019479). Analysis was funded by the Patient Centered Outcomes Research Institute (Project #130; PI: P. Bettger). The Get With The Guidelines-Stroke program is provided by the American Heart Association (AHA)/American Stroke Association and has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janssen Pharmaceutical Companies of Johnson & Johnson, and the AHA Pharmaceutical Roundtable, none of which participated in the design, analysis, article preparation, or approval. NR 15 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP 836 EP 842 DI 10.1161/STROKEAHA.115.011599 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VT UT WOS:000371496200029 PM 26892279 ER PT J AU Diener, HC Selim, MH Molina, CA Greenberg, SM AF Diener, Hans-Christoph Selim, Magdy H. Molina, Carlos A. Greenberg, Steven M. TI Embolic Stroke, Atrial Fibrillation, and Microbleeds Is There a Role for Anticoagulation? SO STROKE LA English DT Article DE carotid stenosis; amyloid; aspirin; anticoagulants; warfarin ID TRANSIENT ISCHEMIC ATTACK; ANTAGONIST ORAL ANTICOAGULANTS; INTRACEREBRAL HEMORRHAGE; CEREBRAL MICROBLEEDS; ANTITHROMBOTIC THERAPY; LOBAR MICROBLEEDS; SUBGROUP ANALYSIS; WARFARIN; METAANALYSIS; RISK C1 [Diener, Hans-Christoph] Univ Hosp Essen, Stroke Ctr, Dept Neurol, Essen, Germany. [Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Hemorrhag Stroke Res Unit, Sch Med, Boston, MA USA. [Selim, Magdy H.] Beth Israel Deaconess Med Ctr, Stroke Div, Boston, MA 02215 USA. [Molina, Carlos A.] Hosp Vall dHebron Barcelona, Dept Neurol, Stroke Unit, Barcelona, Spain. RP Diener, HC (reprint author), Univ Hosp Essen, Stroke Ctr, Dept Neurol, Essen, Germany.; Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Hemorrhag Stroke Res Unit, Sch Med, Boston, MA USA. EM h.diener@uni-essen.de; sgreenberg@mgh.harvard.edu NR 22 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP 904 EP 907 DI 10.1161/STROKEAHA.115.011150 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VT UT WOS:000371496200042 PM 26896435 ER PT J AU Harriott, A Faye, EC Abreu, N Silverman, S Rordorf, G AF Harriott, Andrea Faye, Erica Camargo Abreu, Nicholas Silverman, Scott Rordorf, Guy TI Aneurysmal Subarachnoid and Spinal Hemorrhage Associated With Systemic Lupus Erythematosus SO STROKE LA English DT Editorial Material DE aneurysm; subarachnoid hemorrhage; vasculitis; lupus erythematosus, systemic; stroke ID COMPLICATION C1 [Harriott, Andrea; Faye, Erica Camargo; Abreu, Nicholas; Silverman, Scott; Rordorf, Guy] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. RP Harriott, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM aharriott@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2016 VL 47 IS 3 BP E42 EP E45 DI 10.1161/STROKEAHA.115.012373 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DF6VU UT WOS:000371496400001 PM 26797667 ER PT J AU Tahvildari, M Omoto, M Chen, YH Emami-Naeini, P Inomata, T Dohlman, TH Kaye, AE Chauhan, SK Dana, R AF Tahvildari, Maryam Omoto, Masahiro Chen, Yihe Emami-Naeini, Parisa Inomata, Takenori Dohlman, Thomas H. Kaye, Abigail E. Chauhan, Sunil K. Dana, Reza TI In Vivo Expansion of Regulatory T Cells by Low-Dose Interleukin-2 Treatment Increases Allograft Survival in Corneal Transplantation SO TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; SKIN-GRAFT SURVIVAL; IMMUNE PRIVILEGE; IL-2; TOLERANCE; REJECTION; RAPAMYCIN; DONOR; MICE; ALLORECOGNITION AB Background. Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory Tcells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been proposed for the treatment of autoimmune diseases. In this study, we investigated the effect of low-dose IL-2 administration on Treg function and corneal allograft survival. Methods. Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose systemic IL-2 was administered starting 3 days before grafting until 6 weeks after transplantation. Frequencies of Treg and their immunosuppressive function and antigen specificity were assessed using flow cytometry, in vitro proliferation assays, and adoptive transfer experiments. Frequencies of effector T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks using Kaplan-Meier survival analysis. Results. Treatment with low-dose IL-2 significantly increased frequencies of CD4(+)CD25(+)Foxp3(+) Treg and their immunosuppressive function. It also suppressed alloimmune response as shown by the decreased CD4(+)IFN gamma(+) T cell frequencies and graft infiltration of CD45(+) and CD4(+) cells. Clinical evaluation of the grafts showed significant improvement in long-term corneal allograft survival in the IL-2 treated group compared with controls. Conclusions. Our study is the first to report that treatment with low-dose IL-2 increases survival of corneal allografts. We propose that IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and to improve long-term allograft survival in transplantation. C1 [Tahvildari, Maryam; Omoto, Masahiro; Chen, Yihe; Emami-Naeini, Parisa; Inomata, Takenori; Dohlman, Thomas H.; Kaye, Abigail E.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Tahvildari, Maryam; Omoto, Masahiro; Chen, Yihe; Emami-Naeini, Parisa; Inomata, Takenori; Dohlman, Thomas H.; Kaye, Abigail E.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Emami-Naeini, Parisa] Wayne State Univ, Kresge Eye Inst, Detroit, MI USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Reza_Dana@meei.harvard.edu OI Inomata, Takenori/0000-0003-3435-1055 FU NIH [EY12963] FX This study was funded by NIH Grant EY12963. The authors thank Dr. Susanne Eiglmeier (Schepens Eye Research Institute) for editorial assistance and helpful discussions regarding the project, and Dr. Jing Hua (Schepens Eye Research Institute) for valuable input. NR 41 TC 3 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD MAR PY 2016 VL 100 IS 3 BP 525 EP 532 DI 10.1097/TP.0000000000001044 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DF8BR UT WOS:000371582400023 PM 26881788 ER PT J AU Jain, S Keys, D Martin, S Edelstein, CL Jani, A AF Jain, Swati Keys, Daniel Martin, Sandra Edelstein, Charles L. Jani, Alkesh TI Protection From Apoptotic Cell Death During Cold Storage Followed by Rewarming in 13-Lined Ground Squirrel Tubular Cells: The Role of Prosurvival Factors X-Linked Inhibitor of Apoptosis and PhosphoAkt SO TRANSPLANTATION LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; AKT PHOSPHORYLATION; EPITHELIAL-CELLS; HIBERNATION; INJURY; ISCHEMIA; MITOCHONDRIA; REPERFUSION; PROGRESSION; METABOLISM AB Background. Hibernators, such as the 13-lined ground squirrel, endure severe hypothermia during torpor followed by periodic rewarming (REW) during interbout arousal (IBA), proapoptotic conditions that are lethal to nonhibernatingmammals. We have previously shown that 13-lined ground squirrel tubular cells are protected from apoptotic cell death during IBA. To understand the mechanism of protection, we developed an in vitro model of prolonged cold storage (CS) followed by REW, which is akin to the in vivo changes of hypothermia followed by REW observed during IBA. We hypothesized that renal tubular epithelial cells (RTECs) isolated from hibernating ground squirrels would be protected against apoptosis during CS/REW versus nonhibernating mouse RTECs. Methods. Isolated hibernating ground squirrel and mouse RTECs were subjected to CS at 4 degrees C for 24 hours followed by REW to 37 degrees C for 24 hours (CS/REW). Results. Ground squirrel RTECs had significantly less apoptosis compared to mouse RTECs when subjected to CS/REW. Next, we hypothesized that the mechanism of protection was related to the antiapoptotic proteins X-linked inhibitor of apoptosis (XIAP), phospho-Akt (pAkt), and phospho-BAD. There was a significantly increased pAkt and pBAD expression in ground squirrel versus mouse RTECs subjected to CS/REW. The XIAP expression was maintained in ground squirrel RTECs but was significantly decreased in mouse RTECs after CS/REW. Ground squirrel RTECs in which gene expression of Akt1 and XIAP was silenced lost their protection and demonstrated increased apoptosis and cleaved caspase-3 expression after CS/REW. Conclusions. Our findings suggest that ground squirrel RTECs are protected against apoptosis during prolonged CS/REW by the "prosurvival" factors XIAP and pAkt. C1 [Jain, Swati; Keys, Daniel; Martin, Sandra; Edelstein, Charles L.; Jani, Alkesh] Univ Colorado, Denver, CO 80202 USA. [Edelstein, Charles L.; Jani, Alkesh] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jani, A (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, 12700 East 19th Ave,C281, Aurora, CO 80045 USA. EM Alkesh.jani@ucdenver.edu FU NIH [1 R03 DK96151-01]; VA Merit Award [1I01BX001737] FX This work was supported by NIH 1 R03 DK96151-01 and a VA Merit Award 1I01BX001737. NR 33 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD MAR PY 2016 VL 100 IS 3 BP 538 EP 545 DI 10.1097/TP.0000000000000937 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DF8BR UT WOS:000371582400025 PM 26457601 ER PT J AU Adler, JT Yeh, H Markmann, JF Nguyen, LL AF Adler, Joel T. Yeh, Heidi Markmann, James F. Nguyen, Louis L. TI Temporal Analysis of Market Competition and Density in Renal Transplantation Volume and Outcome SO TRANSPLANTATION LA English DT Article ID KIDNEY-TRANSPLANTATION; UNITED-STATES; ACCESS; RISK AB Background. Kidney transplant centers are distributed unevenly throughout 58 donor service areas (DSAs) in the United States. Market competition and transplant center density may affect transplantation access and outcomes. We evaluated the role of spatial organization of transplant centers in conjunction with market competition in the conduct of kidney transplantation. Methods. The Scientific Registry of Transplant Recipients was queried for market characteristics associated with kidney transplantation between 2003 and 2012. Market competition was calculated using the Herfindahl Hirschman Index. Kidney transplant centers were geocoded to measure spatial organization by the average nearest neighbor (ANN) method. Kidney quality was assessed by kidney donor risk index. A hierarchical negative binomialmixed effects model tested the relationship between market characteristics and annual kidney transplants by DSA. Results. About 152,071 kidney transplants were performed at 229 adult kidney transplant centers in 58 DSAs. Greater market competition was associated with kidney transplant center spatial clustering (P < 0.001). In multivariable analysis, more kidney transplant centers (incidence rate ratio [IRR], 1.04; P = 0.005), 100 more new listings (IRR, 1.02; P = 0.003), 100 more deceased donors (IRR, 1.23; P < 0.001), 100 more new dialysis registrants (IRR, 1.01; P < 0.001), and higher kidney donor risk index (IRR, 1.98; P < 0.001) were associated with increased kidney transplants. Conclusions. After controlling for market characteristics, larger numbers of kidney transplant centers were associated with more kidney transplants and increased utilization of deceased donor kidneys. This underlines the importance of understanding geography as well as competition in improving access to kidney transplantation. C1 [Adler, Joel T.; Nguyen, Louis L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [Adler, Joel T.; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Dept Surg, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. RP Nguyen, LL (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA.; Nguyen, LL (reprint author), Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. EM llnguyen@partners.org OI Adler, Joel/0000-0001-8190-3444 NR 14 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD MAR PY 2016 VL 100 IS 3 BP 670 EP 677 DI 10.1097/TP.0000000000000851 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DF8BR UT WOS:000371582400042 PM 26574684 ER PT J AU Treuting, PM Snyder, JM Ikeno, Y Schofield, PN Ward, JM Sundberg, JP AF Treuting, P. M. Snyder, J. M. Ikeno, Y. Schofield, P. N. Ward, J. M. Sundberg, J. P. TI The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents SO VETERINARY PATHOLOGY LA English DT Article DE aging; pathology; health span; life span; longevity; necropsy; histopathology; rodent; mouse model; animal model; cause of death ID GENETICALLY HETEROGENEOUS MICE; OF-DEATH ASSIGNMENT; EXTENDS LIFE-SPAN; CHRONIC DISEASE; INTERIM-REPORT; ANIMAL-MODELS; MOUSE MODELS; DATA-CAPTURE; RAPAMYCIN; LONGEVITY AB Pathology is a discipline of medicine that adds great benefit to aging studies of rodents by integrating in vivo, biochemical, and molecular data. It is not possible to diagnose systemic illness, comorbidities, and proximate causes of death in aging studies without the morphologic context provided by histopathology. To date, many rodent aging studies do not utilize end points supported by systematic necropsy and histopathology, which leaves studies incomplete, contradictory, and difficult to interpret. As in traditional toxicity studies, if the effect of a drug, dietary treatment, or altered gene expression on aging is to be studied, systematic pathology analysis must be included to determine the causes of age-related illness, moribundity, and death. In this Commentary, the authors discuss the factors that should be considered in the design of aging studies in mice, with the inclusion of robust pathology practices modified after those developed by toxicologic and discovery research pathologists. Investigators in the field of aging must consider the use of histopathology in their rodent aging studies in this era of integrative and preclinical geriatric science (geroscience). C1 [Treuting, P. M.; Snyder, J. M.] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. [Ikeno, Y.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst, San Antonio, TX 78229 USA. [Ikeno, Y.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ikeno, Y.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Ikeno, Y.] South Texas Vet Hlth Care Syst, Audie L Murphy VA Hosp, Geriatr Res & Educ Clin Ctr, San Antonio, TX USA. [Schofield, P. N.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. [Schofield, P. N.; Sundberg, J. P.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Ward, J. M.] Global VetPathol, Montgomery Village, MD USA. RP Treuting, PM (reprint author), Univ Washington, Comparat Pathol, Dept Comparat Med & Histol & Imaging Core, Sch Med, 1-458,Box 357340, Seattle, WA 98195 USA. EM treuting@uw.edu FU BLRD VA [I01 BX001023]; NCI NIH HHS [CA34196, P30 CA034196]; NIA NIH HHS [P30 AG013280, AG13319, AG25707, P01 AG001751, P01AG01751, P30 AG013319, P30 AG025707, P30AG013280]; NIH HHS [R25 OD010450, R25OD010450] NR 81 TC 2 Z9 2 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD MAR PY 2016 VL 53 IS 2 BP 244 EP 249 DI 10.1177/0300985815620629 PG 6 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA DF8PO UT WOS:000371620500003 PM 26792843 ER PT J AU Chien, AT Schiavoni, KH Sprecher, E Landon, BE McNeil, BJ Chernew, ME Schuster, MA AF Chien, Alyna T. Schiavoni, Katherine H. Sprecher, Eli Landon, Bruce E. McNeil, Barbara J. Chernew, Michael E. Schuster, Mark A. TI How Accountable Care Organizations Responded to Pediatric Incentives in the Alternative Quality Contract SO ACADEMIC PEDIATRICS LA English DT Article DE accountable care organizations; payment incentives; pediatrics ID HEALTH-CARE; CHILDREN; PERFORMANCE; MASSACHUSETTS; DISABILITIES; ALGORITHM; PAY AB OBJECTIVE: From 2009 to 2010, 12 accountable care organizations (ACOs) entered into the alternative quality contract (AQC), BlueCross BlueShield of Massachusetts's global payment arrangement. The AQC included 6 outpatient pediatric quality measures among 64 total measures tied to pay-for-performance bonuses and incorporated pediatric populations in their global budgets. We characterized the pediatric infrastructure of these adult-oriented ACOs and obtained leaders' perspectives on their ACOs' response to pediatric incentives. METHODS: We used Massachusetts Health Quality Partners and American Hospital Association Survey data to characterize ACOs' pediatric infrastructure as extremely limited, basic, and substantial on the basis of the extent of pediatric primary care, outpatient specialist, and inpatient services. After ACOs had 16 to 43 months of experience with the AQC, we interviewed 22 leaders to gain insight into how organizations made changes to improve pediatric care quality, tried to reduce pediatric spending, and addressed care for children with special health care needs. RESULTS: ACOs' pediatric infrastructure ranged from extremely limited (eg, no general pediatricians in their primary care workforce) to substantial (eg, 42% of workforce was general pediatricians). Most leaders reported intensifying their pediatric quality improvement efforts and witnessing changes in quality metrics; most also investigated pediatric spending patterns but struggled to change patients' utilization patterns. All reported that the AQC did little to incentivize care for children with special health care needs and that future incentive programs should include this population. CONCLUSIONS: Although ACOs involved in the AQC were adult-oriented, most augmented their pediatric quality improvement and spending reduction efforts when faced with pediatric incentives. C1 [Chien, Alyna T.; Sprecher, Eli; Schuster, Mark A.] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA. [Landon, Bruce E.; McNeil, Barbara J.; Chernew, Michael E.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Chien, Alyna T.; Schiavoni, Katherine H.; Schuster, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. [Schiavoni, Katherine H.] Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. [Landon, Bruce E.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. RP Chien, AT (reprint author), Boston Childrens Hosp, Div Gen Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM alyna.chien@childrens.harvard.edu FU Charles H. Hood Foundation; Agency for Healthcare Research and Quality [K08HS017146] FX This work was financially supported by the Charles H. Hood Foundation. ATC was also supported by the Agency for Healthcare Research and Quality (K08HS017146). The funder had no role in study design, data collection, analysis and interpretation of data, or manuscript preparation. The authors would like to thank their collaborators at BlueCross BlueShield Massachusetts, Dana G. Safran, ScD, and Tony Dodek, MD. NR 26 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAR PY 2016 VL 16 IS 2 BP 200 EP 207 PG 8 WC Pediatrics SC Pediatrics GA DF5AK UT WOS:000371364000015 PM 26523636 ER PT J AU Jarlenski, M Baller, J Borrero, S Bennett, WL AF Jarlenski, Marian Baller, Julia Borrero, Sonya Bennett, Wendy L. TI Trends in Disparities in Low-Income Children's Health Insurance Coverage and Access to Care by Family Immigration Status SO ACADEMIC PEDIATRICS LA English DT Article DE access to care; disparities; health insurance; immigrant ID UNINSURED CHILDREN; UNITED-STATES; EXPANSIONS; MEDICAID; PARENTS; IMPACT AB OBJECTIVE: To examine time trends in disparities in low-income children's health insurance coverage and access to care by family immigration status. METHODS: We used data from the National Survey of Children's Health in 2003 to 2011-2012, including 83,612 children aged 0 to 17 years with family incomes <200% of the federal poverty level. We examined 3 immigration status categories: citizen children with nonimmigrant parents; citizen children with immigrant parents; and immigrant children. We used multivariable regression analyses to obtain adjusted trends in health insurance coverage and access to care.. RESULTS: All low-income children experienced gains in health insurance coverage and access to care from 2003 to 2011-2012, regardless of family immigration status. Relative to citizen children with nonimmigrant parents, citizen children with immigrant parents had a 5 percentage point greater increase in health insurance coverage (P = .06), a 9 percentage point greater increase in having a personal doctor or nurse (P < .01), and an 11 percentage point greater increase in having no unmet medical need (P < .01). Immigrant children had significantly lower health insurance coverage than other groups. However, the group had a 14 percentage point greater increase in having a personal doctor or nurse (P < .01) and a 26 percentage point greater increase in having no unmet medical need (P < .01) relative to citizen children with nonimmigrant parents. CONCLUSIONS: Some disparities in access to care related to family immigration status have lessened over time among children in low-income families, although large disparities still exist. Policy efforts are needed to ensure that children of immigrant parents and immigrant children are able to access health insurance and health care. C1 [Jarlenski, Marian] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, 130 DeSoto St,A647, Pittsburgh, PA 15261 USA. [Jarlenski, Marian; Borrero, Sonya] Univ Pittsburgh, Ctr Womens Hlth Res & Innovat, Pittsburgh, PA USA. [Baller, Julia] Math Policy Res, Washington, DC USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Bennett, Wendy L.