FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Keyhani, S Myers, LJ Cheng, E Hebert, P Williams, LS Bravata, DM AF Keyhani, Salomeh Myers, Laura J. Cheng, Eric Hebert, Paul Williams, Linda S. Bravata, Dawn M. TI Effect of Clinical and Social Risk Factors on Hospital Profiling for Stroke Readmission A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MEDICARE BENEFICIARIES; 30-DAY READMISSION; HEART-FAILURE; CARE; PREDICTION; MORTALITY; IDENTIFY; PATIENT; MODELS; SCALE AB Background: The Centers for Medicare & Medicaid Services (CMS) and Veterans Health Administration (VA) will report 30-day stroke readmission rates as a measure of hospital quality. A national debate on whether social risk factors should be included in models developed for hospital profiling is ongoing. Objective: To compare a CMS-based model of 30-day readmission with a more comprehensive model that includes measures of social risk (such as homelessness) or clinical factors (such as stroke severity and functional status). Design: Data from a retrospective cohort study were used to develop a CMS-based 30-day readmission model that included age and comorbid conditions based on codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (model 1). This model was then compared with one that included administrative social risk factors (model 2). Finally, the CMS model (model 1) was compared with a model that included social risk and clinical factors from chart review (model 3). These 3 models were used to rank hospitals by 30-day risk-standardized readmission rates and examine facility rankings among the models. Setting: Hospitals in the VA. Participants: Patients hospitalized with stroke in 2007. Measurements: 30-day readmission rates. Results: The 30-day readmission rate was 12.8%. The c-statistics for the 3 models were 0.636, 0.646, and 0.661, respectively. All hospitals were classified as performing "as expected" using all 3 models (that is, performance did not differ from the VA national average); therefore, the addition of detailed clinical information or social risk factors did not alter assessment of facility performance. Limitation: A predominantly male veteran cohort limits the generalizability of these findings. Conclusion: In the VA, more comprehensive models that included social risk and clinical factors did not affect hospital comparisons based on 30-day readmission rates. C1 [Keyhani, Salomeh] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Indiana Univ Sch Med, Vet Hlth Adm Hlth Serv Res & Dev, Stroke Qual Enhancement Res Initiat Program, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Ctr Excellence Implementing Evidence Based Practi, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Regenstrief Inst Hlth Care, Indianapolis, IN USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Keyhani, S (reprint author), San Francisco VA Med Ctr, 4150 Clement,111A1, San Francisco, CA 94121 USA. EM salomeh.keyhani@va.gov FU Veterans Health Administration Office of Quality and Performance; Health Services Research and Development Service Quality Enhancement Research Initiative of the Department of Veterans Affairs [RRP 12-192]; National Heart, Lung, and Blood Institute, U. S. Department of Health and Human Services [1R01HL116522-01A1] FX By the Veterans Health Administration Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative of the Department of Veterans Affairs (RRP 12-192) and the National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services (1R01HL116522-01A1). NR 27 TC 9 Z9 9 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 2 PY 2014 VL 161 IS 11 BP 775 EP U51 DI 10.7326/M14-0361 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UJ UT WOS:000347247200006 PM 25437405 ER PT J AU Rubenstein, LV Danz, MS Crain, AL Glasgow, RE Whitebird, RR Solberg, LI AF Rubenstein, Lisa V. Danz, Marjorie S. Crain, A. Lauren Glasgow, Russell E. Whitebird, Robin R. Solberg, Leif I. TI Assessing organizational readiness for depression care quality improvement: relative commitment and implementation capability SO IMPLEMENTATION SCIENCE LA English DT Article DE Depression; Primary care; Quality improvement; Readiness; Measurement ID COLLABORATIVE CARE; RANDOMIZED-TRIAL; INTERVENTION; COSTS; MODEL AB Background: Depression is a major cause of morbidity and cost in primary care patient populations. Successful depression improvement models, however, are complex. Based on organizational readiness theory, a practice s commitment to change and its capability to carry out the change are both important predictors of initiating improvement. We empirically explored the links between relative commitment (i.e., the intention to move forward within the following year) and implementation capability. Methods: The DIAMOND initiative administered organizational surveys to medical and quality improvement leaders from each of 83 primary care practices in Minnesota. Surveys preceded initiation of activities directed at implementation of a collaborative care model for improving depression care. To assess implementation capability, we developed composites of survey items for five types of organizational factors postulated to be collaborative care barriers and facilitators. To assess relative commitment for each practice, we averaged leader ratings on an identical survey question assessing practice priorities. We used multivariable regression analyses to assess the extent to which implementation capability predicted relative commitment. We explored whether relative commitment or implementation capability measures were associated with earlier initiation of DIAMOND improvements. Results: All five implementation capability measures independently predicted practice leaders? relative commitment to improving depression care in the following year. These included the following: quality improvement culture and attitudes (p = 0.003), depression culture and attitudes (p < 0.001), prior depression quality improvement activities (p < 0.001), advanced access and tracking capabilities (p = 0.03), and depression collaborative care features in place (p = 0.03). Higher relative commitment (p = 0.002) and prior depression quality improvement activities appeared to be associated with earlier participation in the DIAMOND initiative. Conclusions: The study supports the concept of organizational readiness to improve quality of care and the use of practice leader surveys to assess it. Practice leaders relative commitment to depression care improvement may be a useful measure of the likelihood that a practice is ready to initiate evidence-based depression care changes. A comprehensive organizational assessment of implementation capability for depression care improvement may identify specific barriers or facilitators to readiness that require targeted attention from implementers. C1 [Rubenstein, Lisa V.; Danz, Marjorie S.] RAND Corp, Santa Monica, CA 90401 USA. [Rubenstein, Lisa V.; Danz, Marjorie S.] Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [Crain, A. Lauren; Whitebird, Robin R.; Solberg, Leif I.] HealthPartners Res Fdn, Minneapolis, MN 55440 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. RP Rubenstein, LV (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM lisar@rand.org FU National Institute of Mental Health [5R01MH080692] FX This research would not have been possible without the active support of many leaders and staff at the Institute for Clinical Systems Improvement, payers (Blue Cross and Blue Shield of Minnesota, First Plan, HealthPartners, Medica, Minnesota Department of Human Services, Preferred One, and U Care), and the medical groups and clinics. The success of the complex process for the clinical leader surveys is a tribute to both the leaders and study staff, in particular Kris Ohnsorg, Beth Molitor, and David Butani. The Veterans Affairs Center for Implementation Practice and Research Support (CIPRS) investigators and staff supported the manuscript development and preparation. The opinions expressed are those of the authors and do not necessarily represent those of the funding agency or the NIH. The support was provided by the National Institute of Mental Health grant number 5R01MH080692. NR 32 TC 2 Z9 2 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD DEC 2 PY 2014 VL 9 AR 173 DI 10.1186/s13012-014-0173-1 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2PT UT WOS:000347432600001 PM 25443652 ER PT J AU Padmanabhan, A Haldar, SM AF Padmanabhan, Arun Haldar, Saptarsi M. TI Neuroprotection in Ischemic Stroke AhR We Making Progress? SO CIRCULATION LA English DT Editorial Material DE Editorials; kynurenine; infarction, middle cerebral artery; neurons; receptors, aryl hydrocarbon; transcription, genetic; tryptophan oxygenase ID ARYL-HYDROCARBON RECEPTOR; GLOBAL BURDEN; MYOCARDIAL-INFARCTION; REGIONAL BURDEN; HEART-DISEASE; MORTALITY; TRENDS; TIME C1 [Padmanabhan, Arun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Haldar, Saptarsi M.] Case Western Reserve Univ, Sch Med, Dept Med, Case Cardiovasc Res Inst, Cleveland, OH 44106 USA. [Haldar, Saptarsi M.] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Cleveland, OH USA. RP Haldar, SM (reprint author), Case Western Reserve Univ, Sch Med, 2103 Cornell Rd,Room 4-525, Cleveland, OH 44106 USA. EM saptarsi.haldar@case.edu NR 17 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2002 EP 2004 DI 10.1161/CIRCULATIONAHA.114.013533 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700009 PM 25359167 ER PT J AU Dudzinski, DM Bhatt, DL Aragam, JR Maron, BA AF Dudzinski, David M. Bhatt, Deepak L. Aragam, Jayashri R. Maron, Bradley A. TI Explaining Unexplained Dyspnea The Ever "Holesome" Heart SO CIRCULATION LA English DT Article DE atrial septal defect sinus venosus; heart defects, congenital; heart failure; hypertension, pulmonary ID ATRIAL-SEPTAL-DEFECT; PULMONARY VENOUS CONNECTION; SUPERIOR VENA-CAVA; CORONARY-SINUS; ECHOCARDIOGRAPHY; REPAIR; ADULT; HYPERTENSION; ANGIOGRAPHY; DISEASE AB A year-old man was evaluated in consultation for unexplained dyspnea. At the time of the initial clinical encounter at our institution, the patient endorsed a 10-year history of progressive exertional dyspnea, which had become debilitating over the preceding 3 months and was characterized by shortness of breath accompanying subtle physical activities such as tying shoelaces. The patient underwent multiple hospital admissions reportedly for the treatment of congestive heart failure ascribed to impaired left ventricular (LV) diastolic function. Review of systems identified postural dizziness and history of near syncope, possible nocturnal dyspnea, and peripheral neuropathy, but not cardiac angina, orthopnea, nocturia, edema, cough, palpitations, syncope, claudication, or other cardiopulmonary symptoms. He related that he was first noted to have a cardiac murmur detected 4 decades previously during a military service physical examination but that the murmur was not characterized further and that he served in the Vietnam conflict without functional limitation. The patient's relevant medical history included rate-controlled atrial fibrillation, 90 pack-year tobacco use (3 packs daily between 21 and 51 years of age), dyslipidemia, systemic hypertension, type 2 diabetes mellitus, moderate chronic obstructive pulmonary disease, obstructive sleep apnea not currently treated, and gastrointestinal bleed caused by colon cancer treated with hemicolectomy 11 years earlier. There was no illicit drug use, but a remote history of heavy alcohol consumption was reported. Family history was unremarkable except that his father died at 55 years of age of myocardial infarction. Medications included aspirin 81 mg daily, warfarin 2 mg daily, losartan 50 mg daily, metoprolol tartrate 25 mg twice daily, simvastatin 10 mg daily, fenofibrate 48 mg daily, albuterol inhaler 90-mu g puffs as needed, and gabapentin 300 mg 3 times daily. C1 [Dudzinski, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dudzinski, David M.] Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. [Bhatt, Deepak L.; Aragam, Jayashri R.; Maron, Bradley A.] Vet Affairs Boston Healthcare Syst, Dept Cardiol, Boston, MA USA. [Bhatt, Deepak L.; Aragam, Jayashri R.; Maron, Bradley A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Aragam, Jayashri R.; Maron, Bradley A.] Harvard Univ, Sch Med, Div Cardiovasc Med, Boston, MA USA. RP Maron, BA (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, PBB 1,77 Ave Louis Pasteur,NRB Rm 0630-OA, Boston, MA 02115 USA. EM bmaron@partners.org FU National Institutes of Health [1K08HL111207-01A1]; Pulmonary Hypertension Association; Pulmonary Vascular Research Institute; Klarman Foundations at Brigham and Women's Hospital FX This work was supported in part by the National Institutes of Health (1K08HL111207-01A1), Pulmonary Hypertension Association, Pulmonary Vascular Research Institute, and Klarman Foundations at Brigham and Women's Hospital to Dr Maron. NR 26 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2057 EP 2066 DI 10.1161/CIRCULATIONAHA.114.010810 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700016 PM 25446059 ER PT J AU January, CT Wann, LS Alpert, JS Calkins, H Cigarroa, JE Cleveland, JC Conti, JB Ellinor, PT Ezekowitz, MD Field, ME Murray, KT Sacco, RL Stevenson, WG Tchou, PJ Tracy, CM Yancy, CW AF January, Craig T. Wann, L. Samuel Alpert, Joseph S. Calkins, Hugh Cigarroa, Joaquin E. Cleveland, Joseph C., Jr. Conti, Jamie B. Ellinor, Patrick T. Ezekowitz, Michael D. Field, Michael E. Murray, Katherine T. Sacco, Ralph L. Stevenson, William G. Tchou, Patrick J. Tracy, Cynthia M. Yancy, Clyde W. CA Writing Comm Members TI 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society SO CIRCULATION LA English DT Article ID WOLFF-PARKINSON-WHITE; VENTRICULAR RATE CONTROL; RADIOFREQUENCY CATHETER MODIFICATION; PERCUTANEOUS CORONARY INTERVENTION; ELEVATION MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; ORAL ANTICOAGULANT-THERAPY; MAINTAINING SINUS RHYTHM; RENIN-ANGIOTENSIN SYSTEM; PLACEBO-CONTROLLED TRIAL C1 [January, Craig T.] Univ Wisconsin Madison, Cardiovasc Med Div, Madison, WI 53706 USA. [Alpert, Joseph S.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. [Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cleveland, Joseph C., Jr.] Univ Colorado, Boulder, CO 80309 USA. [Cleveland, Joseph C., Jr.] Denver Vet Affairs Hosp, Denver, CO USA. [Conti, Jamie B.] Univ Florida, Div Cardiovasc Medi, Gainesville, FL 32611 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ezekowitz, Michael D.] Jefferson Med Coll, Philadelphia, PA USA. [Field, Michael E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Murray, Katherine T.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Nashville, TN USA. [Murray, Katherine T.] Vanderbilt Univ, Sch Med, Div Cardiol, Nashville, TN USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Stevenson, William G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stevenson, William G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Tchou, Patrick J.] Cleveland Clin Fdn, Sect Cardiac Elect & Pacing, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH USA. [Tracy, Cynthia M.] George Washington Univ, Med Ctr, Washington, DC 20052 USA. [Yancy, Clyde W.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Evanston, IL 60208 USA. RP January, CT (reprint author), Univ Wisconsin Madison, Cardiovasc Med Div, Madison, WI 53706 USA. NR 202 TC 351 Z9 377 U1 10 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2071 EP 2104 DI 10.1161/CIR.0000000000000040 PG 34 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700019 PM 24682348 ER PT J AU Mauri, L Kereiakes, DJ Yeh, RW Driscoll-Shempp, P Cutlip, DE Steg, PG Braunwald, E Wiviott, SD Cohen, DJ Holmes, DR Krucoff, MW Hermiller, JB Dauerman, HL Simon, DI Kandzari, DE Garratt, KN Lee, DP Pow, TK Lee, PNV Rinaldi, MJ Massaro, JM AF Mauri, Laura Kereiakes, Dean J. Yeh, Robert W. Driscoll-Shempp, Priscilla Cutlip, Donald E. Steg, Philippe G. Braunwald, Eugene Wiviott, Stephen D. Cohen, David J. Holmes, David R., Jr. Krucoff, Mitchell W. Hermiller, James B. Dauerman, Harold L. Simon, Daniel I. Kandzari, David E. Garratt, Kirk N. Lee, David P. Pow, Thomas K. Lee, Peter N. Ver Rinaldi, Michael J. Massaro, Joseph M. TI Risk and Benefit of Prolonged Dual Antiplatelet Therapy After Drug-eluting Coronary Stents: Primary Endpoint Results from the Dual Antiplatelet Therapy Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Drug eluting stents; Antiplatelet drugs; Clinical trials; Thrombosis C1 [Mauri, Laura; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kereiakes, Dean J.] Lindner Rsch Cntr, Christ Hosp Heart & Vasc Cntr, Lindner Rsch Cntr, Cincinnati, OH USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Driscoll-Shempp, Priscilla] Harvard Clin Rsch Inst, Program Dev & Sponsored Studies, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Steg, Philippe G.] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Holmes, David R., Jr.] Mayo Clin, Rochester, MN USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Durham, NC USA. [Hermiller, James B.] St Vincent Heart Cntr, Indianaoplis, IN USA. [Dauerman, Harold L.] Fletcher Allen Hlth Care, Med, Burlington, VT USA. [Simon, Daniel I.] Univ Hosps Case Med Cntr, Harrington Heart & Vasc Inst, Cleveland, OH USA. [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA USA. [Garratt, Kirk N.] Lenox Hill Hosp, New York, NY 10021 USA. [Lee, David P.] Stanford Univ, Stanford, CA 94305 USA. [Pow, Thomas K.] Great Lakes Heart & Vasc Inst, St Joseph, MI USA. [Lee, Peter N. Ver] Eastern Maine Med Cntr, Bangor, ME USA. [Rinaldi, Michael J.] Carolinas Healthcare Syst, Sanger Heart & Vasc Inst, Charlotte, NC USA. [Massaro, Joseph M.] Harvard Clin Rsch Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2107 EP 2107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700024 ER PT J AU Smith, PK Puskas, J Ascheim, D Voisine, P Ailawadi, G Hung, J Gelijns, A Moskowitz, AJ Perrault, L Parides, M Acker, M Argenziano, M Thourani, V Gammie, J Chen, F Miller, M Page, P Overbey, JR Bagiella, E Dagenais, F Blackstone, E Kron, I Goldstein, D Moquete, E Jeffries, N Gardner, T O'Gara, P Alexander, J Michler, RE AF Smith, Peter K. Puskas, John Ascheim, Deborah Voisine, Pierre Ailawadi, Gorav Hung, Judy Gelijns, Annetine Moskowitz, Alan J. Perrault, Louis Parides, Michael Acker, Michael Argenziano, Michael Thourani, Vinod Gammie, James Chen, Frederick Miller, Marissa Page, Pierre Overbey, Jessica R. Bagiella, Emilia Dagenais, Francois Blackstone, Eugene Kron, Irving Goldstein, Daniel Moquete, Ellen Jeffries, Neal Gardner, Timothy O'Gara, Patrick Alexander, John Michler, Robert E. TI The Surgical Treatment of Moderate Ischemic Mitral Regurgitation: A Randomized Clinical Trial From The Cardiothoracic Surgical Trials Network SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Mitral regurgitation; Coronary artery disease; Coronary artery bypass grafting (CABG); Valvuloplasty; Clinical trials C1 [Smith, Peter K.] Duke Univ, Durham, NC USA. [Puskas, John] Mt Sinai Beth Israel, Surg, New York, NY USA. [Ascheim, Deborah; Gelijns, Annetine; Moskowitz, Alan J.; Parides, Michael; Overbey, Jessica R.; Bagiella, Emilia] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Voisine, Pierre] Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Ailawadi, Gorav; Kron, Irving] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perrault, Louis] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Acker, Michael] Univ Penn, Philadelphia, PA 19104 USA. [Argenziano, Michael] Columbia Univ, Med Ctr, New York, NY USA. [Thourani, Vinod] Emory Univ Hosp Midtown, Atlanta, GA USA. [Gammie, James] Univ Maryland, Baltimore, MD 21201 USA. [Chen, Frederick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Miller, Marissa; Jeffries, Neal] NHLBI, NIH, Bethesda, MD 20892 USA. [Page, Pierre] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Dagenais, Francois] Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Blackstone, Eugene] Cleveland Clin, Cleveland, OH 44106 USA. [Goldstein, Daniel; Michler, Robert E.] Montefiore Einstein Heart Cntr, New York, NY USA. [Gardner, Timothy] Christiana Care Hlth Syst, Newark, DE USA. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alexander, John] Duke Univ, Duke Clin Rsch Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2110 EP 2110 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700032 ER PT J AU Blazing, MA Giugliano, RP DeLemos, J Cannon, CP Musliner, T Tershakovec, AM White, JA Reist, C McCagg, A Braunwald, E Califf, RM AF Blazing, Michael A. Giugliano, Robert P. DeLemos, James Cannon, Christopher P. Musliner, Thomas Tershakovec, Andrew M. White, Jennifer A. Reist, Craig McCagg, Amy Braunwald, Eugene Califf, Robert M. TI On-Treatment Analysis of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Clinical trials; Cholesterol-lowering drugs; Outcomes; LDL; Prevention C1 [Blazing, Michael A.; Califf, Robert M.] Duke Clin Res Inst, Cardiovasc Div, Durham, NC USA. [Giugliano, Robert P.; Cannon, Christopher P.; Braunwald, Eugene] TIMI Study Grp, Cardiovasc Div, Boston, MA USA. [DeLemos, James] Univ Texas SW Med Ctr Dallas, Cardiovasc Div, Dallas, TX 75390 USA. [Musliner, Thomas; Tershakovec, Andrew M.] Merck & Co Inc, Clin Res, Whitehouse Stn, NJ USA. [White, Jennifer A.; Reist, Craig] Duke Clin Res Inst, Durham, NC USA. [McCagg, Amy] TIMI Study Grp, Cardiovasc Div, Boston, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2112 EP 2112 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700037 ER PT J AU Kereiakes, DJ Yeh, RJ Massaro, JM Driscoll-Shempp, P Cutlip, DE Normand, SLT Steg, PG Gershlick, AH Tanguay, JF Windecker, S Garratt, KN Kandzari, DE Lee, DP Simon, DI Iancu, A Trebacz, J Mauri, L AF Kereiakes, Dean J. Yeh, Robert J. Massaro, Joseph M. Driscoll-Shempp, Priscilla Cutlip, Donald E. Normand, Sharon-Lise T. Steg, Philippe G. Gershlick, Anthony H. Tanguay, Jean-Francois Windecker, Stephan Garratt, Kirk N. Kandzari, David E. Lee, David P. Simon, Daniel I. Iancu, Adrian Trebacz, Jaroslaw Mauri, Laura TI Comparison of Ischemic and Bleeding Events After Drug-Eluting Stents or Bare Metal Stents in Subjects Receiving Dual Antiplatelet Therapy: Results from the Randomized Dual Antiplatelet Therapy Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Antiplatelet drugs; Platelet receptor blockers; Percutaneous coronary intervention (PCI) C1 [Kereiakes, Dean J.] Christ Hosp, Heart & Vasc Ctr, Lindner Res Ctr, Cincinnati, OH 45219 USA. [Yeh, Robert J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Massaro, Joseph M.] Harvard Clin Res Inst, Boston, MA USA. [Driscoll-Shempp, Priscilla] Harvard Clin Res Inst, Program Dev, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Steg, Philippe G.] Hop Bichat Claude Bernard, AP HP, Dept Cardiol, F-75877 Paris, France. [Gershlick, Anthony H.] Univ Hosp Leicester Trust, Univ Hosp Leicester, Leicester Cardiovasc Biomed Res Unit, Glenfield Hosp,Natl Inst Hlth Res, Leicester, Leics, England. [Tanguay, Jean-Francois] Inst Cardiol Montreal, Montreal, PQ, Canada. [Windecker, Stephan] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Garratt, Kirk N.] Lenox Hill Hosp, New York, NY 10021 USA. [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA USA. [Lee, David P.] Stanford Univ, Stanford, CA 94305 USA. [Simon, Daniel I.] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Cleveland, OH USA. [Iancu, Adrian] Heart Inst N Stancioiu, Cluj Napoca, Romania. [Trebacz, Jaroslaw] Jan Pawel II Hosp Krakow, Krakow, Poland. [Mauri, Laura] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2113 EP 2113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700040 ER PT J AU January, CT Wann, LS Alpert, JS Calkins, H Cigarroa, JE Cleveland, JC Conti, JB Ellinor, PT Ezekowitz, MD Field, ME Murray, KT Sacco, RL Stevenson, WG Tchou, PJ Tracy, CM Yancy, CW AF January, Craig T. Wann, L. Samuel Alpert, Joseph S. Calkins, Hugh Cigarroa, Joaquin E. Cleveland, Joseph C., Jr. Conti, Jamie B. Ellinor, Patrick T. Ezekowitz, Michael D. Field, Michael E. Murray, Katherine T. Sacco, Ralph L. Stevenson, William G. Tchou, Patrick J. Tracy, Cynthia M. Yancy, Clyde W. CA Soc Thoracic Surgeons TI 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society SO CIRCULATION LA English DT Article DE AHA Scientific Statements; atrial fibrillation; cardio-renal physiology/pathophysiology; cardiovascular surgery: transplantation, ventricular assistance, cardiomyopathy; epidemiology; full revision; health policy and outcome research; other atrial fibrillation ID WOLFF-PARKINSON-WHITE; RADIOFREQUENCY CATHETER ABLATION; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; VENTRICULAR RATE CONTROL; ATRIOVENTRICULAR JUNCTION ABLATION; PERCUTANEOUS CORONARY INTERVENTION; CARDIAC RESYNCHRONIZATION THERAPY; MAINTAINING SINUS RHYTHM; MITRAL-VALVE SURGERY C1 [January, Craig T.] Univ Wisconsin, Cardiovasc Med Div, Madison, WI 53706 USA. [Wann, L. Samuel] Columbia St Marys Cardiovasc Phys, Milwaukee, WI USA. [Alpert, Joseph S.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85721 USA. [Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cleveland, Joseph C., Jr.] Univ Colorado, Boulder, CO 80309 USA. [Cleveland, Joseph C., Jr.] Denver Vet Affairs Hosp, Denver, CO USA. [Conti, Jamie B.] Univ Florida, Div Cardiovasc Med, Gainesville, FL 32611 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ezekowitz, Michael D.] Jefferson Med Coll, Philadelphia, PA 19107 USA. [Field, Michael E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Field, Michael E.] Univ Wisconsin, Sch Med & Publ Hlth, Arrhythmia Serv, Madison, WI 53706 USA. [Murray, Katherine T.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Nashville, TN USA. [Murray, Katherine T.] Vanderbilt Univ, Sch Med, Div Cardiol, Nashville, TN USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Stevenson, William G.] Brigham & Womens Hosp, Cardiac Arrhythmia Program, Boston, MA 02115 USA. [Stevenson, William G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Tchou, Patrick J.] Cleveland Clin Fdn, Sect Cardiac Electrophysiol & Pacing, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH USA. [Tracy, Cynthia M.] George Washington Univ, Med Ctr, Washington, DC 20052 USA. [Yancy, Clyde W.