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Bennett, Wendy L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. RP Jarlenski, M (reprint author), Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, 130 DeSoto St,A647, Pittsburgh, PA 15261 USA. EM marian.jarlenski@pitt.edu OI Jarlenski, Marian/0000-0001-6907-5447 NR 37 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAR PY 2016 VL 16 IS 2 BP 208 EP 215 PG 8 WC Pediatrics SC Pediatrics GA DF5AK UT WOS:000371364000016 PM 26329016 ER PT J AU Kranzler, HR Armeli, S Wetherill, R Feinn, R Tennen, H Gelernter, J Covault, J Pond, T AF Kranzler, Henry R. Armeli, Stephen Wetherill, Reagan Feinn, Richard Tennen, Howard Gelernter, Joel Covault, Jonathan Pond, Timothy TI Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking SO ADDICTION BIOLOGY LA English DT Article DE GRIK1; mediated moderation; personalized treatment; pharmacogenetics; self-efficacy; topiramate ID ALCOHOL DEPENDENCE; 12-STEP; EXPECTATIONS; MODERATION; DRINKERS; PROGRAMS; OUTCOMES AB Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self-efficacy and later-day drinking; and (2) had an indirect effect on drinking via self-efficacy. In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Topiramate's effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach. C1 [Kranzler, Henry R.; Wetherill, Reagan; Pond, Timothy] Univ Penn, Dept Psychiat, Ctr Studies Addict, Perelman Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Armeli, Stephen] Fairleigh Dickinson Univ, Dept Psychol, Teaneck, NJ USA. [Feinn, Richard] Quinnipiac Univ, Frank Netter Sch Med, Dept Med Sci, Hamden, CT USA. [Tennen, Howard] Univ Connecticut, Sch Med, Dept Community Med & Healthcare, Farmington, CT USA. [Covault, Jonathan] Univ Connecticut, Dept Psychiat, Sch Med, Alcohol Res Ctr, Farmington, CT 06107 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Gelernter, Joel] Vet Affairs Connecticut Healthcare Ctr, West Haven, CT USA. RP Kranzler, HR (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, Perelman Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM kranzler@mail.med.upenn.edu FU National Institutes of Health [P60 AA03510, K24 AA13736] FX Supported by National Institutes of Health grants P60 AA03510 and K24 AA13736. Staff members of the Clinical Research and Evaluation Unit of the University of Connecticut Alcohol Research Center and the Center for Studies of Addiction of the University of Pennsylvania Perelman School of Medicine were instrumental in the conduct of the study. NR 31 TC 7 Z9 9 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2016 VL 21 IS 2 BP 450 EP 459 DI 10.1111/adb.12207 PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA DF2CW UT WOS:000371148700020 PM 25496338 ER PT J AU Clarke, TK Smith, AH Gelernter, J Kranzler, HR Farrer, LA Hall, LS Fernandez-Pujals, AM MacIntyre, DJ Smith, BH Hocking, LJ Padmanabhan, S Hayward, C Thomson, PA Porteous, DJ Deary, IJ McIntosh, AM AF Clarke, Toni-Kim Smith, Andrew H. Gelernter, Joel Kranzler, Henry R. Farrer, Lindsay A. Hall, Lynsey S. Fernandez-Pujals, Ana M. MacIntyre, Donald J. Smith, Blair H. Hocking, Lynne J. Padmanabhan, Sandosh Hayward, Caroline Thomson, Pippa A. Porteous, David J. Deary, Ian J. McIntosh, Andrew M. TI Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort SO ADDICTION BIOLOGY LA English DT Article DE Alcohol dependence; cognition; environment; genetics; polygenic; social deprivation ID EXECUTIVE FUNCTIONS; FAMILY HEALTH; OLD-AGE; CHILDREN; INTELLIGENCE; ADOLESCENCE; CHILDHOOD; EDUCATION; CORTEX; ABUSE AB Alcohol dependence is frequently co-morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome-wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n=2750; Yale-Penn GWAS: n=2377) in a population-based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n=9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P=0.009, =-0.027; Yale-Penn: P=0.001, =-0.034) and VF (SAGE: P=0.0008, =-0.036; Yale-Penn: P=0.00005, =-0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P=5.2x10(-7), =-0.054; Yale-Penn: P=0.000012, =-0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders. C1 [Clarke, Toni-Kim; Hall, Lynsey S.; Fernandez-Pujals, Ana M.; MacIntyre, Donald J.; McIntosh, Andrew M.] Univ Edinburgh, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. [Hayward, Caroline; Thomson, Pippa A.] Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh EH10 5HF, Midlothian, Scotland. [Hayward, Caroline; Porteous, David J.] Univ Edinburgh, MRC Human Genet, MRC IGMM, Edinburgh EH10 5HF, Midlothian, Scotland. [Thomson, Pippa A.; Porteous, David J.; Deary, Ian J.; McIntosh, Andrew M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH10 5HF, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH10 5HF, Midlothian, Scotland. [Smith, Andrew H.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, West Haven, CT 06516 USA. [Smith, Andrew H.; Gelernter, Joel] VA CT Healthcare Ctr, West Haven, CT USA. [Smith, Andrew H.] Yale Univ, Sch Med, Med Scientist Training Program, West Haven, CT 06516 USA. [Smith, Andrew H.] Yale Univ, Sch Med, Interdept Neurosci Program, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet & Neurobiol, West Haven, CT 06516 USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med & Publ Hlth, Dept Med, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Neurol, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Biomed Genet, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Epidemiol, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Biostat, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Smith, Blair H.] Univ Dundee, Populat Hlth Sci, Dundee DD1 4HN, Scotland. [Hocking, Lynne J.] Univ Aberdeen, Div Appl Hlth Sci, Aberdeen AB9 1FX, Scotland. [Padmanabhan, Sandosh] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. RP Clarke, TK (reprint author), Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Kennedy Tower, Edinburgh EH10 5HF, Midlothian, Scotland. EM toni.clarke@ed.ac.uk RI Padmanabhan, Sandosh/S-3963-2016; OI Clarke, Toni-Kim/0000-0002-7745-6351; Farrer, Lindsay/0000-0001-5533-4225; MacIntyre, Donald J/0000-0001-6963-1335; Hocking, Lynne J/0000-0002-2414-2826; Padmanabhan, Sandosh/0000-0003-3869-5808; Smith, Blair/0000-0002-5362-9430; McIntosh, Andrew/0000-0002-0198-4588 FU Chief Scientist Office of the Scottish Government; Scottish Funding Council; Scottish Government Health Department, Chief Scientist Office [CZD/16/6]; National Institutes of Health [N01-HG-65403, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, MSTP T32GM07205, CTSA 8UL1TR000142]; Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; GENEVA Coordinating [U01 HG004446]; Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine Dependence (FSCD) [R01 DA013423]; Johns Hopkins University Center for Inherited Disease Research; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH [HHSN268200782096C]; Dr Mortimer and Theresa Sackler Foundation; Biotechnology and Biological Sciences Research Council (BBSRC); Medical Research Council (MRC); Wellcome Trust [104036/Z/14/Z] FX The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office (No. CZD/16/6). Genotyping services for a part of the Yale GWAS study were provided by the Center for Inherited Disease Research (CIDR) and Yale University (Center for Genome Analysis). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (Contract No. N01-HG-65403). The publicly available datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlmnih.gov/projects/gap/cgi-bin/studycgi?study_id=phs000 092.vl.p1 through dbGaP accession number phs000092.vl.p. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEL Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD: R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). The authors TKC and AN NI acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PAT, DTP, IJD and AMM are members of Hie University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged, supported in part by National Institutes of Health grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, MSTP T32GM07205 and CTSA 8UL1TR000142. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. NR 47 TC 3 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2016 VL 21 IS 2 BP 469 EP 480 DI 10.1111/adb.12245 PG 12 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA DF2CW UT WOS:000371148700022 PM 25865819 ER PT J AU Delnomdedieu, M Duvvuri, S Li, DJ Atassi, N Lu, M Brashear, HR Liu, E Ness, S Kupiec, JW AF Delnomdedieu, Marielle Duvvuri, Sridhar Li, David Jianjun Atassi, Nazem Lu, Ming Brashear, H. Robert Liu, Enchi Ness, Seth Kupiec, James W. TI First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer's disease SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article DE Alzheimer's disease; Pharmacokinetics; Monoclonal antibody; Humans; Safety; Immunotherapy; ARIA ID IMAGING ABNORMALITIES; PHASE-3 TRIALS; IMMUNOTHERAPY; BAPINEUZUMAB; SOLANEZUMAB AB Background: In the First-In-Human (FIH), 39-week, randomized, adaptive design study, safety, tolerability, pharmacokinetics and biomarkers were measured in patients with mild-to-moderate Alzheimer's disease (AD) after infusion of a humanized monoclonal antibody to amyloid beta, AAB-003 (NCT01193608; registered 19 August 2010). AAB-003 was developed by modifying bapineuzumab to reduce Fc-receptor-mediated effector function as a strategy to reduce the removal of amyloid from vessel walls associated with amyloid-related imaging abnormalities with edema/effusions (ARIA-E) without diminishing overall amyloid clearance. Methods: Eighty-eight patients with AD received up to three infusions of AAB-003 (or placebo) 13 weeks apart at doses of 0.5, 1, 2, 4 or 8 mg/kg in the FIH trial. Dose escalation was based on safety data reviews using a Bayesian escalation algorithm. Subjects who completed the FIH study were permitted to enter a 1-year open-label extension trial with four additional intravenous infusions of AAB-003 (NCT01369225; registered 10 May 2011). Results: Dose-dependent increases in plasma amyloid beta and AAB-003 were observed. No significant changes in cerebral spinal fluid biomarkers were observed. Pharmacokinetics elimination half-life (21-28 days) clearance and volume of distribution values were consistent across dose groups indicating linearity. ARIA-E was the most notable safety finding detected by magnetic resonance imaging (MRI) at 8 mg/kg in two patients. Three cases of microhemorrhage were observed. No new safety findings or MRI abnormalities were observed for the 52 subjects who received AAB-003 in the extension trial. Conclusion: Based on integrated review of laboratory, electrocardiogram, adverse events, and MRI, AAB-003 was safe and well tolerated up to 8 mg/kg for up to 91 weeks (FIH and extension trials) in patients with mild to moderate AD. Asymptomatic and resolvable ARIA-E was observed after the first or second infusion of AAB-003, similar to bapineuzumab. The AAB-003 dose at which ARIA-E was observed was higher compared to bapineuzumab, supporting the hypothesis that reducing Fc-receptor effector function may reduce the ARIA associated with monoclonal antibodies targeting cerebral amyloid. C1 [Delnomdedieu, Marielle; Duvvuri, Sridhar; Li, David Jianjun; Kupiec, James W.] Pfizer Neurosci Res Unit, Cambridge, MA USA. [Atassi, Nazem] Mass Gen Hosp, Boston, MA USA. [Lu, Ming] Janssen R&D, Spring House, PA USA. [Brashear, H. Robert; Liu, Enchi; Ness, Seth] Janssen R&D, Fremont, CA USA. RP Delnomdedieu, M (reprint author), Pfizer Neurosci Res Unit, Cambridge, MA USA. EM marielle.delnomdedieu@pfizer.com FU Pfizer Inc.; Janssen Research & Development, LLC. FX The studies were sponsored by Pfizer Inc. and Janssen Research & Development, LLC. NA was a paid contractor to Pfizer Inc. during the conduct of the studies and the development of the manuscript. EL (former Janssen employee) was an employee of Janssen R&D during the conduct of the studies and initiation of the manuscript. Eve Pickering provided statistical leadership. Vladimir Dragalin and Michael Krams provided critical input on trial design and originated the adaptive components. Wendy Luca and Maria Graziewicz provided operational and clinical trial support. Jeffrey Miceli provided clinical guidance during the design and execution of the trial. No editorial service was provided. NR 17 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PD MAR 1 PY 2016 VL 8 AR 12 DI 10.1186/s13195-016-0177-y PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DF3AN UT WOS:000371216200001 PM 26925577 ER PT J AU Zent, CS Wang, XV Ketterling, RP Hanson, CA Libby, EN Barrientos, JC Call, TG Chang, JE Liu, JJ Calvo, AR Lazarus, HM Rowe, JM Luger, SM Litzow, MR Tallman, MS AF Zent, Clive S. Wang, Xin Victoria Ketterling, Rhett P. Hanson, Curtis A. Libby, Edward N. Barrientos, Jacqueline C. Call, Timothy G. Chang, Julie E. Liu, Jane J. Calvo, Alejandro R. Lazarus, Hillard M. Rowe, Jacob M. Luger, Selina M. Litzow, Mark R. Tallman, Martin S. TI A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908) SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID OPEN-LABEL; CD20 LOSS; CYCLOPHOSPHAMIDE; FLUDARABINE; CLL; CHLORAMBUCIL; COMBINATION; MECHANISMS; OFATUMUMAB; GUIDELINES AB Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older ( 65 years) patients (median age 76 years, n=31) with treatment naive progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m(2) weekly)(n=16) or low dose (20 mg/m(2) 3x week)(n=15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression-free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti-CD20 mAb therapy as a potentially more effective use of anti-CD20 mAb in the treatment of CLL. Am. J. Hematol. 91:308-312, 2016. (c) 2015 Wiley Periodicals, Inc. C1 [Zent, Clive S.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Zent, Clive S.; Ketterling, Rhett P.; Hanson, Curtis A.; Call, Timothy G.; Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Wang, Xin Victoria] Dana Farber Canc Inst, ECOG ACRIN Biostat Ctr, Boston, MA 02115 USA. [Libby, Edward N.] Seattle Canc Care Alliance, Seattle, WA USA. [Libby, Edward N.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Barrientos, Jacqueline C.] North Shore LIJ Hlth Syst NCORP, Manhasset, NY USA. [Chang, Julie E.] Univ Wisconsin, Madison, WI USA. [Liu, Jane J.] Illinois CancerCare, Peoria, IL USA. [Calvo, Alejandro R.] Kettering Hlth Network, Kettering, OH USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Tallman, Martin S.] Northwestern Univ, Sch Med, Chicago, IL USA. RP Zent, CS (reprint author), Univ Rochester, Med Ctr, Wilmot Canc Inst, 601 Elmswood Ave Box 704, Rochester, NY 14642 USA. EM clive_zent@urmc.rochester.edu FU NCI NIH HHS [UG1 CA189957, CA180790, CA180791, CA180794, CA180799, CA180820, CA180821, CA180853, CA180888, CA189830, CA189953, CA189957, P30 CA008748, U01 CA079778, U10 CA021115, U10 CA023318, U10 CA066636, U10 CA180790, U10 CA180791, U10 CA180794, U10 CA180799, U10 CA180820, U10 CA180821, U10 CA180853, U10 CA180888, UG1 CA189830, UG1 CA189850, UG1 CA189953] NR 34 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 BP 308 EP 312 DI 10.1002/ajh.24265 PG 5 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800255 PM 26662208 ER PT J AU Seftel, MD Neuberg, D Zhang, MJ Wang, HL Ballen, KK Bergeron, J Couban, S Freytes, CO Hamadani, M Kharfan-Dabaja, MA Lazarus, HM Nishihori, T Paulson, K Saber, W Sallan, SE Soiffer, R Tallman, MS Woolfrey, AE DeAngelo, DJ Weisdorf, DJ AF Seftel, Matthew D. Neuberg, Donna Zhang, Mei-Jie Wang, Hai-Lin Ballen, Karen Kuhn Bergeron, Julie Couban, Stephen Freytes, Cesar O. Hamadani, Mehdi Kharfan-Dabaja, Mohamed A. Lazarus, Hillard M. Nishihori, Taiga Paulson, Kristjan Saber, Wael Sallan, Stephen E. Soiffer, Robert Tallman, Martin S. Woolfrey, Ann E. DeAngelo, Daniel J. Weisdorf, Daniel J. CA CIBMTR Dana Farber ALL Consortium TI Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC-CELL TRANSPLANTATION; CONVENTIONAL CONSOLIDATION/MAINTENANCE CHEMOTHERAPY; MINIMAL RESIDUAL DISEASE; 2ND COMPLETE REMISSION; REDUCED-INTENSITY; UNRELATED DONORS; YOUNG-ADULTS; DOSE INTENSIFICATION; GROUP-B AB For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. (c) 2015 Wiley Periodicals, Inc. C1 [Seftel, Matthew D.; Paulson, Kristjan] CancerCare Manitoba, Dept Med Oncol & Haematol, ON2047, Winnipeg, MB R3E 0V9, Canada. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, Mei-Jie; Wang, Hai-Lin; Hamadani, Mehdi; Saber, Wael] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Ballen, Karen Kuhn] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Bergeron, Julie] Hop Maison Neuve Rosemont, Dept Hematol, Montreal, PQ, Canada. [Couban, Stephen] Dalhousie Univ, Queen Elizabeth Hlth Sci Ctr 2, Div Haematol, Halifax, NS, Canada. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kharfan-Dabaja, Mohamed A.; Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Med, Cleveland, OH USA. [Sallan, Stephen E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Soiffer, Robert; DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA. [Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Dept Pediat Hematopoiet Cell Transplant, 1124 Columbia St, Seattle, WA 98104 USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Seftel, MD (reprint author), CancerCare Manitoba, Dept Med Oncol & Haematol, ON2047, Winnipeg, MB R3E 0V9, Canada. EM mseftel@cancercare.mb.ca FU NCI NIH HHS [U24-CA076518, P01 CA068484, P30 CA008748, T32 CA009515, U24 CA076518]; NHLBI NIH HHS [5U10HL069294, U10 HL069294]; PHS HHS [HHSH250201200016C] NR 35 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 BP 322 EP 329 DI 10.1002/ajh.24285 PG 8 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800258 PM 26701142 ER PT J AU Canali, S Core, AB Zumbrennen-Bullough, KB Merkulova, M Schneyer, A Pietrangelo, A Babitt, JL AF Canali, Susanna Core, Amanda B. Zumbrennen-Bullough, Kimberly B. Merkulova, Maria Schneyer, Alan Pietrangelo, Antonello Babitt, Jodie L. TI ACTIVIN B UTILIZES ACTIVIN TYPE II RECEPTORS, BMP TYPE I RECEPTORS, HEMOJUVELIN AND SMAD1/5/8 SELECTIVELY IN HEPATOCYTES TO PROMOTE HEPCIDIN INDUCTION BY INFLAMMATION IN MICE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Canali, Susanna; Core, Amanda B.; Zumbrennen-Bullough, Kimberly B.; Merkulova, Maria; Babitt, Jodie L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol,Program, Cambridge, MA 02138 USA. [Schneyer, Alan] UMass Amherst, Dept Vet & Anim Sci, Amherst, MA USA. [Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Ctr Hemochromatosis, Modena, Italy. RI Pietrangelo, Antonello/K-1517-2016 OI Pietrangelo, Antonello/0000-0002-7411-935X 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 MA 51 BP E251 EP E251 PG 1 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800232 ER PT J AU Kortman, G Mulder, M Richters, T Shanmugam, N Trebicka, E Boekhorst, J Timmerman, H Roelofs, R Wiegerinck, E Laarakkers, C Swinkels, D Bolhuis, A Cherayil, B Tjalsma, H AF Kortman, Guus Mulder, Michelle Richters, Thijs Shanmugam, Nanda Trebicka, Estela Boekhorst, Jos Timmerman, Harro Roelofs, Rian Wiegerinck, Erwin Laarakkers, Coby Swinkels, Dorine Bolhuis, Albert Cherayil, Bobby Tjalsma, Harold TI LOW DIETARY IRON INTAKE RESTRAINS THE INTESTINAL INFLAMMATORY RESPONSE AND PATHOLOGY OF ENTERIC INFECTION BY FOOD-BORNE BACTERIAL PATHOGENS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Kortman, Guus; Mulder, Michelle; Richters, Thijs; Roelofs, Rian; Wiegerinck, Erwin; Laarakkers, Coby; Swinkels, Dorine; Tjalsma, Harold] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Shanmugam, Nanda; Trebicka, Estela; Cherayil, Bobby] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boekhorst, Jos; Timmerman, Harro] NIZO Food Res BV, Nijmegen, Netherlands. [Bolhuis, Albert] Univ Bath, Bath BA2 7AY, Avon, England. 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 MA 16 BP E36 EP E36 PG 1 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800025 ER PT J AU Rubio, A Gourbeyre, O Lin, H Coppin, H Roth, MP Meynard, D AF Rubio, Aude Gourbeyre, Ophelie Lin, Herbert Coppin, Helene Roth, Marie-Paule Meynard, Delphine TI ROLE OF MATRIPTASE-2 ON HEPCIDIN SUPPRESSION IN RESPONSE TO ERYTHROPOIESIS NEEDS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Rubio, Aude; Gourbeyre, Ophelie; Coppin, Helene; Roth, Marie-Paule; Meynard, Delphine] Univ Toulouse 3, CPTP, Inserm U1043, F-31062 Toulouse, France. [Lin, Herbert] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Program Anemia Signaling Res, Boston, MA 02114 USA. RI coppin, helene/G-4326-2013 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 MA 57 BP E257 EP E257 PG 1 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800238 ER PT J AU Williams, DA Gavillet, M AF Williams, David A. Gavillet, Mathilde TI Response to correspondence: Flow cytometric quantification of neutrophil extracellular traps: Limitations of the methodological approach by Ciepiela et al. SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID NETOSIS; MICE C1 [Williams, David A.; Gavillet, Mathilde] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Williams, David A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Gavillet, Mathilde] Univ Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland. RP Williams, DA (reprint author), 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2016 VL 91 IS 3 BP E10 EP E10 DI 10.1002/ajh.24292 PG 1 WC Hematology SC Hematology GA DF2HI UT WOS:000371162800002 PM 26749259 ER PT J AU Heath, B Bernhardt, J Michalski, TJ Crnich, CJ Moehring, R Schmader, KE Olds, D Higgins, PA Jump, RLP AF Heath, Barbara Bernhardt, Jaime Michalski, Thomas J. Crnich, Christopher J. Moehring, Rebekah Schmader, Kenneth E. Olds, Danielle Higgins, Patricia A. Jump, Robin L. P. TI Results of a Veterans Affairs employee education program on antimicrobial stewardship for older adults SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Antimicrobial stewardship; Professional education; Nursing home; Registered nurses; Asymptomatic bacteriuria; Aged ID CARE FACILITIES; NURSES AB We describe a course in the Veterans Affairs (VA) Employee Education System designed to engage nursing staff working in VA long-term care facilities as partners in antimicrobial stewardship. We found that the course addressed an important knowledge gap. Our outcomes suggest opportunities to engage nursing staff in advancing antimicrobial stewardship, particularly in the long-term care setting. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Heath, Barbara; Higgins, Patricia A.; Jump, Robin L. P.] Geriatr Res Educ & Clin Ctr, Cleveland, OH USA. [Bernhardt, Jaime; Michalski, Thomas J.] Louis Stokes Cleveland Vet Affairs Med Ctr, Employee Educ Syst, Cleveland, OH USA. [Crnich, Christopher J.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Crnich, Christopher J.] Univ Wisconsin, Madison, WI USA. [Moehring, Rebekah; Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Moehring, Rebekah; Schmader, Kenneth E.] Duke Univ, Durham, NC USA. [Olds, Danielle] Louis Stokes Cleveland Vet Affairs Med Ctr, Qual Scholars Program, Cleveland, OH USA. [Higgins, Patricia A.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Jump, Robin L. P.] Case Western Reserve Univ, Dept Med, Div Infect Dis & HIV Med, Cleveland, OH 44106 USA. [Jump, Robin L. P.] Louis Stokes Cleveland Vet Affairs Med Ctr, Div Med, Infect Dis Sect, Cleveland, OH USA. RP Jump, RLP (reprint author), Louis Stokes Cleveland VA Med Ctr, GRECC 111C W,10701 East Blvd, Cleveland, OH 44106 USA. EM robin.jump@va.gov FU AHRQ HHS [K08 HS023866] NR 10 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR 1 PY 2016 VL 44 IS 3 BP 349 EP 351 DI 10.1016/j.ajic.2015.09.026 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DF4CS UT WOS:000371295500024 PM 26553404 ER PT J AU Safdar, N Codispoti, N Purvis, S Knobloch, MJ AF Safdar, Nasia Codispoti, Nicolette Purvis, Suzanne Knobloch, Mary Jo TI Patient perspectives on indwelling urinary catheter use in the hospital SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Patient perspectives; Catheter-associated urinary tract infections ID TRACT-INFECTIONS AB Urinary tract infections are one of the most common hospital-acquired infections, with 70%-80% resulting from catheter-associated urinary tract infections (CAUTIs). We undertook a qualitative study to assess patient perspectives of indwelling urinary catheters using a semistructured interview. We found that patient awareness and patient engagement regarding indwelling urinary catheters and their consequences could be improved in the hospital setting. Implementing educational programs incorporating patient preferences for both health care workers and patients is likely to increase the involvement of patients in decision-making regarding urinary catheters and may lead to a decline in CAUTIs. Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Safdar, Nasia; Knobloch, Mary Jo] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, Infect Dis, Dept Med, Madison, WI USA. [Codispoti, Nicolette] Univ Wisconsin, Madison, WI USA. [Purvis, Suzanne] Univ Wisconsin Hosp & Clin, Geriatr, Madison, WI 53792 USA. RP Safdar, N (reprint author), MFCB 5221,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu OI Purvis, Suzanne/0000-0001-5977-5984 FU Agency for Healthcare Research and Quality [R03HS023791] FX Supported by the Agency for Healthcare Research and Quality (grant no. R03HS023791). NR 11 TC 2 Z9 2 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR 1 PY 2016 VL 44 IS 3 BP E23 EP E24 DI 10.1016/j.ajic.2015.10.011 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DF4CS UT WOS:000371295500003 PM 26698670 ER PT J AU Bigdeli, TB Ripke, S Bacanu, SA Lee, SH Wray, NR Gejman, PV Rietschel, M Cichon, S St Clair, D Corvin, A Kirov, G McQuillin, A Gurling, H Rujescu, D Andreassen, OA Werge, T Blackwood, DHR Pato, CN Pato, MT Malhotra, AK O'Donovan, MC Kendler, KS Fanous, AH AF Bigdeli, Tim B. Ripke, Stephan Bacanu, Silviu-Alin Lee, Sang Hong Wray, Naomi R. Gejman, Pablo V. Rietschel, Marcella Cichon, Sven St Clair, David Corvin, Aiden Kirov, George McQuillin, Andrew Gurling, Hugh Rujescu, Dan Andreassen, Ole A. Werge, Thomas Blackwood, Douglas H. R. Pato, Carlos N. Pato, Michele T. Malhotra, Anil K. O'Donovan, Michael C. Kendler, Kenneth S. Fanous, Ayman H. CA Schizophrenia Working Grp Psychiat TI Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; polygenic; GWAS; family history ID ETIOLOGIC HETEROGENEITY; CLASSIFICATION; RISK; SNPS AB Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R-2=0.0021; P=0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P=0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies. (c) 2015 Wiley Periodicals, Inc. C1 [Bigdeli, Tim B.; Kendler, Kenneth S.; Fanous, Ayman H.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Lee, Sang Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA. [Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Rietschel, Marcella] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Heidelberg, Germany. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Cichon, Sven] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, Sven] Life & Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Corvin, Aiden] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Kirov, George; O'Donovan, Michael C.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [McQuillin, Andrew; Gurling, Hugh] UCL, Div Psychiat, Mol Psychiat Lab, London WC1E 6BT, England. [Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany. [Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Andreassen, Ole A.] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway. [Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Werge, Thomas] MHC Sct Hans, Mental Hlth Serv Copenhagen, Inst Biol Psychiat, Copenhagen, Denmark. [Werge, Thomas] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark. [Werge, Thomas] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Copenhagen, Denmark. [Blackwood, Douglas H. R.] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland. [Pato, Carlos N.; Pato, Michele T.; Fanous, Ayman H.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Malhotra, Anil K.] Zucker Hillside Hosp, Glen Oaks, NY USA. [Malhotra, Anil K.] Feinstein Inst Med Res, Manhasset, NY USA. [Malhotra, Anil K.] Hofstra NS LIJ Sch Med, Hempstead, NY USA. [O'Donovan, Michael C.] Cardiff Univ, Natl Ctr Mental Hlth, Cardiff CF10 3AX, S Glam, Wales. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA. [Fanous, Ayman H.] Washington VA Med Ctr, Mental Hlth Serv Line, Washington, DC USA. [Fanous, Ayman H.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. RP Fanous, AH (reprint author), VA Med Ctr, Psychiat Genet Res Program, 50 Irving St NW, Washington, DC 20422 USA. EM ayman.fanous@va.gov RI Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lee, Sang Hong/A-2569-2011; Webb, Bradley/B-1459-2009; Domenici, Enrico/K-8194-2016; McQuillin, Andrew/C-1623-2008; Pantelis, Christos/H-7722-2014; OI Melle, Ingrid /0000-0002-9783-548X; Bruggeman, Richard/0000-0002-3238-8471; Ruderfer, Douglas/0000-0002-2365-386X; Lee, Sang Hong/0000-0001-9701-2718; O'Neill, Francis Anthony/0000-0002-7531-7657; Webb, Bradley/0000-0002-0576-5366; Domenici, Enrico/0000-0001-7436-6919; McQuillin, Andrew/0000-0003-1567-2240; Pantelis, Christos/0000-0002-9565-0238; Corvin, Aiden/0000-0001-6717-4089; Holmans, Peter/0000-0003-0870-9412; Adolfsson, Rolf/0000-0001-9785-8473; Nothen, Markus/0000-0002-8770-2464 FU United States Department of Veterans Affairs Merit Review Program [5I01CX000278]; Netherlands Scientific Organization [NWO480-05-003]; Dutch Brain Foundation; VU University Amsterdam FX Grant sponsor: United States Department of Veterans Affairs Merit Review Program; Grant number: 5I01CX000278; Grant sponsor: Netherlands Scientific Organization; Grant number: NWO480-05-003; Grant sponsor: Dutch Brain Foundation and the VU University Amsterdam. NR 40 TC 1 Z9 1 U1 4 U2 12 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 2016 VL 171 IS 2 BP 276 EP 289 DI 10.1002/ajmg.b.32402 PG 14 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA DF3LM UT WOS:000371245700015 PM 26663532 ER PT J AU Bukhari, OM Sohrabi, K Tavares, M AF Bukhari, Omair M. Sohrabi, Keyvan Tavares, Mary TI Factors affecting patients' adherence to orthodontic appointments SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID FAILED APPOINTMENTS; DURATION; MEDICAID; ATTENDANCE; CHILDREN AB Introduction: Studies show that attendance at orthodontic appointments affects treatment outcomes, treatment duration, and the probability of side effects. The aim of this study was to predict factors that influence patients' attendance at orthodontic appointments. Methods: We conducted a face-to-face guided interview survey of 153 participants from orthodontic clinics in the Greater Boston area. Attendance at scheduled orthodontic appointments was self-reported as always, sometimes, or rarely. Participants' characteristics, including demographics, dental insurance, and oral hygiene practices, were self-reported. Moreover, from dental records, we collected the time that the participants spent undergoing active orthodontic treatment. Multivariable ordered logistic regression was used to report proportional odds ratios and attendance probabilities. A likelihood ratio test was performed to ensure that the proportional odds assumption held. Results: For overall appointment attendance, 76% of the participants reported always attending, 16% reported sometimes attending, and 8% reported rarely attending. Based on multivariable logistic regression (adjusted for age, race, and sex), the participants with optimal oral hygiene practices were almost 6 times (5.9) more likely to attend appointments than those who did not (P = 0.002). The odds of attending appointments decreased significantly (by 23%) for every 6-month increase in treatment duration (P = 0.008). Participants covered by non-Medicaid insurance were 4 times (P = 0.018) more likely to attend appointments than were those with Medicaid insurance. Conclusion: Our findings indicate that adherence to orthodontic treatment follow-up visits was strongly correlated to insurance type, treatment duration, and oral hygiene practices. Unlike previous studies, sex was not a significant predictor of adherence. C1 [Bukhari, Omair M.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Bukhari, Omair M.] Umm Al Qura Univ, Fac Dent, Mecca, Saudi Arabia. [Sohrabi, Keyvan] Univ Washington, Sch Dent, Seattle, WA 98195 USA. [Tavares, Mary] Forsyth Inst, Cambridge, MA USA. [Tavares, Mary] Harvard Univ, Sch Dent Med, Oral Hlth Policy & Epidemiol, Dent Publ Hlth Residency, Boston, MA 02115 USA. RP Bukhari, OM (reprint author), Harvard Univ, Sch Dent Med, Oral Hlth Policy & Epidemiol, REB 204,188 Longwood Ave, Boston, MA 02115 USA. EM omair_bukhari@hsdm.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0889-5406 EI 1097-6752 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD MAR PY 2016 VL 149 IS 3 BP 319 EP 324 DI 10.1016/j.ajodo.2015.07.040 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DF0HZ UT WOS:000371021100007 PM 26926018 ER PT J AU Madariaga, MLL Spencer, PJ Michel, SG La Muraglia, GM O'Neil, MJ Mannon, EC Leblang, C Rosales, IA Colvin, RB Sachs, DH Allan, JS Madsen, JC AF Madariaga, M. L. L. Spencer, P. J. Michel, S. G. La Muraglia, G. M., II O'Neil, M. J. Mannon, E. C. Leblang, C. Rosales, I. A. Colvin, R. B. Sachs, D. H. Allan, J. S. Madsen, J. C. TI Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID REGULATORY T-CELLS; CLINICAL OPERATIONAL TOLERANCE; RENAL-ALLOGRAFTS; TRANSPLANTATION TOLERANCE; HEART-TRANSPLANTATION; WORKING FORMULATION; IMMUNE-MECHANISMS; CUTTING EDGE; LONG-TERM; CLASS-I AB A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n=3), heart-kidneys (n=3), lungs (n=6), and hearts-lungs (n=3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms. C1 [Madariaga, M. L. L.; Spencer, P. J.; Michel, S. G.; La Muraglia, G. M., II; O'Neil, M. J.; Mannon, E. C.; Leblang, C.; Rosales, I. A.; Colvin, R. B.; Sachs, D. H.; Allan, J. S.; Madsen, J. C.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. EM jcmadsen@partners.org FU International Society for Heart and Lung Transplantation and a National Research Service Award; National Heart, Lung, and Blood Institute of the National Institutes of Health [F32HL117540]; Fellowship Grant in Transplantation Biology [T32AI07529]; ASTS-Novartis Scientist Scholarship Grant [C06RR020135-01] FX Dr. Madariaga is an Edward D. Churchill Surgical Research Fellow, Massachusetts General Hospital and a recipient of a fellowship from the International Society for Heart and Lung Transplantation and a National Research Service Award from the National Heart, Lung, and Blood Institute of the National Institutes of Health (F32HL117540). Dr. Spencer is an Edward D. Churchill Surgical Research Fellow, Massachusetts General Hospital, and recipient of a Training Fellowship Grant in Transplantation Biology (T32AI07529). Dr. Michel is a recipient of the 2013 ASTS-Novartis Scientist Scholarship Grant. We acknowledge C06RR020135-01 for construction of the facility utilized for production and maintenance of miniature swine. We are indebted to Mr. J. Scott Arn for herd management and quality control typing. We thank Nicole Brousaides for preparing biopsy samples for histological analysis. NR 37 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2016 VL 16 IS 3 BP 979 EP 986 DI 10.1111/ajt.13489 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA DF3JQ UT WOS:000371240500030 PM 26469344 ER PT J AU Kuo, AS Vijjeswarapu, MA Philip, JH AF Kuo, Alexander S. Vijjeswarapu, Mary A. Philip, James H. TI Incomplete Spontaneous Recovery from Airway Obstruction During Inhaled Anesthesia Induction: A Computational Simulation SO ANESTHESIA AND ANALGESIA LA English DT Article ID DIFFICULT TRACHEAL INTUBATION; GASMAN(R) SIMULATION; SEVOFLURANE; HALOTHANE; PROPOFOL; MODEL AB BACKGROUND: Inhaled induction with spontaneous respiration is a technique used for difficult airways. One of the proposed advantages is if airway patency is lost, the anesthetic agent will spontaneously redistribute until anesthetic depth is reduced and airway patency can be recovered. There are little and conflicting clinical or experimental data regarding the kinetics of this anesthetic technique. We used computer simulation to investigate this situation. METHODS: We used GasMan (R), a computer simulation of inhaled anesthetic kinetics. For each simulation, alveolar ventilation was initiated with a set anesthetic induction concentration. When the vessel-rich group level reached the simulation specified airway obstruction threshold, alveolar ventilation was set at 0 to simulate complete airway obstruction. The time until the vessel-rich group anesthetic level decreased below the airway obstruction threshold was designated time to spontaneous recovery. We varied the parameters for each simulation, exploring the use of sevoflurane and halothane, airway obstruction threshold from 0.5 to 2 minimum alveolar concentration (MAC), anesthetic induction concentration 2 to 4 MAC sevoflurane and 4 to 6 MAC halothane, cardiac output 2.5 to 10 L/min, functional residual capacity 1.5 to 3.5 L, and relative vessel-rich group perfusion 67% to 85%. RESULTS: In each simulation, there were 3 general phases: anesthetic wash-in, obstruction and overshoot, and then slow redistribution. During the first 2 phases, there was a large gradient between the alveolar and vessel-rich group. Alveolar do not reflect vessel-rich group anesthetic levels until the late third phase. Time to spontaneous recovery varied between 35 and 749 seconds for sevoflurane and 13 and 222 seconds for halothane depending on the simulation parameters. Halothane had a faster time to spontaneous recovery because of the lower alveolar gradient and less overshoot of the vessel-rich group, not faster redistribution. Higher airway obstruction thresholds, decreased anesthetic induction, and higher cardiac output reduced time to spontaneous recovery. To a lesser effect, decreased functional residual capacity and the decreased relative vessel-rich groups' perfusion also reduced the time to spontaneous recovery. CONCLUSIONS: Spontaneous recovery after complete airway obstruction during inhaled induction is plausible, but the recovery time is highly variable and depends on the clinical and physiologic situation. These results emphasize that induction is a non-steady-state situation, thus effect-site anesthetic levels should be modeled in future research, not alveolar concentration. Finally, this study provides an example of using computer simulation to explore situations that are difficult to investigate clinically. C1 [Kuo, Alexander S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 75 Francis St, Boston, MA 02115 USA. [Vijjeswarapu, Mary A.; Philip, James H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Vijjeswarapu, MA (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM mvijjeswarapu@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2016 VL 122 IS 3 BP 698 EP 705 DI 10.1213/ANE.0000000000001101 PG 8 WC Anesthesiology SC Anesthesiology GA DE2EZ UT WOS:000370440700002 PM 26745755 ER PT J AU Nair, BG Horibe, M Neradilek, MB Newman, SF Peterson, GN AF Nair, Bala G. Horibe, Mayumi Neradilek, Moni B. Newman, Shu-Fang Peterson, Gene N. TI The Effect of Intraoperative Blood Glucose Management on Postoperative Blood Glucose Levels in Noncardiac Surgery Patients SO ANESTHESIA AND ANALGESIA LA English DT Article ID INDEPENDENT RISK-FACTOR; VASCULAR-SURGERY; PERIOPERATIVE PERIOD; COLORECTAL SURGERY; INSULIN INFUSION; GLYCEMIC CONTROL; CARDIAC-SURGERY; SITE INFECTION; HYPERGLYCEMIA; OUTCOMES AB BACKGROUND: Postoperative hyperglycemia has been associated with poor surgical outcome. The effect of intraoperative glucose management on postoperative glucose levels and the optimal glycemic threshold for initiating insulin are currently unknown. METHODS: We performed a retrospective cohort study of surgery patients who required intraoperative glucose management with data extracted from electronic medical records. In patients who required glucose management, intraoperative glucose levels and insulin therapy were compared against postoperative glucose levels during 3 periods: first postoperative level within 1 hour, within the first 12 hours, and 24 hours of the postoperative period. Logistic regression models that adjusted for patient and surgical factors were used to determine the association between intraoperative glucose management and postoperative glucose levels. RESULTS: In 2440 patients who required intraoperative glucose management, an increase in mean intraoperative glucose level by 10 mg/dL was associated with an increase in postoperative glucose levels by 4.7 mg/dL (confidence interval [CI], 4.1-5.3; P < 0.001) for the first postoperative glucose measurement, 2.6 mg/dL (CI, 2.1-3.1; P < 0.001) for the mean first 12-hour postoperative glucose, and 2.4 mg/dL (CI, 2.0-2.9; P < 0.001) for the mean first 24-hour postoperative glucose levels (univariate analysis). Multivariate analysis showed that these effects depended on (interacted with) body mass index and diabetes status of the patient. Both diabetes status (regression coefficient = 12.2; P < 0.001) and intraoperative steroid use (regression coefficient = 10.2; P < 0.001) had a positive effect on elevated postoperative glucose levels. Intraoperative hyperglycemia (> 180 mg/dL) was associated with postoperative hyperglycemia during the first 12 hours and the first 24 hours. However, interaction with procedure duration meant that this association was stronger for shorter surgeries. When compared with starting insulin for an intraoperative glucose threshold of 140 mg/dL thus avoiding hyperglycemia, initiation of insulin for a hyperglycemia threshold of 180 mg/dL was associated with an increase in postoperative glucose level (7 mg/dL; P < 0.001) and postoperative hyperglycemia incidence (odds ratio = 1.53; P = 0.01). CONCLUSIONS: A higher intraoperative glucose level is associated with a higher postoperative glucose level. Intraoperative hyperglycemia increases the odds for postoperative hyperglycemia. Adequate intraoperative glucose management by initiating insulin infusion when glucose level exceeds 140 mg/dL to prevent hyperglycemia is associated with lower postoperative glucose levels and fewer incidences of postoperative hyperglycemia. However, patient- and procedure-specific variable interactions make the relationship between intraoperative and postoperative glucose levels complicated. C1 [Nair, Bala G.; Newman, Shu-Fang; Peterson, Gene N.] Univ Washington, Dept Anesthesiol & Pain Med, BB 1469 Hlth Sci Bldg,Mail Box 356540, Seattle, WA 98195 USA. [Horibe, Mayumi] VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA USA. [Neradilek, Moni B.] Mt Whisper Light Stat LLC, Seattle, WA USA. [Peterson, Gene N.] Virginia Commonwealth Univ, Dept Anesthesiol, Richmond, VA USA. RP Nair, BG (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, BB 1469 Hlth Sci Bldg,Mail Box 356540, Seattle, WA 98195 USA. EM nairbg@uw.edu FU Patient Safety Innovation Program Grant by the University of Washington FX This research was partly supported by a Patient Safety Innovation Program Grant provided by the University of Washington. NR 25 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2016 VL 122 IS 3 BP 893 EP 902 DI 10.1213/ANE.0000000000001100 PG 10 WC Anesthesiology SC Anesthesiology GA DE2FL UT WOS:000370441900010 PM 26599793 ER PT J AU Pejo, E Santer, P Wang, L Dershwitz, P Husain, SS Raines, DE AF Pejo, Ervin Santer, Peter Wang, Lei Dershwitz, Philip Husain, S. Shaukat Raines, Douglas E. TI gamma-Aminobutyric Acid Type A Receptor Modulation by Etomidate Analogs SO ANESTHESIOLOGY LA English DT Article ID GENERAL ANESTHETIC ETOMIDATE; GABA(A) RECEPTOR; IN-VITRO; BINDING-SITE; METHOXYCARBONYL-ETOMIDATE; OPTICAL ISOMERS; VIVO; CARBOETOMIDATE; PHARMACOLOGY; MECHANISMS AB Background: Etomidate is a highly potent anesthetic agent that is believed to produce hypnosis by enhancing gamma-aminobutyric acid type A (GABA(A)) receptor function. The authors characterized the GABA(A) receptor and hypnotic potencies of etomidate analogs. The authors then used computational techniques to build statistical and graphical models that relate the potencies of these etomidate analogs to their structures to identify the specific molecular determinants of potency. Methods: GABA(A) receptor potencies were defined with voltage clamp electrophysiology using alpha(1)beta(3)gamma(2) receptors harboring a channel mutation (alpha(1)[L264T]) that enhances anesthetic sensitivity (n = 36 to 60 measurements per concentration-response curve). The hypnotic potencies of etomidate analogs were defined using a loss of righting reflexes assay in Sprague Dawley rats (n = 9 to 21 measurements per dose-response curve). Three-dimensional quantitative structure-activity relationships were determined in silico using comparative molecular field analysis. Results: The GABA(A) receptor and hypnotic potencies of etomidate and the etomidate analogs ranged by 91- and 53-fold, respectively. These potency measurements were significantly correlated (r(2) = 0.72), but neither measurement correlated with drug hydrophobicity (r(2) = 0.019 and 0.005, respectively). Statistically significant and predictive comparative molecular field analysis models were generated, and a pharmacophore model was built that revealed both the structural elements in etomidate analogs associated with high potency and the interactions that these elements make with the etomidate-binding site. Conclusions: There are multiple specific structural elements in etomidate and etomidate analogs that mediate GABA(A) receptor modulation. Modifying any one element can alter receptor potency by an order of magnitude or more. C1 [Pejo, Ervin; Santer, Peter; Dershwitz, Philip; Husain, S. Shaukat; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB444, Boston, MA 02114 USA. [Wang, Lei] Certara L P, St Louis, MO USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, Maryland [R01-GM087316]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX This study was funded by grant R01-GM087316 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 39 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2016 VL 124 IS 3 BP 651 EP 663 DI 10.1097/ALN.0000000000000992 PG 13 WC Anesthesiology SC Anesthesiology GA DE5US UT WOS:000370698900019 PM 26691905 ER PT J AU King, MR Ladha, KS Gelineau, AM Anderson, TA AF King, Michael R. Ladha, Karim S. Gelineau, Amanda M. Anderson, T. Anthony TI Perioperative Dextromethorphan as an Adjunct for Postoperative Pain A Meta-analysis of Randomized Controlled Trials SO ANESTHESIOLOGY LA English DT Article ID ASPARTATE RECEPTOR ANTAGONISTS; PATIENT-CONTROLLED ANALGESIA; DOSE ORAL DEXTROMETHORPHAN; DOUBLE-BLIND; MORPHINE CONSUMPTION; LAPAROSCOPIC CHOLECYSTECTOMY; CENTRAL SENSITIZATION; PREEMPTIVE ANALGESIA; GENERAL-ANESTHESIA; OPIOID REQUIREMENT AB Background: N-methyl-d-aspartate receptor antagonists have been shown to reduce perioperative pain and opioid use. The authors performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. Methods: PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Pubget, and EMBASE were searched. Studies were included if they were randomized, double-blinded, placebo-controlled trials written in English, and performed on patients 12 yr or older. For comparison of opioid use, included studies tracked total consumption of IV or intramuscular opioids over 24 to 48 h. Pain score comparisons were performed at 1, 4 to 6, and 24 h postoperatively. Difference in means (MD) was used for effect size. Results: Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD, -10.51 mg IV morphine equivalents; 95% CI, -16.48 to -4.53 mg; P = 0.0006). In 884 patients from 13 trials, pain at 1 h favored dextromethorphan (MD, -1.60; 95% CI, -1.89 to -1.31; P < 0.00001). In 950 patients from 13 trials, pain at 4 to 6 h favored dextromethorphan (MD, -0.89; 95% CI, -1.11 to -0.66; P < 0.00001). In 797 patients from 12 trials, pain at 24 h favored dextromethorphan (MD, -0.92; 95% CI, -1.24 to -0.60; P < 0.00001). Conclusion: This meta-analysis suggests that dextromethorphan use perioperatively reduces the postoperative opioid consumption at 24 to 48 h and pain scores at 1, 4 to 6, and 24 h. C1 [King, Michael R.; Ladha, Karim S.; Gelineau, Amanda M.; Anderson, T. Anthony] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St GRJ 409, Boston, MA 02114 USA. [King, Michael R.; Ladha, Karim S.; Gelineau, Amanda M.; Anderson, T. Anthony] Harvard Univ, Sch Med, 55 Fruit St GRJ 409, Boston, MA USA. [Ladha, Karim S.] Toronto Gen Hosp, Dept Anesthesia, Toronto, ON, Canada. [Ladha, Karim S.] Univ Toronto, Toronto, ON, Canada. RP Anderson, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St GRJ 409, Boston, MA 02114 USA.; Anderson, TA (reprint author), Harvard Univ, Sch Med, 55 Fruit St GRJ 409, Boston, MA USA. EM tanderson9@mgh.harvard.edu FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health [Bethesda, Maryland] Award) [UL1 TR001102]; Harvard University (Cambridge, Massachusetts) FX This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health [Bethesda, Maryland] Award UL1 TR001102) and financial contributions from Harvard University (Cambridge, Massachusetts) and its affiliated academic healthcare centers. NR 61 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2016 VL 124 IS 3 BP 696 EP 705 DI 10.1097/ALN.0000000000000950 PG 10 WC Anesthesiology SC Anesthesiology GA DE5US UT WOS:000370698900023 PM 26587683 ER PT J AU Nemcova, L Jansova, D Vodickova-Kepkova, K Vodicka, P Jeseta, M Machatkova, M Kanka, J AF Nemcova, Lucie Jansova, Denisa Vodickova-Kepkova, Katerina Vodicka, Petr Jeseta, Michal Machatkova, Marie Kanka, Jiri TI Detection of genes associated with developmental competence of bovine oocytes SO ANIMAL REPRODUCTION SCIENCE LA English DT Article DE Oocyte; Embryo; Bovine; Developmental competence; Transcription ID IN-VITRO MATURATION; DIFFERENT MEIOTIC COMPETENCE; MITOCHONDRIAL-DNA CONTENT; TERMINATION CODONS UAA; HUMAN MPS1 KINASE; FOLLICLE SIZE; MLF1-INTERACTING PROTEIN; TRANSCRIPTIONAL ACTIVITY; PREIMPLANTATION EMBRYOS; ANTRAL FOLLICLES AB The developmental competence of oocytes is acquired progressively during folliculogenesis and is linked to follicular size. It has been documented that oocytes originating from larger follicles exhibit a greater ability to develop to the blastocyst stage. The differences in cytoplasmic factors such as mRNA transcripts could explain the differences in oocyte developmental potential. We used bovine oligonucleotide microarrays to characterize differences between the gene expression profiles of germinal vesicle stage (GV) oocytes with greater developmental competence from medium follicles (MF) and those with less developmental competence from small follicles (SF). After normalizing the microarray data, our analysis found differences in the level of 60 transcripts (>= 1.4 fold), corresponding to 49 upregulated and 11 downregulated transcripts in MF oocytes compared to SF oocytes. The gene expression data were classified according to gene ontology, the majority of the genes were associated with the regulation of transcription, translation, the cell cycle, and mitochondria) activity. A subset of 16 selected genes was validated for GV oocytes by quantitative real-time RT-PCR; significant differences (P<0.01) were found in the level of TAF1A,MTRF1L, ATP5C1, UBL5 and MAP3K13 between the MF and SF oocytes. After maturation the transcript level remained stable for ATP5F1, BRD7, and UBL5 in both oocyte categories. The transcript level of another 13 genes substantially dropped in the MF and/or SF oocytes. It can be concluded that the developmental competence of bovine oocytes and embryos may be a quantitative trait dependent on small changes in the transcription profiles of many genes. (C) 2016 Elsevier B.V. All rights reserved. C1 [Nemcova, Lucie; Jansova, Denisa; Vodickova-Kepkova, Katerina; Vodicka, Petr; Kanka, Jiri] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Dev Biol Lab, Libechov, Czech Republic. [Vodicka, Petr] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Vodicka, Petr] Harvard Univ, Sch Med, Charlestown, MA USA. [Jeseta, Michal; Machatkova, Marie] Vet Res Inst, Dept Genet & Reprod, CS-62132 Brno, Czech Republic. RP Nemcova, L (reprint author), Acad Sci Czech Republic, Inst Anim Physiol & Genet, Dev Biol Lab, Libechov, Czech Republic. EM nemcova@iapg.cas.cz RI Jeseta, Michal/A-3159-2013; Vodicka, Petr/C-3845-2009 OI Jeseta, Michal/0000-0003-1778-3454; Vodicka, Petr/0000-0002-6605-9158 FU Ministry of Education, Youth and Sport of the Czech Republic [LD 14104]; IAPG, AS CR v.v.i. [RVO: 67985904] FX This study was supported by grant LD 14104 from the Ministry of Education, Youth and Sport of the Czech Republic. Additional support was provided by institutional research concept RVO: 67985904 (IAPG, AS CR v.v.i.). NR 67 TC 2 Z9 2 U1 6 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4320 EI 1873-2232 J9 ANIM REPROD SCI JI Anim. Reprod. Sci. PD MAR PY 2016 VL 166 BP 58 EP 71 DI 10.1016/j.anireprosci.2016.01.004 PG 14 WC Agriculture, Dairy & Animal Science; Reproductive Biology SC Agriculture; Reproductive Biology GA DF2QR UT WOS:000371189400008 PM 26811294 ER PT J AU Nakhlis, F Gilmore, L Gelman, R Bedrosian, I Ludwig, K Hwang, ES Willey, S Hudis, C Iglehart, JD Lawler, E Ryabin, NY Golshan, M Schnitt, SJ King, TA AF Nakhlis, Faina Gilmore, Lauren Gelman, Rebecca Bedrosian, Isabelle Ludwig, Kandice Hwang, E. Shelley Willey, Shawna Hudis, Clifford Iglehart, J. Dirk Lawler, Elizabeth Ryabin, Nicole Y. Golshan, Mehra Schnitt, Stuart J. King, Tari A. TI Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID UP SURGICAL EXCISION; TERM-FOLLOW-UP; NEEDLE-BIOPSY; CLINICAL-SIGNIFICANCE; PATHOLOGICAL FINDINGS; BREAST-CANCER; HYPERPLASIA; LESIONS; RISK; MALIGNANCY AB Background. Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB. Methods. Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations. Results. A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3 %; 95 % confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1 %; 95 % CI 0.01-7) by central pathology review. Conclusions. In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3 % by local pathology and 1 % by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings. C1 [Nakhlis, Faina; Gelman, Rebecca; Iglehart, J. Dirk; Lawler, Elizabeth; Ryabin, Nicole Y.; Golshan, Mehra] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Gilmore, Lauren] Mt Auburn Hosp, Cambridge, MA USA. [Hudis, Clifford] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Med Serv, 1275 York Ave, New York, NY 10021 USA. [Bedrosian, Isabelle] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ludwig, Kandice] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Hwang, E. Shelley] Duke Univ, Med Ctr, Durham, NC USA. [Willey, Shawna] Georgetown Univ, Ctr Canc, Washington, DC USA. [Iglehart, J. Dirk; Golshan, Mehra] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Schnitt, Stuart J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [King, Tari A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10021 USA. RP King, TA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10021 USA. EM tking7@partners.org FU NCI NIH HHS [P30 CA008748] NR 35 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2016 VL 23 IS 3 BP 722 EP 728 DI 10.1245/s10434-015-4922-4 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA DF4QL UT WOS:000371334600005 PM 26542585 ER PT J AU Merrill, AL Coopey, SB Tang, R McEvoy, MP Specht, MC Hughes, KS Gadd, MA Smith, BL AF Merrill, Andrea L. Coopey, Suzanne B. Tang, Rong McEvoy, Maureen P. Specht, Michele C. Hughes, Kevin S. Gadd, Michelle A. Smith, Barbara L. TI Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CARCINOMA IN-SITU; 20-YEAR FOLLOW-UP; ONCOLOGY CONSENSUS GUIDELINE; RANDOMIZED-TRIAL; CONSERVATIVE TREATMENT; AMERICAN SOCIETY; LOCAL RECURRENCE; RE-EXCISION; CANCER; THERAPY AB Background. The 2014 guidelines endorsed by Society of Surgical Oncology, the American Society of Breast Surgeons, and the American Society for Radiation Oncology advocate "no ink on tumor'' as the new margin requirement for breast-conserving therapy (BCT). We used our lumpectomy margins database from 2004 to 2006 to predict the effect of these new guidelines on BCT. Methods. Patients with neoadjuvant therapy, pure ductal carcinoma-in situ, or incomplete margin data were excluded. We applied new ("no ink on tumor'') and old (>= 2 mm) margin guidelines and compared rates of positive margins, reexcision, and rates of residual disease found at reexcision. Results. A total of 437 lumpectomy surgeries met the eligibility criteria. Eighty-six percent had invasive ductal carcinoma, 12 % invasive lobular carcinoma, and 2 % invasive ductal carcinoma and invasive lobular carcinoma. Using a >= 2 mm margin standard, 36 % of lumpectomies had positive margins compared to 18 % using new guidelines (p < 0.0001). Seventy-seven percent of patients with "ink on tumor'' had residual disease found at reexcision. Fifty percent of subjects with margins <2 mm had residual disease (p = 0.0013) but would not have undergone reexcision under the new guidelines. With margins of >= 2 mm, residual tumor was seen in the shaved margins of 14 % of lumpectomies. Residual tumor was more common in reexcisions for ductal carcinoma-in situ <2 mm from a margin than for invasive cancer (53 vs. 40 %), although this was not statistically significant. Conclusions. Use of new lumpectomy margin guidelines would have reduced reoperation for BCT by half in our patient cohort. However, residual disease was present in many patients who would not have been reexcised with the new guidelines. Long-term follow-up of local recurrence rates is needed to determine if this increase in residual disease is clinically significant. C1 [Merrill, Andrea L.; Coopey, Suzanne B.; Tang, Rong; McEvoy, Maureen P.; Specht, Michele C.; Hughes, Kevin S.; Gadd, Michelle A.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. [Tang, Rong] Cent S Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Div Breast Surg,Hunan Canc Hosp, Changsha, Hunan, Peoples R China. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. EM blsmith1@mgh.harvard.edu NR 26 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2016 VL 23 IS 3 BP 729 EP 734 DI 10.1245/s10434-015-4916-2 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA DF4QL UT WOS:000371334600006 PM 26467458 ER PT J AU Mattos, D Gfrerer, L Ling, ITC Reish, RG Hughes, KS Halpern, EF Cetrulo, C Colwell, AS Winograd, JM Yaremchuk, MJ Austen, WG Liao, EC AF Mattos, David Gfrerer, Lisa Ling, Irving T. C. Reish, Richard G. Hughes, Kevin S. Halpern, Elkan F. Cetrulo, Curtis Colwell, Amy S. Winograd, Jonathan M. Yaremchuk, Michael J. Austen, William G., Jr. Liao, Eric C. TI Occult Histopathology and Its Predictors in Contralateral and Bilateral Prophylactic Mastectomies SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID REDUCTION MAMMAPLASTY SPECIMENS; BRCA2 MUTATION CARRIERS; LYMPH-NODE BIOPSY; IMMEDIATE BREAST RECONSTRUCTION; CANCER RISK; WOMEN; EXPERIENCE; CARCINOMA; TRENDS AB Background. The last decade has seen an increasing prevalence of prophylactic mastectomies with decreasing age of patients treated for breast cancer. Data are limited on the prevalence of histopathologic abnormalities in this population. This study aimed to measure the prevalence of histopathologic findings in contralateral prophylactic mastectomy (CPM) and bilateral prophylactic mastectomy (BPM) patients and identify predictors of findings. Methods. Our institution's prophylactic mastectomies from 2004 to 2011 were reviewed. Breast specimens with prior malignancies were excluded. Patient factors and pathology reports were collected. Independent predictive factors were identified with univariate and multivariate logistic analysis. Results. A total of 524 specimens in 454 patients were identified. Malignancy was found in 7.0 % of CPM and 5.7 % of BPM specimens. In CPM patients, ipsilateral lobular carcinoma-in situ [odds ratio (OR) 4.0] and mammogram risk group (OR 2.0) were predictive of malignancy. Age group (OR 1.5), ipsilateral lobular carcinoma-in situ (OR 2.3), and prior bilateral salpingo-oophorectomy (OR 0.3) were predictive of moderate-to high-risk histopathology. Only increasing age group was predictive of increased moderate-to high-risk histopathology in BPM patients (OR 2.3). There were no independent predictors of malignancy in BPM. BRCA status was not predictive in either CPM or BPM. Conclusions. Patients with lobular carcinoma-in situ in the index breast or high-risk mammograms have a higher prevalence of malignancies. Although BRCA patients may benefit from prophylactic mastectomy, the genetic diagnosis does not increase the prevalence of detecting occult pathology. BPM patients can be counseled about relative risk, where occult pathology increases with age. C1 [Mattos, David; Gfrerer, Lisa; Ling, Irving T. C.; Reish, Richard G.; Cetrulo, Curtis; Colwell, Amy S.; Winograd, Jonathan M.; Yaremchuk, Michael J.; Austen, William G., Jr.; Liao, Eric C.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Liao, EC (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. EM cliao@partners.org NR 31 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2016 VL 23 IS 3 BP 767 EP 775 DI 10.1245/s10434-015-4896-2 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA DF4QL UT WOS:000371334600011 PM 26577123 ER PT J AU Hanyuda, A Kim, SA Martinez-Fernandez, A Qian, ZR Yamauchi, M Nishihara, R Morikawa, T Liao, XY Inamura, K Mima, K Cao, Y Zhang, XH Wu, KN Chan, AT Giovannucci, EL Meyerhardt, JA Fuchs, CS Shivdasani, RA Ogino, S AF Hanyuda, Akiko Kim, Sun A. Martinez-Fernandez, Alejandro Qian, Zhi Rong Yamauchi, Mai Nishihara, Reiko Morikawa, Teppei Liao, Xiaoyun Inamura, Kentaro Mima, Kosuke Cao, Yin Zhang, Xuehong Wu, Kana Chan, Andrew T. Giovannucci, Edward L. Meyerhardt, Jeffrey A. Fuchs, Charles S. Shivdasani, Ramesh A. Ogino, Shuji TI Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; BODY-MASS INDEX; INSULIN-RECEPTOR SUBSTRATE-1; LIFE-STYLE FACTORS; PHYSICAL-ACTIVITY; COLON-CANCER; MICROSATELLITE INSTABILITY; RISK-FACTORS; PIK3CA MUTATION AB Background. High-level physical activity is associated with lower colorectal cancer (CRC) mortality, likely through insulin sensitization. Insulin receptor substrate 1 (IRS1) is a mediator of insulin and insulin-like growth factor (IGF) signaling pathways, and its down-regulation is associated with insulin resistance. Therefore, we hypothesized that tumor IRS1 expression status might modify cellular sensitivity to insulin and IGF, and the prognostic association of physical activity. Methods. We assessed IRS1 expression level in 371 stage I-III rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study by immunohistochemistry. In survival analysis, Cox proportional hazards model was used to assess an interaction between post-diagnosis physical activity (ordinal scale of sex-specific quartiles Q1 to Q4) and IRS1 expression (ordinal scale of negative, low, and high), controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation level, and KRAS, BRAF, and PIK3CA mutation status. Results. There was a statistically significant interaction between post-diagnosis physical activity and tumor IRS1 expression in CRC-specific mortality analysis (P-interaction = 0.005). Multivariable hazard ratio (95 % confidence interval) for higher post-diagnosis physical activity (Q3-Q4 vs. Q1-Q2) was 0.15 (0.02-1.38) in the IRS1-negative group, 0.45 (0.19-1.03) in the IRS1-low group, and 1.32 (0.50-3.53) in the IRS1-high group. Conclusions. The association of post-diagnosis physical activity with colorectal carcinoma patient survival may differ by tumor IRS1 expression level. If validated, tumor IRS1 expression status may serve as a predictive marker to identify subgroups of patients who might gain greater survival benefit from an increased level of exercise. C1 [Hanyuda, Akiko; Nishihara, Reiko; Cao, Yin; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Kim, Sun A.; Martinez-Fernandez, Alejandro; Qian, Zhi Rong; Yamauchi, Mai; Nishihara, Reiko; Morikawa, Teppei; Liao, Xiaoyun; Inamura, Kentaro; Mima, Kosuke; Zhang, Xuehong; Chan, Andrew T.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Shivdasani, Ramesh A.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Sun A.; Martinez-Fernandez, Alejandro; Qian, Zhi Rong; Yamauchi, Mai; Nishihara, Reiko; Morikawa, Teppei; Liao, Xiaoyun; Inamura, Kentaro; Mima, Kosuke; Zhang, Xuehong; Chan, Andrew T.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Shivdasani, Ramesh A.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Nishihara, Reiko] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Nishihara, Reiko; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Inamura, Kentaro] JFCR, Inst Canc, Div Pathol, Tokyo, Japan. [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Zhang, Xuehong; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Ogino, S (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Ogino, S (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.; Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [UM1 CA167552, K07 CA190673, P01 CA055075, P01 CA087969, P01 CA55075, P01 CA87969, P50 CA127003, R01 CA118553, R01 CA137178, R01 CA151993, R01 CA169141, R35 CA197735, UM1 CA186107]; NIDDK NIH HHS [K24 DK098311] NR 75 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2016 VL 23 IS 3 BP 908 EP 917 DI 10.1245/s10434-015-4967-4 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA DF4QL UT WOS:000371334600030 PM 26577117 ER PT J AU Lu, N Dubreuil, M Zhang, YQ Neogi, T Rai, SK Ascherio, A Hernan, MA Choi, HK AF Lu, Na Dubreuil, Maureen Zhang, Yuqing Neogi, Tuhina Rai, Sharan K. Ascherio, Alberto Hernan, Miguel A. Choi, Hyon K. TI Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CORONARY-HEART-DISEASE; URIC-ACID; PARKINSON-DISEASE; INCIDENT GOUT; URATE; DEMENTIA; DRUGS; SERUM; ANTIOXIDANTS; INHIBITION AB Objective While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, the antioxidant effects of uric acid may have neuroprotective benefits. We evaluated the potential impact of incident gout on the risk of developing Alzheimer's disease (AD) in a general population context. Methods We conducted an age-matched, sex-matched, entry-time-matched and body mass index (BMI)-matched cohort study using data from The Health Improvement Network, an electronic medical record database representative of the UK general population, from 1 January 1995 to 31 December 2013. Up to five non-gout individuals were matched to each case of incident gout by age, sex, year of enrolment and BMI. We compared incidence rates of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline. Multivariate hazard ratios (HRs) were calculated, while adjusting for smoking, alcohol use, physician visits, social deprivation index, comorbidities and medication use. We repeated the same analysis among patients with incident osteoarthritis (OA) as a negative control exposure. Results We identified 309 new cases of AD among 59 224 patients with gout (29% female, mean age 65 years) and 1942 cases among 238 805 in the comparison cohort over a 5-year median follow up (1.0 vs 1.5 per 1000 person-years, respectively). Univariate (age-matched, sex-matched, entry-time-matched and BMI-matched) and multivariate HRs for AD among patients with gout were 0.71 (95% CI 0.62 to 0.80) and 0.76 (95% CI 0.66 to 0.87), respectively. The inverse association persisted among subgroups stratified by sex, age group (<75 and >= 75 years), social deprivation index and history of CV disease. The association between incident OA and the risk of incident AD was null. Conclusions These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, supporting the purported potential neuroprotective role of uric acid. C1 [Lu, Na; Choi, Hyon K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. [Lu, Na; Dubreuil, Maureen; Zhang, Yuqing; Neogi, Tuhina] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Dubreuil, Maureen] Boston Univ, Sch Med, Dept Med, Sect Rheumatol, Boston, MA 02118 USA. [Rai, Sharan K.] Univ British Columbia, Arthritis Res Ctr Canada, Vancouver, BC V5Z 1M9, Canada. [Ascherio, Alberto; Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM choi.hyon@mgh.harvard.edu OI Neogi, Tuhina/0000-0002-9515-1711 FU NIAMS [P60AR047785, R01AR056291, R01AR065944] FX This work was supported in part by grants from NIAMS (P60AR047785, R01AR056291 and R01AR065944). NR 40 TC 8 Z9 8 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2016 VL 75 IS 3 BP 547 EP 551 DI 10.1136/annrheumdis-2014-206917 PG 5 WC Rheumatology SC Rheumatology GA DF1DD UT WOS:000371077700010 PM 25739830 ER PT J AU Grubaugh, AL Clapp, JD Frueh, BC Tuerk, PW Knapp, RG Egede, LE AF Grubaugh, Anouk L. Clapp, Joshua D. Frueh, B. Christopher Tuerk, Peter W. Knapp, Rebecca G. Egede, Leonard E. TI Open trial of exposure therapy for PTSD among patients with severe and persistent mental illness SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Severe mental illness (SMI); Posttraumatic stress disorder (PTSD); Trauma; Exposure therapy; Prolonged exposure ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; QUALITY-OF-LIFE; SCHIZOAFFECTIVE DISORDER; PSYCHOMETRIC PROPERTIES; DSM-IV; SCHIZOPHRENIA; TRAUMA; VETERANS; ADULTS AB Objective: There are few empirical data regarding effective treatment of trauma-related symptoms among individuals with severe mental illness (SMI; e.g., bipolar disorder, schizophrenia). This under examined clinical issue is significant because rates of trauma and PTSD are higher among individuals with SMI relative to the general population, and there are sufficient data to suggest that PTSD symptoms exacerbate the overall course and prognosis of SMI. Method: 34 veterans with SMI received prolonged exposure (PE) for PTSD using an open trial study design. Results: Data suggest that PE is feasible to implement, well-tolerated, and results in clinically significant decreases in PTSD severity in patients with SMI. Mean CAPS scores improved 27.2 points from baseline to immediate post [95% CI for mean change: -44.3, - 10.1; p = 0.002, paired t-test, and treatment gains were maintained at 6 months [mean change from baseline to 6-months, W-16.1; 95% CI: -31.0, -1.2; p = 0.034, paired t-test]. Conclusions: The current data support the use of exposure-based interventions for PTSD among individuals with SMI and highlight the need for rigorous randomized efficacy trials investigating frontline PTSD interventions in this patient population. (C) 2015 Published by Elsevier Ltd. C1 [Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. [Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 109 Bee St, Charleston, SC 29401 USA. [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, 200 W Kawili St, Hilo, HI 96720 USA. [Knapp, Rebecca G.] Med Univ S Carolina, Dept Publ Hlth Sci, 135 Cannon St, Charleston, SC 29403 USA. [Egede, Leonard E.