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Yancy, Clyde W.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Evanston, IL 60208 USA. RP January, CT (reprint author), Univ Wisconsin, Cardiovasc Med Div, Madison, WI 53706 USA. FU NHLBI NIH HHS [R01 HL096844] NR 550 TC 241 Z9 258 U1 3 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP E199 EP E267 DI 10.1161/CIR.0000000000000041 PG 69 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700002 PM 24682347 ER PT J AU Olliac, B Birmes, P Bui, E Allenou, C Brunet, A Claudet, I de Gauzy, JS Grandjean, H Raynaud, JP AF Olliac, Bertrand Birmes, Philippe Bui, Eric Allenou, Charlotte Brunet, Alain Claudet, Isabelle de Gauzy, Jerome Sales Grandjean, Helene Raynaud, Jean-Philippe TI Validation of the French Version of the Child Post-Traumatic Stress Reaction Index: Psychometric Properties in French Speaking School-Aged Children SO PLOS ONE LA English DT Article ID TEST-RETEST RELIABILITY; ADOLESCENT SURVIVORS; BEHAVIOR PROBLEMS; NATURAL DISASTER; SNIPER ATTACK; DSM-III; DISORDER; SYMPTOMS; TRAUMA; PTSD AB Background: Although the reliable and valid Child Post-Traumatic Stress Reaction Index (CPTS-RI) is a widely used measure of posttraumatic stress disorder (PTSD) symptoms in children, it has not been validated in French-speaking populations. The present study aims to assess the psychometric properties of the CPTS-RI in three samples of French-speaking school-children. Methods: Data was obtained from three samples. Sample 1 was composed of 106 children (mean (SD) age=11.7(0.7), 50% females) victims of an industrial disaster. Sample 2 was composed of 50 children (mean (SD) age=10.8(2.6), 44% females) who had received an orthopaedic surgical procedure after an accident. Sample 3 was composed of 106 children (mean (SD) age=11.7(2.2), 44% females) admitted to an emergency department after a road traffic accident. We tested internal consistency using Cronbach's alpha. We examined test-retest reliability using intraclass correlation coefficient. In order to assess the convergent validity of the French version of the CPTS-RI and the Clinician Administered PTS Scale-Child and Adolescent (CAPS-CA), spearman-correlation coefficient was computed. To verify the validity of the cut-off scores, a ROC curve was constructed which evaluated the sensitivity and specificity of each score compared to the diagnosis with the CAPS-CA. We also used principal components analysis with varimax rotation to study the structure of the French version of the CPTS-RI. Results: Cronbach's alpha coefficient was 0.87 for the French version of the CPTS-RI. Two-week test-retest intraclass correlation coefficient (n=30) was 0.67. The French version of the CPTS-RI was well correlated with the CAPS-CA (r=0.76, p<0.001). Taking the CAPS-CA as the diagnostic reference, with a diagnostic cutoff of >24 for the CPTS-RI, the sensitivity and specificities were 100% and 62.6%, respectively. The French version of the CPTS-RI demonstrated a three-factor structure. Conclusions: The CPTS-RI is reliable and valid in French-speaking children. C1 [Olliac, Bertrand] INSERM, Unite Mixte Rech 1094, Limoges, France. [Olliac, Bertrand] Univ Limoges, Sch Med, Inst Neuroepidemiol & Trop Neurol, CNRS,FR GEIST 3503, Limoges, France. [Olliac, Bertrand; Grandjean, Helene] Univ Toulouse 3, INSERM, Unite Mixte Rech 1027, F-31062 Toulouse, France. [Olliac, Bertrand] Ctr Hosp Esquirol, Pole Hosp, Univ Psychiat Enfant & Adolescent, Limoges, France. [Birmes, Philippe; Bui, Eric; Allenou, Charlotte] Univ Toulouse, Univ Toulouse 3, Ctr Hosp Univ Toulouse, Hop Casselardit,Lab Stress Traumat LST EA 4560, Toulouse, France. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Brunet, Alain] McGill Univ, Montreal, PQ, Canada. [Brunet, Alain] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Claudet, Isabelle] Ctr Hosp Univ Toulouse, Hop Enfants, Unite Urgences Pediat, Toulouse, France. [de Gauzy, Jerome Sales] Ctr Hosp Univ Toulouse, Hop Enfants, Serv Chirurg Orthoped Traumatol & Plast, Toulouse, France. [Raynaud, Jean-Philippe] Univ Toulouse 3, CHU Toulouse, Hop La Grave, INSERM,Unite Mixte Rech 1027, F-31062 Toulouse, France. RP Olliac, B (reprint author), INSERM, Unite Mixte Rech 1094, Limoges, France. EM bertrand.olliac@ch-esquirol-limoges.fr RI Bui, Eric/J-8347-2015; Claudet, Isabelle/G-9457-2016 OI Bui, Eric/0000-0002-1413-6473; Claudet, Isabelle/0000-0002-3868-8483 FU Ministry of Health, PHRC FX This study was supported by the Ministry of Health, PHRC (Programme Hospitalier de Recherche Clinique) 2002 and 2004. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 70 TC 0 Z9 0 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 2 PY 2014 VL 9 IS 12 AR e112603 DI 10.1371/journal.pone.0112603 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU8TQ UT WOS:000345869700020 PM 25460912 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Blood Pressure Targets Still Struggling for the Right Answer SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE diabetes; elderly; goals; guidelines; hypertension ID HYPERTENSION; MANAGEMENT; GUIDELINES; SOCIETY C1 [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY 10029 USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 110,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 13 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 2 PY 2014 VL 64 IS 21 BP 2204 EP 2206 DI 10.1016/j.jacc.2014.07.994 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW0EA UT WOS:000345961900005 PM 25447262 ER PT J AU Chavez, L Huang, Y Luong, K Agarwal, S Iyer, LM Pastor, WA Hench, VK Frazier-Bowers, SA Korol, E Liu, S Tahiliani, M Wang, YS Clark, TA Korlach, J Pukkila, PJ Aravind, L Rao, A AF Chavez, Lukas Huang, Yun Luong, Khai Agarwal, Suneet Iyer, Lakshminarayan M. Pastor, William A. Hench, Virginia K. Frazier-Bowers, Sylvia A. Korol, Evgenia Liu, Shuo Tahiliani, Mamta Wang, Yinsheng Clark, Tyson A. Korlach, Jonas Pukkila, Patricia J. Aravind, L. Rao, Anjana TI Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TET; 5mC; 5fC; 5caC; SMRT-seq ID EMBRYONIC STEM-CELLS; BASIDIOMYCETE COPRINUS-CINEREUS; EUKARYOTIC DNA METHYLATION; SINGLE-MOLECULE; COMPLEX MODIFICATIONS; ESCHERICHIA-COLI; MAMMALIAN DNA; TET PROTEINS; 5-METHYLCYTOSINE; 5-HYDROXYMETHYLCYTOSINE AB TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution. We have used the method to map the distribution of oxi-mC across the genome of Coprinopsis cinerea, a basidiomycete that encodes 47 TET/JBP paralogs in a previously unidentified class of DNA transposons. Like 5-methylcytosine residues from which they are derived, oxi-mC modifications are enriched at centromeres, TET/JBP transposons, and multicopy paralogous genes that are not expressed, but rarely mark genes whose expression changes between two developmental stages. Our study provides evidence for the emergence of an epigenetic regulatory system through recruitment of selfish elements in a eukaryotic lineage, and describes a method to map all three different species of oxi-mCs simultaneously. C1 [Chavez, Lukas; Huang, Yun; Pastor, William A.; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. [Chavez, Lukas; Huang, Yun] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA. [Luong, Khai; Clark, Tyson A.; Korlach, Jonas] Pacific Biosci, Menlo Pk, CA 94025 USA. [Agarwal, Suneet] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Hench, Virginia K.; Frazier-Bowers, Sylvia A.; Pukkila, Patricia J.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Korol, Evgenia; Tahiliani, Mamta] NYU, Langone Med Ctr, Skirball Inst, New York, NY 10016 USA. [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Environm Toxicol Grad Program, Riverside, CA 92521 USA. [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Rao, Anjana] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92093 USA. [Rao, Anjana] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92093 USA. RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. EM arao@liai.org OI Huang, Yun/0000-0001-5950-9168; Chavez, Lukas/0000-0002-8718-8848 FU NIH [R01 HD065812, R01 AI44432, R01 CA151535, K08 HL089150, R01 CA101864]; California Institute for Regenerative Medicine Grant [RM1-01729]; Leukemia Society of America Translational Research Program [6187-12]; Howard Hughes Medical Institute through the Undergraduate Science Education Program; Harvard Catalyst; Harvard Clinical and Translational Science Center [NIH] [1 UL1 RR 025758-02]; Leukemia and Lymphoma Society; National Science Foundation; Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation; National Library of Medicine, NIH FX This work was supported by NIH Grants R01 HD065812 (to A.R.), R01 AI44432 (to A.R.), R01 CA151535 (to A.R.), K08 HL089150 (to S.A.), and R01 CA101864 (to Y.W.); California Institute for Regenerative Medicine Grant RM1-01729 (to A.R.); Leukemia Society of America Translational Research Program Award 6187-12 (to A.R.); a grant to University of North Carolina Chapel Hill from the Howard Hughes Medical Institute through the Undergraduate Science Education Program (to P.J.P.); a pilot grant from Harvard Catalyst, the Harvard Clinical and Translational Science Center [NIH Grant 1 UL1 RR 025758-02 (to S.A.)]; a postdoctoral fellowship from the Leukemia and Lymphoma Society (to Y.H.); a predoctoral fellowship from the National Science Foundation (to W.A.P.); a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation (to L.C.); and intramural funds of the National Library of Medicine, NIH (L.A. and L.M.I.). NR 52 TC 4 Z9 4 U1 4 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP E5149 EP E5158 DI 10.1073/pnas.1419513111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800004 PM 25406324 ER PT J AU Morgan, EA Katzman, LE Georgian-Smith, D Owings, RA Pinkus, GS DeAngelo, DJ AF Morgan, E. A. Katzman, L. E. Georgian-Smith, D. Owings, R. A. Pinkus, G. S. DeAngelo, D. J. TI Hairy cell leukemia presenting as a palpable breast mass SO JOURNAL OF HEMATOPATHOLOGY LA English DT Article DE Hairy cell leukemia; Extramedullary; Breast; Extranodal ID LYMPHOPROLIFERATIVE DISORDERS; INVOLVEMENT; EXPRESSION; DIAGNOSIS; NEOPLASMS; AUTOPSY; CD103 AB Hairy cell leukemia (HCL) is a rare mature B cell malignancy that typically involves the bone marrow, peripheral blood, and spleen. Clinically detectable lymph node infiltration occurs in aminority of patients, and extranodal tissue involvement of sites such as the central nervous system, gastrointestinal tract, and skin is uncommon. Consequently, the vast majority of patients with HCL present with pancytopenia and splenomegaly but without lymphadenopathy or soft tissue masses. Herein we present a unique case of HCL presenting as a palpable breast mass without concomitant marrow or peripheral blood involvement and without radiologic evidence of other sites of disease. Several features of the tumor cell infiltrate (ample pale cytoplasm, nested appearance) evoked other entities that would more typically involve breast tissue such as the alveolar or solid variants of invasive lobular carcinoma. However, the immunophenotypic and molecular characteristics of the tumor cells were indistinguishable from classic HCL. The significant challenge in this case was recognizing this entity outside of its usual clinical and anatomic context. Although rare, HCL should be a diagnostic consideration in tumors arising at extramedullary/extranodal sites including the breast. C1 [Morgan, E. A.; Owings, R. A.; Pinkus, G. S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Katzman, L. E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Georgian-Smith, D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [DeAngelo, D. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Morgan, EA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM eamorgan@partners.org NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1868-9256 EI 1865-5785 J9 J HEMATOP JI J. Hematop. PD DEC PY 2014 VL 7 IS 4 BP 181 EP 187 DI 10.1007/s12308-014-0221-4 PG 7 WC Hematology; Pathology SC Hematology; Pathology GA CU7ZT UT WOS:000363761100007 ER PT J AU Gutierrez, B Kaatz, A Chu, S Ramirez, D Samson-Samuel, C Carnes, M AF Gutierrez, Belinda Kaatz, Anna Chu, Sarah Ramirez, Dennis Samson-Samuel, Clem Carnes, Molly TI "Fair Play'': A Videogame Designed to Address Implicit Race Bias Through Active Perspective Taking SO GAMES FOR HEALTH JOURNAL LA English DT Article ID ASSOCIATION TEST; ACADEMIC MEDICINE; STIGMATIZED GROUP; MINORITY FACULTY; RACIAL BIAS; EMPATHY; ATTITUDES; STEREOTYPES; INFORMATION; PREJUDICE AB Objective: Having diverse faculty in academic health centers will help diversify the healthcare workforce and reduce health disparities. Implicit race bias is one factor that contributes to the underrepresentation of Black faculty. We designed the videogame "Fair Play'' in which players assume the role of a Black graduate student named Jamal Davis. As Jamal, players experience subtle race bias while completing "quests'' to obtain a science degree. We hypothesized that participants randomly assigned to play the game would have greater empathy for Jamal and lower implicit race bias than participants randomized to read narrative text describing Jamal's experience. Materials and Methods: University of Wisconsin-Madison graduate students were recruited via e-mail and randomly assigned to play "Fair Play'' or read narrative text through an online link. Upon completion, participants took an Implicit Association Test to measure implicit bias and answered survey questions assessing empathy toward Jamal and awareness of bias. Results: As hypothesized, gameplayers showed the least implicit bias but only when they also showed high empathy for Jamal (P = 0.013). Gameplayers did not show greater empathy than text readers, and women in the text condition reported the greatest empathy for Jamal (P = 0.008). However, high empathy only predicted lower levels of implicit bias among those who actively took Jamal's perspective through gameplay (P = 0.014). Conclusions: A videogame in which players experience subtle race bias as a Black graduate student has the potential to reduce implicit bias, possibly because of a game's ability to foster empathy through active perspective taking. C1 [Gutierrez, Belinda; Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Gutierrez, Belinda; Kaatz, Anna; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem] Univ Wisconsin, Games Learning & Soc, Madison, WI 53715 USA. [Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem] Univ Wisconsin, Dept Curriculum & Instruct, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. RP Gutierrez, B (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM bgutierrez@wisc.edu FU NIGMS NIH HHS [DP4 GM096822, R25 GM083252] NR 67 TC 3 Z9 3 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2161-783X EI 2161-7856 J9 GAMES HEALTH J JI Games Health J. PD DEC PY 2014 VL 3 IS 6 BP 371 EP 378 DI 10.1089/g4h.2013.0071 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA CU2WW UT WOS:000363385400006 PM 26192644 ER PT J AU Jones, BL Smith, SM AF Jones, Brian L. Smith, Stephen M. TI Choice of Crystalloid and Mortality in Sepsis-All in the Timing? SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Jones, Brian L.; Smith, Stephen M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Smith, Stephen M.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. RP Jones, BL (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. OI Smith, Stephen/0000-0002-0331-7615 NR 3 TC 2 Z9 4 U1 0 U2 0 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 DEC PY 2014 VL 42 IS 12 BP E796 EP E796 DI 10.1097/CCM.0000000000000594 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA CS4XX UT WOS:000362080700008 PM 25402300 ER PT J AU Byne, W AF Byne, William TI The First Year of LGBT Health: A Year of LGBT Progress in the United States SO LGBT HEALTH LA English DT Editorial Material DE LGBT; Medicare; same-sex marriage; sex reassignment surgery; pre-exposure prophylaxis C1 [Byne, William] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Byne, William] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Byne, W (reprint author), James J Peters VAMC, Res Bldg,Room 2F39 130 West Kingsbridge Rd, Bronx, NY 10467 USA. EM william.byne@mssm.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD DEC PY 2014 VL 1 IS 4 BP 239 EP 241 DI 10.1089/lgbt.2014.0085 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QK UT WOS:000361691400001 PM 26789849 ER PT J AU Blosnich, JR Brown, GR Wojcio, S Jones, KT Bossarte, RM AF Blosnich, John R. Brown, George R. Wojcio, Sybil Jones, Kenneth T. Bossarte, Robert M. TI Mortality Among Veterans with Transgender-Related Diagnoses in the Veterans Health Administration, FY2000-2009 SO LGBT HEALTH LA English DT Article DE mortality; suicide; transgender persons; veterans ID GENDER IDENTITY DISORDER; PSYCHIATRIC COMORBIDITY; SUICIDAL IDEATION; RISK BEHAVIORS; HIV PREVALENCE; UNITED-STATES; CARE; SYSTEM; TRANSSEXUALISM; PEOPLE AB Purpose: The aims of this project were to document all-cause and suicide mortality among Veteran Healthcare Administration (VHA) utilizers with The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis consistent with transgender status. Methods: The study population consisted of VHA patients identified as having any one of four diagnosis codes indicating transgender status (n = 5,117) gathered from the VA National Patient Care Database. Mortality data were gathered from the National Death Index from 2000-2009 for 1,277 veterans with transgender-related ICD-9-CM diagnoses. The remaining 3,840 were not searched because they had VHA utilization after 2009 (indicating they were alive). Person-time at risk (person-years) for crude rates were calculated based on the time from an individual's index diagnosis to either death or the end of FY 2009. Causes of death were categorized using ICD-10 code groups. Results: Approximately 9.3% (n = 309) veterans with transgender-related ICD-9-CM diagnoses died across the study period. Although diseases of the circulatory system and neoplasms were the first and second leading causes of death, respectively, the other ranked causes of mortality differed somewhat from patterns for the US during the same time span. The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses across the 10-year period was approximately 82/100,000 person-years, which approximated the crude suicide death rates for other serious mental illness in VHA (e.g., depression, schizophrenia). The average age of suicide decedents was 49.4 years. Conclusion: The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses is higher than in the general population, and they may be dying by suicide at younger ages than their veteran peers without transgender-related ICD-9-CM diagnoses. Future research, such as age-adjusted rates or accounting for psychiatric co-morbidities, will help to better clarify if the all-cause and suicide mortality rates are elevated for veterans with transgender-related ICD-9-CM diagnoses. C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Blosnich, John R.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Brown, George R.; Jones, Kenneth T.] VA Cent Off, Off Hlth Equ, Washington, DC USA. [Brown, George R.] E Tennessee State Univ, Dept Psychiat & Behav Sci, Johnson City, TN 37614 USA. [Wojcio, Sybil; Bossarte, Robert M.] VISN2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU VISN2 Center of Excellence for Suicide Prevention; Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System FX This work was partially supported by the VISN2 Center of Excellence for Suicide Prevention and a postdoctoral fellowship to JRB through the Department of Veterans Affairs Office of Academic Affiliations and the Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System. NR 56 TC 5 Z9 5 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD DEC PY 2014 VL 1 IS 4 BP 269 EP 276 DI 10.1089/lgbt.2014.0050 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QK UT WOS:000361691400007 PM 26789855 ER PT J AU White, JM Gordon, JR Mimiaga, MJ AF White, Jaclyn M. Gordon, Janna R. Mimiaga, Matthew J. TI The Role of Substance Use and Mental Health Problems in Medication Adherence Among HIV-Infected MSM SO LGBT HEALTH LA English DT Article DE medication adherence; mental health; substance use; MSM ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; POSITIVE MEN; RISK BEHAVIOR; ALCOHOL-USE; BODY-IMAGE; SEX; DEPRESSION; METAANALYSIS AB Mental health and substance abuse problems are highly prevalent among HIV-infected men who have sex with men (MSM) and frequently interfere with antiretroviral therapy (ART) adherence. Novel interventions that address underlying psychosocial health problems are necessary for improving ART adherence to enhance HIV-related health outcomes and suppress HIV viral load in an effort to prevent transmission to uninfected partners. This brief review describes the mental health problems and specific substances that pose the greatest threat to medication adherence among MSM and summarizes findings from recent intervention trials that simultaneously address ART adherence and comorbid psychosocial factors among HIV-infected MSM. C1 [White, Jaclyn M.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Gordon, Janna R.; Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP White, JM (reprint author), Fenway Hlth, Ansin Bldg,8th Floor 1340 Boylston St, Boston, MA 02215 USA. EM jwhite@fenwayhealth.org NR 38 TC 2 Z9 2 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD DEC PY 2014 VL 1 IS 4 BP 319 EP 322 DI 10.1089/lgbt.2014.0020 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QK UT WOS:000361691400013 PM 26789859 ER PT J AU Berger, AH Brooks, AN Imielinski, M Cherniack, A Duke, F Kaplan, N Wala, J Meyerson, M AF Berger, Alice H. Brooks, Angela N. Imielinski, Marcin Cherniack, Andrew Duke, Fujiko Kaplan, Nathan Wala, Jeremiah Meyerson, Matthew TI NF1, MET, and RIT1 mutations are RAS-pathway driver events in lung adenocarcinoma SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Berger, Alice H.; Brooks, Angela N.; Imielinski, Marcin; Cherniack, Andrew; Duke, Fujiko; Wala, Jeremiah] Broad Inst, Cambridge, MA USA. [Kaplan, Nathan; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 SU 12 MA PR08 DI 10.1158/1557-3125.RASONC14-PR08 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000119 ER PT J AU Chen, Z Weisberg, E Cheng, K Kung, AL Bradner, J Griffin, J Wong, KK AF Chen, Zhao Weisberg, Ellen Cheng, Katherine Kung, Andrew L. Bradner, James Griffin, James Wong, Kwok-Kin TI Improve MEK/ERK targeting in mutant KRAS lung cancer SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Chen, Zhao; Weisberg, Ellen; Cheng, Katherine; Bradner, James; Griffin, James; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kung, Andrew L.] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 SU 12 MA B01 DI 10.1158/1557-3125.RASONC14-B01 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000052 ER PT J AU Cichowski, K AF Cichowski, Karen TI Developing therapies for Rasdriven cancers SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Cichowski, Karen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ludwig Ctr,Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 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 DEC PY 2014 VL 12 SU 12 MA IA02 DI 10.1158/1557-3125.RASONC14-IA02 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000097 ER PT J AU Hahn, WC AF Hahn, William C. TI Systematic functional genomics and KRAS SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 SU 12 MA IA08 DI 10.1158/1557-3125.RASONC14-IA08 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000102 ER PT J AU Haigis, KM AF Haigis, Kevin M. TI Regulation of K-Ras function by lysine acetylation SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Haigis, Kevin M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 SU 12 MA IA03 DI 10.1158/1557-3125.RASONC14-IA03 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000098 ER PT J AU Hunter, J Lim, SM Ficcarro, SB Choi, HG Gurbani, D Xie, T Marto, JA Gray, NS Westover, K AF Hunter, John Lim, Sang Min Ficcarro, Scott B. Choi, Hwan Geun Gurbani, Deepak Xie, Ting Marto, Jarrod A. Gray, Nathanael S. Westover, Ken TI Crystal structure of K-Ras G12C bound to an active site inhibitor SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Hunter, John; Gurbani, Deepak; Westover, Ken] UT Southwestern Med Ctr, Dallas, TX USA. [Lim, Sang Min; Ficcarro, Scott B.; Choi, Hwan Geun; Xie, Ting; Marto, Jarrod A.; Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2014 VL 12 SU 12 MA PR07 DI 10.1158/1557-3125.RASONC14-PR07 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000118 ER PT J AU Leshchiner, ES Bellairs, J Bird, GH Opoku-Nsiah, K Godes, M Walensky, LD AF Leshchiner, Elizaveta S. Bellairs, Joseph Bird, Gregory H. Opoku-Nsiah, Kwadwo Godes, Marina Walensky, Loren D. TI Direct inhibition of oncogenic KRAS by hydrocarbon- stapled SOS1 helices SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Leshchiner, Elizaveta S.; Bellairs, Joseph; Bird, Gregory H.; Opoku-Nsiah, Kwadwo; Godes, Marina; Walensky, Loren D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2014 VL 12 SU 12 MA B41 DI 10.1158/1557-3125.RASONC14-B41 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000081 ER PT J AU Ganske, I Hoyler, M Fox, SE Morris, DJ Lin, SJ Slavin, SA AF Ganske, Ingrid Hoyler, Marguerite Fox, Sharon E. Morris, Donald J. Lin, Samuel J. Slavin, Sumner A. TI Delayed Hypersensitivity Reaction to Acellular Dermal Matrix in Breast Reconstruction The Red Breast Syndrome? SO ANNALS OF PLASTIC SURGERY LA English DT Article ID ALLODERM PERFORMANCE; SURGERY; COMPLICATIONS; IRRADIATION; INFECTION AB Background Acellular dermal matrix (ADM) has become a valuable tool in reconstructive breast surgery, in part because it has been considered to be a non-reactive and non-immunogenic entity. However, some patients who undergo breast reconstruction with ADMs develop postoperative erythema overlying their ADM grafts. The etiology of this phenomenon is poorly understood. Methods In this article, we summarize clinical cases in which patients developed localized breast erythema following reconstruction with ADMs. We review what is known about postoperative breast erythema after ADM-based breast reconstructions and the possible antigenicity of biologic mesh implants. Results We report 4 implant-based breast reconstruction patients who developed erythematous reactions overlying the region where ADM was placed: one demonstrated a delayed-type hypersensitivity reaction on punch biopsy of the affected skin, leading to removal of the biologic product; 2 others had a similar clinical presentation that responded to corticosteroids without removal of the biologic material, with 1 patient experiencing recrudescence of erythema that responded fully to a second course of corticosteroids; and a fourth showed erythema that was only moderately responsive to antibiotic therapy but which improved consistently after the patient initiated chemotherapy. Conclusion We propose that the etiology of erythema overlying ADM grafts, and the so-called red breast syndrome, may in some patients be a delayed-type hypersensitivity reaction to the ADM product. Affected patients may benefit from treatment with corticosteroids or similar medications, and that such treatment may, in some cases, enable patients to retain the ADM grafts and enable salvage of the reconstructed breast. C1 [Ganske, Ingrid] Harvard Combined Plast Surg Residency, Boston, MA USA. [Hoyler, Marguerite] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Sharon E.] Beth Israel Deaconess Med Ctr Pathol Residency, Boston, MA USA. [Morris, Donald J.; Lin, Samuel J.; Slavin, Sumner A.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast Surg, Boston, MA 02215 USA. RP Slavin, SA (reprint author), 1101 Beacon St,Suite 7E, Brookline, MA USA. EM ssbsj@aol.com NR 22 TC 5 Z9 6 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-7043 EI 1536-3708 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD DEC PY 2014 VL 73 SU 2 BP S139 EP S143 DI 10.1097/SAP.0000000000000130 PG 5 WC Surgery SC Surgery GA CQ4HU UT WOS:000360566300005 PM 24691314 ER PT J AU Kaida, A Matthews, LT Ashaba, S Tsai, AC Kanters, S Robak, M Psaros, C Kabakyenga, J Boum, Y Haberer, JE Martin, JN Hunt, PW Bangsberg, DR AF Kaida, Angela Matthews, Lynn T. Ashaba, Scholastic Tsai, Alexander C. Kanters, Steve Robak, Magdalena Psaros, Christina Kabakyenga, Jerome Boum, Yap Haberer, Jessica E. Martin, Jeffrey N. Hunt, Peter W. Bangsberg, David R. TI Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE depression; pregnancy; postpartum; perinatal; HIV infection; antiretroviral therapy; mental health; maternal health; Uganda ID CD4 CELL COUNT; HOPKINS SYMPTOM CHECKLIST-25; COMMON MENTAL-DISORDERS; RURAL UGANDA; GLOBAL BURDEN; MATERNAL DEPRESSION; TREATING DEPRESSION; SEROPOSITIVE WOMEN; INCOME COUNTRIES; POSITIVE WOMEN AB Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18-49 years) initiating ART in rural Uganda (2005-2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (012 months post-pregnancy outcome), or non-pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27-37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95-245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and "never married" were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non-pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health. C1 [Kaida, Angela] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Matthews, Lynn T.; Tsai, Alexander C.; Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ashaba, Scholastic; Tsai, Alexander C.; Kabakyenga, Jerome; Boum, Yap; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Robak, Magdalena; Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Div Global Psychiat, Boston, MA 02114 USA. [Kanters, Steve] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Psaros, Christina] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Boum, Yap] Epictr Mbarara, Mbarara, Uganda. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kaida, A (reprint author), Simon Fraser Univ, Fac Hlth Sci, Blusson Hall Room 10522,8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM kangela@sfu.ca FU US National Institutes of Health [R21HD069194, R01MH054907, P30AI027763, U01CA066529]; Sullivan Family Foundation; Canadian Institutes of Health Research (CIHR) doctoral research award; [K23MH095655]; [K23MH096620]; [K23MH096651]; [K24MH087227] FX Supported by the US National Institutes of Health R21HD069194, R01MH054907, P30AI027763, and U01CA066529; and the Sullivan Family Foundation. L.T.M. received support from K23MH095655, A.C.T. received support from K23MH096620, S.K. received support from a Canadian Institutes of Health Research (CIHR) doctoral research award, C.P. received support from K23MH096651, and D.R.B. received support from K24MH087227. NR 85 TC 4 Z9 4 U1 2 U2 4 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 DEC 1 PY 2014 VL 67 SU 4 BP S179 EP S187 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CH6BM UT WOS:000354120600003 PM 25436816 ER PT J AU Matthews, LT Milford, C Kaida, A Ehrlich, MJ Ng, C Greener, R Mosery, FN Harrison, A Psaros, C Safren, SA Bajunirwe, F Wilson, IB Bangsberg, DR Smit, JA AF Matthews, Lynn T. Milford, Cecilia Kaida, Angela Ehrlich, Matthew J. Ng, Courtney Greener, Ross Mosery, F. N. Harrison, Abigail Psaros, Christina Safren, Steven A. Bajunirwe, Francis Wilson, Ira B. Bangsberg, David R. Smit, Jennifer A. TI Lost Opportunities to Reduce Periconception HIV Transmission: Safer Conception Counseling By South African Providers Addresses Perinatal but not Sexual HIV Transmission SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE safer conception; client-provider communication; HIV prevention; South Africa ID REPRODUCTIVE DECISION-MAKING; ANTIRETROVIRAL THERAPY; DISCORDANT COUPLES; SERODISCORDANT COUPLES; FERTILITY INTENTIONS; INFECTED INDIVIDUALS; PROSPECTIVE COHORT; RISK BEHAVIOR; WOMEN; MEN AB Introduction: Safer conception strategies create opportunities for HIV-serodiscordant couples to realize fertility goals and minimize periconception HIV transmission. Patient-provider communication about fertility goals is the first step in safer conception counseling. Methods: We explored provider practices of assessing fertility intentions among HIV-infected men and women, attitudes toward people living with HIV (PLWH) having children, and knowledge and provision of safer conception advice. We conducted in-depth interviews (9 counselors, 15 nurses, 5 doctors) and focus group discussions (6 counselors, 7 professional nurses) in eThekwini District, South Africa. Data were translated, transcribed, and analyzed using content analysis with NVivo10 software. Results: Among 42 participants, median age was 41 (range, 28-60) years, 93% (39) were women, and median years worked in the clinic was 7 (range, 1-27). Some providers assessed women's, not men's, plans for having children at antiretroviral therapy initiation, to avoid fetal exposure to efavirenz. When conducted, reproductive counseling included CD4 cell count and HIV viral load assessment, advising mutual HIV status disclosure, and referral to another provider. Barriers to safer conception counseling included provider assumptions of HIV seroconcordance, low knowledge of safer conception strategies, personal feelings toward PLWH having children, and challenges to tailoring safer sex messages. Conclusions: Providers need information about HIV serodiscordance and safer conception strategies to move beyond discussing only perinatal transmission and maternal health for PLWH who choose to conceive. Safer conception counseling may be more feasible if the message is distilled to delaying conception attempts until the infected partner is on antiretroviral therapy. Designated and motivated nurse providers may be required to provide comprehensive safer conception counseling. C1 [Matthews, Lynn T.; Ng, Courtney; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.; Ng, Courtney; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Milford, Cecilia; Greener, Ross; Mosery, F. N.; Smit, Jennifer A.] Univ Witwatersrand, MatCH Res Maternal Adolescent & Child Hlth Res, Dept Obstet & Gynaecol, Fac Hlth Sci, Durban, South Africa. [Kaida, Angela] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Ehrlich, Matthew J.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. [Matthews, Lynn T.; Psaros, Christina; Safren, Steven A.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Harrison, Abigail] Brown Univ, Dept Behav & Social Sci, Sch Publ Hlth, Providence, RI 02912 USA. [Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bajunirwe, Francis] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Wilson, Ira B.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Smit, Jennifer A.] Univ KwaZulu Natal, Sch Pharm & Pharmacol, Fac Hlth Sci, Durban, South Africa. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU NICHD [R03-HD072602]; Canada-Sub-Saharan Africa HIV/AIDS Network (CANSSA); NIH [K23 MH095655, K24MH87227, K24MH094214, K23MH096651]; Harvard CFAR [P30 AI060354] FX Supported by the NICHD (R03-HD072602) and the Canada-Sub-Saharan Africa HIV/AIDS Network (CANSSA). The analysis was also supported by NIH grants K23 MH095655, K24MH87227, K24MH094214, K23MH096651, and the Harvard CFAR (P30 AI060354). NR 43 TC 19 Z9 19 U1 1 U2 5 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 DEC 1 PY 2014 VL 67 SU 4 BP S210 EP S217 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CH6BM UT WOS:000354120600007 PM 25436820 ER PT J AU Arora, S Yan, H Fan, H Cho, I Luo, B Gai, X Zhou, Y Handorf, E Andrakes, MD Golemis, EA Nicolas, E Yen, TY Hall, M Enders, GH AF Arora, S. Yan, H. Fan, H. Cho, I. Luo, B. Gai, X. Zhou, Y. Handorf, E. Andrake, M. D. Golemis, E. A. Nicolas, E. Yen, T. Y. Hall, M. Enders, G. H. TI CONSTITUTIONAL PREDISPOSITION TO DNA DOUBLE STRAND BREAKS DEFINES A NEW CLASS OF FAMILIAL COLON CANCER. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Arora, S.; Yan, H.; Enders, G. H.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. [Fan, H.; Cho, I.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Luo, B.] Fox Chase Canc Ctr, Inst Personalized Med, Philadelphia, PA 19111 USA. [Gai, X.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol, Boston, MA USA. [Zhou, Y.; Handorf, E.] Fox Chase Canc Ctr, Epidemiol & Biostat, Philadelphia, PA 19111 USA. [Andrake, M. D.] Fox Chase Canc Ctr, Mol Modeling Facil, Philadelphia, PA 19111 USA. [Golemis, E. A.; Yen, T. Y.] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA. [Nicolas, E.] Fox Chase Canc Ctr, Genotyping & Real Time PCR, Philadelphia, PA 19111 USA. [Hall, M.] Fox Chase Canc Ctr, Med Oncol & Clin Genet, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1110 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102355 ER PT J AU Florian, S Chittajallu, DR Kohler, RH Orth, JD Weissleder, R Danuser, G Mitchison, TJ AF Florian, S. Chittajallu, D. R. Kohler, R. H. Orth, J. D. Weissleder, R. Danuser, G. Mitchison, T. J. TI Intravital microscopy suggests that induction of mitotic arrest by antimitotic cancer drugs does not predict their efficacy in fibrosarcoma mouse xenograft tumors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Florian, S.; Weissleder, R.; Mitchison, T. J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Chittajallu, D. R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Kohler, R. H.; Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Orth, J. D.] Univ Colorado, MCD Biol, Boulder, CO 80309 USA. [Danuser, G.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA M19 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106068 ER PT J AU Florian, S Chittajallu, DR Kohler, RH Orth, JD Weissleder, R Danuser, G Mitchison, TJ AF Florian, S. Chittajallu, D. R. Kohler, R. H. Orth, J. D. Weissleder, R. Danuser, G. Mitchison, T. J. TI Intravital microscopy suggests that induction of mitotic arrest by antimitotic cancer drugs does not predict their efficacy in fibrosarcoma mouse xenograft tumors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Florian, S.; Weissleder, R.; Mitchison, T. J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Chittajallu, D. R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Kohler, R. H.; Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Orth, J. D.] Univ Colorado, MCD Biol, Boulder, CO 80309 USA. [Danuser, G.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P139 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100140 ER PT J AU Gallegos, LL Ng, MR Sowa, ME White, A Selfors, L Zervantonakis, I Dhakal, S Singh, P Harper, JW Brugge, JS AF Gallegos, L. L. Ng, M. R. Sowa, M. E. White, A. Selfors, L. Zervantonakis, I. Dhakal, S. Singh, P. Harper, J. W. Brugge, J. S. TI A functional proteomic study identifies multiple novel regulators of epithelial cell-cell adhesion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Gallegos, L. L.; White, A.; Selfors, L.; Zervantonakis, I.; Dhakal, S.; Singh, P.; Harper, J. W.; Brugge, J. S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Ng, M. R.] Massachusetts Gen Hosp, Radiat Oncol, Boston, MA 02114 USA. [Sowa, M. E.] Warp Dr Bio LLC, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P574 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101202 ER PT J AU Lewis, WR Malarkey, EB Pasek, RC Porath, J Birket, SE Saunier, S Antignac, C Knowles, MR Zariwala, M Kesterson, B Rowe, SM Lechtreck, KF Drummond, IA Parant, JM Porter, ME Hildebrandt, F Yoder, BK Berbari, NF AF Lewis, W. R. Malarkey, E. B. Pasek, R. C. Porath, J. Birket, S. E. Saunier, S. Antignac, C. Knowles, M. R. Zariwala, M. Kesterson, B. Rowe, S. M. Lechtreck, K. F. Drummond, I. A. Parant, J. M. Porter, M. E. Hildebrandt, F. Yoder, B. K. Berbari, N. F. TI Growth Arrest Specific 8 Mutant Mouse Reveals a Conserved Role for Motile Cilia Function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lewis, W. R.; Malarkey, E. B.; Yoder, B. K.] Univ Alabama Birmingham, Cell Dev & Integrat Biol, Birmingham, AL USA. [Pasek, R. C.] Vanderbilt Univ, Cell & Dev Biol, Nashville, TN 37235 USA. [Porath, J.] Boston Childrens Hosp, Nephrol, Boston, MA USA. [Birket, S. E.; Rowe, S. M.] Univ Alabama Birmingham, Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Saunier, S.] Paris Descartes Univ, Paris, France. [Antignac, C.] Inst Natl Sante & Rech Med, Paris, France. [Knowles, M. R.; Zariwala, M.] Univ N Carolina, Pulm Res & Treatment Ctr, Cyst Fibrosis, Chapel Hill, NC USA. [Kesterson, B.] Univ Alabama Birmingham, Genet, Birmingham, AL USA. [Lechtreck, K. F.] Univ Georgia, Cellular Biol, Athens, GA 30602 USA. [Drummond, I. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Parant, J. M.] Univ Alabama Birmingham, Toxicol, Pharmacol, Birmingham, AL USA. [Porter, M. E.] Univ Minnesota, Sch Med, Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Hildebrandt, F.] Boston Childrens Hosp, Nephrol, Boston, MA USA. [Berbari, N. F.] Indiana Univ Purdue Univ, Biol, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1770 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104235 ER PT J AU Liu, M Bashir, M Williams, KJ Werth, VP AF Liu, M. Bashir, M. Williams, K. J. Werth, V. P. TI Novel roles for cholesterol and the cytoskeleton in the formation of neutrophil extracellular traps. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Liu, M.; Bashir, M.; Werth, V. P.] Univ Penn, Dermatol, Philadelphia, PA 19104 USA. [Liu, M.; Bashir, M.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Liu, M.; Williams, K. J.] Temple Univ, Med, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1678 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104143 ER PT J AU Marteil, G Guerrero, A Godinho, S Machado, P Loncarek, J Mendonca, S Fonseca, I Pellman, D Bettencourt-Dias, M AF Marteil, G. Guerrero, A. Godinho, S. Machado, P. Loncarek, J. Mendonca, S. Fonseca, I. Pellman, D. Bettencourt-Dias, M. TI Cancer-wide survey of centrosomes reveals centriole fragmentation as a novel origin of supernumerary centrosomes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Marteil, G.; Machado, P.; Mendonca, S.; Fonseca, I.; Bettencourt-Dias, M.] Gulbenkian Inst Sci, Oeiras, Portugal. [Guerrero, A.] Univ Nacl Autonoma Mexico, Inst Biotechnol, Oeiras, Portugal. [Godinho, S.] Barts Canc Inst, London, England. [Machado, P.] EMBL, Heidelberg, Germany. [Loncarek, J.] NCI, NIH, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. [Pellman, D.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1026 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102271 ER PT J AU Pellman, D Spektor, A Zhang, C Francis, J Meyerson, M AF Pellman, D. Spektor, A. Zhang, C. Francis, J. Meyerson, M. TI Complex chromosomal rearrangements from the missegregation of intact chromosomes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Pellman, D.; Spektor, A.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Zhang, C.; Francis, J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1847 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104306 ER PT J AU Webster, MR Xu, M Kinzler, KA Kaur, A Appleton, J O'Connell, MP Marchbank, K Valiga, A Dang, VM Perego, M Zang, G Slipicevic, A Keeney, F Lehrmann, E Wood, W Becker, K Kossenkov, A Frederick, D Flaherty, K Xu, X Herlyn, M Murphy, ME Weeraratna, AT AF Webster, M. R. Xu, M. Kinzler, K. A. Kaur, A. Appleton, J. O'Connell, M. P. Marchbank, K. Valiga, A. Dang, V. M. Perego, M. Zang, G. Slipicevic, A. Keeney, F. Lehrmann, E. Wood, W., III Becker, K. Kossenkov, A. Frederick, D. Flaherty, K. Xu, X. Herlyn, M. Murphy, M. E. Weeraratna, A. T. TI Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Webster, M. R.; Kaur, A.; Appleton, J.; O'Connell, M. P.; Marchbank, K.; Valiga, A.; Dang, V. M.; Perego, M.; Zang, G.; Slipicevic, A.; Herlyn, M.; Weeraratna, A. T.] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis, Philadelphia, PA 19104 USA. [Xu, M.; Kinzler, K. A.; Lehrmann, E.; Wood, W., III; Becker, K.] NIA, Baltimore, MD 21224 USA. [Keeney, F.] Wistar Inst Anat & Biol, Microscopy, Philadelphia, PA 19104 USA. [Kossenkov, A.] Wistar Inst Anat & Biol, Bioinformat, Philadelphia, PA 19104 USA. [Frederick, D.; Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Xu, X.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Murphy, M. E.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1878 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104325 ER PT J AU Zhang, H Li, H Ganem, N Pellman, D AF Zhang, H. Li, H. Ganem, N. Pellman, D. TI Epigenetic downregulation of SPINT2 in aneuploidy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Zhang, H.; Li, H.; Pellman, D.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Ganem, N.] Boston Univ, Sch Med, Canc Ctr, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1935 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104382 ER PT J AU Wang, MC Oakley, HD Carr, CE Sowa, JN Ruvkun, G AF Wang, Meng C. Oakley, Holly D. Carr, Christopher E. Sowa, Jessica N. Ruvkun, Gary TI Gene Pathways That Delay Caenorhabditis elegans Reproductive Senescence SO PLOS GENETICS LA English DT Article ID DROSOPHILA-MELANOGASTER; NATURAL MENOPAUSE; LIFE-SPAN; CORRELATED RESPONSES; C-ELEGANS; AGE; SELECTION; MOTHERS; HERITABILITY; MORTALITY AB Reproductive senescence is a hallmark of aging. The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood. From a full genome RNA interference (RNAi) screen, we identified 32 Caenorhabditis elegans gene inactivations that delay reproductive senescence and extend reproductive lifespan. We found that many of these gene inactivations interact with insulin/IGF-1 and/or TGF-beta endocrine signaling pathways to regulate reproductive senescence, except nhx-2 and sgk-1 that modulate sodium reabsorption. Of these 32 gene inactivations, we also found that 19 increase reproductive lifespan through their effects on oocyte activities, 8 of them coordinate oocyte and sperm functions to extend reproductive lifespan, and 5 of them can induce sperm humoral response to promote reproductive longevity. Furthermore, we examined the effects of these reproductive aging regulators on somatic aging. We found that 5 of these gene inactivations prolong organismal lifespan, and 20 of them increase healthy life expectancy of an organism without altering total life span. These studies provide a systemic view on the genetic regulation of reproductive senescence and its intersection with organism longevity. The majority of these newly identified genes are conserved, and may provide new insights into age-associated reproductive senescence during human aging. C1 [Wang, Meng C.; Oakley, Holly D.; Sowa, Jessica N.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Wang, Meng C.; Oakley, Holly D.; Sowa, Jessica N.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wang, Meng C.; Carr, Christopher E.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Wang, Meng C.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Carr, Christopher E.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA USA. RP Wang, MC (reprint author), Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. EM wmeng@bcm.edu; ruvkun@molbio.mgh.harvard.edu FU National Institute of Health [RO0AG034988, RO1AG045183, R37AG014161]; Ellison Medical Foundation [AG-NS-0756-11]; Burroughs Wellcome Fund FX This study was funded by National Institute of Health grant RO0AG034988 (MCW), RO1AG045183 (MCW), R37AG014161 (GR), http://www.nih.gov, The Ellison Medical Foundation grant AG-NS-0756-11 (MCW), http://www.ellisonfoundation.org, and The Burroughs Wellcome Fund (JNS). http://www.bwfund.org. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 6 Z9 6 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2014 VL 10 IS 12 AR e1004752 DI 10.1371/journal.pgen.1004752 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900004 PM 25474471 ER PT J AU Erlendsson, AM Anderson, RR Manstein, D Waibel, JS AF Erlendsson, Andres M. Anderson, R. Rox Manstein, Dieter Waibel, Jill S. TI Developing Technology: Ablative Fractional Lasers Enhance Topical Drug Delivery SO DERMATOLOGIC SURGERY LA English DT Article ID BASAL-CELL CARCINOMA; PHOTODYNAMIC THERAPY; TRANSDERMAL DELIVERY C1 [Erlendsson, Andres M.; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Erlendsson, Andres M.] Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen NV, Denmark. [Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Waibel, Jill S.] Miami Dermatol & Laser Inst, Miami, FL USA. RP Erlendsson, AM (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,Their 2, Boston, MA 02114 USA. EM andres.erlendsson@gmail.com FU Alma; L'Oreal; Lumenis; Sciton/Candela; Harvest Technologies/Solta FX Laser equipment loaned by Lumenis Inc. J. S. Waibel has received research grants from Alma, L'Oreal, Lumenis, Sciton/Candela, and Harvest Technologies/Solta. The other authors have indicated no significant interest with commercial supporters. NR 12 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 2014 VL 40 IS 12 SU S BP S142 EP S146 DI 10.1097/DSS.0000000000000207 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA CD4MU UT WOS:000351057900005 PM 25417565 ER PT J AU Shelton, JB Skolarus, TA Ordin, D Malin, J Antonio, A Ryoo, J Saigal, CS AF Shelton, Jeremy B. Skolarus, Ted A. Ordin, Diana Malin, Jennifer Antonio, AnnaLiza Ryoo, Joan Saigal, Christopher S. TI Validating Electronic Cancer Quality Measures at Veterans Health Administration SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SURGERY REPORT CARDS; MEDICAL-RECORDS; PROSTATE-CANCER; CLINICAL-DATA; PERFORMANCE; DELIVERY; VALIDITY; AFFAIRS; REFORM AB Objectives To assess the feasibility and validity of developing electronic clinical quality measures (eCQMs) of cancer care quality from existing metrics, using electronic health records, administrative, and cancer registry data. Study Design Retrospective comparison of quality indicators using chart abstracted versus electronically available data from multiple sources. Methods We compared the sensitivity and specificity of eCQMs created from structured data from electronic health records (EHRs) linked to administrative and cancer registry data to data abstracted from patients' electronic health records. Twenty-nine measures of care were assessed in 15,394 patients with either incident lung or prostate cancer from 2007 and 2008, respectively, and who were treated in the Veteran's Health Administration (VHA). Results It was feasible to develop eCQMs for 11 of 18 (61%) lung cancer measures, 4 (22%) of which were considered to be valid measures of the care constructs. Among prostate cancer measures, 6 of 11 (55%) were feasible, and 4 (36%) were both feasible and valid. Of the 29 metrics, data was available to create eCQMs for 17 (59%) cancer care metrics, and 8 (28%) were considered valid. Conclusions In a large integrated healthcare system with nationally standardized electronic health records, administrative, and cancer registry data, 28% of cancer quality measures developed for chart abstraction could be translated into valid eCQMs. These results raise much concern about the development of electronic clinical quality measures for cancer care, particularly in healthcare environments where data are disparate in both form and location C1 [Antonio, AnnaLiza] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shelton, Jeremy B.] VA Greater Los Angeles Healthcare Syst, Urol, Informat, HSR&D, Los Angeles, CA USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Oncol, Los Angeles, CA USA. [Skolarus, Ted A.] Univ Michigan, VA Ann Arbor Healthcare Syst, Urol, HSR&D, Ann Arbor, MI 48109 USA. [Ordin, Diana] VA, Washington, DC USA. [Ryoo, Joan] Kaiser Permanente Med Ctr, Los Angeles, CA 90034 USA. [Saigal, Christopher S.