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 135 Rutledge Ave,POB 250593, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, 135 Rutledge Ave,POB 250593, Charleston, SC 29425 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu NR 58 TC 1 Z9 1 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD MAR PY 2016 VL 78 BP 1 EP 12 DI 10.1016/j.brat.2015.12.006 PG 12 WC Psychology, Clinical SC Psychology GA DF5DX UT WOS:000371373100001 PM 26797658 ER PT J AU Erpelding, N Simons, L Lebel, A Serrano, P Pielech, M Prabhu, S Becerra, L Borsook, D AF Erpelding, Nathalie Simons, Laura Lebel, Alyssa Serrano, Paul Pielech, Melissa Prabhu, Sanjay Becerra, Lino Borsook, David TI Rapid treatment-induced brain changes in pediatric CRPS SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Cortical thickness; Voxel-based morphometry; Functional connectivity; Chronic pain; Neuropathic pain; Children; Hippocampus; Prefrontal cortex; Periaqueductal gray ID REGIONAL PAIN SYNDROME; CHRONIC BACK-PAIN; TRANSCRANIAL MAGNETIC STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; REFLEX SYMPATHETIC DYSTROPHY; TRIGEMINAL NEUROPATHIC PAIN; WHITE-MATTER ABNORMALITIES; MEDIATED CHRONIC PAIN; GRAY-MATTER; FUNCTIONAL CONNECTIVITY AB To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age +/- A SD = 13.3 +/- A 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation. C1 [Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Becerra, Lino; Borsook, David] Boston Childrens Hosp, PAIN Grp, Ctr Pain & Brain, 9 Hope Ave, Waltham, MA 02453 USA. [Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Prabhu, Sanjay; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Boston, MA USA. [Prabhu, Sanjay] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Becerra, Lino; Borsook, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Becerra, Lino; Borsook, David] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. RP Erpelding, N (reprint author), Boston Childrens Hosp, PAIN Grp, Ctr Pain & Brain, 9 Hope Ave, Waltham, MA 02453 USA. EM nathalie.erpelding@gmail.com FU National Institute of Neurological Disorders and Stroke [R01-NS-065051, K24-NS-064050]; National Institute of Child Health and Human Development [HD-067202]; Mayday Foundation, New York FX This study was primarily supported by National Institute of Neurological Disorders and Stroke Grants R01-NS-065051 and K24-NS-064050 (to D. Borsook), by National Institute of Child Health and Human Development K23 Career Development Award HD-067202 (to L. Simons), and by a Grant from the Mayday Foundation, New York. We would like to thank Charles Berde, MD Ph.D. for his support through the Sara Page Mayo Endowment for Pediatric Pain Research. We would like to thank Simona Sava, Ph.D. for contributing to the data collection. NR 147 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAR PY 2016 VL 221 IS 2 BP 1095 EP 1111 DI 10.1007/s00429-014-0957-8 PG 17 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DF5GP UT WOS:000371380100022 PM 25515312 ER PT J AU Beker, S Goldin, M Menkes-Caspi, N Kellner, V Chechik, G Stern, EA AF Beker, Shlomit Goldin, Miri Menkes-Caspi, Noa Kellner, Vered Chechik, Gal Stern, Edward A. TI Amyloid-beta disrupts ongoing spontaneous activity in sensory cortex SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Alzheimer's disease; Membrane potential; Synaptic summation; Plaques; LFP; Firing patterns ID NEURONS IN-VIVO; CAT VISUAL-CORTEX; MEMBRANE-POTENTIAL FLUCTUATIONS; ALZHEIMERS-DISEASE; MOUSE MODEL; FUNCTIONAL CONNECTIVITY; SYNAPTIC INTEGRATION; NETWORK ACTIVITY; FRONTAL-CORTEX; BARREL CORTEX AB The effect of Alzheimer's disease pathology on activity of individual neocortical neurons in the intact neural network remains obscure. Ongoing spontaneous activity, which constitutes most of neocortical activity, is the background template on which further evoked-activity is superimposed. We compared in vivo intracellular recordings and local field potentials (LFP) of ongoing activity in the barrel cortex of APP/PS1 transgenic mice and age-matched littermate Controls, following significant amyloid-beta (A beta) accumulation and aggregation. We found that membrane potential dynamics of neurons in A beta-burdened cortex significantly differed from those of nontransgenic Controls: durations of the depolarized state were considerably shorter, and transitions to that state frequently failed. The spiking properties of APP/PS1 neurons showed alterations from those of Controls: both firing patterns and spike shape were changed in the APP/PS1 group. At the population level, LFP recordings indicated reduced coherence within neuronal assemblies of APP/PS1 mice. In addition to the physiological effects, we show that morphology of neurites within the barrel cortex of the APP/PS1 model is altered compared to Controls. These results are consistent with a process where the effect of A beta on spontaneous activity of individual neurons amplifies into a network effect, reducing network integrity and leading to a wide cortical dysfunction. C1 [Beker, Shlomit; Goldin, Miri; Menkes-Caspi, Noa; Kellner, Vered; Chechik, Gal; Stern, Edward A.] Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. [Stern, Edward A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. RP Stern, EA (reprint author), Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. EM sterned@mail.biu.ac.il FU National Institute on Aging at the National Institute on Health [AG024238]; Legacy Heritage Bio-Medical Program of the Israel Science Foundation [688/10]; Marie Curie European Reintegration Grant within the 7th European Community Framework Programme [PERG03-GA-2008-230981] FX This work was supported by the National Institute on Aging at the National Institute on Health (Grant Number AG024238); the Legacy Heritage Bio-Medical Program of the Israel Science Foundation (Grant Number 688/10); and Marie Curie European Reintegration Grant within the 7th European Community Framework Programme (Grant Number PERG03-GA-2008-230981). We thank Profs. Israel Nelken and Moshe Abeles for their helpful suggestions on this manuscript. NR 46 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAR PY 2016 VL 221 IS 2 BP 1173 EP 1188 DI 10.1007/s00429-014-0963-x PG 16 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DF5GP UT WOS:000371380100027 PM 25523106 ER PT J AU Luke, JJ LoRusso, P Shapiro, GI Krivoshik, A Schuster, R Yamazaki, T Arai, Y Fakhoury, A Dmuchowski, C Infante, JR AF Luke, Jason J. LoRusso, Patricia Shapiro, Geoffrey I. Krivoshik, Andrew Schuster, Robin Yamazaki, Takao Arai, Yukinori Fakhoury, Allam Dmuchowski, Carl Infante, Jeffrey R. TI ASP9853, an inhibitor of inducible nitric oxide synthase dimerization, in combination with docetaxel: preclinical investigation and a Phase I study in advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Phase I clinical trial; Tumor; ASP9853; Taxane; Nitric oxide synthase dimerization; Docetaxel ID SUPPRESSOR-CELLS; CANCER; NO; CHEMOTHERAPY; GROWTH; MODULATION; EXPRESSION; MECHANISM; APOPTOSIS; SURVIVIN AB ASP9853 is an inhibitor of inducible nitric oxide (NO) synthase (iNOS) dimerization, which results in decreased NO production. Here, we report preclinical pharmacology of ASP9853 and the impact of ASP9853 in combination with a taxane on tumor volume in vivo. In addition, a Phase I open-label study of ASP9853 plus docetaxel was conducted to assess this combination in patients with advanced solid tumors. The preclinical efficacy of ASP9853 in combination with a taxane was studied in tumor-bearing mice. In the clinic, patients with solid tumors that had progressed or failed to respond to previous therapies were treated with once-daily ASP9853 in combination with docetaxel once every 3 weeks to assess safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) of the combination. ASP9853 in combination with docetaxel showed greater tumor growth inhibition than docetaxel alone against non-small lung cancer xenografts. Twenty patients were treated with ASP9853 and docetaxel. Five patients experienced neutropenic dose-limiting toxicities. Owing to overall toxicity that limited further dose escalation, the ASP9853 concentrations predicted for efficacy, based on the preclinical data, were not achieved. Due to toxicity and lack of clear efficacy, the study was terminated without determination of MTD or RP2D. Inhibition of iNOS by ASP9853 in combination with docetaxel was not tolerable and resulted in the possible potentiation of neutropenia. Manipulation of the iNOS pathway, with or without chemotherapy, appears to be more complicated than initially expected. C1 [Luke, Jason J.] Univ Chicago Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. [LoRusso, Patricia] Yale Smilow Canc Ctr, New Haven, CT USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Krivoshik, Andrew; Schuster, Robin; Yamazaki, Takao; Fakhoury, Allam; Dmuchowski, Carl] Astellas Pharma Global Dev Inc, 1 Astellas Way, Northbrook, IL USA. [Arai, Yukinori] Astellas Pharma Inc, Drug Discovery Res, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. [Infante, Jeffrey R.] PLLC, Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. RP Luke, JJ (reprint author), Univ Chicago Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM jluke@medicine.bsd.uchicago.edu FU Astellas Pharma Inc. FX We would like to thank Michelle Utton-Mishra, Choice Healthcare Solutions, for medical writing assistance, funded by Astellas Pharma Inc. NR 34 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2016 VL 77 IS 3 BP 549 EP 558 DI 10.1007/s00280-016-2967-0 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA DF3LQ UT WOS:000371246100010 PM 26811179 ER PT J AU Peng, SW Mattox, A Best, SR Barbu, AM Burns, JA Akpeng, B Jeang, J Yang, B Ishida, E Hung, CF Wu, TC Pai, SI AF Peng, Shiwen Mattox, Austin Best, Simon R. Barbu, Anca M. Burns, James A. Akpeng, Belinda Jeang, Jessica Yang, Benjamin Ishida, Eiichi Hung, Chien-Fu Wu, Tzyy-Choou Pai, Sara I. TI Identification of the murine H-2D(b) and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Human papillomavirus; Vaccine; T cell epitope; MHC class I; Recurrent respiratory papillomatosis; Immunotherapy ID RECURRENT RESPIRATORY PAPILLOMATOSIS; HUMAN-PAPILLOMAVIRUS TYPE-11; DNA VACCINES; IMMUNE-RESPONSES; CALRETICULIN; ANTIGEN; PEPTIDES; MODEL; E6 AB Recurrent respiratory papillomatosis is caused by human papillomavirus (HPV) infection, most commonly types 6 (HPV-6) and 11 (HPV-11). Due to failed host immune responses, HPV is unable to be cleared from the host, resulting in recurrent growth of HPV-related lesions that can obstruct the lumen of the airway within the upper aerodigestive tract. In our murine model, the HPV-6b and HPV-11 E7 antigens are not innately immunogenic. In order to enhance the host immune responses against the HPV E7 antigen, we linked calreticulin (CRT) to HPV-6b E7 and found that vaccinating C57BL/6 mice with the HPV-6b CRT/E7 DNA vaccine is able to induce a CD8(+) T cell response that recognizes an H-2D(b)-restricted E7aa21-29 epitope. Additionally, vaccination of HLA-A*0201 transgenic mice with HPV-6b CRT/E7 DNA generated a CD8(+) T cell response against the E7aa82-90 epitope that was not observed in the wild-type C57BL/6 mice, indicating this T cell response is restricted to HLA-A*0201. In vivo cytotoxic T cell killing assays demonstrated that the vaccine-induced CD8(+) T cells are able to efficiently kill target cells. Interestingly, the H-2D(b)-restricted E7aa21-29 sequence and the HLA-A*0201-restricted E7aa82-90 sequence are conserved between HPV-6b and HPV-11 and may represent shared immunogenic epitopes. The identification of the HPV-6b/HPV-11 CD8(+) T cell epitopes facilitates the evaluation of various immunomodulatory strategies in preclinical models. More importantly, the identified HLA-A*0201-restricted T cell epitope may serve as a peptide vaccination strategy, as well as facilitate the monitoring of vaccine-induced HPV-specific immunologic responses in future human clinical trials. C1 [Peng, Shiwen; Jeang, Jessica; Yang, Benjamin; Hung, Chien-Fu; Wu, Tzyy-Choou] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Mattox, Austin; Hung, Chien-Fu; Wu, Tzyy-Choou] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Best, Simon R.] Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Barbu, Anca M.; Burns, James A.; Akpeng, Belinda; Ishida, Eiichi; Pai, Sara I.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. [Wu, Tzyy-Choou] Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Wu, Tzyy-Choou] Johns Hopkins Med Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Pai, SI (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM sara.pai@mgh.harvard.edu FU NCI NIH HHS [1R01CA181538-01A1]; NIDCR NIH HHS [R01 DE025340] NR 22 TC 0 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAR PY 2016 VL 65 IS 3 BP 261 EP 271 DI 10.1007/s00262-016-1793-x PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DF8TD UT WOS:000371631100002 PM 26759151 ER PT J AU Bommarito, D Martin, A Forcade, E Nastke, MD Ritz, J Bellucci, R AF Bommarito, Davide Martin, Allison Forcade, Edouard Nastke, Maria-Dorothea Ritz, Jerome Bellucci, Roberto TI Enhancement of tumor cell susceptibility to natural killer cell activity through inhibition of the PI3K signaling pathway SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE NK cells; PI3K; Immunotherapy; shRNA; Tyrosine kinase inhibitors ID LENTIVIRAL RNAI LIBRARY; KINASE INHIBITORS; CANCER-TREATMENT; SORAFENIB; SUNITINIB; IMMUNITY; IMMUNOSURVEILLANCE; REACTIVITY; RECEPTORS; CARCINOMA AB Natural killer (NK) cells are the primary effectors of the innate immune response against virus-infected cells or cells that have undergone malignant transformation. NK cells recognize their targets through a complex array of activating and inhibitory receptors, which regulate the intensity of the effector response against individual target cells. However, many studies have shown that tumor cells can escape immune cell recognition through a variety of mechanisms, developing resistance to NK cell killing. Using a lentiviral shRNA library, we previously demonstrated that several common signaling pathways modulate susceptibility of tumor cells to NK cell activity. In this study, we focused on one of the genes (PI3KCB), identified in this genetic screen. The PI3KCB gene encodes an isoform of the catalytic subunit of PI3K called P110 beta. The PI3K pathway has been linked to diverse cellular functions, but has never been associated with susceptibility to NK cell activity. Gene silencing of PI3KCB resulted in increased susceptibility of several tumor cell lines to NK cell lytic activity and induced increased IFN-gamma secretion by NK cells. Treatment of primary tumor cells with two different PI3K inhibitors also increased target cell susceptibility to NK cell activity. These effects are due, at least in part, to modulation of several activating and inhibitory ligands and appear to be correlated with PI3K signaling pathway inhibition. These findings identify a new and important role of PI3KCB in modulating tumor cell susceptibility to NK cells and open the way to future combined target immunotherapies. C1 [Bommarito, Davide; Martin, Allison; Forcade, Edouard; Nastke, Maria-Dorothea; Ritz, Jerome; Bellucci, Roberto] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,M526, Boston, MA 02215 USA. [Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, 450 Brookline Ave,M530, Boston, MA 02215 USA. [Forcade, Edouard; Ritz, Jerome; Bellucci, Roberto] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Forcade, Edouard; Ritz, Jerome; Bellucci, Roberto] Harvard Univ, Sch Med, Boston, MA USA. RP Ritz, J; Bellucci, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,M526, Boston, MA 02215 USA.; Ritz, J (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, 450 Brookline Ave,M530, Boston, MA 02215 USA.; Ritz, J; Bellucci, R (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.; Ritz, J; Bellucci, R (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM Jerome_ritz@dfci.Harvard.edu; Roberto_Bellucci@dfci.harvard.edu FU NIH [R21AI088521, P01CA078378, PO1CA142106, CA183560]; Multiple Myeloma Research Foundation (MMRF); Claudia Adams Barr Research Program FX R21AI088521 (NIH), Multiple Myeloma Research Foundation (MMRF) and Claudia Adams Barr Research Program (Roberto Bellucci), P01CA078378 (NIH), PO1CA142106 (NIH), CA183560 (NIH) (Jerome Ritz). NR 44 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAR PY 2016 VL 65 IS 3 BP 355 EP 366 DI 10.1007/s00262-016-1804-y PG 12 WC Oncology; Immunology SC Oncology; Immunology GA DF8TD UT WOS:000371631100010 PM 26883876 ER PT J AU Danis, E Yamauchi, T Echanique, K Zhang, X Haladyna, JN Riedel, SS Zhu, N Xie, HF Orkin, SH Armstrong, SA Bernt, KM Neff, T AF Danis, Etienne Yamauchi, Taylor Echanique, Kristen Zhang, Xi Haladyna, Jessica N. Riedel, Simone S. Zhu, Nan Xie, Huafeng Orkin, Stuart H. Armstrong, Scott A. Bernt, Kathrin M. Neff, Tobias TI Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia SO CELL REPORTS LA English DT Article ID REPRESSIVE COMPLEX 2; ACUTE MYELOID-LEUKEMIA; METHYLTRANSFERASE GENE EZH2; MLL-REARRANGED LEUKEMIA; GROUP PROTEIN EZH2; SOMATIC MUTATIONS; G-CSF; DIFFERENTIATION; INHIBITION; TRANSFORMATION AB Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Poly-comb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell-and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients. C1 [Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Zhang, Xi; Haladyna, Jessica N.; Riedel, Simone S.; Bernt, Kathrin M.; Neff, Tobias] Univ Colorado Denver, Dept Pediat, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO 80045 USA. [Zhu, Nan] Blood Ctr Wisconsin, Blood Res Inst, Stem Cell Biol & Hematopoiesis Program, Milwaukee, WI 53226 USA. [Xie, Huafeng; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart H.] HHMI, Boston, MA 02115 USA. [Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, Dept Med, New York, NY 10065 USA. [Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, Dept Pediat, New York, NY 10065 USA. [Bernt, Kathrin M.; Neff, Tobias] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA. RP Bernt, KM; Neff, T (reprint author), Univ Colorado Denver, Dept Pediat, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO 80045 USA.; Bernt, KM; Neff, T (reprint author), Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA. EM kathrin.bernt@ucdenver.edu; tobias.neff@ucdenver.edu RI Bernt, Kathrin/L-1826-2016; OI Bernt, Kathrin/0000-0002-5400-0482; Neff, Tobias/0000-0002-0188-8393 FU National Cancer Institute (NCI) [K08CA154777]; University of Colorado Denver, Section for Pediatric Hematology/Oncology; Cancer League Colorado; Sidney Kimmel Foundation for Cancer Research; National Heart, Lung, and Blood Institute [K08HL102264]; NCI (Shared Resource of the University of Colorado Cancer Center) [P30CA046934]; Children's Hospital Colorado Research Institute FX We thank Karen Helm and the staff at the flow cytometry core for assistance with FACS and cell sorting. We thank Katrina Diener and Ted Shade at the Genomics core of the University of Colorado AMC. We thank Ken Jones at the Bioinformatics core for help with Illumina data analysis. We thank Tracy Haney and Holly Goold for animal Husbandry. We thank Patricia Ernst and Craig Jordan for critically reading the manuscript. This work was supported by National Cancer Institute (NCI) grant K08CA154777 (T.N.); start-up funds from University of Colorado Denver, Section for Pediatric Hematology/Oncology, and the Children's Hospital Colorado Research Institute (T.N.); the Cancer League Colorado (T.N.); the Sidney Kimmel Foundation for Cancer Research (T.N.); National Heart, Lung, and Blood Institute grant K08HL102264 (K.M.B.); and NCI grant P30CA046934 (Shared Resource of the University of Colorado Cancer Center). NR 72 TC 5 Z9 5 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR 1 PY 2016 VL 14 IS 8 BP 1953 EP 1965 DI 10.1016/j.celrep.2016.01.064 PG 13 WC Cell Biology SC Cell Biology GA DF3BC UT WOS:000371217700015 PM 26904942 ER PT J AU Wu, JQ Keng, VW Patmore, DM Kendall, JJ Patel, AV Jousma, E Jessen, WJ Choi, K Tschida, BR Silverstein, KAT Fan, DH Schwartz, EB Fuchs, JR Zou, YS Kim, MO Dombi, E Levy, DE Huang, G Cancelas, JA Stemmer-Rachamimov, AO Spinner, RJ Largaespada, DA Ratner, N AF Wu, Jianqiang Keng, Vincent W. Patmore, Deanna M. Kendall, Jed J. Patel, Ami V. Jousma, Edwin Jessen, Walter J. Choi, Kwangmin Tschida, Barbara R. Silverstein, Kevin A. T. Fan, Danhua Schwartz, Eric B. Fuchs, James R. Zou, Yuanshu Kim, Mi-Ok Dombi, Eva Levy, David E. Huang, Gang Cancelas, Jose A. Stemmer-Rachamimov, Anat O. Spinner, Robert J. Largaespada, David A. Ratner, Nancy TI Insertional Mutagenesis Identifies a STAT3/Arid1b/beta-catenin Pathway Driving Neurofibroma Initiation SO CELL REPORTS LA English DT Article ID NERVE SHEATH TUMORS; NATURAL ANTISENSE TRANSCRIPTS; PANCREATIC-CANCER; BETA-CATENIN; CELLS; NF1; PROGRESSION; GENE; ACTIVATION; TYPE-1 AB To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/beta-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and beta-catenin activity. beta-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and beta-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3 beta and the SWI/SNF gene Arid1b to increase beta-catenin. Knockdown of Arid1b or Gsk3 beta in Stat3(fl/fl); Nf1(fl/fl); DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/beta-catenin pathway inhibitors in neurofibroma therapeutic trials. C1 [Wu, Jianqiang; Patmore, Deanna M.; Kendall, Jed J.; Patel, Ami V.; Jousma, Edwin; Jessen, Walter J.; Choi, Kwangmin; Huang, Gang; Cancelas, Jose A.; Ratner, Nancy] Univ Cincinnati, Cincinnati Childrens Hosp, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Zou, Yuanshu; Kim, Mi-Ok] Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati Childrens Hosp Res Fdn, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Keng, Vincent W.; Tschida, Barbara R.; Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Keng, Vincent W.; Largaespada, David A.] Univ Minnesota, Dept Pediat Cell Biol & Dev, Minneapolis, MN 55455 USA. [Keng, Vincent W.; Tschida, Barbara R.