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Shelton, JB (reprint author), Vet Affairs Surg, 13301 Wilshire Blvd,Bldg 500, Los Angeles, CA 90073 USA. EM jeremy.shelton@va.gov FU Veterans Affairs Office of Analytics and Business Intelligence; UCLA Career Development Program in Cancer Prevention and Control Research R25 Grant [CA 087949-13] FX This study was funded by the Veterans Affairs Office of Analytics and Business Intelligence. This study was supported in part by the UCLA Career Development Program in Cancer Prevention and Control Research R25 Grant CA 087949-13 (JBS). NR 42 TC 1 Z9 1 U1 2 U2 3 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2014 VL 20 IS 12 BP 1041 EP + PG 16 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3TS UT WOS:000351005400013 PM 25526392 ER PT J AU Cutler, C AF Cutler, Corey TI Timing of allogeneic stem cell transplantation for myelodysplastic syndromes and aplastic anemia SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID MARROW-TRANSPLANTATION; DECISION-ANALYSIS; OLDER PATIENTS; AZACITIDINE; FLUDARABINE; MDS; AGE; ALEMTUZUMAB; REGIMENS; LEUKEMIA AB Allogeneic hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) is a potentially curative procedure, but is associated with a significant risk of morbidity and mortality. With the recent approval of disease-modifying agents, the appropriate timing of allogeneic HSCT needs to be addressed. Similarly, the optimal use of these disease-modifying agents before HSCT needs to be determined. In severe aplastic anemia, HSCT is a proven cure, but HLA-matched sibling donors are found in fewer than 25% of newly diagnosed patients. The use of early unrelated donor HSCT is an evolving concept that will become more accepted as improvements in HSCT outcomes continue. C1 [Cutler, Corey] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Cutler, C (reprint author), Harvard Univ, Dana Farber Canc Inst, Div Hematol Malignancies, Med,Med Sch, 450 Brookline Ave, Boston, MA 02215 USA. EM corey_cutler@dfci.harvard.edu NR 27 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 77 EP 81 DI 10.1182/asheducation-2014.1.77 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600011 ER PT J AU Harris, NL AF Harris, Nancy Lee TI Indolent lymphoma: follicular lymphoma and the microenvironment-insights from the microscope SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID REGULATORY T-CELLS; CENTER B-CELLS; DEPENDENT ANTIBODY-RESPONSES; TUMOR-ASSOCIATED MACROPHAGES; GERMINAL CENTER RESPONSE; NON-HODGKIN-LYMPHOMA; IN-VIVO EXPRESSION; SOMATIC HYPERMUTATION; COSTIMULATORY MOLECULE; MONOCLONAL-ANTIBODIES AB Follicular lymphomas (FLs) are neoplasms of germinal center (GC) B cells, which retain many of the morphologic, immunophenotypic, genetic, and functional features of normal GC B cells. Both normal GCs and neoplastic follicles of FL also contain non-neoplastic cells (microenvironment) that influence and are influenced by the GC and FL B cells and are likely important for tumor cell survival. Many insights into the nature of the GC/FL microenvironment have come from morphologic and immunophenotypic analysis, both before and after the discoveries from gene expression profiling. This chapter reviews what we have learned from the microscope and highlights the pitfalls involved in trying to enumerate cells in the microenvironment for clinical prognostication. C1 [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, Nancy Lee] Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Mailstop Warren Bldg,Rm 219, Boston, MA 02114 USA. EM nlharris@partners.org NR 71 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 158 EP 162 DI 10.1182/asheducation-2014.1.158 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600022 ER PT J AU Silverman, LB AF Silverman, Lewis B. TI Balancing cure and long-term risks in acute lymphoblastic leukemia SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID FARBER-CANCER-INSTITUTE; CHILDRENS ONCOLOGY GROUP; ACUTE MYELOID-LEUKEMIA; JUDE LIFETIME COHORT; CHILDHOOD-CANCER; CRANIAL IRRADIATION; DOXORUBICIN THERAPY; LATE CARDIOTOXICITY; RANDOMIZED-TRIAL; ADULT SURVIVORS AB Cure rates for children and adolescents with acute lymphoblastic leukemia (ALL) have improved dramatically over the last few decades. With this success has come increasing recognition of the adverse late effects of treatment. The significant long-term sequelae in the earliest cohort of long-term survivors treated in the 1970s and 1980s are well documented. To reduce the incidence of these late effects, the majority of pediatric patients treated on more contemporary regimens receive less intensive treatment than did those treated 30-40 years ago. However, current therapies are not risk free; children treated with contemporary regimens remain at risk for developing long-term toxicities, including cardiac dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms. One of the great challenges facing clinical investigators today is to identify interventions that will reduce the frequency and severity of long-term toxicities without adversely affecting cure rates. The use of dexrazoxane as a cardioprotectant (to prevent anthracycline-associated cardiotoxicity) and alternate-week dosing of dexamethasone (to reduce the risk of osteonecrosis) are examples of 2 such successful strategies. This article provides an overview of the long-term toxicities associated with current therapies and reviews results of clinical trials designed to minimize the burden of cure in long-term survivors. C1 [Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Silverman, Lewis B.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM lewis_silverman@dfci.harvard.edu NR 49 TC 0 Z9 0 U1 4 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 190 EP 197 PG 8 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600027 ER PT J AU Sison, EAR Silverman, LB AF Sison, Edward Allan R. Silverman, Lewis B. TI CNS prophylaxis in pediatric acute lymphoblastic leukemia SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Review ID CRANIAL IRRADIATION; OUTCOMES; CHILDREN; THERAPY; TRIAL AB ` C1 [Sison, Edward Allan R.] Baylor Coll Med, Texas Childrens Canc & Hematol Ctr, Sect Pediat Hematol Oncol, Houston, TX 77030 USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Silverman, Lewis B.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA USA. RP Sison, EAR (reprint author), Texas Childrens Canc & Hematol Ctr, Pediat Hematol Oncol, 6701 Fannin St,Suite 1510, Houston, TX 77030 USA. EM ersison@txch.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 198 EP 201 DI 10.1182/asheducation-2014.1.198 PG 4 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600028 ER PT J AU Richardson, PG Laubach, JP Munshi, NC Anderson, KC AF Richardson, Paul G. Laubach, Jacob P. Munshi, Nikhil C. Anderson, Kenneth C. TI Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all? SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; THALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED PHASE-3; AUTOLOGOUS TRANSPLANTATION; STANDARD CHEMOTHERAPY; CONSOLIDATION THERAPY; INDUCTION TREATMENT; INITIAL TREATMENT; ELIGIBLE PATIENTS AB For the last 20 years, high-dose therapy with autologous stem cell transplantation (ASCT) for multiple myeloma has been considered a standard frontline treatment for younger patients with adequate organ function. With the introduction of novel agents, specifically thalidomide, bortezomib, and lenalidomide, the role of ASCT has changed in several ways. First, novel agents have been incorporated successfully as induction regimens, increasing the response rate before ASCT, and are now being used as part of both consolidation and maintenance with the goal of extending progression-free and overall survival. These approaches have shown considerable promise with significant improvements in outcome. Furthermore, the efficacy of novel therapeutics has also led to the investigation of these agents upfront without the immediate application of ASCT, and compelling preliminary results have been reported. Next-generation novel agents and the use of monoclonal antibodies have raised the possibility of not only successful salvage strategies to facilitate delayed transplantation for younger patients, but also the prospect of an nontransplantation approach achieving the same outcome. Moreover, this could be achieved without incurring acute toxicity or long-term complications that are inherent to high-dose alkylation, and melphalan exposure in particular. At present, the role of ASCT has therefore become an area of debate: should it be used upfront in all eligible patients, or should it be used as a salvage treatment at the time of progression for patients achieving a high quality of response with initial therapy? There is a clear need to derive a consensus that is useful for clinicians considering both protocol-directed and non-protocol-directed options for their patients. Participation in ongoing prospective randomized trials is considered vital. While preliminary randomized data from studies in Europe favor early ASCT with novel agents, differences in both agents and the combinations used, as well as limited information on overall survival and benefit for specific patient subsets, suggest that one size does not fit all. Specifically, the optimal approach to treatment of younger patients eligible for ASCT remains a key area for further research. A rigid approach to its use outside of a clinical study is difficult to justify and participation in prospective studies should be a priority. C1 [Richardson, Paul G.; Laubach, Jacob P.; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu FU R.J. Corman Multiple Myeloma Research Fund FX This work was supported in part by the R.J. Corman Multiple Myeloma Research Fund. The authors gratefully acknowledge the invaluable contribution of Michelle Maglio in the preparation of this manuscript. NR 57 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 255 EP 261 DI 10.1182/asheducation-2014.1.255 PG 7 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600037 ER PT J AU Sabatine, MS Mega, JL AF Sabatine, Marc S. Mega, Jessica L. TI Pharmacogenomics of antiplatelet drugs SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; CLOPIDOGREL PLATELET REACTIVITY; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; CYP2C19 GENOTYPE; STENT THROMBOSIS; CLINICAL-OUTCOMES; CARDIOVASCULAR EVENTS; GENETIC POLYMORPHISMS AB Clopidogrel, a platelet P2Y(12) inhibitor, is one of the most widely prescribed drugs in cardiovascular medicine because it reduces ischemic and thrombotic complications. It is a prodrug requiring biotransformation into the active metabolite by the hepatic cytochrome 450 system, especially the CYP2C19 enzyme. Candidate gene studies and genome-wide association studies have identified loss-of-function CYP2C19 variants to be associated with a diminished pharmacologic response. Specifically, compared with noncarriers, carriers of at least one copy of a loss-of-function CYP2C19 allele have similar to 30% lower levels of active clopidogrel metabolite and similar to 25% relatively less platelet inhibition with clopidogrel. Moreover, in patients treated with clopidogrel predominantly for percutaneous coronary intervention, carriers of 1 or 2 CYP2C19 loss-of-function alleles are at increased risk for major adverse cardiovascular outcomes, with an similar to 1.5-fold increase in the risk of cardiovascular death, myocardial infarction, or stroke as well as an similar to 3-fold increase in risk for stent thrombosis. Tripling the dose of clopidogrel in carriers of a CYP2C19 loss-of-function allele can achieve on-treatment platelet reactivity comparable to that seen with the standard 75 mg dose in wild-type individuals, but the impact on clinical outcomes remains unknown. Alternatively, 2 third-generation P2Y(12) inhibitors are available: prasugrel and ticagrelor. These drugs are superior to clopidogrel in reducing ischemic outcomes and are unaffected by CYP2C19 loss-of-function alleles. C1 [Sabatine, Marc S.; Mega, Jessica L.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Sabatine, Marc S.; Mega, Jessica L.] Harvard Univ, Sch Med, Boston, MA USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU Abbott Laboratories; Amgen; AstraZeneca; AstraZeneca/Bristol Myers Squibb; Critical Diagnostics; Daiichi-Sankyo; Eisai; Genzyme; Intarcia; Merck; Roche Diagnsotics; Sanofi-Aventis; Takeda; Bayer Healthcare; Bristol-Myers Squibb; Daiichi Sankyo; Johnson Johnson; Accumetrics; Nanosphere; National Institutes of Health National Heart, Lung and Blood Institute FX Conflict-of-interest disclosures: M.S.S. has received research funding from Abbott Laboratories, Amgen, AstraZeneca, AstraZeneca/Bristol Myers Squibb, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, Intarcia, Merck, Roche Diagnsotics, Sanofi-Aventis, and Takeda and has received honoraria from Amgen, AstraZeneca, Intarcia, Sanofi-Aventis, Bristol-Myers Squibb, MyoKardia, Pfizer, and Zeus. J.L.M. has received research funding from Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Sanofi-Aventis, Accumetrics, Nanosphere, and the National Institutes of Health National Heart, Lung and Blood Institute and has consulted for WebMD and American Genomics. Off-label drug use: Clopidogrel at doses beyond the approved dose. NR 59 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 343 EP 347 DI 10.1182/asheducation-2014.1.343 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600050 ER PT J AU Levine, M Goldstein, JN AF Levine, Michael Goldstein, Joshua N. TI Bleeding complications of targeted oral anticoagulants: what is the risk? SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID ACUTE VENOUS THROMBOEMBOLISM; NONVALVULAR ATRIAL-FIBRILLATION; ACUTE CORONARY SYNDROME; MODERATE RENAL IMPAIRMENT; VITAMIN-K ANTAGONISTS; INTRACEREBRAL HEMORRHAGE; RANDOMIZED-TRIALS; WARFARIN; DABIGATRAN; RIVAROXABAN AB The vitamin K antagonists (VKAs) are a widely used class of agent to prevent thromboembolism. In recent years, numerous alternatives to VKAs have been developed, the target-specific oral anticoagulants (TSOACs), which are available in clinical practice. Currently available agents target thrombin and factor Xa. The most significant side effect of these agents, as with VKAs, is the development of bleeding complications. In this review, the risks of major bleeding complications with the TSOACs will be discussed. Data from meta-analyses, randomized controlled trials, and observational studies will be used to highlight bleeding complications associated with TSOACs and warfarin. We highlight the most common causes of major bleeding, GI and intracranial hemorrhage. C1 [Levine, Michael] Univ So Calif, Sect Med Toxicol, Dept Emergency Med, Los Angeles, CA USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgoldstein@partners.org RI Goldstein, Joshua/H-8953-2016 NR 60 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 504 EP 509 DI 10.1182/asheducation-2014.1.504 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600074 ER PT J AU Nikiforow, S Alyea, EP AF Nikiforow, Sarah Alyea, Edwin P. TI Maximizing GVL in allogeneic transplantation: role of donor lymphocyte infusions SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCIES; ADOPTIVE IMMUNOTHERAPY; CONDITIONING REGIMEN; MYELOGENOUS LEUKEMIA; LEUKOCYTE INFUSION; MULTIPLE-MYELOMA AB Donor lymphocyte infusions (DLIs) can induce complete and durable remissions in some patients with hematologic malignancies who have relapsed after allogeneic transplantation, providing definitive evidence of a GVL effect. Despite the great promise initially envisioned for DLI as a method to augment GVL after transplantation, it utility is limited by low response rates in diseases other than chronic myelogenous leukemia and by the development of GVHD, the principal complication of DLI. To maximize GVL potency while minimizing toxicity, cellular effectors active in GVL need to be elucidated. Insight into mechanisms of GVL, such as reversal of in situ T-cell exhaustion, may allow identification of patients who will respond to DLI based on the presence of tumor-infiltrating lymphocytes in the BM. Understanding the clinical factors that influence the effectiveness and abrogate the toxicity of DLI, such as cell dose and timing of DLI after transplantation, will allow further optimization of DLI. This chapter reviews novel strategies that maximize the GVL effect of DLI by enhancing activity while limiting toxicity. C1 [Nikiforow, Sarah; Alyea, Edwin P.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mailstop DA-02048, Boston, MA 02215 USA. EM edwin_alyea@dfci.harvard.edu NR 37 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 570 EP 575 DI 10.1182/asheducation-2014.1.570 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600086 ER PT J AU Sturmberg, J Lanham, HJ AF Sturmberg, Joachim Lanham, Holly J. TI Understanding health care delivery as a complex system Achieving best possible health outcomes for individuals and communities by focusing on interdependencies SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE complexity in health; efficient and effective health system; health care reform; health systems reform; non-linear dynamics; patient-centred care; person-centred medicine ID SOCIAL SUPPORT; MEDICAL HOMES; MORTALITY; CONSULTATION; LESSONS; ECOLOGY; CANCER AB Rationale, aims and objectives The concept of emergence offers a new way of thinking about multimorbidity and chronic disease. Results and conclusions Multimorbidity and chronic disease are the end results of ongoing perturbations and interconnected activities of simpler substructures that collectively constitute the complex adaptive superstructure known as us, the person or patient. Medical interventions cause perturbations of many different subsystems within the patient, hence they are not limited to the person's bodily function, but also affect his general health perception and his interactions with his external environments. Changes in these domains inevitably have consequences on body function, and close the feedback loop of illness/disease, recovery and regained health. C1 [Sturmberg, Joachim] Univ Newcastle, Dept Gen Practice, Newcastle, NSW 2260, Australia. [Lanham, Holly J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lanham, Holly J.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Sturmberg, J (reprint author), Univ Newcastle, Dept Gen Practice, Newcastle, NSW 2260, Australia. EM jp.sturmberg@gmail.com NR 45 TC 3 Z9 3 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 EI 1365-2753 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD DEC PY 2014 VL 20 IS 6 BP 1005 EP 1009 DI 10.1111/jep.12142 PG 5 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA CC6BS UT WOS:000350450200043 PM 24797788 ER PT J AU Ahamadani, FAB Louis, H Ugwi, P Hines, R Pomerleau, M Ahn, R Burke, TF Nelson, BD AF Ahamadani, F. A. B. Louis, H. Ugwi, P. Hines, R. Pomerleau, M. Ahn, R. Burke, T. F. Nelson, B. D. TI Perinatal health care in a conflict-affected setting: evaluation of health-care services and newborn outcomes at a regional medical centre in Iraq SO EASTERN MEDITERRANEAN HEALTH JOURNAL LA English DT Article ID CHALLENGES; INFECTION AB A field-based assessment was conducted to assess maternal and newborn health-care services, perinatal and newborn outcomes and associated risk factors at Bint Al-Huda Maternal and Newborn Teaching Hospital, a large referral hospital in southern Iraq. The multi-method approach used interviews, discussions, observation and review of perinatal and newborn outcome data. There is limited assessment of maternal vital signs, labour pattern, fetal response, and complications during pregnancy and labour. Perinatal and neonatal mortality rates are 27.4/1000 births and 30.9/1000 live births respectively. Associated neonatal mortality factors were gestational age < 37 weeks, male sex, birth weight < 2.5 kg, maternal age > 35 years, rural maternal residence and vaginal delivery. Improving birth outcomes in southern Iraq requires evidence-based clinical guidelines, additional supplies and equipment, quality improvement initiatives and in-service training. C1 [Ahamadani, F. A. B.] Bint Al Huda Maternal & Child Teaching Hosp, Dhi Qar Governorate, Nasiriyah, Iraq. [Louis, H.; Ugwi, P.; Hines, R.; Ahn, R.; Burke, T. F.; Nelson, B. D.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Pomerleau, M.] MGH Inst Hlth Profess, Boston, MA USA. [Ahn, R.; Burke, T. F.; Nelson, B. D.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, B. D.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com FU Iraq Regional Ministry of Health; International Children's Heart Foundation FX Iraq Regional Ministry of Health and the International Children's Heart Foundation. NR 16 TC 0 Z9 0 U1 1 U2 2 PU WHO EASTERN MEDITERRANEAN REGIONAL OFFICE PI NASR CITY, CAIRO PA P. O. BOX 7608, NASR CITY, CAIRO, EGYPT SN 1020-3397 EI 1687-1634 J9 E MEDITERR HEALTH J JI East Mediterr. Health J. PD DEC PY 2014 VL 20 IS 12 BP 789 EP 795 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CC8JP UT WOS:000350614800006 PM 25664517 ER PT J AU Hackney, M McKee, K AF Hackney, Madeleine McKee, Kathleen TI Community-based Adapted Tango Dancing for Individuals with Parkinson's Disease and Older Adults SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 94; Dance; tango; balance; pedagogy; dissemination; exercise; older adults; Parkinson's Disease; mobility impairments; falls ID PHYSICAL-ACTIVITY; BALANCE; IMPAIRMENT; MOVEMENT; GAIT; BEHAVIORS; EXERCISE; PROFILE; WALKING; STROKE AB Adapted tango dancing improves mobility and balance in older adults and additional populations with balance impairments. It is composed of very simple step elements. Adapted tango involves movement initiation and cessation, multi-directional perturbations, varied speeds and rhythms. Focus on foot placement, whole body coordination, and attention to partner, path of movement, and aesthetics likely underlie adapted tango's demonstrated efficacy for improving mobility and balance. In this paper, we describe the methodology to disseminate the adapted tango teaching methods to dance instructor trainees and to implement the adapted tango by the trainees in the community for older adults and individuals with Parkinson's Disease (PD). Efficacy in improving mobility (measured with the Timed Up and Go, Tandem stance, Berg Balance Scale, Gait Speed and 30 sec chair stand), safety and fidelity of the program is maximized through targeted instructor and volunteer training and a structured detailed syllabus outlining class practices and progression. C1 [Hackney, Madeleine] Emory Univ, Ctr Visual & Neurocognit Rehabil, Div Gen Med & Geriatr, Atlanta VAMC,Dept Med,Sch Med, Atlanta, GA 30322 USA. [McKee, Kathleen] Brigham & Womans Hosp, Harvard Neurol Residency Program, Boston, MA 02115 USA. [McKee, Kathleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McKee, K (reprint author), Brigham & Womans Hosp, Harvard Neurol Residency Program, Boston, MA 02115 USA. EM madeleine.hackney@gmail.com FU Dan and Merrie Boone Foundation; Emory Center for Injury Control; Emory Center for Health in Aging; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454]; Emory School of Medicine Discovery Program; Department of VA R&D Service Career Development Awards [E7108M, N0870W] FX We would like to thank the teachers, Ronda and Manuel Patino, and Gabriela Lopez of Tango Rio, Erik Renz, Sarah Kelley Kerr, Mark Needelman and Shelley Brooks. We also acknowledge volunteers Adrienne Wimberly, Allison Bascas, Marco Coelho, Dabin Choi, Carly DiLeo, Margaret Fang, Kevin Huang, Twinkle Mehta, Malije Obi, Mina Taheb, Diana Tiwari, Kedra Woodard, Dawa Tsering, Sabine Povian, Dhondup Tso King, Mylinh Vo, Rebecca Dillard and Marisa Warner. We acknowledge Medlock Gardens retirement community for providing space for the adapted tango workshop, Clairmont Oaks retirement community and Wesley Woods Towers for providing space for the interventions and we thank the administrative staff of each institution. We acknowledge Dr. William De L'Aune for statistical assistance. The study was supported by the Dan and Merrie Boone Foundation, the Emory Center for Injury Control, and the Emory Center for Health in Aging. This study was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Emory School of Medicine Discovery Program supported KE McKee, and Department of VA R&D Service Career Development Awards (E7108M and N0870W) supported ME Hackney. We would also like to thank Mr. Aaron Bozzorg. NR 40 TC 3 Z9 3 U1 3 U2 11 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2014 IS 94 AR e52066 DI 10.3791/52066 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB1AE UT WOS:000349358000023 ER PT J AU Mulki, L Sweigard, JH Connor, KM AF Mulki, Lama Sweigard, J. Harry Connor, Kip M. TI Assessing Leukocyte-endothelial Interactions Under Flow Conditions in an Ex Vivo Autoperfused Microflow Chamber Assay SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 94; Leukocyte recruitment; endothelium; flow chamber; adhesion; velocity; rolling; integrins; ex vivo ID SELECTIN GLYCOPROTEIN LIGAND-1; CELL-ADHESION; P-SELECTIN; NEUTROPHIL TRANSMIGRATION; INFLAMMATORY RESPONSE; KINETIC-ANALYSIS; IN-VITRO; AFFINITY; MOLECULES; BINDING AB Leukocyte-endothelial interactions are early and critical events in acute and chronic inflammation and can, when dysregulated, mediate tissue injury leading to permanent pathological damage. Existing conventional assays allow the analysis of leukocyte adhesion molecules only after the extraction of leukocytes from the blood. This requires the blood to undergo several steps before peripheral blood leukocytes (PBLs) can be ready for analysis, which in turn can stimulate PBLs influencing the research findings. The autoperfused micro flow chamber assay, however, allows scientists to study early leukocytes functional dysregulation using the systemic flow of a live mouse while having the freedom of manipulating a coated chamber. Through a disease model, the functional expression of leukocyte adhesion molecules can be assessed and quantified in a micro-glass chamber coated with immobilized endothelial adhesion molecules ex vivo. In this model, the blood flows between the right common carotid artery and left external jugular vein of a live mouse under anesthesia, allowing the interaction of native PBLs in the chamber. Real-time experimental analysis is achieved with the assistance of an intravital microscope as well as a Harvard Apparatus pressure device. The application of a flow regulator at the input point of the glass chamber allows comparable physiological flow conditions amongst the experiments. Leukocyte rolling velocity is the main outcome and is measured using the National Institutes of Health open-access software ImageJ. In summary, the autoperfused micro flow chamber assay provides an optimal physiological environment to study leukocytes endothelial interaction and allows researchers to draw accurate conclusions when studying inflammation. C1 [Mulki, Lama; Sweigard, J. Harry; Connor, Kip M.] Harvard Univ, Angiogenesis Lab, Dept Ophthalmol, Med Sch,Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Mulki, Lama] St Elizabeths Med Ctr, Brighton, MA 02135 USA. RP Connor, KM (reprint author), Harvard Univ, Angiogenesis Lab, Dept Ophthalmol, Med Sch,Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. EM kip_connor@meei.harvard.edu OI Connor, Kip/0000-0002-2048-9080 FU National Eye Institute of the National Institutes of Health [R01EY022084/S1, T32EY007145, P30EY014104]; Massachusetts Lions Eye Research Fund; Special Scholar Award from Research to Prevent Blindness FX Research reported in this publication was supported by National Eye Institute of the National Institutes of Health under award numbers: R01EY022084/S1 (KMC), T32EY007145 (HS) and P30EY014104. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Massachusetts Lions Eye Research Fund (K.M.C.) and a Special Scholar Award from Research to Prevent Blindness (to K.M.C.). NR 27 TC 0 Z9 0 U1 0 U2 3 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2014 IS 94 AR e52130 DI 10.3791/52130 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB1AE UT WOS:000349358000029 ER PT J AU Tenente, IM Tang, Q Moore, JC Langenau, DM AF Tenente, Ines M. Tang, Qin Moore, John C. Langenau, David M. TI Normal and Malignant Muscle Cell Transplantation into Immune Compromised Adult Zebrafish SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Immunology; Issue 94; zebrafish; immune compromised; transplantation; muscle; rhabdomyosarcoma; rag2(E450fs); rag2(fb101); fluorescent; transgenic ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-PROPAGATING CELLS; TRANSGENIC ZEBRAFISH; EMBRYONAL RHABDOMYOSARCOMA; BRACHYDANIO-RERIO; REGENERATION; FREQUENCY; MODEL; FISH; PATHWAY AB Zebrafish have become a powerful tool for assessing development, regeneration, and cancer. More recently, allograft cell transplantation protocols have been developed that permit engraftment of normal and malignant cells into irradiated, syngeneic, and immune compromised adult zebrafish. These models when coupled with optimized cell transplantation protocols allow for the rapid assessment of stem cell function, regeneration following injury, and cancer. Here, we present a method for cell transplantation of zebrafish adult skeletal muscle and embryonal rhabdomyosarcoma (ERMS), a pediatric sarcoma that shares features with embryonic muscle, into immune compromised adult rag2(E450fs) homozygous mutant zebrafish. Importantly, these animals lack T cells and have reduced B cell function, facilitating engraftment of a wide range of tissues from unrelated donor animals. Our optimized protocols show that fluorescently labeled muscle cell preparations from alpha-actin-RFP transgenic zebrafish engraft robustly when implanted into the dorsal musculature of rag2 homozygous mutant fish. We also demonstrate engraftment of fluorescent-transgenic ERMS where fluorescence is confined to cells based on differentiation status. Specifically, ERMS were created in AB-strain myf5-GFP; mylpfa-mCherry double transgenic animals and tumors injected into the peritoneum of adult immune compromised fish. The utility of these protocols extends to engraftment of a wide range of normal and malignant donor cells that can be implanted into dorsal musculature or peritoneum of adult zebrafish. C1 [Tenente, Ines M.; Tang, Qin; Moore, John C.; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Tenente, Ines M.; Tang, Qin; Moore, John C.; Langenau, David M.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Tenente, Ines M.] Univ Porto, GABBA Inst Ciencias Biomed Abel Salazar, P-4100 Oporto, Portugal. RP Moore, JC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM moore.john@mgh.harvard.edu; DLANGENAU@mgh.harvard.edu FU Alex's Lemonade Stand Foundation; American Cancer Society; MGH Howard Goodman Fellowship; US National Institutes of Health [R24OD016761, 1R01CA154923]; CNY Flow Cytometry Core and Flow Image Analysis, shared instrumentation grant [1S10RR023440-01A1]; Portuguese Foundation for Science and Technology (Fundacao para a Ciencia e Tecnologia - FCT); China Scholarship Council FX This work is supported by Alex's Lemonade Stand Foundation (D.M.L.), American Cancer Society (D.M.L.), the MGH Howard Goodman Fellowship (D.M.L.), and US National Institutes of Health grants R24OD016761 and 1R01CA154923 (D.M.L.). CNY Flow Cytometry Core and Flow Image Analysis, shared instrumentation grant number 1S10RR023440-01A1. I.M.T. is funded by a fellowship from the Portuguese Foundation for Science and Technology (Fundacao para a Ciencia e Tecnologia - FCT). Q.T. is funded by the China Scholarship Council. We thank Angela Volorio for her helpful comments and advice. NR 33 TC 2 Z9 2 U1 0 U2 5 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2014 IS 94 AR e52597 DI 10.3791/52597 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB1AE UT WOS:000349358000079 ER PT J AU Koistinen, A Turunen, R Vuorinen, T Soderlund-Venermo, M Camargo, CA Ruuskanen, O Jartti, T AF Koistinen, Annamari Turunen, Riitta Vuorinen, Tytti Soderlund-Venermo, Maria Camargo, Carlos A., Jr. Ruuskanen, Olli Jartti, Tuomas TI Vitamin D, virus etiology, and atopy in first-time wheezing children in Finland SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Letter ID ADOLESCENTS; LEVEL; RISK C1 [Koistinen, Annamari; Turunen, Riitta; Ruuskanen, Olli; Jartti, Tuomas] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Turunen, Riitta; Vuorinen, Tytti] Univ Turku, Dept Virol, Turku, Finland. [Soderlund-Venermo, Maria] Univ Helsinki, Dept Virol, Haartman Inst, Helsinki, Finland. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Koistinen, A (reprint author), Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. EM amkois@utu.fi NR 10 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-6157 EI 1399-3038 J9 PEDIAT ALLERG IMM-UK JI Pediatr. Allergy Immunol. PD DEC PY 2014 VL 25 IS 8 BP 834 EP 837 DI 10.1111/pai.12308 PG 4 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA CB1FS UT WOS:000349373000022 PM 25387768 ER PT J AU Fischer, S Wallins, JS Bueno, EM Kueckelhaus, M Chandawarkar, A Diaz-Siso, JR Larson, A Murphy, GF Annino, DJ Caterson, EJ Pomahac, B AF Fischer, Sebastian Wallins, Joe S. Bueno, Ericka M. Kueckelhaus, Maximilian Chandawarkar, Akash Diaz-Siso, J. Rodrigo Larson, Allison Murphy, George F. Annino, Donald J. Caterson, Edward J. Pomahac, Bohdan TI Airway Recovery after Face Transplantation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FACIAL TRANSPLANTATION; NASAL OBSTRUCTION; SEPTAL DEVIATION; BREATHING ROUTE; TRACHEOSTOMY; SLEEP; CRANIOSYNOSTOSIS; VENTILATION; DISEASE AB Background: Severe facial injuries can compromise the upper airway by reducing airway volume, obstructing or obliterating the nasal passage, and interfering with oral airflow. Besides the significant impact on quality of life, upper airway impairments can have life-threatening or life-altering consequences. The authors evaluated improvements in functional airway after face transplantation. Methods: Between 2009 and 2011, four patients underwent face transplantation at the authors' institution, the Brigham and Women's Hospital. Patients were examined preoperatively and postoperatively and their records reviewed for upper airway infections and sleeping disorders. The nasal mucosa was biop-sied after face transplantation and analyzed using scanning electron microscopy. Volumetric imaging software was used to evaluate computed tomographic scans of the upper airway and assess airway volume changes before and after transplantation. Results: Before transplantation, two patients presented an exposed naked nasal cavity and two suffered from occlusion of the nasal passage. Two patients required tracheostomy tubes and one had a prosthetic nose. Sleeping disorders were seen in three patients, and chronic cough was diagnosed in one. After transplantation, there was no significant improvement in sleeping disorders. The incidence of sinusitis increased because of mechanical interference of the donor septum and disappeared after surgical correction. All patients were decannulated after transplantation and were capable of nose breathing. Scanning electron micrographs of the respiratory mucosa revealed viable tissue capable of mucin production. Airway volume significantly increased in all patients. Conclusions: Face transplantation successfully restored the upper airway in four patients. Unhindered nasal breathing, viable respiratory mucosa, and a significant increase in airway volume contributed to tracheostomy decannulation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Div Plast Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Div Plast Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Div Otolarynagol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Dermatopathol,Dept Pathol, Cambridge, MA 02138 USA. Ruhr Univ Bochum, BG Univ Hosp Bergmannsheil, Dept Plast Surg, Bochum, Germany. Heidelberg Univ, BG Trauma Ctr Ludwigshafen, Burn Trauma Ctr, Dept Hand Plast & Reconstruct Surg, D-69115 Heidelberg, Germany. Dana Farber Canc Inst, Boston, MA USA. RP Pomahac, B (reprint author), Brigham & Womens Hosp, Plast Surg Transplantat & Burn Ctr, 75 Francis St, Boston, MA 02115 USA. EM bpomahac@partners.org RI Larson, Allison/N-4263-2015 OI Larson, Allison/0000-0001-8534-7078 NR 33 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 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2014 VL 134 IS 6 BP 946E EP 954E DI 10.1097/PRS.0000000000000752 PG 9 WC Surgery SC Surgery GA CB2LF UT WOS:000349458200010 PM 25415117 ER PT J AU Steenkamp, MM Boasso, AM Nash, WP Litz, BT AF Steenkamp, Maria M. Boasso, Alyssa M. Nash, William P. Litz, Brett T. TI Does Mental Health Stigma Change Across the Deployment Cycle? SO MILITARY MEDICINE LA English DT Article ID BARRIERS; CARE; AFGHANISTAN; IRAQ; LEADERSHIP; VETERANS; VALIDITY AB Objectives: Prior research on mental health stigma in military personnel has been cross-sectional. We prospectively examined the course of perceived mental health stigma in a cohort of deployed U. S. combat Marines. Methods: Participants (N = 768) were assessed 1 month before a 7-month deployment to Afghanistan, and again at 1, 5, and 8 months postdeployment. We also examined three predictors of the course of stigma: post-traumatic stress disorder symptom severity, vertical and horizontal unit cohesion, and mental health treatment utilization while deployed. Results: Perceptions of stigma remained largely stable across the deployment cycle, with latent growth curve analyses revealing a statistically significant but small decrease in stigma over time. Lower post-traumatic stress disorder symptoms and greater perceived vertical and horizontal support predicted decreases in stigma over time, whereas mental health treatment utilization in theater did not predict the course of stigma. Conclusions: Perceived stigma was low and largely stable over time. C1 [Steenkamp, Maria M.; Boasso, Alyssa M.; Litz, Brett T.] VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. [Nash, William P.] Boston VA Res Inst, Jamaica Plain, MA 02130 USA. RP Steenkamp, MM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. FU VA Health Service Research and Development [SDR 09-0128]; Navy Bureau of Medicine and Surgery, and Headquarters, U.S. Marine Corps FX The authors acknowledge the Marine Resiliency Study team who made this work possible, and Dr. Annie Fox for helpful input on this article. This study was funded by VA Health Service Research and Development (SDR 09-0128), the Navy Bureau of Medicine and Surgery, and Headquarters, U.S. Marine Corps. NR 16 TC 1 Z9 1 U1 1 U2 7 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD DEC PY 2014 VL 179 IS 12 BP 1449 EP 1452 DI 10.7205/MILMED-D-14-00188 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CA7MB UT WOS:000349100300008 PM 25469966 ER PT J AU Sitkovsky, MV AF Sitkovsky, Michail V. TI Therapeutic manipulation of hypoxia-A2-adenosinergic suppression and redirection of immune response SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Sitkovsky, Michail V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. [Sitkovsky, Michail V.] Harvard Inst Med, Canc Vaccine Ctr, DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 658 EP 659 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700016 ER PT J AU Schwarzschild, MA AF Schwarzschild, Michael A. TI Purine targets in Parkinson's trials: from adenosine to urate SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Schwarzschild, Michael A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 723 EP 723 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700179 ER PT J AU Marechal, A Zou, L AF Marechal, Alexandre Zou, Lee TI A LARGe surprise links ATR and Rho SO CELL CYCLE LA English DT Editorial Material DE ATR; DNA Damage; LARG; Rho Signaling; Replication Stress Response; Tel2 ID DNA-DAMAGE C1 [Marechal, Alexandre; Zou, Lee] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Marechal, A (reprint author), Harvard Univ, Med Sch, Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA. EM amarechal@mgh.harvard.edu; zou.lee@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 1 PY 2014 VL 13 IS 23 BP 3627 EP 3627 DI 10.4161/15384101.2014.980705 PG 1 WC Cell Biology SC Cell Biology GA AZ6KQ UT WOS:000348329200005 PM 25551359 ER PT J AU Ovaska, MT Madanat, R Tukiainen, E Pulliainen, L Sintonen, H Makinen, TJ AF Ovaska, Mikko T. Madanat, Rami Tukiainen, Erkki Pulliainen, Lea Sintonen, Harri Makinen, Tatu J. TI Flap reconstruction for soft-tissue defects with exposed hardware following deep infection after internal fixation of ankle fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Ankle fracture; Infection; Flap reconstruction; Health-related quality of life ID PRESSURE WOUND THERAPY; VACUUM-ASSISTED CLOSURE; BREVIS MUSCLE FLAP; LOWER-EXTREMITY TRAUMA; FAILED FREE FLAPS; PERONEUS BREVIS; LOWER LEG; SCORING SCALE; COVERAGE; MANAGEMENT AB The aim of the present study was to determine the outcome for patients treated with flap reconstruction following deep ankle fracture infection with exposed hardware. Out of 3041 consecutive ankle fracture operations in 3030 patients from 2006 to 2011, we identified 56 patients requiring flap reconstruction following deep infection. Thirty-two of these patients could be examined at a follow-up visit. Olerud-Molander Ankle (OMA) score, 15D score, Numeric Rating Scale (NRS), and clinical examination were used to assess the outcome. A total of 58 flap reconstructions were performed in 56 patients with a mean age of 57 years (range 25-93 years) and mean follow-up time of 52 months. The most commonly used reconstruction was a distally based peroneus brevis muscle flap with a split-thickness skin graft. A microvascular free flap was required in only one patient. 22 (39%) patients required subsequent surgical interventions because of a flap-related complication. With flap reconstruction, hardware could eventually be salvaged in 53% of patients with a non-consolidated fracture. The mean OMA score was fair or poor in 53% of the patients, and only 56% had recovered their pre-injury level of function. Half of the patients had shoe wear limitations. The 15D score showed a significantly poorer health-related quality of life compared to an age-standardised sample of the general population. The mean pain NRS was 2.1 (range 0-6), and the mean satisfaction NRS was 6.6 (range 0-10). Our study showed that successful treatment of a soft-tissue defect with exposed hardware following ankle fracture infections can be achieved with local flaps. Despite eventual reconstructive success, complications are common. Patients perceive a poorer health-related quality of life, have shoe wear limitations, and only half of them achieve their pre-injury level of function. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ovaska, Mikko T.; Madanat, Rami; Makinen, Tatu J.] Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, SF-00260 Helsinki, Finland. [Madanat, Rami] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA USA. [Madanat, Rami] Harvard Univ, Sch Med, Boston, MA USA. [Tukiainen, Erkki; Pulliainen, Lea] Univ Helsinki, Cent Hosp, Dept Plast & Reconstruct Surg, SF-00260 Helsinki, Finland. [Sintonen, Harri] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki 00014, Finland. [Makinen, Tatu J.] Mt Sinai Hosp, Div Orthopaed Surg, Toronto, ON M5G 1X5, Canada. RP Ovaska, MT (reprint author), Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, Topeliuksenkatu 5, SF-00260 Helsinki, Finland. EM mikko.ovaska@hus.fi FU Helsinki University Central Hospital; Jane and Aatos Erkko Foundation; Paivikki and Sakari Sohlberg Foundation; Paulo Foundation FX The study was supported by Helsinki University Central Hospital, and by grants from the Jane and Aatos Erkko Foundation, the Paivikki and Sakari Sohlberg Foundation, and the Paulo Foundation. The funding source had no influence or involvement in the study. NR 39 TC 1 Z9 1 U1 1 U2 2 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 DEC PY 2014 VL 45 IS 12 BP 2029 EP 2034 DI 10.1016/j.injury.2014.10.006 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CA1DB UT WOS:000348652100039 PM 25458066 ER PT J AU Mellema, JJ Doornberg, JN Guitton, TG Ring, D AF Mellema, Jos J. Doornberg, Job N. Guitton, Thierry G. Ring, David CA Sci Variation Grp TI Biomechanical studies: Science (f)or common sense? SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Biomechanical; Orthopaedic; Fracture; Fixation ID LOCKING PLATE FIXATION; CALCIUM-PHOSPHATE CEMENT; SCREW FIXATION; INTERNAL-FIXATION; PROXIMAL HUMERUS; SHAFT FRACTURES; DISTAL RADIUS; BLADE-PLATE; AUGMENTATION; OLECRANON AB Introduction: It is our impression that many biomechanical studies invest substantial resources studying the obvious: that more and larger metal is stronger. The purpose of this study is to evaluate if a subset of biomechanical studies comparing fixation constructs just document common sense. Methods: Using a web-based survey, 274 orthopaedic surgeons and 81 medical students predicted the results of 11 biomechanical studies comparing fracture fixation constructs (selected based on the authors' sense that the answer was obvious prior to performing the study). Sensitivity, specificity, and accuracy were calculated according to standard formulas. The agreement among the observers was calculated by using a multirater kappa, described by Siegel and Castellan. Results: The accuracy of predicting outcomes was 80% or greater for 10 of 11 studies. Accuracy was not influenced by level of experience (i.e., time in practice and medical students vs. surgeons). There were substantial differences in accuracy between observers from different regions. The overall categorical rating of inter-observer reliability according to Landis and Koch was moderate (kappa = 0.55; standard error (SE) = 0.01). Conclusion: The results of a subset of biomechanical studies comparing fracture fixation constructs can be predicted prior to doing the study. As these studies are time and resource intensive, one criterion for proceeding with a biomechanical study should be that the answer is not simply a matter of common sense. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mellema, Jos J.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02163 USA. [Doornberg, Job N.; Guitton, Thierry G.] Univ Amsterdam, Acad Med Ctr, Orthopaed Residency Program PGY 4, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02163 USA. EM dring@partners.org OI Kennedy, Stephen/0000-0001-8177-4988; Guitton, Thierry/0000-0002-2599-1985; Gummerson, Nigel/0000-0002-5727-8041; Borris, Lars/0000-0002-0527-1518; Ring, David/0000-0002-6506-4879; Soong, Maximillian/0000-0003-0333-8181; Bainbridge, Lionel/0000-0001-7987-2845; adolfsson, lars/0000-0001-7873-3093 NR 33 TC 4 Z9 4 U1 0 U2 4 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 DEC PY 2014 VL 45 IS 12 BP 2035 EP 2039 DI 10.1016/j.injury.2014.09.014 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CA1DB UT WOS:000348652100040 PM 25306381 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Disability after nondisplaced and minimally displaced radial head fractures: Misleading conclusions SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Letter C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM memenendez@partners.org; dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 4 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2014 VL 45 IS 12 BP 2117 EP 2117 DI 10.1016/j.injury.2014.07.023 PG 1 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CA1DB UT WOS:000348652100064 PM 25150753 ER PT J AU Kerns, E Patel, S Cohen, DM AF Kerns, Eric Patel, Shweta Cohen, David M. TI Hourly oral sodium chloride for the rapid and predictable treatment of hyponatremia SO CLINICAL NEPHROLOGY LA English DT Article DE osmoregulation; arginine vasopressin; hyponatremia; sodium chloride ID OPTIC CHIASM GLIOMA; INAPPROPRIATE SECRETION; NONOBSTRUCTIVE HYDROCEPHALUS; ANTIDIURETIC-HORMONE; HYPERTONIC SALINE; WATER; OVERCORRECTION; VALPROATE; ASCITES; ABNORMALITIES AB Hypertonic NaCl is first-line therapy for acute, severe and symptomatic hyponatremia; however, its use is often restricted to the intensive care unit (ICU). A 35-year-old female inpatient with an optic chiasm glioma and ventriculoperitoneal shunt for hydrocephalus developed acute hyponatremia (sodium 122 mEq/L) perhaps coinciding with haloperidol treatment. The sum of her urinary sodium and potassium concentrations was markedly hypertonic vis-a-vis plasma; it was inferred that serum sodium concentration would continue to fall even in the complete absence of fluid intake. Intravenous (IV) 3% NaCl was recommended; however, a city-wide public health emergency precluded her transfer to the ICU. She was treated with hourly oral NaCl tablets in a dose calculated to deliver the equivalent of 0.5 mL/kg/h of 3% NaCl with an objective of increasing the serum sodium concentration by 6 mEq/L. She experienced a graded and predictable increase in serum sodium concentration. A slight overshoot to 129 mEq/L was rapidly corrected with 0.25 l of D5W, and she stabilized at 127 mEq/L. We conclude that hourly oral NaCl, in conjunction with careful monitoring of the serum sodium concentration, may provide an attractive alternative to IV 3% NaCl for selected patients with severe hyponatremia. C1 [Kerns, Eric; Patel, Shweta; Cohen, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Cohen, David M.] Portland VA Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Mailcode CH12R,3303 SW Bond Ave, Portland, OR 97239 USA. EM cohend@ohsu.edu FU National Institutes of Health; Department of Veterans Affairs; American Heart Association FX This work is supported by grants from the National Institutes of Health, the Department of Veterans Affairs, and the American Heart Association. The authors have no conflict of interest related to the contents of this manuscript. NR 33 TC 2 Z9 2 U1 2 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD DEC PY 2014 VL 82 IS 6 BP 397 EP 401 DI 10.5414/CN108014 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AZ6SM UT WOS:000348350000008 PM 23816479 ER PT J AU Carrithers, MD AF Carrithers, Michael D. TI Update on Disease-Modifying Treatments for Multiple Sclerosis SO CLINICAL THERAPEUTICS LA English DT Review DE immune therapy; multiple sclerosis; interferon; glatiramer; natalizumab; fumarate ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLACEBO-CONTROLLED TRIAL; INTERFERON BETA-1A THERAPY; CONTROLLED PHASE-3 TRIAL; QUALITY-OF-LIFE; DOUBLE-BLIND; GLATIRAMER ACETATE; IMMUNE SURVEILLANCE; ORAL TERIFLUNOMIDE; DIMETHYL FUMARATE AB Purpose: The purpose of this review is to discuss the selection and use of disease- modifying treatments for patients with relapsing forms of multiple sclerosis (MS). Methods: PubMed was searched (1966-2014) using the terms multiple sclerosis, treatment, interferon, glatiramer acetate, dimethyl fumarate, fingolimod, teri-flunomide, natalizumab, rituximab, and alemtuzumab. Findings: MS is a chronic neurological disorder that can cause a substantial degree of disability. Because of its usual onset in young adults, patients may require treatment for several decades. Currently available agents include platform injectable therapies, newer oral agents, and second-line monoclonal antibody treatments. Treatment decisions have become more complex with the introduction of new approaches, and a major goal is to balance perceived efficacy and tolerability in a specific patient with the relative impact of disease activity and adverse events on quality of life. Here the options for disease-modifying treatments for relapsing forms of MS are reviewed, and current and future challenges are discussed. Implications: An evidence-based approach can be used for the selection of disease-modifying treatments based on disease phenotype and severity, adverse events, and perceived efficacy. Published by Elsevier HS Journals, Inc. C1 [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Neurol Serv, William S Middleton Mem Vet Hosp,Dept Neurol, Madison, WI 53706 USA. [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Neurol Serv, William S Middleton Mem Vet Hosp,Dept Pathol, Madison, WI 53706 USA. [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Program Cellular & Mol Pathol, Madison, WI 53706 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu FU Biogen-Idec/Elan; U.S. Department of Veterans Affairs; National Multiple Sclerosis Society; NIH FX Dr. Carrithers has currently or previously received research funding from Biogen-Idec/Elan, the U.S. Department of Veterans Affairs, the National Multiple Sclerosis Society, and NIH. NR 65 TC 17 Z9 18 U1 2 U2 22 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD DEC PY 2014 VL 36 IS 12 BP 1938 EP 1945 DI 10.1016/j.clinthera.2014.08.006 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AZ2OK UT WOS:000348072500009 PM 25218310 ER PT J AU Krsmanovic, A Tripp, DA Nickel, JC Shoskes, DA Pontari, M Litwin, MS McNaughton-Collins, MF AF Krsmanovic, Adrijana Tripp, Dean A. Nickel, J. Curtis Shoskes, Daniel A. Pontari, Michel Litwin, Mark S. McNaughton-Collins, Mary F. TI Psychosocial mechanisms of the pain and quality of life relationship for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL LA English DT Article ID CYSTITIS/PAINFUL BLADDER SYNDROME; COPING INVENTORY; FOLLOW-UP; VALIDATION; MEN; PREDICTORS; SYMPTOMS; COHORT AB Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent, chronic pelvic pain condition largely unresponsive to medical interventions. Psychosocial risk factors are associated with poor outcomes in CP/CPPS, but have not been examined for their intervening roles between pain and reduced quality of life (QoL). This study aimed to determine if psychosocial risk factors (i.e., patient coping and catastrophizing) mediate the association between pain and QoL. Methods: Using a cross sectional design, 175 men with CP/CPPS (mean age 46.83; SD 10.86) were recruited from tertiary care urology clinics and completed questionnaires on demographics, pain, QoL, pain coping, depression, and catastrophizing. An exploratory factor analysis was conducted and aggregate factor scores were examined to improve the amount of meaningful measurement to be used in multiple mediations. The models specified multiple risk factors as mechanisms between pain and both physical and mental QoL as the primary outcome measurements. Results: Four aggregate psychosocial factor scores were produced from the psychosocial measures (i.e., illness and wellness-focused behavioural coping, depression and catastrophizing). Illnessfocused coping partially mediated the relationship between pain and physical QoL. However, catastrophizing and illness-focused coping fully mediated the relation between pain and mental QoL, showing the association between pain and mental QoL was no longer significant when catastrophizing and illness-focused coping were in the model. Conclusion: Psychosocial factors function as mechanisms between higher pain and they are associated diminished mental QoL. These results introduce illness-focused coping as an important biopsychosocial target in CP/CPPS management. C1 [Krsmanovic, Adrijana; Tripp, Dean A.; Nickel, J. Curtis] Queens Univ, Kingston, ON K7L 3N6, Canada. [Shoskes, Daniel A.] Glickman Urol & Kidney Inst, Cleveland, OH USA. [Pontari, Michel] Temple Univ, Philadelphia, PA 19122 USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [McNaughton-Collins, Mary F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Krsmanovic, A (reprint author), Queens Univ, 62 Arch St, Kingston, ON K7L 3N6, Canada. EM Oak93@queensu.ca NR 30 TC 5 Z9 5 U1 5 U2 8 PU CANADIAN UROLOGICAL ASSOCIATION PI DORVAL PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA SN 1911-6470 EI 1920-1214 J9 CUAJ-CAN UROL ASSOC JI CUAJ-Can. Urol. Assoc. J. PD DEC PY 2014 VL 8 IS 11-12 BP 403 EP 408 DI 10.5489/cuaj.2179 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AY6ZJ UT WOS:000347710800025 PM 25553153 ER PT J AU Balvers, RK Belcaid, Z van den Hengel, SK Kloezeman, J Wakimoto, H Hoeben, RC Debets, R Leenstra, S Dirven, C Lamfers, MLM AF Balvers, Rutger K. Belcaid, Zineb van den Hengel, Sanne K. Kloezeman, Jenneke Wakimoto, Hiroaki Hoeben, Rob C. Debets, Reno Leenstra, Sieger Dirven, Clemens Lamfers, Martine L. M. TI T-cell derived cellular vehicles demonstrate intraparenchymal tropism for infiltrative glioma and effective delivery of Delta24-RGD SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 8th International Conference on Oncolytic Virus Therapeutics CY APR 10-13, 2014 CL Lincoln Coll & Examinat Sch, Oxford, ENGLAND HO Lincoln Coll & Examinat Sch C1 [Balvers, Rutger K.; Belcaid, Zineb; Kloezeman, Jenneke; Leenstra, Sieger; Dirven, Clemens; Lamfers, Martine L. M.] Erasmus MC, Dept Neurosurg, Brain Tumor Ctr, Rotterdam, Netherlands. [van den Hengel, Sanne K.; Hoeben, Rob C.] LUMC Leiden, Dept Mol Cell Biol, Leiden, Netherlands. [Wakimoto, Hiroaki] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Mol Neurosurg Lab, Boston, MA 02114 USA. [Debets, Reno] Erasmus MC Canc Inst, Dept Med Oncol, Lab Expt Tumor Immunol, Rotterdam, Netherlands. EM z.belcaid@erasmusmc.nl NR 0 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 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2014 VL 25 IS 12 MA 21 BP A11 EP A11 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AW6AT UT WOS:000346352600022 ER PT J AU Kaufmann, JK Nakashima, H Nguyen, T Nakano, I Chiocca, EA AF Kaufmann, J. K. Nakashima, H. Nguyen, T. Nakano, I. Chiocca, E. A. TI Specific Inhibition of Histone Deacetylase 6 Can Support Oncolytic Herpes Virus Replication and Spread in Glioma Stem Cells SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 8th International Conference on Oncolytic Virus Therapeutics CY APR 10-13, 2014 CL Lincoln Coll & Examinat Sch, Oxford, ENGLAND HO Lincoln Coll & Examinat Sch C1 [Kaufmann, J. K.; Nakashima, H.; Nguyen, T.] Brigham & Womens Hosp, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA. [Kaufmann, J. K.; Nakashima, H.; Nguyen, T.; Chiocca, E. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nakano, I.] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA. [Nakano, I.] Ohio State Univ, James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Chiocca, E. A.] Brigham & Womens Hosp, Dana Faber Canc Inst, Harvey Cushing Neurooncol Labs, Dept Neurosurg, Boston, MA 02115 USA. EM jkaufmann@partners.org NR 4 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2014 VL 25 IS 12 MA 8 BP A5 EP A5 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AW6AT UT WOS:000346352600009 ER PT J AU Nakashima, H Shaik, I Nguyen, T Elder, JB Chiocca, EA AF Nakashima, Hiroshi Shaik, Imran Tran Nguyen Elder, J. Bradley Chiocca, E. Antonio TI Hypoxia-regulated transformation of replication-defective vectors into oncolytic viruses in cellular vehicles for brain tumor therapy SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 8th International Conference on Oncolytic Virus Therapeutics CY APR 10-13, 2014 CL Lincoln Coll & Examinat Sch, Oxford, ENGLAND HO Lincoln Coll & Examinat Sch C1 [Nakashima, Hiroshi; Tran Nguyen; Chiocca, E. Antonio] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvey Cushing Neurooncol Res Labs, Dept Neurosurg, Boston, MA 02115 USA. [Nakashima, Hiroshi; Tran Nguyen; Chiocca, E. Antonio] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shaik, Imran; Elder, J. Bradley] Ohio State Univ, Dept Neurosurg, Dardinger Neurooncol Labs, Wexner Med Ctr, Columbus, OH 43210 USA. [Shaik, Imran; Elder, J. Bradley] James Canc Hosp, Columbus, OH 43210 USA. EM HNakashima@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2014 VL 25 IS 12 MA 34 BP A17 EP A17 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AW6AT UT WOS:000346352600035 ER PT J AU Peters, C Wakimoto, H Tshilenge, KT Kanai, R Rabkin, SD AF Peters, Cole Wakimoto, Hiro Tshilenge, Kizito-Tshitoko Kanai, Ryuichi Rabkin, Samuel D. TI Glioblastoma stem cells are resistant to gamma 34.5 deficient herpes simplex virus 1 replication SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 8th International Conference on Oncolytic Virus Therapeutics CY APR 10-13, 2014 CL Lincoln Coll & Examinat Sch, Oxford, ENGLAND HO Lincoln Coll & Examinat Sch C1 Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. EM colepeters@fas.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2014 VL 25 IS 12 MA 17 BP A9 EP A9 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AW6AT UT WOS:000346352600018 ER PT J AU Huang, LY Krayer, M Roubil, JGS Huang, YY Holten, D Lindsey, JS Hamblin, MR AF Huang, Liyi Krayer, Michael Roubil, John G. S. Huang, Ying-Ying Holten, Dewey Lindsey, Jonathan S. Hamblin, Michael R. TI Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY ROLE; IN-VITRO; PHOTOPHYSICAL PROPERTIES; STAPHYLOCOCCUS-AUREUS; CANDIDA-ALBICANS; CENTRAL METAL; PHOTOSENSITIZERS; OXYGEN; INFECTIONS; CELLS AB Three stable synthetic mono-substituted cationic bacteriochlorins (BC37, BC38 and BC39) were recently reported to show exceptional activity (low nanomolar) in mediating photodynamic killing of human cancer cells after a 24 h incubation upon excitation with near-infrared light (730 nm). The presence of cationic quaternary ammonium groups in each compound suggested likely activity as antimicrobial photosensitizers. Herein this hypothesis was tested against a panel of pathogenic microorganisms that have all recently drawn attention due to increased drug-resistance (Gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis; Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii; and fungal yeasts, Candida albicans and Cryptococcus neoformans). All three bacteriochlorins were highly effective against both Gram-positive species (>6 logs of eradication at <= 200 nM and 10 J/cm(2)). The dicationic bacteriochlorin (BC38) was best against the Gram-negative species (>6 logs at 1-2 mu M) whereas the lipophilic monocationic bacteriochlorin (BC39) was best against the fungi (>6 logs at 1 mu M). The bacteriochlorins produced substantial singlet oxygen (and apparently less Type-1 reactive-oxygen species such as hydroxyl radical) as judged by activation of fluorescent probes and comparison with 1H-phenalen-l-one-2-sulfonic acid; the order of activity was BC37 > BC38 > BC39. A short incubation time (30 min) resulted in selectivity for microbial cells over HeLa human cells. The highly active photodynamic inactivation of microbial cells may stem from the amphiphilic and cationic features of the bacteriochlorins. (C) 2014 Elsevier B.V. All rights reserved. C1 [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China. [Huang, Liyi; Roubil, John G. S.; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Liyi; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Krayer, Michael; Lindsey, Jonathan S.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. [Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR414, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Lindsey, Jonathan/J-7761-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R41AI072854, R01AI050875]; National Natural Science Foundation of China [81260239, 81472002]; Guangxi Scientific and Technological Projects [2013BC26041, 1355005-1-2] FX This work was supported by US NIH grants R41AI072854 (to NIRvana Pharmaceuticals Inc.) and R01AI050875 (to M.R. Hamblin). Liyi Huang was supported by National Natural Science Foundation of China (81260239, 81472002), Guangxi Scientific and Technological Projects (2013BC26041, 1355005-1-2). NR 35 TC 7 Z9 7 U1 3 U2 20 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD DEC PY 2014 VL 141 BP 119 EP 127 DI 10.1016/j.jphotobiol.2014.09.016 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AY6FJ UT WOS:000347662400015 PM 25463659 ER PT J AU Wilner, JG Vranceanu, AM Blashill, AJ AF Wilner, Julianne G. Vranceanu, Ana-Maria Blashill, Aaron J. TI Neuroticism prospectively predicts pain among adolescents: Results from a nationally representative sample SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Pain; Neuroticism; Adolescents ID PROTECTIVE PARENTAL RESPONSES; EMOTIONAL DISORDERS; FREQUENCY; DISABILITY; SEVERITY; PATTERNS; CHILDREN AB Objective: The purpose of this study is to assess the prospective relationship of neuroticism to frequency of headaches and stomachaches in adolescents. Methods: Participants were 3,676 adolescents sampled from Wave 1 (mean age 16) and Wave 2 (mean age 17) of the National Longitudinal Study of Adolescent Health (i.e., Add Health), a comprehensive, nationally representative, longitudinal data set. Binary variables were created to isolate participants who reported high versus low/medium frequency of pain. Subsequently, Wave 2 pain variables were modeled based on Wave 1 neuroticism, controlling for Wave 1 pain and demographics. Results: Elevated neuroticism at Wave I prospectively predicted increased odds of high frequency of headaches (odds ratio = 1.4,95% Cl [1.2, 1.8], p =.001) and stomachaches at Wave 2 (odds ratio = 1.5, 95% Cl [1.1, 2.01, p =.004). Conclusions: This is the first known study to examine and find evidence for the prospective relationship between neuroticism and pain among a nationally representative sample of adolescents. Results indicated that after controlling for baseline pain, elevated neuroticism longitudinally predicted increased odds of high frequency of pain, one year later. Given recent advances in treatment for neuroticism, clinicians should be aware of these relationships and incorporate multidisciplinary treatments in the care of adolescents who experience high levels of pain. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wilner, Julianne G.; Vranceanu, Ana-Maria; Blashill, Aaron J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Vranceanu, Ana-Maria; Blashill, Aaron J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Wilner, JG (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jgwilner@mgh.harvard.edu FU NIMH NIH HHS [K23 MH096647] NR 27 TC 3 Z9 3 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 2014 VL 77 IS 6 BP 474 EP 476 DI 10.1016/j.jpsychores.2014.10.012 PG 3 WC Psychiatry SC Psychiatry GA AY7LM UT WOS:000347741700006 PM 25466384 ER PT J AU Clark, T Roos, M AF Clark, Tim Roos, Marco TI Recent applications of web semantics in eLifeScience SO JOURNAL OF WEB SEMANTICS LA English DT Editorial Material ID BIOMEDICAL-ONTOLOGY; NATIONAL-CENTER C1 [Clark, Tim] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Clark, Tim] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roos, Marco] Leiden Univ, Med Ctr, Leiden, Netherlands. RP Clark, T (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM tim_clark@harvard.edu NR 21 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-8268 J9 J WEB SEMANT JI J. Web Semant. PD DEC PY 2014 VL 29 BP 1 EP 2 DI 10.1016/j.websem.2014.11.005 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA AZ6LK UT WOS:000348331100001 ER PT J AU Pedersen, MM Holt, NE Grande, L Kurlinski, LA Beauchamp, MK Kiely, DK Petersen, J Leveille, S Bean, JF AF Pedersen, Mette M. Holt, Nicole E. Grande, Laura Kurlinski, Laura A. Beauchamp, Marla K. Kiely, Dan K. Petersen, Janne Leveille, Suzanne Bean, Jonathan F. TI Mild Cognitive Impairment Status and Mobility Performance: An Analysis From the Boston RISE Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cognition; Functional performance; Successful aging ID LATE-LIFE FUNCTION; LOWER-EXTREMITY FUNCTION; VERBAL-LEARNING TEST; OLDER-ADULTS; PHYSICAL PERFORMANCE; GAIT SPEED; DISABILITY INSTRUMENT; CURVED-PATH; RELIABILITY; WALKING AB Background. The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. Methods. An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (aMCI), nonmemory domains (naMCI), and multiple domains (mdMCI). Linear regression models were used to assess the association between MCI status and mobility performance in the Habitual Gait Speed, Figure of 8 Walk, Short Physical Performance Battery, and self-reported Late Life Function and Disability Instrument's Basic Lower Extremity and Advanced Lower Extremity function scales. Results. Participants had a mean age of 76.6 years, and 42% were characterized with MCI. Participants with MCI performed significantly worse than participants without MCI (No-MCI) on all performance and self-report measures (p < .01). All MCI sub-types performed significantly worse than No-MCI on all mobility measures (p < .05) except for aMCI versus No-MCI on the Figure of 8 Walk (p = .054) and Basic Lower Extremity (p = .11). Moreover, compared with aMCI, mdMCI manifested worse performance on the Figure of 8 Walk and Short Physical Performance Battery, and naMCI manifested worse performance on Short Physical Performance Battery and Basic Lower Extremity. Conclusions. Among older community-dwelling primary care patients, performance on a broad range of mobility measures was worse among those with MCI, appearing poorest among those with nonmemory MCI. C1 [Pedersen, Mette M.; Holt, Nicole E.; Kurlinski, Laura A.; Beauchamp, Marla K.; Kiely, Dan K.; Bean, Jonathan F.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Pedersen, Mette M.; Petersen, Janne] Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, Hvidovre, Denmark. [Grande, Laura] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Grande, Laura] Boston Univ Sch Med, Dept Psychiat, Boston, MA USA. [Beauchamp, Marla K.; Bean, Jonathan F.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Leveille, Suzanne] Univ Massachusetts, Dept Nursing, Boston, MA 02125 USA. RP Pedersen, MM (reprint author), Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, Kettegaard Alle 30, Hvidovre, Denmark. EM mette.merete.pedersen@regionh.dk RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU National Institute on Aging [R01 AG032052-03]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [1K24HD070966-01]; National Center for Research Resources [1 UL1 RR025758-04]; Capital Region of Denmark; University of Copenhagen FX This work was supported by the National Institute on Aging (R01 AG032052-03); the Eunice Kennedy Shriver National Institute of Child Health and Human Development (1K24HD070966-01 to J.B.); the National Center for Research Resources (1 UL1 RR025758-04); the Capital Region of Denmark (to M.M.P.); and the University of Copenhagen (to M.M.P.). NR 48 TC 5 Z9 5 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2014 VL 69 IS 12 BP 1511 EP 1518 DI 10.1093/gerona/glu063 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ6OX UT WOS:000348339800008 PM 24799356 ER PT J AU Predina, JD Morse, CR AF Predina, J. D. Morse, C. R. TI Minimally invasive esophagectomy and its current role in esophageal cancer SO MINERVA CHIRURGICA LA English DT Article DE Esophagus; Esophagectomy; Surgical procedures; minimally invasive; Morbidity; Mortality ID IVOR-LEWIS ESOPHAGECTOMY; OUTCOMES; MORTALITY; VOLUME AB The incidence of esophageal cancer has increased over the previous 4 decades. In 2014 alone, it is estimated that there will be 18,000 patients diagnosed with esophageal cancer, and 15,000 deaths from the disease. Esophagectomy, most commonly with adjuvant chemotherapy and radiation to treat locoregional spread, is the primary vehicle to offer patients cure. Open approaches (transthoracic Ivor Lewis, transhiatal, left thoracoabdominal, and 'three phase' McKeown esophagectomy) have been the most common, and are associated with significant morbidity and mortality. With this morbidity in mind, minimally invasive esophagectomy (MIE) has gained enthusiasm from the surgical community as an approach to minimize post-operative morbidity without sacrificing long-term outcomes. In this article, we review the basic steps of the three major approaches to MIE. We also review the recent data which supports the surgical field's growing enthusiasm for this approach to esophageal cancer. Based on our review of current data, we conclude that patients undergoing MIE have improved short-term outcomes with regard to morbidity and quality of life, with no adverse effects of the quality of oncologic resection. C1 [Predina, J. D.; Morse, C. R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Morse, CR (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM crmorse@partners.org NR 18 TC 2 Z9 2 U1 1 U2 4 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4733 EI 1827-1626 J9 MINERVA CHIR JI Minerva Chir. PD DEC PY 2014 VL 69 IS 6 BP 363 EP 370 PG 8 WC Surgery SC Surgery GA AZ1PQ UT WOS:000348011000007 ER PT J AU Gerstner, ER AF Gerstner, Elizabeth R. TI Is a picture really worth a 1000 words? SO NEURO-ONCOLOGY LA English DT Editorial Material ID RESPONSE ASSESSMENT; GLIOBLASTOMA; PROGRESSION; CRITERIA; SURVIVAL; ANTIBODY; GLIOMA C1 [Gerstner, Elizabeth R.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Gerstner, Elizabeth R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Gerstner, ER (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM egerstner@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2014 VL 16 IS 12 BP 1563 EP 1564 DI 10.1093/neuonc/nou309 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CA0JK UT WOS:000348604000001 PM 25326497 ER PT J AU Bott, NT Johnson, ET Schutt, N Galifianakis, N Subas, T Pollock, J Pressman, P Kramer, JH Possin, KL AF Bott, Nicholas T. Johnson, Erica T. Schutt, Norbert Galifianakis, Nicholas Subas, Trishna Pollock, Jessica Pressman, Peter Kramer, Joel H. Possin, Katherine L. TI Sensitive measures of executive dysfunction in non-demented Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Mild cognitive impairment; Executive function; Cognitive control; Working memory ID MILD COGNITIVE IMPAIRMENT; RIVASTIGMINE; DEMENTIA AB Background: We examined the sensitivity of different executive function measures for detecting deficits in Parkinson's disease patients without dementia. Methods: Twenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales. Results: No significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores. Conclusions: The NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bott, Nicholas T.; Johnson, Erica T.; Subas, Trishna; Pressman, Peter; Kramer, Joel H.; Possin, Katherine L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Schutt, Norbert; Pollock, Jessica] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Schutt, Norbert; Pollock, Jessica] Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Galifianakis, Nicholas] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. RP Bott, NT (reprint author), 675 Nelson Rising Lane,Suite 190,Box 1207, San Francisco, CA 94158 USA. EM nbott@stanford.edu FU National Institute on Aging [K23AG037566, R01AG032289, P50AG023501]; Larry L Hillblom Foundation (Miller); Hellman Family Foundation; Michael J. Fox Foundation FX This study was supported by the National Institute on Aging (Possin: K23AG037566; Kramer: R01AG032289; Miller: P50AG023501), the Larry L Hillblom Foundation (Miller, 2007/21), the Hellman Family Foundation, and MJFF2011, MRI signature of Parkinson's disease from the Michael J. Fox Foundation. NR 16 TC 2 Z9 2 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD DEC PY 2014 VL 20 IS 12 BP 1430 EP 1433 DI 10.1016/j.parkreldis.2014.10.007 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AY6FF UT WOS:000347662000021 PM 25454318 ER PT J AU Rohatgi, S Jagannathan, JP Rosenthal, MH Kim, KW Ramaiya, NH Krajewski, KM AF Rohatgi, Saurabh Jagannathan, Jyothi P. Rosenthal, Michael H. Kim, Kyung Won Ramaiya, Nikhil H. Krajewski, Katherine M. TI Vascular Toxicity Associated With Chemotherapy and Molecular Targeted Therapy: What Should a Radiologist Know? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE chemotherapy; embolism; hemorrhage; molecular targeted therapy; thrombosis ID HEPATIC VENOOCCLUSIVE DISEASE; VENOUS THROMBOEMBOLIC EVENTS; STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; CANCER-PATIENTS; COLORECTAL-CANCER; BEVACIZUMAB; THROMBOSIS; THALIDOMIDE; CT AB OBJECTIVE. Venous and arterial thromboembolic events and rarely hemorrhage are complications of chemotherapy and, more recently, of molecular targeted therapy in patients with solid and hematologic malignancies. This article will use a drug-based approach to illustrate, with examples, vessel damage and end-organ damage induced by molecular targeted therapy and chemotherapy in cancer patients and will provide a clinical perspective. CONCLUSION. Imaging plays a key role in the detection of complications of cancer therapies. A high index of suspicion and an awareness of modern-day drug toxicities are key to the early diagnosis and management of these complications. C1 [Rohatgi, Saurabh] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Rohatgi, Saurabh] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Rohatgi, Saurabh] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Rohatgi, S (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM sarohatgi@gmail.com RI Rosenthal, Michael/D-4080-2015 NR 39 TC 2 Z9 2 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2014 VL 203 IS 6 BP 1353 EP 1362 DI 10.2214/AJR.13.11967 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY4DD UT WOS:000347527500051 PM 25415715 ER PT J AU Haaga, JR Haaga, R Patel, I Love, Z Moulter, J AF Haaga, John R. Haaga, Rebecca Patel, Indravadan Love, Zachary Moulter, Joseph TI ALPHA Glycolytic Vasculogenesis Better Correlates With MRI and CT Imaging Techniques Than the Traditional Oxygen Vasculogenesis Theory SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE glycolysis; lactate; vascular growth factors; vasculogenesis ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL BLOOD-VOLUME; CONTRAST-ENHANCED MRI; HEPATOCELLULAR-CARCINOMA; IN-VIVO; VASCULAR-PERMEABILITY; CANCER-CELLS; INTERSTITIAL FLUID; FACTOR EXPRESSION; PROSTATE-CANCER AB OBJECTIVE. Traditional vasculogenesis has many contradictions related to treatment and imaging. This occurs because cancer also uses glycolysis, which does not need oxygen or arteries. Glycolytic lactate supports many procancer processes but high levels of it inhibit glycolysis. CONCLUSION. To avoid this, lactate induces vascular growth factors that initiate glycolytic vasculogenesis ALPHA (acidic lactate sequentially induces first lymphangiogenesis, phlebogenesis, and then arteriogenesis). The sequence of vessel development is lymphatics, veins, and then arteries. Modern contrast imaging depends more on veins than arteries, which is more consistent with ALPHA than the traditional theory. C1 [Haaga, John R.