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Silverstein, Kevin A. T.; Fan, Danhua] Univ Minnesota, Biostat & Informat, Minneapolis, MN 55455 USA. [Schwartz, Eric B.; Fuchs, James R.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Dombi, Eva] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Levy, David E.] NYU, Sch Med, Dept Pathol, 550 First Ave, New York, NY 10016 USA. [Levy, David E.] NYU, Sch Med, Inst Canc, 550 First Ave, New York, NY 10016 USA. [Cancelas, Jose A.] Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Spinner, Robert J.] Mayo Clin, Dept Neurol Surg, Rochester, MN 55905 USA. [Keng, Vincent W.] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China. RP Ratner, N (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org OI Keng, Vincent/0000-0003-3473-0653; Levy, David/0000-0002-7320-7788 FU NIH [R01 NS28840, P50 NS057531]; DAMD New Investigator Award [W81XWH-11-1-0259]; Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant; American Cancer Society [IRG-67-00344] FX We thank the Minnesota Supercomputing Institute for computational resources for sequence analysis, Dr. Ari Melnick (Weil Cornell Medical School) for assistance in design of histone modification analysis, and Ms. Huiqing Li for animal husbandry. This work was supported by NIH R01 NS28840 (N.R.), NIH P50 NS057531 (N.R. and D.A.L.), a DAMD New Investigator Award (W81XWH-11-1-0259), an Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant (J.W.), and the American Cancer Society (IRG-67-003-44) (J.R.F.). The CHTN provided some benign neurofibromas used in this study. NR 40 TC 4 Z9 4 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR 1 PY 2016 VL 14 IS 8 BP 1979 EP 1990 DI 10.1016/j.celrep.2016.01.074 PG 12 WC Cell Biology SC Cell Biology GA DF3BC UT WOS:000371217700017 PM 26904939 ER PT J AU Antman, EM Bierer, BE AF Antman, Elliott M. Bierer, Barbara E. TI Standards for Clinical Research Keeping Pace With the Technology of the Future SO CIRCULATION LA English DT Editorial Material DE Editorials; clinical trial; ethics; research ethics; research methodology ID TRIALS; HEALTH C1 [Antman, Elliott M.; Bierer, Barbara E.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,Off Level One, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu FU NCATS NIH HHS [KL2 TR000168, KL2 TR001100]; NCRR NIH HHS [KL2 RR025757] NR 12 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 1 PY 2016 VL 133 IS 9 BP 823 EP 825 DI 10.1161/CIRCULATIONAHA.116.020976 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DF4VG UT WOS:000371348900001 PM 26927004 ER PT J AU Kubiak, DW Farmakiotis, D Arons, V Hollins, RM Rostas, SE Weiser, LM Baden, LR Marty, FM Koo, S AF Kubiak, David W. Farmakiotis, Dimitrios Arons, Viktoria Hollins, Randy M. Rostas, Sara E. Weiser, Linda M. Baden, Lindsey R. Marty, Francisco M. Koo, Sophia TI Utility of in-house fluconazole disk diffusion susceptibility testing in the treatment of candidemia SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Candidemia; Fluconazole; Disk diffusion susceptibility testing ID GLOBAL ANTIFUNGAL SURVEILLANCE; INVASIVE CANDIDIASIS; CANCER-PATIENTS; GLABRATA; RISK; VORICONAZOLE; OUTCOMES; FAILURE; PROGRAM AB Among 302 first candidemia episodes, 210 (69.6%) were initially treated with an echinocandin or polyene (E/P) antifungal drug. In 137 (72.5%) patients with fluconazole-susceptible isolates, treatment was changed to fluconazole based on disk diffusion susceptibility testing. Clinical outcomes were not compromised in patients receiving E/P who were de-escalated to fluconazole for treatment of candidemia based on disk diffusion results. (C) 2016 Elsevier Inc. All rights reserved. C1 [Kubiak, David W.; Arons, Viktoria; Hollins, Randy M.; Rostas, Sara E.] Brigham & Womens Hosp, Dept Pharm, 75 Francis St, Boston, MA 02115 USA. [Kubiak, David W.; Baden, Lindsey R.; Marty, Francisco M.; Koo, Sophia] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Farmakiotis, Dimitrios] Brown Univ, Warren Alpert Med Sch, Div Infect Dis, Rhode Isl Hosp, 593 Eddy St, Providence, RI 02115 USA. [Weiser, Linda M.] Brigham & Womens Hosp, Clin Microbiol Lab, 75 Francis St, Boston, MA 02115 USA. [Baden, Lindsey R.; Marty, Francisco M.; Koo, Sophia] Dana Farber Canc Inst, Div Infect Dis, 450 Brookline Ave, Boston, MA 02215 USA. [Baden, Lindsey R.; Marty, Francisco M.; Koo, Sophia] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kubiak, DW (reprint author), Brigham & Womens Hosp, Dept Pharm, 75 Francis St, Boston, MA 02115 USA.; Kubiak, DW; Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.; Koo, S (reprint author), Dana Farber Canc Inst, Div Infect Dis, 450 Brookline Ave, Boston, MA 02215 USA.; Koo, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM dwkubiak@partners.org; skoo@bwh.harvard.edu OI Koo, Sophia/0000-0002-4973-7439 FU National Institutes of Health [K23 AI097225] FX Funding: There was no financial support for this study. SK is supported by a grant from the National Institutes of Health (K23 AI097225). NR 16 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAR PY 2016 VL 84 IS 3 BP 223 EP 226 DI 10.1016/j.diagmicrobio.2015.11.018 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA DF2PP UT WOS:000371186500012 PM 26763713 ER PT J AU Salihovic, S Ganna, A Fall, T Broeckling, CD Prenni, JE van Bavel, B Lind, PM Ingelsson, E Lind, L AF Salihovic, Samira Ganna, Andrea Fall, Tove Broeckling, Corey D. Prenni, Jessica E. van Bavel, Bert Lind, P. Monica Ingelsson, Erik Lind, Lars TI The metabolic fingerprint of p,p '-DDE and HCB exposure in humans SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Organochlorine pesticides; Human exposure; Metabolomics; Metabolic effects; DDT; HCB AB Background: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown. Objectives: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Methods: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression. Results: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides. Conclusions: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Salihovic, Samira; Fall, Tove; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden. [Ganna, Andrea] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ganna, Andrea] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ganna, Andrea] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Broeckling, Corey D.; Prenni, Jessica E.] Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA. [Salihovic, Samira; van Bavel, Bert] Univ Orebro, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden. [Lind, P. Monica] Univ Uppsala Hosp, Dept Med Sci Occupat & Environm Med, Uppsala, Sweden. [Ingelsson, Erik] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Lind, Lars] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, SE-75141 Uppsala, Sweden. RP Salihovic, S (reprint author), Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden. EM samira.salihovic@medsci.uu.se OI Prenni, Jessica/0000-0002-0337-8450; Ganna, Andrea/0000-0002-8147-240X FU Swedish Research Council (VR); Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) FX This study was supported by the Swedish Research Council (VR) and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS). We greatly acknowledge Erik Lampa and Stefan Gustafsson for technical assistance. NR 39 TC 1 Z9 2 U1 12 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD MAR PY 2016 VL 88 BP 60 EP 66 DI 10.1016/j.envint.2015.12.015 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA DF4YU UT WOS:000371359300009 PM 26720637 ER PT J AU Colicino, E Giuliano, G Power, MC Lepeule, J Wilker, EH Vokonas, P Brennan, KJM Fossati, S Hoxha, M Spiro, A Weisskopf, MG Schwartz, J Baccarelli, AA AF Colicino, Elena Giuliano, Giulia Power, Melinda C. Lepeule, Johanna Wilker, Elissa H. Vokonas, Pantel Brennan, Kasey J. M. Fossati, Serena Hoxha, Mirjam Spiro, Avron, III Weisskopf, Marc G. Schwartz, Joel Baccarelli, Andrea A. TI Long-term exposure to black carbon, cognition and single nucleotide polymorphisms in microRNA processing genes in older men SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Air pollution; Black carbon; Cognitive function; Single nucleotide polymorphisms; MicroRNA ID PARTICULATE AIR-POLLUTION; ELDERLY-MEN; NEURODEGENERATIVE DISORDERS; DISEASE; EXPRESSION; CANCER; CELLS; RISK; RNAI; SMN AB Introduction: Air pollution exposure has been linked to impaired cognitive aging, but little is known about biomarkers modifying this association. MicroRNAs (miRNAs) control gene expression and neuronal programming. miRNA levels vary due to single nucleotide polymorphisms (SNPs) in genes processing miRNAs from precursor molecules. Objectives: To investigate whether SNPs in miRNA-processing genes are associated with cognition and modify the relationship between black carbon (BC), marker of traffic-related pollution, and cognitive functions. Methods: 533 Normative Aging Study men (mean +/- SD 72 +/- 7 years) were tested times (mean = 1.7 times) using seven cognitive tests between 1995 and 2007. We tested interactions of 16 miRNA-related SNPs with 1-year average BC from a validated land-use-regression model. We used covariate-adjusted logistic regression for low (25) Mini-Mental tate Examination (MMSE) and mixed-effect regression for a global cognitive score combining six other tests. Results: Global cognition was negatively associated with the homozygous minor variant of rs595961 AGO) (-0.42SD; 95%CI: (-0.71, -0.13)) relative to the major variant. BC-MMSE association was stronger in heterozygous carriers of rs11077 XPO5 (OR = 1.99; 95%CI: (1.39, 2.85)) and minor variant carriers of GEMIN4 rs2740348 (OR = 134; 95%CI: (1.05, 1.7)), compared to their major variant. The BC-global-cognition association was stronger in heterozygous carriers of GEMIN4 rs4968104 (-0.10SD; 95%CI: (-0.18, -0.02)), and GEMIN4 rs910924 (-0.09SD; 95%Cl: (-0.17, -0.02)) relative to the major variant. Blood miRNA expression analyses showed associations only of XPO5 rs11077 with miR-9 and miR-96. Conclusions: Carriers of particular miRNA-processing SNPs had higher susceptibility to BC in BC-cognition associations, possibly due to influences on miRNA expression. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Colicino, Elena; Giuliano, Giulia; Power, Melinda C.; Lepeule, Johanna; Wilker, Elissa H.; Brennan, Kasey J. M.; Fossati, Serena; Weisskopf, Marc G.; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Power, Melinda C.; Weisskopf, Marc G.; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. [Wilker, Elissa H.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, 330 Brookline Ave, Boston, MA 02215 USA. [Vokonas, Pantel; Spiro, Avron, III] VA Boston Healthcare Syst, 330 Brookline Ave, Boston, MA 02215 USA. [Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, 330 Brookline Ave, Boston, MA 02215 USA. [Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. [Fossati, Serena] Univ Milan, Dept Biomed & Clin Sci L Sacco, Via Festa Perdono 7, I-20122 Milan, Italy. [Hoxha, Mirjam] Univ Milan, Dept Clin Sci & Community Hlth, Via Festa Perdono 7, I-20122 Milan, Italy. [Hoxha, Mirjam] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Prevent Med, Epidemiol Unit, Via Francesco Sforza 33, I-20122 Milan, Italy. RP Colicino, E (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM ecolicin@hsph.harvard.edu; g.giuliano6@campus.unimib.it; melinda.c.power@gmail.com; jlepeule@hsph.harvard.edu; ewilker@bidmc.harvard.edu; pantel.vokonas@va.gov; kbrennan@hsph.harvard.edu; sfossati@hsph.harvard.edu; mirjam.hoxha@unimi.it; aspiro3@bu.edu; mweissko@hsph.harvard.edu; joel@hsph.harvard.edu; abaccare@hsph.harvard.edu RI LEPEULE, Johanna/K-1085-2016; Colicino, Elena/Q-4973-2016; OI Colicino, Elena/0000-0002-1875-8448; Fossati, Serena/0000-0002-7484-5837 FU NIEHS [R01ES021733, R01ES015172, R01ES014663, R21ES020010]; EPA [RD832416]; CSR&D Research Career Scientist award; US Department of Agriculture, Agricultural Research Service [53-K06-510]; Cooperative Studies Program/ERIC; US Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) FX EC is supported by a grant from the NIEHS (R01ES021733). Other support comes was provided by NIEHS grants R01ES015172, R01ES014663 and R21ES020010, and EPA grant RD832416. Cognitive data collection at the VA NAS was supported by a VA Merit Review and a CSR&D Research Career Scientist award to AS. Additional support was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510).; The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 50 TC 0 Z9 0 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD MAR PY 2016 VL 88 BP 86 EP 93 DI 10.1016/j.envint.2015.12.014 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA DF4YU UT WOS:000371359300013 PM 26724585 ER PT J AU El-Hachem, N Grossmann, P Blanchet-Cohen, A Bateman, AR Bouchard, N Archambault, J Aerts, HJWL Haibe-Kains, B AF El-Hachem, Nehme Grossmann, Patrick Blanchet-Cohen, Alexis Bateman, Alain R. Bouchard, Nicolas Archambault, Jacques Aerts, Hugo J. W. L. Haibe-Kains, Benjamin TI Characterization of Conserved Toxicogenomic Responses in Chemically Exposed Hepatocytes across Species and Platforms SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID INDUCED LIVER-INJURY; GENE-EXPRESSION DATA; IN-VITRO; TRANSCRIPTOMIC RESPONSES; PROBE LEVEL; VIVO; HEPATOCARCINOGENS; CARCINOGENICITY; MICROARRAYS; PREDICTION AB BACKGROUND: Genome-wide expression profiling is increasingly being used to identify-transcriptional changes induced by drugs and environmental stressors. In this context, the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system (TG-GATEs) project generated transcriptional profiles from rat liver samples and human/rat cultured primary hepatocytes exposed to more than 100 different chemicals. OBJECTIVES: To assess the capacity of the cell culture models to recapitulate pathways induced by chemicals in vivo, we leveraged the TG-GATEs data set to compare the early transcriptional responses observed in the liver of rats treated with a large set of chemicals with those of cultured rat and human primary hepatocytes challenged with the same compounds in vitro. METHODS: We developed a new pathway-based computational pipeline that efficiently combines gene set enrichment analysis (GSEA) using pathways from the Reactome database with biclustering to identify common modules of pathways that are modulated by several chemicals in vivo and in vitro across species. RESULTS: We found that some chemicals induced conserved patterns of early transcriptional responses in in vitro and in vivo settings, and across human and rat genomes. These responses involved pathways of cell survival, inflammation, xenobiotic metabolism, oxidative stress, and apoptosis. Moreover, our results support the transforming growth factor beta receptor (TGF-beta R) signaling pathway as a candidate biomarker associated with exposure to environmental toxicants in primary human hepatocytes. CONCLUSIONS: Our integrative analysis of toxicogenomics data provides a comprehensive overview of biochemical perturbations affected by a large panel of chemicals. Furthermore, we show that the early toxicological response occurring in animals is recapitulated in human and rat primary hepatocyte cultures at the molecular level, indicating that these models reproduce key pathways in response to chemical stress. These findings expand our understanding and interpretation of -toxicogenomics data from human hepatocytes exposed to environmental toxicants. C1 [El-Hachem, Nehme] Inst Rech Clin Montreal, Integrat Syst Biol, Montreal, PQ H2W 1R7, Canada. [El-Hachem, Nehme] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Grossmann, Patrick; Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Grossmann, Patrick; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Blanchet-Cohen, Alexis] Inst Rech Clin Montreal, Bioinformat, Montreal, PQ H2W 1R7, Canada. [Bateman, Alain R.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Bouchard, Nicolas] Inst Rech Clin Montreal, Mol Biol Neural Dev, Montreal, PQ H2W 1R7, Canada. [Archambault, Jacques] Inst Rech Clin Montreal, Mol Virol Lab, Montreal, PQ H2W 1R7, Canada. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. [Haibe-Kains, Benjamin] Princess Margaret Canc Ctr, Univ Hlth Network, 101 Coll St, Toronto, ON M5G 1L7, Canada. [Haibe-Kains, Benjamin] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Aerts, HJWL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA.; Haibe-Kains, B (reprint author), Princess Margaret Canc Ctr, Univ Hlth Network, 101 Coll St, Toronto, ON M5G 1L7, Canada. EM hugo@jimmy.harvard.edu; bhaibeka@uhnresearch.ca RI Haibe-Kains, Benjamin/D-3702-2011; Aerts, Hugo/P-6350-2015; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Aerts, Hugo/0000-0002-2122-2003; Archambault, Jacques/0000-0001-8107-3428 FU Institut de Recherches Cliniques de Montreal (IRCM); Gattuso Slaight Personalized Cancer Medicine Fund at Princess Margaret Cancer Centre; diXa, a part of the European Union (EU) Seventh Framework Programme [RI-283775]; National Institutes of Health (NIH-USA) [U01CA190234] FX N.E.-H. was supported by an Institut de Recherches Cliniques de Montreal (IRCM) doctoral fellowship. B.H.-K. was supported by the Gattuso Slaight Personalized Cancer Medicine Fund at Princess Margaret Cancer Centre. H.J.W.L.A. was supported by diXa, a part of the European Union (EU) Seventh Framework Programme, under grant agreement number no. RI-283775. We also acknowledge financial support from the National Institutes of Health (NIH-USA U01CA190234). NR 42 TC 2 Z9 2 U1 2 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2016 VL 124 IS 3 BP 313 EP 320 DI 10.1289/ehp.1409157 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DF6CJ UT WOS:000371442500017 PM 26173225 ER PT J AU Wang, L Manson, JE Rautiainen, S Gaziano, JM Buring, JE Tsai, MY Sesso, HD AF Wang, Lu Manson, JoAnn E. Rautiainen, Susanne Gaziano, J. Michael Buring, Julie E. Tsai, Michael Y. Sesso, Howard D. TI A prospective study of erythrocyte polyunsaturated fatty acid, weight gain, and risk of becoming overweight or obese in middle-aged and older women SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE Fatty acids; Prospective study; Women; Obesity; Weight gain ID RANDOMIZED CONTROLLED-TRIAL; SELF-REPORTED WEIGHT; CARDIOVASCULAR-DISEASE; DIETARY-FAT; LINOLEIC-ACID; PRIMARY PREVENTION; CHOLESTERYL ESTER; PHYSICAL-ACTIVITY; GENE-EXPRESSION; NATIONAL-HEALTH AB omega 3 and omega 6 fatty acids (FA) may have divergent effects on the development of obesity. We examined the association of baseline erythrocyte omega 3 and omega 6 FA composition with body weight change and the risk of becoming overweight or obese in the Women's Health Study (WHS) participants. We identified 534 women who had baseline erythrocyte FA measured and a baseline body mass index (BMI) of 18.5-< 25 kg/m(2). Body weight was updated at a total of six time points during follow-up. Weight gain during a mean of 10.4-year follow-up increased with increasing quartiles of baseline erythrocyte cis omega 6 FA, omega 6/omega 3 ratio, and trans FA while decreased with increasing cis omega 3 FA. After multivariable adjustment including total energy intake and physical activity, the weight gain (kg) in the highest versus the lowest quartile was 3.08 versus 2.32 for erythrocyte cis omega 6 FA (p (trend) 0.04), 2.07 versus 2.92 for cis omega 3 FA (p (trend) 0.08), 2.93 versus 2.05 for omega 6/omega 3 ratio (p (trend) 0.046), and 3.03 versus 2.27 for trans FA (p (trend) 0.06). Among individual FA, the associations were significant for 18:2 omega 6, 18:3 omega 6, and trans 18:1 and marginally significant for 20:3 omega 6 and trans 18:2. The risk of becoming overweight or obese (defined as BMI a parts per thousand yen25 kg/m(2) at any follow-up time point) increased across increasing omega 6/omega 3 ratio (multivariable model p (trend) 0.04). In this prospective study, we found suggestive evidence that erythrocyte cis omega 6 FA may be positively associated, and cis omega 3 FA inversely associated with weight gain in initially normal-weight women. C1 [Wang, Lu; Manson, JoAnn E.; Gaziano, J. Michael; Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02215 USA. [Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rautiainen, Susanne] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Gaziano, J. Michael; Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, St Paul, MN USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02215 USA. EM lwang@research.bwh.harvard.edu FU American Heart Association [0735390N]; National Institutes of Health, Bethesda, MD [CA047988, HL043851, HL080467]; National Heart, Lung, and Blood Institutes [HL095649] FX We are indebted to the 39,876 participants in the Women's Health Study for their dedicated and conscientious collaboration, and to the entire staff of the Women's Health Study for their assistance in designing and conducting the trial. This study was supported by a national scientist development grant funded by American Heart Association (0735390N) and research grants CA047988, HL043851, and HL080467 from the National Institutes of Health, Bethesda, MD. Dr. Wang was supported by Grant HL095649 from the National Heart, Lung, and Blood Institutes. These grants provided funding for study conduction, data collection, data analysis, and manuscript writing. NR 60 TC 2 Z9 2 U1 3 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 EI 1436-6215 J9 EUR J NUTR JI Eur. J. Nutr. PD MAR PY 2016 VL 55 IS 2 BP 687 EP 697 DI 10.1007/s00394-015-0889-y PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DF3RD UT WOS:000371262400024 PM 25820817 ER PT J AU Jordan, TH Talarico, RH Schuberth, JM AF Jordan, Thomas H. Talarico, Ross H. Schuberth, John M. TI Letter Regarding: The Fate of the Fixed Syndesmosis Over Time SO FOOT & ANKLE INTERNATIONAL LA English DT Letter C1 [Jordan, Thomas H.] Kaiser Permanente Med Grp, Santa Rosa, CA USA. [Talarico, Ross H.] Podiat Surg Sect, San Francisco, CA USA. [Talarico, Ross H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schuberth, John M.] Kaiser Fdn Hosp, Dept Orthoped Surg, Foot & Ankle Surg, San Francisco, CA USA. RP Schuberth, JM (reprint author), Kaiser Fdn Hosp, Dept Orthoped Surg, Foot & Ankle Surg, San Francisco, CA USA. EM jmfoot@aol.com NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAR PY 2016 VL 37 IS 3 BP 344 EP 344 DI 10.1177/1071100715627352 PG 1 WC Orthopedics SC Orthopedics GA DF4JS UT WOS:000371314500015 PM 26921312 ER PT J AU Klingaman, EA Hoerster, KD Aakre, JM Viverito, KM Medoff, DR Goldberg, RW AF Klingaman, Elizabeth A. Hoerster, Katherine D. Aakre, Jennifer M. Viverito, Kristen M. Medoff, Deborah R. Goldberg, Richard W. TI Veterans with PTSD report more weight loss barriers than Veterans with no mental health disorders SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Veterans; Post-traumatic stress disorder; Weight management; MOVE ID POSTTRAUMATIC-STRESS-DISORDER; PHYSICAL-ACTIVITY; SELF-EFFICACY; BEHAVIORAL ACTIVATION; ANXIETY DISORDERS; MILITARY SERVICE; HEART-DISEASE; RISK-FACTOR; DEPRESSION; MORTALITY AB Objective: This study characterized and compared Veterans of the United States Armed Forces with posttraumatic stress disorder ( PTSD) to Veterans with no mental health disorders on self-reported measures of factors that influence success in weight management programs. Method: We examined the relation of PTSD diagnosis with weight loss plan, reasons for overweight/obesity and barriers to dieting and physical exercise among 171,884 Veterans. Statistically significant variables in chi-square tests (P<.05) with at least a small effect size were then compared via multivariate logistic regression analyses. Results: Both groups reported high ratings of importance and confidence regarding changing weight loss behaviors and were preparing or actively engaging in efforts to manage their weight. Compared to Veterans without mental health disorders, more Veterans with PTSD endorsed 27 of the 28 barriers to changing eating and physical habits. Conclusions: The results of this study help to explain the lower rates of success of Veterans with PTSD in weight loss programs. Results suggest that a comprehensive, integrated approach to promoting weight loss in Veterans with PTSD is needed. Published by Elsevier Inc. C1 [Klingaman, Elizabeth A.; Aakre, Jennifer M.; Medoff, Deborah R.; Goldberg, Richard W.] US Dept Vet Affairs, Capitol Healthcare Network, Mental Illness Res Educ & Clin Ctr, 10 North Greene St,Annex Suite 720, Baltimore, MD 21201 USA. [Klingaman, Elizabeth A.; Aakre, Jennifer M.; Medoff, Deborah R.; Goldberg, Richard W.] Univ Maryland, Sch Med, Dept Psychiat, 737 West Lombard St, Baltimore, MD 21201 USA. [Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, 1660 South Columbian Way S-116, Seattle, WA 98108 USA. [Hoerster, Katherine D.] Univ Washington, Dept Psychiat & Behav Sci, 1959 Northeast Pacific St,Box 356560,Room BB1644, Seattle, WA 98195 USA. [Viverito, Kristen M.] Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev Serv, Mental Healthcare & Outcomes Res, North Little Rock, AR 72114 USA. [Viverito, Kristen M.] Univ Arkansas Med Sci, Inst Psychiat Res, Div Hlth Serv Res, 4301 West Markham,554, Little Rock, AR 72205 USA. RP Klingaman, EA (reprint author), Baltimore VA Med Ctr, VA Maryland Healthcare Syst, 10 North Greene St,Annex Suite 720, Baltimore, MD 21201 USA. EM elizabeth.klingaman@va.gov; Katherine.hoerster@va.gov; jennifer.aakre@va.gov; Kristen.viverito@va.gov; dmedoff@psych.umaryland.edu; richard.goldberg@va.gov FU Department of Veterans Affairs (VA) Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; VA Health Services Research and Development Fellowship; VA Career Development Award (HSRD) [CDA 12-263]; VA Capitol Healthcare Network Mental Illness Research, Education and Clinical Center; Central Arkansas Veterans Healthcare System Center for Mental Healthcare and Outcomes Research FX This research is supported by the Department of Veterans Affairs (VA) Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment and the VA Health Services Research and Development Fellowship. Dr. Hoerster is supported by VA Career Development Award (HSR&D CDA 12-263). It is the result of work supported with resources and the use of facilities at the VA Capitol Healthcare Network Mental Illness Research, Education and Clinical Center and the Central Arkansas Veterans Healthcare System Center for Mental Healthcare and Outcomes Research. Special thanks to Susan Raffa, Ken Jones and Tony Rogers for their contributions to this manuscript. NR 51 TC 4 Z9 4 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR-APR PY 2016 VL 39 BP 1 EP 7 DI 10.1016/j.genhosppsych.2015.11.003 PG 7 WC Psychiatry SC Psychiatry GA DF3KY UT WOS:000371244000001 PM 26719103 ER PT J AU Saint-Andre, V Federation, AJ Lin, CY Abraham, BJ Reddy, J Lee, TI Bradner, JE Young, RA AF Saint-Andre, Violaine Federation, Alexander J. Lin, Charles Y. Abraham, Brian J. Reddy, Jessica Lee, Tong Ihn Bradner, James E. Young, Richard A. TI Models of human core transcriptional regulatory circuitries SO GENOME RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; PROTEIN-DNA INTERACTIONS; BINDING MICROARRAY DATA; NANOG GENE-EXPRESSION; SUPER-ENHANCERS; SELF-RENEWAL; ES CELLS; COLORECTAL-CANCER; IDENTITY GENES; CHROMATIN ARCHITECTURE AB A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type specific transcriptional regulation in healthy and diseased cells. C1 [Saint-Andre, Violaine; Abraham, Brian J.; Reddy, Jessica; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Federation, Alexander J.; Lin, Charles Y.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Reddy, Jessica; Young, Richard A.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Saint-Andre, V; Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.; Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Young, RA (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Bradner, JE (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM violaine.saintandre@gmail.com; james_bradner@dfci.harvard.edu; young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU Foundation for the National Institutes of Health [HG002668]; National Science Foundation FX We thank members of the Young lab, especially Ana D'Alessio, Zi Peng Fan, and Jurian Schuijers for helpful discussions. This work was supported by the Foundation for the National Institutes of Health grant HG002668 (R.A.Y.). A.J.F. was funded by a National Science Foundation graduate fellowship, and B.J.A. is the Hope Funds for Cancer Research Grillo-Marxuach Family Fellow. NR 133 TC 7 Z9 8 U1 1 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2016 VL 26 IS 3 BP 385 EP 396 DI 10.1101/gr.197590.115 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA DF5EF UT WOS:000371373900010 PM 26843070 ER PT J AU Quevrain, E Maubert, MA Michon, C Chain, F Marquant, R Tailhades, J Miquel, S Carlier, L Bermudez-Humaran, LG Pigneur, B Lequin, O Kharrat, P Thomas, G Rainteau, D Aubry, C Breyner, N Afonso, C Lavielle, S Grill, JP Chassaing, G Chatel, JM Trugnan, G Xavier, R Langella, P Sokol, H Seksik, P AF Quevrain, E. Maubert, M. A. Michon, C. Chain, F. Marquant, R. Tailhades, J. Miquel, S. Carlier, L. Bermudez-Humaran, L. G. Pigneur, B. Lequin, O. Kharrat, P. Thomas, G. Rainteau, D. Aubry, C. Breyner, N. Afonso, C. Lavielle, S. Grill, J-P Chassaing, G. Chatel, J. M. Trugnan, G. Xavier, R. Langella, P. Sokol, H. Seksik, P. TI Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease SO GUT LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; SEGMENTED FILAMENTOUS BACTERIA; REGULATORY T-CELLS; CAMPYLOBACTER-CONCISUS; EPITHELIAL BARRIER; FECAL MICROBIOTA; TIGHT JUNCTION; IMMUNE-SYSTEM; GUT; COLITIS AB Background Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. Methods Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Antiinflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. Results The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-kappa B pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. Conclusions A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-kappa B pathway in intestinal epithelial cells and to prevent colitis in an animal model. C1 [Quevrain, E.; Maubert, M. A.; Marquant, R.; Tailhades, J.; Carlier, L.; Pigneur, B.; Lequin, O.; Thomas, G.; Rainteau, D.; Lavielle, S.; Grill, J-P; Chassaing, G.; Trugnan, G.; Sokol, H.; Seksik, P.] Univ Paris 06, Sorbonne Univ, Paris, France. [Quevrain, E.; Maubert, M. A.; Pigneur, B.; Thomas, G.; Rainteau, D.; Grill, J-P; Trugnan, G.; Sokol, H.; Seksik, P.] CHU St Antoine 27, INSERM, ERL 1157, Paris, France. [Quevrain, E.; Maubert, M. A.; Pigneur, B.; Thomas, G.; Rainteau, D.; Grill, J-P; Trugnan, G.; Sokol, H.; Seksik, P.] CHU St Antoine 27, Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France. [Quevrain, E.; Maubert, M. A.; Marquant, R.; Tailhades, J.; Carlier, L.; Pigneur, B.; Lequin, O.; Thomas, G.; Rainteau, D.; Lavielle, S.; Grill, J-P; Chassaing, G.; Trugnan, G.; Sokol, H.; Seksik, P.] CNRS, UMR, Paris, France. [Maubert, M. A.; Rainteau, D.; Trugnan, G.] Hop St Antoine, AP HP, Dept Plateforme Metabol PM2, Peptidom & Dosage Medicaments, Paris, France. [Michon, C.; Chain, F.; Miquel, S.; Bermudez-Humaran, L. G.; Kharrat, P.; Aubry, C.; Breyner, N.; Chatel, J. M.; Langella, P.; Sokol, H.] INRA, Micalis UMR1319, Jouy En Josas, France. [Michon, C.; Chain, F.; Miquel, S.; Bermudez-Humaran, L. G.; Kharrat, P.; Aubry, C.; Breyner, N.; Chatel, J. M.; Langella, P.] AgroParisTech, UMR Micalis, Jouy En Josas, France. [Marquant, R.; Tailhades, J.; Carlier, L.; Lequin, O.; Lavielle, S.; Chassaing, G.] PSL Res Univ, Ecole Normale Super, Dept Chim, 24 Rue Lhomond, Paris, France. [Afonso, C.] Univ Rouen, COBRA IRCOF, UMR 6014, Mont St Aignan, France. [Xavier, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sokol, H.; Seksik, P.] Hop St Antoine, AP HP, Serv Gastroenterol & Nutr, F-75571 Paris, France. RP Seksik, P (reprint author), Hop St Antoine, Serv Gastroenterol & Nutr, 184 Rue Faubourg St Antoine, F-75571 Paris 12, France. EM philippe.seksik@sat.aphp.fr RI Afonso, Carlos/E-9736-2011; OI Afonso, Carlos/0000-0002-2406-5664; PIGNEUR, Benedicte/0000-0002-5324-9964; sokol, harry/0000-0002-2914-1822 FU Association Francois Aupetit; Agence Nationale de la Recherche [Mi2]; French FUI (Fond Unique Interministeriel; FUI) [F1010012D]; FEDER (Fonds Europeen de Developpement Regional; Bourgogne) [34606]; Burgundy Region; Conseil General [21]; Grand Dijon; Merck Medication Familiale (Dijon, France); Biovitis (Saint Etienne de Chomeil, France) FX We thank Association Francois Aupetit (2009) and Agence Nationale de la Recherche (Mi2 2010) for funding this work. This last study was a part of the FPARIS collaborative project selected and supported by the Vitagora Competitive Cluster and funded by the French FUI (Fond Unique Interministeriel; FUI no. F1010012D), the FEDER (Fonds Europeen de Developpement Regional; Bourgogne no. 34606), the Burgundy Region, the Conseil General 21, and the Grand Dijon. This work was also supported by Merck Medication Familiale (Dijon, France) and Biovitis (Saint Etienne de Chomeil, France). NR 50 TC 39 Z9 40 U1 23 U2 45 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD MAR PY 2016 VL 65 IS 3 BP 415 EP 425 DI 10.1136/gutjnl-2014-307649 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DF4ME UT WOS:000371321700010 PM 26045134 ER PT J AU Hinchcliff, E Rauh-Hain, JA Clemmer, JT Diver, E Hall, T Stall, J Growdon, W Clark, R Schorge, J AF Hinchcliff, Emily Rauh-Hain, J. Alejandro Clemmer, Joel T. Diver, Elisabeth Hall, Tracilyn Stall, Jennifer Growdon, Whitfield Clark, Rachel Schorge, John TI Racial disparities in survival in malignant germ cell tumors of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian germ cell tumors; Rare tumors; Racial disparities; Ovarian cancer ID CANCER DATA-BASE; BLACK-AND-WHITE; UNITED-STATES; CERVICAL-CANCER; WOMEN; CARE; CHEMOTHERAPY; QUALITY; TRENDS; RATES AB Objective. To investigate racial disparities with respect to adjuvant treatment and survival inpatients presenting with malignant ovarian germ cell tumors (OGCT). Methods. The National Cancer Database (NCDB) was used to identify women diagnosed with OGCT. Demographic data were abstracted, including stratification by race and histology. Standard univariate and multivariate analyses using logistic regression were performed to describe predictors of adjuvant treatment. Kaplan-Meier and Cox proportional hazards survival methods were used to evaluate racial differences in survival between African American (AA) and white (W) women. Results. The study population included 2196 patients, with 1654 (753%) W and 328 (14.9%) AA women. Histologic distribution varied significantly by race (p < 0.0001), but neither age nor stage at presentation showed racial differences (p = 0.086 and p = 0209, respectively). AA received more chemotherapy than W (W: 54.6%, AA: 65.5%, p = 0.008), but in multivariate analysis there was no statistically significant difference in any adjuvant treatment modality. Despite similar treatment, and independent of histology, survival varied significantly by race with 91% (CI 0.89-0.93) five year survival in W patients compared to 84% five year survival in AA (CI 0.8-0.89) (p = 0.02). These disparities were most pronounced in advanced stage disease, with 5 year survival of 84% (CI 0.79-0.89) in W compared to 61% (CI 0.48-0.78) for AA in stage III (p = 0.0002), and 54% (CI 0.42-0.68) compared to 14% (CI 0.03-0.71) for stage IV (p = 0.05). Conclusions. AA with OGCT have significantly worse 5 year survival when compared to W patients despite similar rates and modalities of adjuvant treatment. (C) 2016 Elsevier Inc. All rights reserved. C1 [Hinchcliff, Emily; Rauh-Hain, J. Alejandro; Clemmer, Joel T.; Diver, Elisabeth; Hall, Tracilyn; Growdon, Whitfield; Clark, Rachel; Schorge, John] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Hinchcliff, Emily] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. [Stall, Jennifer] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hinchcliff, Emily; Rauh-Hain, J. Alejandro; Diver, Elisabeth; Hall, Tracilyn; Stall, Jennifer; Growdon, Whitfield; Clark, Rachel; Schorge, John] Harvard Univ, Sch Med, Boston, MA USA. RP Hinchcliff, E (reprint author), Massachusetts Gen Hosp, Div Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM ehinchcliff@partners.org NR 26 TC 2 Z9 2 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2016 VL 140 IS 3 BP 463 EP 469 DI 10.1016/j.ygyno.2016.01.006 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DF5DT UT WOS:000371372700016 PM 26773470 ER PT J AU Gockley, AA Melamed, A Joseph, NT Clapp, M Sun, SY Goldstein, DP Horowitz, NS Berkowitz, RS AF Gockley, Allison A. Melamed, Alexander Joseph, Naima T. Clapp, Mark Sun, Sue Yazaki Goldstein, Donald P. Horowitz, Neil S. Berkowitz, Ross S. TI The effect of adolescence and advanced maternal age on the incidence of complete and partial molar pregnancy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Complete mole; Partial mole; Maternal age ID PARTIAL HYDATIDIFORM MOLE; ORIGIN; RISK AB Objective. To compare the age-specific incidence of complete (CM) and partial molar (PM) pregnancy in a large tertiary care center in the United States. Methods. Incidence rates of CM and PM per 10,000 live births were calculated using databases from Brigham and Women's Hospital, between 2000 and 2013. Age-specific rates were calculated for women younger than 20 years old (adolescents), 20-39 years old (average age), and 40 years and older (advanced maternal age). Pearson chi(2) test was used to evaluate potential differences among groups. Rate ratios (RR) and 95% confidence intervals (CI) were used to compare risk of molar pregnancy among average age women with that of adolescents and women of advanced age. Holm-Bonferonni adjustment was used to correct for multiple comparisons. Results. Between 2000 and 2013, there were 255 molar pregnancies (140 CM and 115 PM) and 105,942 live births, corresponding to a molar pregnancy rate of 24 per 10,000 live births (95% CI 21-27). Rates of CM and PM were 13 (95% CI 11-16) and 11 (95% CI 9-14) per 10,000 live births respectively. The incidence of CM differed significantly among maternal age groups (p < 0.001). Compared to average age women, adolescents were 7.0 times as likely to develop CM (95% CI 3.6-8.9, p < 0.001), and women with advanced maternal age were nearly twice as likely (1.9, 95% CI 1.8-4.7, p = 0.002). The rate of PM did not vary significantly among age groups (p = 026). Conclusions. Adolescence and advanced maternal age were associated with increased risk of complete mole, but not partial mole. (C) 2016 Elsevier Inc. All rights reserved. C1 [Gockley, Allison A.; Melamed, Alexander; Joseph, Naima T.; Clapp, Mark; Goldstein, Donald P.; Horowitz, Neil S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. [Gockley, Allison A.; Melamed, Alexander; Joseph, Naima T.; Clapp, Mark] Massachusetts Gen Hosp, Vincent Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Gockley, Allison A.; Melamed, Alexander; Joseph, Naima T.; Clapp, Mark] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Goldstein, Donald P.; Horowitz, Neil S.; Berkowitz, Ross S.] Harvard Canc Ctr, Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, Gynecol Oncol Program, Boston, MA USA. [Sun, Sue Yazaki] Univ Fed Sao Paulo, UNIFESP, Paulista Sch Med, Dept Obstet, Sao Paulo, SP, Brazil. [Sun, Sue Yazaki] Univ Fed Sao Paulo, UNIFESP, Paulista Sch Med, Trophoblast Dis,Ctr Sao Paulo Hosp, Sao Paulo, SP, Brazil. [Sun, Sue Yazaki; Goldstein, Donald P.; Horowitz, Neil S.; Berkowitz, Ross S.] Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, ASBI, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org OI Melamed, Alexander/0000-0002-0654-0863 FU Donald P. Goldstein Trophoblastic Tumor Registry Endowment; Dyett Family Trophoblastic Disease Research and Registry Endowment FX This research was supported by the Donald P. Goldstein Trophoblastic Tumor Registry Endowment and the Dyett Family Trophoblastic Disease Research and Registry Endowment. NR 19 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2016 VL 140 IS 3 BP 470 EP 473 DI 10.1016/j.ygyno.2016.01.005 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DF5DT UT WOS:000371372700017 PM 26777992 ER PT J AU Lozo, S Eckardt, MJ Altawil, Z Nelson, BD Ahn, R Khisa, W Burke, TF AF Lozo, Svjetlana Eckardt, Melody J. Altawil, Zaid Nelson, Brett D. Ahn, Roy Khisa, Weston Burke, Thomas F. TI Prevalence of unrepaired third- and fourth-degree tears among women taken to the operating room for repair of presumed obstetric fistula during two fistula camps in Kenya SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Obstetric fistula; Third- and fourth-degree obstetric tears; Fistula camp; Obstetric lacerations ID MANAGEMENT AB Introduction and hypothesis More than 2 million women on earth today are said to be suffering from obstetric fistula (OF), a communication between the vagina and either the urinary tract or rectum. Since unrepaired third- and fourth-degree perineal tears often manifest with symptoms identical to OF, we hypothesized that the global burden of OF is in part due to these unrepaired deep obstetric tears. Methods Four consultant gynecologists retrospectively reviewed the medical and operative records of all obstetric fistula cases that underwent surgical repair during the July and August, 2014, Kenyatta National Hospital and Embu Provincial Hospital Fistula Camps in Kenya. Results One hundred and eighty charts were reviewed. All 180 women had fecal incontinence (FI), urinary incontinence (UI), or both as their primary complaint. Sixty of the 180 (33 %) women had isolated FI as their presenting symptom, and at operation, 57 of these 60 (95 %) were found to have unrepaired third-and fourth-degree obstetric tears. Ninety-two of the 180 (51 %) women with OF symptoms ultimately had true OF confirmed at operation. Conclusion These findings suggest that many women with OF symptoms in Kenya may harbor unrepaired third- and fourth-degree tears. Additionally, women with isolated FI may be more likely to suffer from third-and fourth-degree tears than from true OF. Immediate postpartum diagnosis and repair of third- and fourth-degree perineal tears could significantly reduce the overall burden of women with symptoms of OF. C1 [Lozo, Svjetlana; Eckardt, Melody J.; Altawil, Zaid; Nelson, Brett D.; Ahn, Roy; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 125 Nashua St,Suite 910, Boston, MA 02114 USA. [Nelson, Brett D.; Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Khisa, Weston] Kenyatta Natl Hosp, Sect Urogynecol, Dept Reprod Hlth, Nairobi, Kenya. RP Burke, TF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 125 Nashua St,Suite 910, Boston, MA 02114 USA.; Burke, TF (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM tfburke@mgh.harvard.edu OI Nelson, Brett/0000-0002-5049-1798 FU Massachusetts General Hospital; Ujenzi Charitable Trust FX Support for this study came from the Massachusetts General Hospital and the Ujenzi Charitable Trust. NR 19 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 EI 1433-3023 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD MAR PY 2016 VL 27 IS 3 BP 463 EP 466 DI 10.1007/s00192-015-2850-2 PG 4 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA DF2OD UT WOS:000371182300018 PM 26407562 ER PT J AU Longo, DL Michelotti, F Consolino, L Bardini, P Digilio, G Xiao, G Sun, PZ Aime, S AF Longo, Dario Livio Michelotti, Filippo Consolino, Lorena Bardini, Paola Digilio, Giuseppe Xiao, Gang Sun, Phillip Zhe Aime, Silvio TI In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents SO INVESTIGATIVE RADIOLOGY LA English DT Article DE iodixanol; iohexol; iomeprol; CT; MRI; x-ray; contrast agents; tumor; ioversol; CEST ID TRANSFER CEST MRI; CONTRAST AGENT; EXTRACELLULAR PH; ACIDOCEST MRI; QUANTITATIVE DESCRIPTION; COMPUTED-TOMOGRAPHY; 7 T; IOPAMIDOL; BRAIN; POWER AB Objectives The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. Materials and Methods The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 mu T and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. Results The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R-2 = 0.70, P < 0.01). Conclusions The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information. C1 [Longo, Dario Livio] Univ Turin, CNR, Ist Biostrutture & Bioimmagini, Ctr Mol Biotechnol, Turin, Italy. [Michelotti, Filippo; Consolino, Lorena; Bardini, Paola; Aime, Silvio] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Mol Imaging Ctr, Turin, Italy. [Digilio, Giuseppe] Univ Piemonte Orientale, Dept Sci & Technol Innovat, Alessandria, Italy. [Xiao, Gang] Hanshan Normal Univ, Dept Math & Stat, Hanshan, Guangdong, Peoples R China. [Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sun, Phillip Zhe] Harvard Univ, Sch Med, Boston, MA USA. RP Longo, DL (reprint author), CNR, Ist Biostrutture & Bioimmagini, Mol Biotechonol Ctr, Via Nizza 52, I-10126 Turin, Italy. EM dario.longo@unito.it OI Digilio, Giuseppe/0000-0003-2397-2913; Longo, Dario/0000-0002-6906-9925 FU European Community's Seventh Framework Programme [602306]; MIUR project PRIN [2010B5B2NL] FX Conflicts of interest and sources of funding: Support by the European Community's Seventh Framework Programme (mitigate project 602306) and by MIUR project PRIN no 2010B5B2NL. NR 53 TC 2 Z9 2 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0020-9996 EI 1536-0210 J9 INVEST RADIOL JI Invest. Radiol. PD MAR PY 2016 VL 51 IS 3 BP 155 EP 162 DI 10.1097/RLI.0000000000000217 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE2UF UT WOS:000370482000002 PM 26460826 ER PT J AU Swenson, ER AF Swenson, Erik R. TI Reply to Drs. Teppema and Berendsen SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Letter ID CARBONIC-ANHYDRASE INHIBITION; VENTILATORY RESPONSES; AMMONIUM-CHLORIDE; ACETAZOLAMIDE; HYPOXIA; HUMANS; ACIDOSIS C1 [Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM erik.swenson@va.gov NR 10 TC 0 Z9 0 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR 1 PY 2016 VL 120 IS 5 BP 565 EP 565 DI 10.1152/japplphysiol.00872.2015 PG 1 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA DF6CN UT WOS:000371442900011 PM 26933003 ER PT J AU Urayama, A Grubb, JH Sly, WS Banks, WA AF Urayama, Akihiko Grubb, Jeffrey H. Sly, William S. Banks, William A. TI Pharmacologic manipulation of lysosomal enzyme transport across the blood-brain barrier SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Blood-brain barrier; beta-glucuronidase; enzyme replacement therapy; brain uptake; mannose 6-phosphate receptor ID MANNOSE 6-PHOSPHATE RECEPTOR; MUCOPOLYSACCHARIDOSIS TYPE-VII; ALPHA-MANNOSIDOSIS MICE; REPLACEMENT-THERAPY; MEDIATED TRANSPORT; BETA-GLUCURONIDASE; MOUSE MODEL; LIGAND INTERACTIONS; INSULIN TRANSPORT; PERMEABILITY AB The adult blood-brain barrier, unlike the neonatal blood-brain barrier, does not transport lysosomal enzymes into brain, making enzyme replacement therapy ineffective in treating the central nervous system symptoms of lysosomal storage diseases. However, enzyme transport can be re-induced with alpha-adrenergics. Here, we examined agents that are known to alter the blood-brain barrier transport of large molecules or to induce lysosomal enzyme transport across the blood-brain barrier ((+/-)epinephrine, insulin, retinoic acid, and lipopolysaccharide) in 2-week-old and adult mice. In 2-week-old adolescent mice, all these pharmacologic agents increased brain and heart uptake of phosphorylated human beta-glucuronidase. In 8-week-old adult mice, manipulations with (+/-)epinephrine, insulin, and retinoic acid were significantly effective on uptake by brain and heart. The increased uptake of phosphorylated human b-glucuronidase was inhibited by mannose 6-phosphate for the agents (+/-)epinephrine and retinoic acid and by L-NG-nitroarginine methyl ester for the agent lipopolysaccharide in neonatal and adult mice. An in situ brain perfusion study revealed that retinoic acid directly modulated the transport of phosphorylated human beta-glucuronidase across the blood-brain barrier. The present study indicates that there are multiple opportunities to at least transiently induce phosphorylated human beta-glucuronidase transport at the adult blood-brain barrier. C1 [Urayama, Akihiko] Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA. [Grubb, Jeffrey H.] Ultragenyx Pharmaceut Inc, Lysosomal Res, Novato, CA USA. [Grubb, Jeffrey H.; Sly, William S.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Urayama, A (reprint author), Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA. EM Akihiko.Urayama@uth.tmc.edu FU Sanfilippo Syndrome Medical Research Foundation; Veterans Affairs Merit Review; National Institutes of Health [NS050547, AG029839]; National Institutes of Health Grant [GM34182] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by The Sanfilippo Syndrome Medical Research Foundation (WAB and WSS), Veterans Affairs Merit Review (WAB), National Institutes of Health Grants NS050547 and AG029839 (to WAB), and National Institutes of Health Grant GM34182 (to WSS). NR 40 TC 1 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2016 VL 36 IS 3 BP 476 EP 486 DI 10.1177/0271678X15614589 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA DF4ER UT WOS:000371301100004 PM 26661222 ER PT J AU Khamaisi, M Katagiri, S Keenan, H Park, K Maeda, Y Li, Q Qi, WE Thomou, T Eschuk, D Tellechea, A Veves, A Huang, CY Orgill, DP Wagers, A King, GL AF Khamaisi, Mogher Katagiri, Sayaka Keenan, Hillary Park, Kyoungmin Maeda, Yasutaka Li, Qian Qi, Weier Thomou, Thomas Eschuk, Danielle Tellechea, Ana Veves, Aris Huang, Chenyu Orgill, Dennis Paul Wagers, Amy King, George L. TI PKC delta inhibition normalizes the wound-healing capacity of diabetic human fibroblasts SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-C; INSULIN-RESISTANCE; FOOT ULCERS; CULTURED FIBROBLASTS; ENDOTHELIAL-CELLS; EXTREME-DURATION; VEGF EXPRESSION; MOLECULAR-BASIS; IN-VITRO; REPAIR AB Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the delta isoform of protein kinase C (PKC delta) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin-induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKC delta or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKC delta expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKC delta elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKC delta inhibition as a potential therapy to improve wound healing in diabetic patients. C1 [Khamaisi, Mogher; Katagiri, Sayaka; Keenan, Hillary; Park, Kyoungmin; Maeda, Yasutaka; Li, Qian; Qi, Weier; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Vasc Cell Biol, Boston, MA 02115 USA. [Khamaisi, Mogher] Technion Israel Inst Technol, Rambam Med Ctr, Inst Endocrinol Diabet & Metab, Haifa, Israel. [Khamaisi, Mogher] Technion Israel Inst Technol, RB Rappaport Fac Med, Haifa, Israel. [Thomou, Thomas] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Thomou, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Eschuk, Danielle; Tellechea, Ana; Veves, Aris] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Huang, Chenyu] Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Med Ctr, Dept Plast Reconstruct & Aesthet Surg, Beijing 100084, Peoples R China. [Orgill, Dennis Paul] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Plast Surg,Dept Surg, Boston, MA 02115 USA. [Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy] Harvard Stem Cell Inst, Cambridge, MA USA. [Wagers, Amy] Howard Hughes Med Inst, Cambridge, MA USA. [Wagers, Amy] Harvard Univ, Sch Med, Dept Stem Cell & Regenerat Biol, Paul F Glenn Labs Biol Mech Aging, Cambridge, MA 02138 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, One Joslin Pl, Boston, MA USA. EM George.King@joslin.harvard.edu FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1R24DK090961-01, DP3 DK094333-01]; Juvenile Diabetes Research Foundation (JDRF) [17-2013-310]; Diabetic Research Center (DRC) Group [P30DK036836]; Beatson Foundation Gift; Dianne Nunnally Hoppes Fund; Hearst Foundation; Gillian Reny Stepping Strong Fund FX This study was supported by grants from the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (1R24DK090961-01 and DP3 DK094333-01, to G.L. King); the Juvenile Diabetes Research Foundation (JDRF) (17-2013-310, to H. Keenan); the Diabetic Research Center (DRC) Group (P30DK036836); the Beatson Foundation Gift; and the Dianne Nunnally Hoppes Fund. This study was also supported by a William Randolph Hearst Fellowship provided by the Hearst Foundation (to M. Khamaisi) and by the Gillian Reny Stepping Strong Fund (to D.P. Orgill). We thank the Medalists and their families, the people who donated skin samples, the National Disease Research Interchange (NDRI) for coordinating the donations, and the Medalist study staff (Liane Tinsley, Stephanie D'Eon, Stephanie Hastings, and David M. Pober) at the Joslin Diabetes Center. We also thank Patti Muehter for her excellent assistance with manuscript preparation. NR 64 TC 5 Z9 5 U1 4 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2016 VL 126 IS 3 BP 837 EP 853 DI 10.1172/JCI82788 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DF2SI UT WOS:000371193700007 PM 26808499 ER PT J AU Yu, HY Artomov, M Brahler, S Stander, MC Shamsan, G Sampson, MG White, JM Kretzler, M Miner, JH Jain, S Winkler, CA Mitra, RD Kopp, JB Daly, MJ Shaw, AS AF Yu, Haiyang Artomov, Mykyta Braehler, Sebastian Stander, M. Christine Shamsan, Ghaidan Sampson, Matthew G. White, J. Michael Kretzler, Matthias Miner, Jeffrey H. Jain, Sanjay Winkler, Cheryl A. Mitra, Robi D. Kopp, Jeffrey B. Daly, Mark J. Shaw, Andrey S. TI A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis (Retracted Article. See vol 126, pg 1603, 2016) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Retracted Publication ID RESISTANT NEPHROTIC SYNDROME; HIV-ASSOCIATED NEPHROPATHY; EMBRYONIC STEM-CELLS; PODOCYTE INJURY; CD2-ASSOCIATED PROTEIN; GLOMERULAR-DISEASES; AFRICAN-AMERICANS; RNA INTERFERENCE; RENAL-DISEASE; MUTATIONS AB Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein 1:1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes. C1 [Yu, Haiyang; Braehler, Sebastian; Stander, M. Christine; Shamsan, Ghaidan; White, J. Michael; Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Artomov, Mykyta; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Artomov, Mykyta; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Artomov, Mykyta; Daly, Mark J.] Broad Inst, Cambridge, MA USA. [Artomov, Mykyta] Harvard Univ, Dept Chem, 12 Oxford St, Cambridge, MA 02138 USA. [Sampson, Matthew G.] Univ Michigan, Pediat Nephrol, Ann Arbor, MI 48109 USA. [Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Miner, Jeffrey H.; Jain, Sanjay] Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USA. [Winkler, Cheryl A.] NCI, Mol Genet Epidemiol Studies Sect, Frederick, MD 21701 USA. [Mitra, Robi D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH, Bethesda, MD USA. [Shaw, Andrey S.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. RP Shaw, AS (reprint author), Genentech Inc, One DNA Way,Mail Stop 93B, San Francisco, CA 94080 USA.; Daly, MJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Analyt & Translat Genet Unit, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM mjdaly@atgu.mgh.harvard.edu; shawa6@gene.com FU NIDDK; HHMI; Intramural Research Programs of the NIDDK; NCI; Deutsche Forschungsgemeinschaft (DFG) FX This project was supported by grants from the NIDDK (to A.S. Shaw, J.H. Miner, M. Kretzler, and M.G. Sampson); the HHMI (to A.S. Shaw); and the Intramural Research Programs of the NIDDK (to J.B. Kopp), NCI (to C.A. Winkler), and the Deutsche Forschungsgemeinschaft (DFG) (to S. Brahler). We thank V. Vasioukhin for sharing Dlg5+/- mice, overexpression and RNAi lentiviral plasmids, and histology stainings of Dlg5-/- kidney. We also thank C. Der for sharing the Arhgefl7 cDNA construct. We also thank R. Kopan and members of the Shaw laboratory for critical discussions. NR 60 TC 4 Z9 4 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2016 VL 126 IS 3 BP 1067 EP 1078 DI 10.1172/JCI82592 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DF2SI UT WOS:000371193700025 PM 26901816 ER PT J AU Finkelstein, JS Lee, H Leder, BZ Burnett-Bowie, SAM Goldstein, DW Hahn, CW Hirsch, SC Linker, A Perros, N Servais, AB Taylor, AP Webb, ML Youngner, JM Yu, EW AF Finkelstein, Joel S. Lee, Hang Leder, Benjamin Z. Burnett-Bowie, Sherri-Ann M. Goldstein, David W. Hahn, Christopher W. Hirsch, Sarah C. Linker, Alex Perros, Nicholas Servais, Andrew B. Taylor, Alexander P. Webb, Matthew L. Youngner, Jonathan M. Yu, Elaine W. TI Gonadal steroid-dependent effects on bone turnover and bone mineral density in men SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; ESTROGEN-RECEPTOR; AROMATASE DEFICIENCY; CORTICAL BONE; OLDER MEN; TESTOSTERONE LEVELS; SERUM TESTOSTERONE; ESTRADIOL LEVELS; MALE SKELETON; ELDERLY MEN AB BACKGROUND. Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS. One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS. As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dI were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS. Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. C1 [Finkelstein, Joel S.; Leder, Benjamin Z.; Burnett-Bowie, Sherri-Ann M.; Goldstein, David W.; Hahn, Christopher W.; Hirsch, Sarah C.; Linker, Alex; Perros, Nicholas; Servais, Andrew B.; Taylor, Alexander P.; Webb, Matthew L.; Youngner, Jonathan M.; Yu, Elaine W.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM jfinkelstein@partners.org FU AbbVie Inc.; AstraZeneca Pharmaceuticals LP; NIH FX AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH. NR 46 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2016 VL 126 IS 3 BP 1114 EP 1125 DI 10.1172/JCI84137 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DF2SI UT WOS:000371193700029 PM 26901812 ER PT J AU Farhat, MR Jacobson, KR Franke, MF Kaur, D Sloutsky, A Mitnick, CD Murray, M AF Farhat, Maha R. Jacobson, Karen R. Franke, Molly F. Kaur, Devinder Sloutsky, Alex Mitnick, Carole D. Murray, Megan TI Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GENOTYPE MTBDRSL ASSAY; DRUG-RESISTANCE; PULMONARY TUBERCULOSIS; ANTIBIOTIC-RESISTANCE; FUNCTIONAL-ANALYSIS; COMPLEX STRAINS; SUSCEPTIBILITY; EPIDEMIOLOGY; POPULATION; MOXIFLOXACIN AB Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early-versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early-and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. C1 [Farhat, Maha R.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Farhat, Maha R.; Franke, Molly F.; Mitnick, Carole D.; Murray, Megan] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Jacobson, Karen R.] Boston Univ, Sch Med, Infect Dis Sect, Boston, MA 02118 USA. [Jacobson, Karen R.] Univ Stellenbosch, DST NRF Ctr Excellence Biomed TB Res, MRC Ctr Mol & Cellular Biol, Div Mol Biol & Human Genet,Fac Med & Hlth Sci, ZA-7505 Tygerberg, South Africa. [Kaur, Devinder; Sloutsky, Alex] Univ Massachusetts, Sch Med, Massachusetts Supranat TB Reference Lab, Boston, MA 02125 USA. [Mitnick, Carole D.] Brigham & Womens Hosp, Dept Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. [Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Farhat, MR (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.; Farhat, MR (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. EM mrfarhat@partners.org OI Farhat, Maha/0000-0002-3871-5760; Jacobson, Karen/0000-0003-4239-3685 FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [U19-AI109755]; HHS \ NIH \ Fogarty International Center (FIC) [K01 TW009213]; American Lung Association [RG-270912-N]; Harvard University Center for AIDS Research (HU CFAR) [P30 AI060354] FX Parker B Francis provided funding to Maha Farhat. HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Megan Murray under grant number U19-AI109755. HHS vertical bar NIH vertical bar Fogarty International Center (FIC) provided funding to Karen Jacobson under grant number K01 TW009213. American Lung Association provided funding to Maha Farhat under grant number RG-270912-N. Harvard University Center for AIDS Research (HU CFAR) provided funding to Maha Farhat and Karen Jacobson under grant number P30 AI060354. NR 42 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2016 VL 54 IS 3 BP 727 EP 733 DI 10.1128/JCM.02775-15 PG 7 WC Microbiology SC Microbiology GA DF2EC UT WOS:000371152200032 PM 26763957 ER PT J AU Winchester, RJ Williams, JS Wolfman, TE Egede, LE AF Winchester, Rhonda J. Williams, Joni S. Wolfman, Tamara E. Egede, Leonard E. TI Depressive symptoms, serious psychological distress, diabetes distress and cardiovascular risk factor control in patients with type 2 diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes; Diabetes distress; Depressive symptoms; Serious psychological distress; Cardiovascular disease risk factor ID CLINICAL DEPRESSION; GENERAL-POPULATION; GLYCEMIC CONTROL; SCREENING SCALE; MENTAL-ILLNESS; MORTALITY; HEALTH; ADULTS; K6 AB Objective: This study examined the association between cardiovascular disease (CVD) risk factor control and elevated depressive symptoms (EDS), serious psychological distress (SPD), and diabetes distress (DD) in patients with type 2 diabetes (T2DM). Methods: This was a cross-sectional study of adults seen at an academic medical center and Veterans Affairs Medical Center in the southeastern US. Linear regression models were computed using CVD risk factors as clinically meaningful outcomes (glycosylated hemoglobin A1c (HbA1c); systolic (SBP) and diastolic (DBP) blood pressure; and low-density lipoprotein cholesterol (LDL-C)); EDS, SPD, and DD were primary independent variables. Covariates included sociodemographics and comorbidities. Results: The sample consisted of 361 adults. Correlation analyses showed significant relationships between DD and HbA1c, DBP, and LDL-C. Adjusted linear regression models showed DD to be significantly associated with HbA1c and LDL-C, and SPD to be significantly associated only with LDL-C. In the fully adjusted model, DD remained significantly associated with HbA1c ((beta = 4349; 95% CI (-0.649, 2.222)). Conclusions: In this sample of adults with T2DM, DD and SPD were significantly associated with CVD risk factors; however, after controlling for covariates, only DD was shown to be significantly associated with poor glycemic control. Practice implications: Strategies are warranted to examine the relationship between DD and CVD risk factor control in patients with T2DM. Published by Elsevier Inc. C1 [Winchester, Rhonda J.; Williams, Joni S.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,POB 250593, Charleston, SC 29425 USA. [Williams, Joni S.; Wolfman, Tamara E.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, 96 Jonathan Lucas St,Suite 803,MSC 623, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, 109 Beet St, Charleston, SC 29401 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Hlth Equ & Rural Outreach Innovat Ctr, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM runwithjane@gmail.com; stromjl@musc.edu; wolfmant@musc.edu; egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699] FX Funding Source: This study was supported by Grant K24DK093699 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 0 Z9 0 U1 9 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR PY 2016 VL 30 IS 2 BP 312 EP 317 DI 10.1016/j.jdiacomp.2015.11.010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DF2SW UT WOS:000371195100022 PM 26657725 ER PT J AU Gokduman, K Avsaroglu, MD Cakiris, A Ustek, D Gurakan, GC AF Gokduman, Kurtulus Avsaroglu, M. Dilek Cakiris, Aris Ustek, Duran Gurakan, G. Candan TI Recombinant plasmid-based quantitative Real-Time PCR analysis of Salmonella enterica serotypes and its application to milk samples SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Salmonella; invA; ttrRSBC; Recombinant plasmids; Real-Time PCR; Milk ID MEDIATED ISOTHERMAL AMPLIFICATION; POLYMERASE-CHAIN-REACTION; ESCHERICHIA-COLI; FECAL SAMPLES; LISTERIA-MONOCYTOGENES; VIABLE SALMONELLAE; RAPID DETECTION; RISK-ASSESSMENT; MULTIPLEX PCR; MESSENGER-RNA AB The aim of the current study was to develop, a new, rapid, sensitive and quantitative Salmonella detection method using a Real-Time PCR technique based on an inexpensive, easy to produce, convenient and standardized recombinant plasmid positive control. To achieve this, two recombinant plasmids were constructed as reference molecules by cloning the two most commonly used Salmonella-specific target gene regions, invA and ttrRSBC The more rapid detection enabled by the developed method (21 h) compared to the traditional culture method (90 h) allows the quantitative evaluation of Salmonella (quantification limits of 10(1) CFU/ml and 10(0) CFU/ml for the invA target and the ttrRSBC target, respectively), as illustrated using milk samples. Three advantages illustrated by the current study demonstrate the potential of the newly developed method to be used in routine analyses in the medical, veterinary, food and water/environmental sectors: I - The method provides fast analyses including the simultaneous detection and determination of correct pathogen counts; II - The method is applicable to challenging samples, such as milk; III - The method's positive controls (recombinant plasmids) are reproducible in large quantities without the need to construct new calibration curves. (C) 2016 Elsevier B.V. All rights reserved. C1 [Gokduman, Kurtulus; Gurakan, G. Candan] Middle E Tech Univ, Dept Biotechnol, TR-06800 Ankara, Turkey. [Avsaroglu, M. Dilek] Ahi Evran Univ, Dept Agr Biotechnol, TR-40100 Kirsehir, Turkey. [Cakiris, Aris; Ustek, Duran] Istanbul Univ, Expt Med Res Inst, TR-34393 Istanbul, Turkey. [Gurakan, G. Candan] Middle E Tech Univ, Dept Food Engn, TR-06800 Ankara, Turkey. [Gokduman, Kurtulus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Gokduman, Kurtulus] Beykent Univ, TR-34500 Istanbul, Turkey. [Ustek, Duran] Medipol Univ, Sch Med, Dept Med Genet, TR-34810 Istanbul, Turkey. [Ustek, Duran] Medipol Univ, Sch Med, REMER, TR-34810 Istanbul, Turkey. RP Gokduman, K (reprint author), Middle E Tech Univ, Dept Biotechnol, TR-06800 Ankara, Turkey. EM k.gokduman@gmail.com RI Ustek, Duran/C-3484-2009; OI Ustek, Duran/0000-0002-0060-2859; Gokduman, Kurtulus/0000-0003-2692-5434 FU Middle East Technical University (METU) [BAP-03-14-2010-05] FX This study was supported by Middle East Technical University (METU) research fund: BAP-03-14-2010-05. NR 65 TC 0 Z9 0 U1 3 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 EI 1872-8359 J9 J MICROBIOL METH JI J. Microbiol. Methods PD MAR PY 2016 VL 122 BP 50 EP 58 DI 10.1016/j.mimet.2016.01.008 PG 9 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA DF5CA UT WOS:000371368200011 PM 26820062 ER PT J AU Hirsch, JA Falcone, GJ Brook, AL Fiorella, D Gonzalez, RG Leslie-Mazwi, TM AF Hirsch, Joshua A. Falcone, Guido J. Brook, Allan L. Fiorella, David Gonzalez, R. Gilberto Leslie-Mazwi, Thabele M. TI Stroke is ascendant: is it time for TICI to be more than just a score? SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material DE Stroke ID ACUTE ISCHEMIC-STROKE; RANDOMIZED-TRIAL C1 [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendovasc Serv, Boston, MA 02114 USA. [Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Brook, Allan L.] Montefiore Med Ctr, Albert Einstein Coll Med, Intervent Neuroradiol, Bronx, NY 10467 USA. [Fiorella, David] SUNY Stony Brook, Cerebrovasc Ctr, Dept Neurosurg, Med Ctr, Stony Brook, NY 11794 USA. [Gonzalez,