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Haaga, Rebecca] St Vincent Hosp, Dept Pathol, Cleveland, OH USA. [Patel, Indravadan] Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02114 USA. [Love, Zachary] Northwestern Univ Hosp, Dept Intervent Radiol, Chicago, IL USA. [Moulter, Joseph] Case Western Reserve Univ, Case Ctr Imaging Res, Cleveland, OH 44106 USA. RP Haaga, JR (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Dept Radiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM john.haaga@uhhospitals.org NR 88 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2014 VL 203 IS 6 BP W724 EP W734 DI 10.2214/AJR.13.11762 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY4DD UT WOS:000347527500019 PM 25415739 ER PT J AU Kang, SK Turan, EA Eisenberg, JD Lee, PA Kong, CY Pandharipande, PV AF Kang, Stella K. Turan, Ekin A. Eisenberg, Jonathan D. Lee, Pablo A. Kong, Chung Yin Pandharipande, Pari V. TI Microsimulation Model of CT Versus MRI Surveillance of Bosniak IIF Renal Cystic Lesions: Should Effects of Radiation Exposure Affect Selection of Imaging Strategy? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE Bosniak IIF renal lesions; CT; MRI; radiation exposure; renal cell carcinoma ID NEPHRON-SPARING SURGERY; NORMAL CONTRALATERAL KIDNEY; OPEN PARTIAL NEPHRECTOMY; CONTRAST-ENHANCED US; CELL CARCINOMA; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; INDUCED CANCER; CONVENIENT APPROXIMATION; CLASSIFICATION-SYSTEM AB OBJECTIVE. The objective of this study was to quantify the effects of radiation-induced cancer risks in patients with Bosniak category IIF lesions undergoing CT versus MRI surveillance. MATERIALS AND METHODS. We developed a Markov-Monte Carlo model to determine life expectancy losses attributable to radiation-induced cancers in hypothetical patients undergoing CT versus MRI surveillance of Bosniak IIF lesions. Our model tracked hypothetical patients as they underwent imaging surveillance for up to 5 years, accounting for potential lesion progression and treatment. Estimates of radiation-induced cancer mortality were generated using a published organ-specific radiation-risk model based on Biological Effects of Ionizing Radiation VII methods. The model also incorporated surgical mortality and renal cancer-specific mortality. Our primary outcome was life expectancy loss attributable to radiation-induced cancers. A sensitivity analysis was performed to assess the stability of the results with variability in key parameters. RESULTS. The mean number of examinations per patient was 6.3. In the base case, assuming 13 mSv per multiphase CT examination, 64-year-old men experienced an average life expectancy decrease of 5.5 days attributable to radiation-induced cancers from CT; 64-year-old women experienced a corresponding life expectancy loss of 6.9 days. The results were most sensitive to patient age: Life expectancy loss attributable to radiation-induced cancers increased to 21.6 days in 20-year-old women and 20.0 days in 20-year-old men. Varied assumptions of each modality's (CT vs MRI) depiction of lesion complexity also impacted life expectancy losses. CONCLUSION. Microsimulation modeling shows that radiation-induced cancer risks from CT surveillance for Bosniak IIF lesions minimally affect life expectancy. However, as progressively younger patients are considered, increasing radiation risks merit stronger consideration of MRI surveillance. C1 [Kang, Stella K.] NYU, Langone Med Ctr, Dept Radiol, New York, NY 10016 USA. [Kang, Stella K.; Turan, Ekin A.; Eisenberg, Jonathan D.; Lee, Pablo A.; Kong, Chung Yin; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Yin; Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kang, SK (reprint author), NYU, Langone Med Ctr, Dept Radiol, 550 First Ave, New York, NY 10016 USA. EM stella.kang@nyumc.org RI Kang, Stella/O-7003-2015; OI Kang, Stella/0000-0003-2402-3787 FU AUR GE Radiology Research Academic Fellowship; National Cancer Institute [K25CA133141, K07CA133097] FX S. K. Kang and this investigation were supported in part by an AUR GE Radiology Research Academic Fellowship Award; this investigation was also supported in part by the National Cancer Institute (award no. K25CA133141 to C. Y. Kong and award no. K07CA133097 to P. V. Pandharipande). NR 57 TC 0 Z9 0 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2014 VL 203 IS 6 BP W629 EP W636 DI 10.2214/AJR.14.12550 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY4DD UT WOS:000347527500008 PM 25415728 ER PT J AU Clark, KB AF Clark, Kevin B. TI Evolution of affective and linguistic disambiguation under social eavesdropping pressures SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID NONHUMAN PRIMATE; INFORMATION; LANGUAGE; VOCALIZATIONS; COMPREHENSION; STRATEGIES; RESOLUTION; MONKEYS AB Contradicting new dual-pathway models of language evolution, cortico-striatal-thalamic circuitry disambiguate uncertainties in affective prosody and propositional linguistic content of language production and comprehension, predictably setting limits on useful complexity of articulate phonic and/or signed speech. Such limits likely evolved to ensure public information is discriminated by intended communicants and safeguarded against the ecological pressures of social eavesdropping within and across phylogenetic boundaries. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Clark, KB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. EM kbclarkphd@yahoo.com NR 32 TC 0 Z9 0 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 2014 VL 37 IS 6 DI 10.1017/S0140525X13003993 PG 6 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA AZ2IE UT WOS:000348056700007 ER PT J AU Meier, IB Gu, Y Guzaman, VA Wiegman, AF Schupf, N Manly, JJ Luchsinger, JA Viswanathan, A Martinez-Ramirez, S Greenberg, SM Mayeux, R Brickman, AM AF Meier, Irene B. Gu, Yian Guzaman, Vanessa A. Wiegman, Anne F. Schupf, Nicole Manly, Jennifer J. Luchsinger, Jose A. Viswanathan, Anand Martinez-Ramirez, Sergi Greenberg, Steven M. Mayeux, Richard Brickman, Adam M. TI Lobar Microbleeds Are Associated with a Decline in Executive Functioning in Older Adults SO CEREBROVASCULAR DISEASES LA English DT Article DE Microbleeds; Cognition; Cerebral amyloid angiopathy; MRI; Longitudinal design ID CEREBRAL AMYLOID ANGIOPATHY; SMALL VESSEL DISEASE; COGNITIVE FUNCTION; ALZHEIMER-DISEASE; CARIBBEAN HISPANICS; NORTHERN MANHATTAN; AFRICAN-AMERICANS; BRAIN MICROBLEEDS; ROTTERDAM SCAN; IMPAIRMENT AB Background: Normal aging is associated with a decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, 'aging,' per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds - magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy - are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults. Methods: Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 months intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15 +/- 5.02 years). Microbleeds were rated visually on axial view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal views to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n = 11) and fewer than 2 (n = 186) lobar microbleeds and examined longitudinal cognitive change beginning 9.47 +/- 3.13 years before the MRI scan. Results: Subjects with 2 or more lobar microbleeds had worse executive functioning at the visit closest to the MRI scan (beta = -0.044; p < 0.001) and had a faster decline in executive function over time (beta = -0.072; p = 0.012) than subjects with fewer than 2 lobar microbleeds. The two groups were similar in age at scan date, education, ethnicity, sex distribution, and cognitive performance at first visit. Conclusions: Lobar microbleeds, a marker of cerebral amyloid angiopathy, are associated with an accelerated rate of executive function decline. The presence of cerebral amyloid angiopathy may be an important source of cognitive decline in aging. Future work should examine how cerebral amyloid angiopathy interacts with neurodegenerative processes, such as Alzheimer's disease. (C) 2014 S. Karger AG, Basel C1 [Meier, Irene B.; Gu, Yian; Guzaman, Vanessa A.; Wiegman, Anne F.; Schupf, Nicole; Manly, Jennifer J.; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Meier, Irene B.] Univ Zurich, Div Psychiat Res & Psychogeriatr Med, Zurich, Switzerland. [Schupf, Nicole; Manly, Jennifer J.; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Coll Phys & Surg, GH Sergievsky Ctr, New York, NY 10032 USA. [Schupf, Nicole; Luchsinger, Jose A.; Mayeux, Richard] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Manly, Jennifer J.; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Luchsinger, Jose A.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Viswanathan, Anand; Martinez-Ramirez, Sergi; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Brickman, AM (reprint author), Columbia Univ, Coll Phys & Surg, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, 630 West 168th St,P&S Box 16, New York, NY 10032 USA. EM amb2139@columbia.edu FU NIH [AG034189, AG037212, AG042483]; VELUX Foundation; Synapsis Foundation FX This work was supported by grants from NIH (AG034189, AG037212, AG042483), the VELUX Foundation, and the Synapsis Foundation. NR 32 TC 9 Z9 9 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD DEC PY 2014 VL 38 IS 5 BP 377 EP 383 DI 10.1159/000368998 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AZ2EF UT WOS:000348046700009 PM 25427958 ER PT J AU Sundberg, TB Xavier, RJ Schreiber, SL Shamji, AF AF Sundberg, Thomas B. Xavier, Ramnik J. Schreiber, Stuart L. Shamji, Alykhan F. TI Small-molecule control of cytokine function: new opportunities for treating immune disorders SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; ARYL-HYDROCARBON RECEPTOR; PATHOGENIC T(H)17 CELLS; CROHNS-DISEASE; IL-12/IL-23 INHIBITOR; HISTONE DEACETYLASES; IL-10 PRODUCTION; HDAC INHIBITORS; DRUG DISCOVERY AB Manipulating cytokine function with protein-based drugs has proven effective for treating a wide variety of autoimmune and autoinflammatory disorders. However, the limited ability of protein-based drugs to modulate intracellular targets, including many implicated by studies of the genetics and physiology of these diseases, and to coordinately neutralize redundant inflammatory cytokines, suggests an important and complementary role for small molecules in immunomodulatory drug development. The recent clinical approval of Janus kinase and phosphodiesterase inhibitors, along with emerging evidence from other compound classes, firmly establish small molecules as effective tools for modulating therapeutically relevant proteins that give rise to aberrant cytokine signaling or mediate its downstream consequences. C1 [Sundberg, Thomas B.; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Schreiber, Stuart L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Shamji, AF (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. EM ashamji@broadinstitute.org FU Leona M. and Harry B. Helmsley Charitable Trust FX The Leona M. and Harry B. Helmsley Charitable Trust (R.J.X, A.F.S., T.B.S., S.L.S.) provided support for the authors of this manuscript. S.L.S is an investigator of the Howard Hughes Medical Institute. NR 86 TC 6 Z9 6 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1367-5931 EI 1879-0402 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD DEC PY 2014 VL 23 BP 23 EP 30 DI 10.1016/j.cbpa.2014.08.013 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AY5ES UT WOS:000347596500005 PM 25222143 ER PT J AU Chiang, S Stern, JM Engel, J Levin, HS Haneef, Z AF Chiang, Sharon Stern, John M. Engel, Jerome, Jr. Levin, Harvey S. Haneef, Zulfi TI Differences in graph theory functional connectivity in left and right temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Brain imaging; Epilepsy; Functional MRI; Graph theory; Functional reorganization ID STRUCTURAL CONNECTIVITY; COGNITIVE DECLINE; HUMAN BRAIN; SMALL-WORLD; NETWORKS; MRI; MEMORY; FMRI; LATERALIZATION; ABNORMALITIES AB Purpose: To investigate lateralized differences in limbic system functional connectivity between left and right temporal lobe epilepsy (TLE) using graph theory. Methods: Interictal resting state fMRI was performed in 14 left TLE patients, 11 right TLE patients, and 12 controls. Graph theory analysis of 10 bilateral limbic regions of interest was conducted. Changes in edgewise functional connectivity, network topology, and regional topology were quantified, and then left and right TLE were compared. Results: Limbic edgewise functional connectivity was predominantly reduced in both left and right TLE. More regional connections were reduced in right TLE, most prominently involving reduced interhemispheric connectivity between the bilateral insula and bilateral hippocampi. A smaller number of limbic connections were increased in TLE, more so in left than in right TLE. Topologically, the most pronounced change was a reduction in average network betweenness centrality and concurrent increase in left hippocampal betweenness centrality in right TLE. In contrast, left TLE exhibited a weak trend toward increased right hippocampal betweenness centrality, with no change in average network betweenness centrality. Conclusion: Limbic functional connectivity is predominantly reduced in both left and right TLE, with more pronounced reductions in right TLE. In contrast, left TLE exhibits both edgewise and topological changes that suggest a tendency toward reorganization. Network changes in TLE and lateralized differences thereof may have important diagnostic and prognostic implications. Published by Elsevier B.V. C1 [Chiang, Sharon] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Stern, John M.; Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Levin, Harvey S.] Baylor Coll Med, Dept Phys Med, Houston, TX 77030 USA. [Levin, Harvey S.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Haneef, Zulfi] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Haneef, Zulfi] VA Med Ctr, Neurol Care Line, Houston, TX USA. RP Haneef, Z (reprint author), Baylor Coll Med, Dept Neurol, One Baylor Plaza,MS NB302, Houston, TX 77030 USA. EM zulfi.haneef@bcm.edu OI Chiang, Sharon/0000-0002-4548-4550 FU Epilepsy Foundation of America; National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences [2T15LM007093-21]; National Institute of Health [5T32CA096520-07]; Leff Family Foundation; National Institute of Neurological Disorders and Stroke [P01 NS02808, R01 NS33310, U01 NS42372, P20 NS80181]; Moody Foundation; Baylor College of Medicine Computational and Integrative Biomedical Research Center FX Funding for design and conduct of this study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript was provided by the Epilepsy Foundation of America. Support for this publication was provided by the National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences (Grant #2T15LM007093-21) (SC); the National Institute of Health (Grant #5T32CA096520-07) (SC); the Leff Family Foundation (JMS); the National Institute of Neurological Disorders and Stroke (Grants #P01 NS02808, R01 NS33310, U01 NS42372, P20 NS80181) (JE); the Moody Foundation (HSL); Epilepsy Foundation of America (Research Grants Program) (ZH); and the Baylor College of Medicine Computational and Integrative Biomedical Research Center Seed Grant Awards (ZH). NR 51 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2014 VL 108 IS 10 BP 1770 EP 1781 DI 10.1016/j.eplepsyres.2014.09.023 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA AY3RP UT WOS:000347500600011 PM 25445238 ER PT J AU Lankford, HV Swenson, ER AF Lankford, Harvey V. Swenson, Erik R. TI Dilated Hearts at High Altitude: Words From On High SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE altitude; cor pulmonale; dilated; Everest; heart; pulmonary; ventricle ID OPERATION EVEREST-II; MOUNTAIN-SICKNESS; EXTREME ALTITUDE; FAILURE; MASS AB Lankford, Harvey V, Erik R Swenson. Dilated hearts at high altitude: Words from on high. High Alt Med Biol 15:511-519, 2014.From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary. C1 [Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lankford, HV (reprint author), 8001 Riverside Dr, Richmond, VA 23225 USA. EM h.lankford@gmail.com NR 62 TC 2 Z9 2 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD DEC 1 PY 2014 VL 15 IS 4 BP 511 EP 519 PG 9 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA AX0HB UT WOS:000346632500032 PM 25369424 ER PT J AU Vick, JC Campbell, TF Shriberg, LD Green, JR Truemper, K Rusiewicz, HL Moore, CA AF Vick, Jennell C. Campbell, Thomas F. Shriberg, Lawrence D. Green, Jordan R. Truemper, Klaus Rusiewicz, Heather Leavy Moore, Christopher A. TI Data-Driven Subclassification of Speech Sound Disorders in Preschool Children SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID CLASSIFICATION-SYSTEM SDCS; UNDIFFERENTIATED LINGUAL GESTURES; LIP MUSCLE-ACTIVITY; LANGUAGE IMPAIRMENT; CHILDHOOD APRAXIA; DEVELOPMENTAL APRAXIA; RELIABILITY; COORDINATION; EXTENSIONS; KINEMATICS AB Purpose: The purpose of the study was to determine whether distinct subgroups of preschool children with speech sound disorders (SSD) could be identified using a subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes, or SUBARP). Of specific interest was finding evidence of a subgroup of SSD exhibiting performance consistent with atypical speech motor control. Method: Ninety-seven preschool children with SSD completed speech and nonspeech tasks. Fifty-three kinematic, acoustic, and behavioral measures from these tasks were input to SUBARP. Results: Two distinct subgroups were identified from the larger sample. The 1st subgroup (76%; population prevalence estimate = 67.8%-84.8%) did not have characteristics that would suggest atypical speech motor control. The 2nd subgroup (10.3%; population prevalence estimate = 4.3%-16.5%) exhibited significantly higher variability in measures of articulatory kinematics and poor ability to imitate iambic lexical stress, suggesting atypical speech motor control. Both subgroups were consistent with classes of SSD in the Speech Disorders Classification System (SDCS; Shriberg et al., 2010a). Conclusion: Characteristics of children in the larger subgroup were consistent with the proportionally large SDCS class termed speech delay; characteristics of children in the smaller subgroup were consistent with the SDCS subtype termed motor speech disorder-not otherwise specified. The authors identified candidate measures to identify children in each of these groups. C1 [Vick, Jennell C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Campbell, Thomas F.; Truemper, Klaus] Univ Texas Dallas, Richardson, TX 75083 USA. [Shriberg, Lawrence D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53706 USA. [Green, Jordan R.] MGH Inst Hlth Profess, Boston, MA USA. [Rusiewicz, Heather Leavy] Duquesne Univ, Pittsburgh, PA 15219 USA. [Moore, Christopher A.] US Dept Vet Affairs, Washington, DC USA. RP Vick, JC (reprint author), Case Western Reserve Univ, Cleveland, OH 44106 USA. EM jennell@case.edu FU National Institute on Deafness and Other Communication Disorders [R01 DC00822]; American Speech-Language-Hearing Foundation FX Funding for this project was provided by the National Institute on Deafness and Other Communication Disorders (Grant R01 DC00822; principal investigator, Christopher A. Moore) and the American Speech-Language-Hearing Foundation (New Century Scholars Doctoral Scholarship to Jennell C. Vick). We are especially grateful to the participants and their families, who graciously volunteered their time for this project. In addition, we gratefully acknowledge those whose work was critical for participant recruitment, data acquisition, data extraction, and computer programming: Tammy Nash, Jill Brady, Dayna Pitcairn, Denise Balason, Stacey Pavelko, Mitzi Kweder, Katherine Moreland, Lakshmi Venkatesh, Sharon Gretz, Kevin Reilly, Roger Steeve, Kathryn Connaghan, Yumi Sumida, Alyssa Mosely, Rossella Belli, Ettore Cavallaro, Jeanette Wu, Jenny Morus, Kelsey Moore, Mary Reeves, Nicholas Moon, Dennis Tang, Adam Politis, Andrea Kettler, Laura Worthen, Dara Cohen, Heather Mabie, Rebecca Mental, Michelle Foye, and Greg Lee. NR 60 TC 3 Z9 3 U1 2 U2 9 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 EI 1558-9102 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2014 VL 57 IS 6 BP 2033 EP 2050 DI 10.1044/2014_JSLHR-S-12-0193 PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4MK UT WOS:000348195300001 PM 25076005 ER PT J AU Engel, PA AF Engel, Peter A. TI Does metabolic failure at the synapse cause Alzheimer's disease? SO MEDICAL HYPOTHESES LA English DT Article ID AMYLOID PRECURSOR PROTEIN; TRAUMATIC BRAIN-INJURY; LONG-TERM DEPRESSION; IN-VIVO; AXONAL-TRANSPORT; INTERCELLULAR COMMUNICATION; APOLIPOPROTEIN-E; NEURODEGENERATIVE DISEASES; TAU HYPERPHOSPHORYLATION; FUNCTIONAL CONNECTIVITY AB Alzheimer's disease (AD) a neurodegenerative disorder of widely distributed cortical networks evolves over years while A beta (A beta) oligomer neurotoxicity occurs within seconds to minutes. This disparity combined with disappointing outcomes of anti-amyloid clinical trials challenges the centrality of A beta as principal mediator of neurodegeneration. Reconsideration of late life AD as the end-product of intermittent regional failure of the neuronal support system to meet the needs of vulnerable brain areas offers an alternative point of view. This model introduces four ideas: (1) That All is a synaptic signaling peptide that becomes toxic in circumstances of metabolic stress. (2) That intense synaptic energy and maintenance requirements of cortical hubs may exceed resources during peak demand initiating a neurotoxic cascade in these selectively vulnerable regions. (3) That axonal transport to and from neuron soma cannot account fully for high mitochondrial densities and other requirements of distant terminal axons. (4) That neurons as specialists in information management, delegate generic support functions to astrocytes and other cell types. Astrocytes use intercellular transport by exosomes and tunneling nanotubes (TNTs) to deliver mitochondria, substrates and protein reprocessing services to axonal sites distant from neuronal soma. This viewpoint implicates the brain's support system and its disruption by various age and disease-related insults as significant mediators of neurodegenerative disease. A better understanding of this system should broaden concepts of neurodegeneration and facilitate development of effective treatments. Published by Elsevier Ltd. C1 [Engel, Peter A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Cambridge, MA 02138 USA. RP Engel, PA (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM peter.engel@va.gov NR 121 TC 2 Z9 2 U1 4 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD DEC PY 2014 VL 83 IS 6 BP 802 EP 808 DI 10.1016/j.mehy.2014.10.013 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY5EJ UT WOS:000347595600037 PM 25456790 ER PT J AU Sakadzic, S Mandeville, ET Gagnon, L Musacchia, JJ Yaseen, MA Yucel, MA Lefebvre, J Lesage, F Dale, AM Eikermann-Haerter, K Ayata, C Srinivasan, VJ Lo, EH Devor, A Boas, DA AF Sakadzic, Sava Mandeville, Emiri T. Gagnon, Louis Musacchia, Joseph J. Yaseen, Mohammad A. Yucel, Meryem A. Lefebvre, Joel Lesage, Frederic Dale, Anders M. Eikermann-Haerter, Katharina Ayata, Cenk Srinivasan, Vivek J. Lo, Eng H. Devor, Anna Boas, David A. TI Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue SO NATURE COMMUNICATIONS LA English DT Article ID BLOOD-FLOW; VASCULAR NETWORK; CAPILLARIES; TRANSPORT; VESSELS; BRAIN; TENSION; CORTEX; MICROCIRCULATION; METABOLISM AB What is the organization of cerebral microvascular oxygenation and morphology that allows adequate tissue oxygenation at different activity levels? We address this question in the mouse cerebral cortex using microscopic imaging of intravascular O-2 partial pressure and blood flow combined with numerical modelling. Here we show that parenchymal arterioles are responsible for 50% of the extracted O-2 at baseline activity, and the majority of the remaining O-2 exchange takes place within the first few capillary branches. Most capillaries release little O-2 at baseline acting as an O-2 reserve that is recruited during increased neuronal activity or decreased blood flow. Our results challenge the common perception that capillaries are the major site of O-2 delivery to cerebral tissue. The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of blood-oxygen-level dependent (BOLD) contrast in functional magnetic resonance imaging and for evaluating microvascular O-2 delivery capacity to support cerebral tissue in disease. C1 [Sakadzic, Sava; Gagnon, Louis; Musacchia, Joseph J.; Yaseen, Mohammad A.; Yucel, Meryem A.; Srinivasan, Vivek J.; Devor, Anna; Boas, David A.] Massachusetts Gen Hosp, Dept Radiol, MHG MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Opt Div, Charlestown, MA 02129 USA. [Sakadzic, Sava; Mandeville, Emiri T.; Gagnon, Louis; Musacchia, Joseph J.; Yaseen, Mohammad A.; Yucel, Meryem A.; Eikermann-Haerter, Katharina; Ayata, Cenk; Srinivasan, Vivek J.; Lo, Eng H.; Devor, Anna; Boas, David A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Mandeville, Emiri T.; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Mandeville, Emiri T.; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Gagnon, Louis; Lefebvre, Joel; Lesage, Frederic] Ecole Polytech, Dept Genie Elect, Montreal, PQ H3C 3A7, Canada. [Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Eikermann-Haerter, Katharina; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Neurosci Intens Care Unit, Boston, MA 02114 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sakadzic, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, MHG MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Opt Div, Charlestown, MA 02129 USA. EM sava.sakadzic@mgh.harvard.edu FU American Heart Association [SDG7600037]; National Institute of Health [EB000790, NS055104, NS057476, K99AG042026] FX We would like to thank Sergei A. Vinogradov and Emmanouil Rousakis for providing the oxygen-sensitive dye and for their help with the PO2 imaging. We would also like to thank support from the American Heart Association (grant SDG7600037) and from the National Institute of Health (grants EB000790, NS055104, NS057476 and K99AG042026). NR 43 TC 26 Z9 26 U1 2 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 DEC PY 2014 VL 5 AR 5734 DI 10.1038/ncomms6734 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY5KO UT WOS:000347611200003 PM 25483924 ER PT J AU Velazquez, ER Hoebers, F Aerts, HJWL Rietbergen, MM Brakenhoff, RH Leemans, RC Speel, EJ Straetmans, J Kremer, B Lambin, P AF Velazquez, Emmanuel Rios Hoebers, Frank Aerts, Hugo J. W. L. Rietbergen, Michelle M. Brakenhoff, Ruud H. Leemans, Rene C. Speel, Ernst-Jan Straetmans, Jos Kremer, Bernd Lambin, Philippe TI Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Oropharyngeal cancer; Human papillomavirus; Decision support systems; Outcome prediction; Predictive nomogram ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; CANCER; SURVIVAL; RADIOTHERAPY; RISK; COMORBIDITY; HEAD; CARE; EXPRESSION AB Purpose: Due to the established role of the human papillomavirus (HPV), the optimal treatment for oropharyngeal carcinoma is currently under debate. We evaluated the most important determinants of treatment outcome to develop a multifactorial predictive model that could provide individualized predictions of treatment outcome in oropharyngeal carcinoma patients. Methods: We analyzed the association between clinico-pathological factors and overall and progression-free survival in 168 OPSCC patients treated with curative radiotherapy or concurrent chemo-radiation. A multivariate model was validated in an external dataset of 189 patients and compared to the TNM staging system. This nomogram will be made publicly available at www.predictcancer.org. Results: Predictors of unfavorable outcomes were negative HPV-status, moderate to severe comorbidity, T3-T4 classification, N2b-N3 stage, male gender, lower hemoglobin levels and smoking history of more than 30 pack years. Prediction of overall survival using the multi-parameter model yielded a C-index of 0.82 (95% CI, 0.76-0.88). Validation in an independent dataset yielded a C-index of 0.73 (95% CI, 0.66-0.79. For progression-free survival, the model's C-index was 0.80 (95% Cl, 0.76-0.88), with a validation C-index of 0.67, (95% Cl, 0.59-0.74). Stratification of model estimated probabilities showed statistically different prognosis groups in both datasets (p < 0.001). Conclusion: This nomogram was superior to TNM classification or HPV status alone in an independent validation dataset for prediction of overall and progression-free survival in OPSCC patients, assigning patients to distinct prognosis groups. These individualized predictions could be used to stratify patients for treatment de-escalation trials. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Velazquez, Emmanuel Rios; Hoebers, Frank; Lambin, Philippe] Maastricht Univ, Res Inst GROW, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Velazquez, Emmanuel Rios; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Rad Oncol, Boston, MA 02115 USA. [Rietbergen, Michelle M.; Brakenhoff, Ruud H.; Leemans, Rene C.] Maastricht Univ, Med Ctr, Dept Pathol, GROW Res Inst, Maastricht, Netherlands. [Speel, Ernst-Jan] Maastricht Univ, Med Ctr, Dept Pathol, Maastricht, Netherlands. [Straetmans, Jos; Kremer, Bernd] Maastricht Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Maastricht, Netherlands. RP Velazquez, ER (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,JF518, Boston, MA 02115 USA. EM Emmanuel_Rios@dfci.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU CTMM framework (AIRFORCE project) [030-103]; EU (METOXIA); EU (EURECA); EU (ARTFORCE); euroCAT (IVA Interreg); Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454] FX Authors acknowledge financial support from the CTMM framework (AIRFORCE project, Grant 030-103), EU 6th and 7th framework program (METOXIA, EURECA, ARTFORCE), euroCAT (IVA Interreg - www.eurocat.info) and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454). NR 27 TC 12 Z9 12 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 2014 VL 113 IS 3 BP 324 EP 330 DI 10.1016/j.radonc.2014.09.005 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AY5EX UT WOS:000347596900004 ER PT J AU Damato, AL Devlin, PM Bhagwat, MS Buzurovic, I Friesen, S Hansen, JL Lee, LJ Molodowitch, C Nguyen, PL O'Farrell, DA Viswanathan, AN Williams, CL Killoran, JH Cormack, RA AF Damato, Antonio L. Devlin, Phillip M. Bhagwat, Mandar S. Buzurovic, Ivan Friesen, Scott Hansen, Jorgen L. Lee, Larissa J. Molodowitch, Christina Nguyen, Paul L. O'Farrell, Desmond A. Viswanathan, Akila N. Williams, Christopher L. Killoran, Joseph H. Cormack, Robert A. TI Independent brachytherapy plan verification software: Improving efficacy and efficiency SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Brachytherapy; Errors; Plan verification ID TREATMENT DELIVERY ERRORS; RADIATION-THERAPY; QUALITY-ASSURANCE; INTERSTITIAL BRACHYTHERAPY; CLINICAL RADIOTHERAPY; COMPUTERIZED RECORD; TECHNOLOGIES; ONCOLOGY; IMPACT; RATES AB Background and purpose: To compare the pre-treatment brachytherapy plan verification by a physicist assisted by custom plan verification software (SAV) with those performed manually (MV). Materials and methods: All HDR brachytherapy plans used for treatment in 2013, verified using either SAV or MV, were retrospectively reviewed. Error rate (number of errors/number of plans) was measured and verification time calculated. All HDR brachytherapy safety events recorded between 2010 and 2013 were identified. The rate of patient-related safety events (number of events/number of fractions treated) and the impact of SAV on the underlying errors were assessed. Results: Three/106 errors (2.8%) were found in the SAV group and 24/273 (8.8%) in the MV group (p = 0.046). The mean +/- 1 standard deviation plan verification time was 8.4 +/- 4.0 min for SAV and 11.6 +/- 5.3 for MV (p = 0.006). Seven safety events out of 4729 fractions delivered (0.15%) were identified. Four events (57%) were associated with plan verification and could have been detected by SAV. Conclusions: We found a safety event rate in HDR brachytherapy of 0.15%. SAV significantly reduced the number of undetected errors in HDR treatment plans compared to MV, and reduced the time required for plan verification. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Damato, Antonio L.; Devlin, Phillip M.; Bhagwat, Mandar S.; Buzurovic, Ivan; Friesen, Scott; Hansen, Jorgen L.; Lee, Larissa J.; Molodowitch, Christina; Nguyen, Paul L.; O'Farrell, Desmond A.; Viswanathan, Akila N.; Williams, Christopher L.; Killoran, Joseph H.; Cormack, Robert A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Damato, AL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASB1,L2,75 Francis St, Boston, MA 02115 USA. EM adamato@lroc.harvard.edu RI Buzurovic, Ivan/C-8036-2011 OI Buzurovic, Ivan/0000-0001-9632-3434 NR 31 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 2014 VL 113 IS 3 BP 420 EP 424 DI 10.1016/j.radonc.2014.09.015 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AY5EX UT WOS:000347596900020 PM 25458129 ER PT J AU Shah, MA Enzinger, PC AF Shah, Manish A. Enzinger, Peter C. TI Evidence-Based Management of Advanced Gastric Cancer: Current and Emerging Targeted Therapies SO SEMINARS IN ONCOLOGY LA English DT Editorial Material AB Gastric cancer is the second leading cause of cancer mortality and the fourth most common malignancy worldwide. An estimated 21,600 new cases of gastric cancer were diagnosed in the United States in 2013, and more than 10,000 people died of the disease. Although treatment of resectable gastric cancer has improved over the last two decades, little progress has been made in advanced gastric cancer. After a patient has progressed on first-line treatment, no second-line treatment for gastric cancer has yet been approved by the US Food and Drug Administration. Several clinical trials for therapies targeting aberrant signaling pathways either have concluded or are underway. These targeted treatments have the potential to substantially improve patient outcomes. However, with each new treatment, clinicians must stay abreast of a new wave of data on underlying mechanisms, efficacy, and safety, to provide their patients with optimal care. The magnitude of information surrounding emerging treatments for advanced gastric cancer can be daunting; this monograph will provide hospital-based clinicians with a much-needed, concise overview of the available data. C1 [Shah, Manish A.] Weill Cornell Med Coll, New York, NY USA. [Shah, Manish A.] New York Presbyterian Hosp, Ctr Adv Digest Care, New York, NY USA. [Enzinger, Peter C.] Harvard Univ, Sch Med, Boston, MA USA. [Enzinger, Peter C.] Dana Farber Canc Inst, Ctr Esophageal & Gastr Canc, Boston, MA 02115 USA. RP Shah, MA (reprint author), Weill Cornell Med Coll, New York, NY 10065 USA. EM mas9313@med.cornell.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2014 VL 41 IS 6 BP S2 EP S2 DI 10.1053/j.seminoncol.2014.10.002 PG 1 WC Oncology SC Oncology GA AY6CQ UT WOS:000347655600015 ER PT J AU Liu, S Ren, JA Gu, GS Wang, GF Han, G Yan, DS Ren, HJ Wu, XW Xia, QY Zhou, B Chen, J Zhao, YZ Li, JS AF Liu, Song Ren, Jianan Gu, Guosheng Wang, Gefei Han, Gang Yan, Dongsheng Ren, Huajian Wu, Xiuwen Xia, Qiuyuan Zhou, Bo Chen, Jun Zhao, Yunzhao Li, Jieshou TI Comparative Outcomes of Trocar Puncture With Sump Drain, Percutaneous Drainage, and Surgical Drainage in the Management of Intra-abdominal Abscesses in Crohn's Disease SO SURGICAL INNOVATION LA English DT Article DE Crohn's disease; abscess; drainage; intra-abdominal; inflammatory bowel disease ID PELVIC ABSCESS; COMPLICATIONS; SMOKING; RISK; TERM AB Background. Intra-abdominal abscess is a common complication in Crohn's disease (CD). Traditional percutaneous catheter drainage (PCD) and surgical intervention could not obtain satisfactory results in some cases. We herein demonstrate a novel management option and compare it with traditional strategies. Methods. A total of 77 patients were retrospectively collected into 3 groups. Postoperative complication, postoperative recurrence of abscess, subsequent surgery, ultimate stoma creation rate, and survival rate were analyzed. Results. Patients were divided into the trocar group (n = 21), PCD group (n = 25), and surgery group (n = 31). The incidences of postoperative complication as well as the incidence of recurrent abscess were lowest in trocar group, and ultimate stoma creation rate was highest in the surgery group. Subsequent surgery after initial intervention and survival rate during the follow-up period were similar among the 3 groups. Conclusions. Trocar puncture with sump drain had lower incidence of postoperative complication, postoperative recurrence of abscess, and ultimate stoma creation compared with conventional PCD and surgical interventions. This novel technique might be an optimal option in the management of intra-abdominal abscesses in CD. C1 [Liu, Song; Ren, Jianan; Gu, Guosheng; Wang, Gefei; Yan, Dongsheng; Ren, Huajian; Wu, Xiuwen; Zhou, Bo; Chen, Jun; Zhao, Yunzhao; Li, Jieshou] Nanjing Univ, Sch Med, Dept Surg, Jinling Hosp, Nanjing 210002, Jiangsu, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Diseaes, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA USA. [Han, Gang] Jilin Univ, Gen Surg Ctr, Changchun 130023, Peoples R China. [Xia, Qiuyuan] Nanjing Univ, Sch Med, Dept Pathol, Jinling Hosp, Nanjing 210002, Jiangsu, Peoples R China. RP Ren, JA (reprint author), Nanjing Univ, Sch Med, Dept Surg, Jinling Hosp, 305 East Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM jiananr@gmail.com FU National Natural Science Foundation of China [81270478]; Climbing Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars [BK2010017]; High-Level Personnel Training Project [BRA2011232]; China Scholarship Council FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the National Natural Science Foundation of China, No. 81270478 (JR); Climbing Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars, No. BK2010017 (JR); High-Level Personnel Training Project, No. BRA2011232 (JR); and China Scholarship Council (award to SL for study at Massachusetts General Hospital, Harvard Medical School). NR 34 TC 2 Z9 3 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1553-3506 EI 1553-3514 J9 SURG INNOV JI Surg. Innov. PD DEC PY 2014 VL 21 IS 6 BP 580 EP 589 DI 10.1177/1553350614526787 PG 10 WC Surgery SC Surgery GA AZ2ZW UT WOS:000348098600005 PM 24667522 ER PT J AU Lee, LY Koehler, UA Zhang, L Roenneburg, D Werner, S Johnson, JA Foley, DP AF Lee, Lung-Yi Koehler, Ulrike A. Zhang, Li Roenneburg, Drew Werner, Sabine Johnson, Jeffrey A. Foley, David P. TI Activation of the Nrf2-ARE Pathway in Hepatocytes Protects Against Steatosis in Nutritionally Induced Non-alcoholic Steatohepatitis in Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE liver; Nrf2; antioxidants; steatosis; NASH; transgenic mice ID HIGH-FAT DIET; OXIDATIVE STRESS; LIPID-ACCUMULATION; HEPATIC STEATOSIS; NRF2-NULL MICE; LIVER-DISEASE; ALPHA-SMA; EXPRESSION; GENES; KEAP1 AB Oxidative stress is implicated in the development of non-alcoholic steatohepatitis (NASH). The Nrf2-antioxidant response element pathway protects cells from oxidative stress. Studies have shown that global Nrf2 deficiency hastens the progression of NASH. The purpose of this study was to determine whether long-term hepatocyte-specific activation of Nrf2 mitigates NASH progression. Transgenic mice expressing a constitutively active Nrf2 construct in hepatocytes (AlbCre+/caNrf2+) and littermate controls were generated. These mice were fed standard or methionine-choline-deficient (MCD) diet, a diet used to induce NASH development in rodents. After 28 days of MCD dietary feeding, mice developed significant increases in steatosis, inflammation, oxidative stress, and HSC activation compared with those mice on standard diet. AlbCre+/caNrf2+ animals had significantly decreased serum transaminases and reduced steatosis when compared with the AlbCre+/caNrf2- animals. This significant reduction in steatosis was associated with increased expression of genes involved in triglyceride export (MTTP) and beta-oxidation (CPT2). However, there were no differences in the increased oxidative stress, inflammation, and HSC activation from MCD diet administration between the AlbCre+/caNrf2- and AlbCre+/caNrf2+ animals. We conclude that hepatocyte-specific activation of Nrf2-mediated gene expression decreased hepatocellular damage and steatosis in a dietary model of NASH. However, hepatocyte-specific induction of Nrf2-mediated gene expression alone is insufficient to mitigate inflammation, oxidative stress, and HSC activation in this nutritional NASH model. C1 [Lee, Lung-Yi; Zhang, Li; Roenneburg, Drew; Foley, David P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53726 USA. [Koehler, Ulrike A.; Werner, Sabine] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland. [Johnson, Jeffrey A.] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Ctr Neurosci, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Foley, David P.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Foley, DP (reprint author), Clin Sci Ctr H4 766, 600 Highland Ave, Madison, WI 53792 USA. EM foley@surgery.wisc.edu FU Clinical and Translational Science Award (CTSA) program through National Institutes of Health National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award; National Institutes of Health [T32 CA090217]; American College of Surgeons Resident Research Scholarship; Swiss National Science Foundation [310030_132884]; Boehringer Ingelheim Fonds FX The Clinical and Translational Science Award (CTSA) program, through the National Institutes of Health National Center for Advancing Translational Sciences (NCATS) (UL1TR000427 to D.P.F.); the American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award (to D.P.F.), National Institutes of Health (T32 CA090217 to L.-Y.L.), the American College of Surgeons Resident Research Scholarship (to L.-Y.L.), the Swiss National Science Foundation (310030_132884 to S.W.); and a predoctoral fellowship from the Boehringer Ingelheim Fonds (U.A.K.). NR 37 TC 5 Z9 5 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2014 VL 142 IS 2 BP 361 EP 374 DI 10.1093/toxsci/kfu184 PG 14 WC Toxicology SC Toxicology GA AY5MZ UT WOS:000347617800006 PM 25294219 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Ruling in or out a source of gastrointestinal bleeding SO UNITED EUROPEAN GASTROENTEROLOGY JOURNAL LA English DT Article DE Bayes' formula; gastrointestinal bleeding; gastrointestinal endoscopy; medical decision analysis; outcome research AB Background and aims: The search for a source of gastrointestinal bleeding is associated with two distinct approaches of trying to rule in a specific diagnosis or rule out any potential source of bleeding. The study aim was to understand the conceptual differences underlying the two searches. Methods: The performance of endoscopy as diagnostic test is analyzed in terms of Bayes' formula. Results: The performance of gastrointestinal endoscopy to rule in a suspected lesion is mostly influenced by its underlying specificity. Because the specificity of endoscopy is less likely to be affected by procedural exigencies, the demands on pre-procedural prep and general quality can be more relaxed. In contradistinction, the performance of endoscopy to rule out a suspected bleeding site is mostly influenced by its sensitivity, which can easily be compromised by suboptimal procedural conditions. Conclusions: Paradoxically, the more urgent, focused, and important search (to rule in a bleeding site), carries less stringent criteria for its execution than the more general and aimless search (to rule out a bleeding site) that frequently ends up just empty handed. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 6 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 2050-6406 EI 2050-6414 J9 UNITED EUR GASTROENT JI United European Gastroenterol. J. PD DEC PY 2014 VL 2 IS 6 BP 471 EP 474 DI 10.1177/2050640614557319 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AY8AS UT WOS:000347777400003 PM 25436110 ER PT J AU Alcala-Cerra, G Young, AMH Moscote-Salazar, LR Paternina-Caicedo, A AF Alcala-Cerra, Gabriel Young, Adam M. H. Rafael Moscote-Salazar, Luis Paternina-Caicedo, Angel TI Efficacy and Safety of Subdural Drains After Burr-Hole Evacuation of Chronic Subdural Hematomas: Systematic Review and Meta-Analysis of Randomized Controlled Trials SO WORLD NEUROSURGERY LA English DT Article DE Burr-hole; Chronic subdural hematoma; Closed-system drainage; Recurrence; Reoperation ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; CLINICAL ARTICLE; NATIONAL-SURVEY; RISK-FACTORS; RECURRENCE; MANAGEMENT; RECOMMENDATIONS; CRANIOSTOMY; IRRIGATION; ISCHEMIA AB OBJECTIVE: To determine whether the use of a subdural drain after burr-hole evacuation of a chronic subdural hematoma is safe and effective in preventing recurrence and subsequent operations, and as such improving functional outcomes. METHODS: The literature search included the following databases: PubMed, the National Institutes of Health/National Library of Medicine, Clinical Trials Registry, CENTRAL (The Cochrane Library), EMBASE, and LILACS. The search was performed in June 2013, and did not have restrictions or filters with regard to language or year of publication. Methodologic quality was assessed through the Jadad's scale. Primary outcomes were recurrence and reoperation rates. Secondary outcomes were functional outcome, mortality, and postoperative complications. Results were presented as pooled Mantel-Haenszel relative risks (RR), with 95% confidence intervals (95% CI). RESULTS: A total of 7 randomized controlled trials were analyzed. Three studies were classified as high methodologic quality and four as low quality. Pooled RR were symptomatic recurrence (RR 0.51; 95% CI 0.36-0.75), reoperation (RR 0.5; 95% CI 0.34-0.74), poor functional outcome (RR 0.61, 95% CI 0.39-0.98), mortality (RR 0.67, 95% CI 0.37-1.22), and postoperative complications (RR 1.28, 95% CI 0.78-2.11). There was no statistically significant heterogeneity within the outcomes. CONCLUSIONS: The meta-analysis demonstrates that the insertion of a subdural drain was associated with a statistically significant reduction in the risk of symptomatic recurrence and the requirement for further surgical intervention of chronic subdural hematoma after surgical evacuation. Furthermore, it was associated with statistically significant improvements in both short-term and long-term functional outcome. C1 [Alcala-Cerra, Gabriel; Rafael Moscote-Salazar, Luis; Paternina-Caicedo, Angel] Univ Cartagena, Hlth Sci & Neurosci Res Grp CISNEURO, Cartagena De Indias, Colombia. [Alcala-Cerra, Gabriel] Univ Cartagena, Fac Med, Dept Neurosurg, Cartagena De Indias, Colombia. [Young, Adam M. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Young, Adam M. H.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 2QQ, England. RP Alcala-Cerra, G (reprint author), Univ Cartagena, Hlth Sci & Neurosci Res Grp CISNEURO, Cartagena De Indias, Colombia. EM alcalag@egresado.uninorte.edu.co RI Paternina-Caicedo, Angel/N-4496-2015 OI Paternina-Caicedo, Angel/0000-0002-6332-5174 NR 58 TC 7 Z9 7 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD DEC PY 2014 VL 82 IS 6 DI 10.1016/j.wneu.2014.08.012 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AY5TZ UT WOS:000347635900099 PM 25118059 ER PT J AU Wheeler, LA Chiocca, EA AF Wheeler, Lee Adam Chiocca, E. Antonio TI Predicting Outcomes: Recursive Partitioning Analysis (RPA) Prognostic Algorithm for Patients with Metastatic Sarcoma to the Brain SO WORLD NEUROSURGERY LA English DT Editorial Material DE Brain metastases; Recursive partitioning analysis (RPA); Sarcoma; Surgery ID SOLID TUMORS; EPIDEMIOLOGY; CANCER; MANAGEMENT; CHILDREN; TRENDS C1 [Wheeler, Lee Adam] Harvard Univ, Brigham & Womens Faulkner Hosp, Sch Med, Dept Neurosurg,Inst Neurosci, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Brigham & Womens Faulkner Hosp, Sch Med, Dept Neurosurg,Inst Neurosci, Boston, MA 02115 USA. EM EAChiocca@partners.org NR 25 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD DEC PY 2014 VL 82 IS 6 DI 10.1016/j.wneu.2014.09.015 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AY5TZ UT WOS:000347635900075 PM 25246369 ER PT J AU Sartor, CE Wang, ZH Xu, K Kranzler, HR Gelernter, J AF Sartor, Carolyn E. Wang, Zuoheng Xu, Ke Kranzler, Henry R. Gelernter, Joel TI The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African-American and European-American Women and Men SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Childhood Adversity; ADH1B; Alcohol; African Americans ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; MAO-A GENE; SEXUAL-ABUSE; PSYCHIATRIC-DISORDER; SEMISTRUCTURED ASSESSMENT; JEWISH POPULATION; DRINKING HABITS; YOUNG ADULTHOOD; DRUG-DEPENDENCE AB BackgroundThe ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes. This study examined the joint effects of variation in ADH1B and childhood adversitya well-documented risk factor for alcohol problems and moderator of genetic liability to psychiatric outcomeson maximum drinks consumed in a 24-hour period (maxdrinks) and alcohol use disorder (AUD) symptoms. MethodsData were drawn from 2,617 African-American (AA) and 1,436 European-American (EA) participants (42% female) in a multisite genetic study of substance dependence. We tested the most significant ADH1B single nucleotide polymorphisms for alcohol dependence from a genomewide association study with this sample, ADH1B-rs1229984 (Arg48His) and ADH1B-rs2066702 (Arg370Cys), in EA and AA subsamples, respectively. ResultsOrdinal regression analyses conducted separately by sex and population revealed significant main effects for childhood adversity for both alcohol phenotypes in AA women and men and for maxdrinks in EA women. A significant rs1229984 by childhood adversity interaction was observed for AUD symptoms in EA men. Unexposed His-allele carriers reported a mean of 3.6 AUD criteria, but adversity-exposed His-allele carriers endorsed approximately the same number (6.3) as those without the protective allele (6.3 and 7.0 for adversity-exposed and -unexposed groups, respectively). ConclusionsResults suggest that under conditions of childhood adversity, the His allele does not exert its protective effects in EA men (OR=0.57, CI: 0.32 to 1.01; p=0.056). Findings highlight the robust risk effect conferred by childhood adversity and the importance of considering population and sex in genetically informative investigations of its association with alcohol outcomes. C1 [Sartor, Carolyn E.; Xu, Ke; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Wang, Zuoheng] Yale Univ, Sch Med, Dept Biostat, New Haven, CT USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, Educ & Clin Ctr, Mental Illness Res VISN4, Philadelphia, PA USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Gelernter, Joel] VA Connecticut Healthcare Syst, West Haven, CT USA. RP Sartor, CE (reprint author), Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Dept Psychiat, 950 Campbell Ave 151D, West Haven, CT 06516 USA. EM carolyn.sartor@yale.edu FU NIH [DA12849, DA00167, DA12690, AA017921, AA11330, AA13736]; CTSA [KL2 RR024138]; Robert E. Leet and Clara Guthrie Patterson Trust; APA/Merck Early Academic Career Award Program; VA CT and Philadelphia VA Mental Illness Research, Education, and Clinical Centers FX The following investigators oversaw subject recruitment and assessment at their respective sites: Roger Weiss, M.D. (McLean Hospital), Kathleen Brady, M.D., Ph.D. and Raymond Anton, M.D. (Medical University of South Carolina), and David Oslin, M.D. (University of Pennsylvania). This work was supported by NIH grants DA12849, DA00167, DA12690, AA017921, AA11330, and AA13736, CTSA KL2 RR024138, the Robert E. Leet and Clara Guthrie Patterson Trust, the APA/Merck Early Academic Career Award Program, and the VA CT and Philadelphia VA Mental Illness Research, Education, and Clinical Centers. NR 47 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2907 EP 2914 DI 10.1111/acer.12572 PG 8 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500006 PM 25410943 ER PT J AU Metten, P Iancu, OD Spence, SE Walter, NAR Oberbeck, D Harrington, CA Colville, A McWeeney, S Phillips, TJ Buck, KJ Crabbe, JC Belknap, JK Hitzemann, RJ AF Metten, Pamela Iancu, Ovidiu D. Spence, Stephanie E. Walter, Nicole A. R. Oberbeck, Denesa Harrington, Christina A. Colville, Alexandre McWeeney, Shannon Phillips, Tamara J. Buck, Kari J. Crabbe, John C. Belknap, John K. Hitzemann, Robert J. TI Dual-Trait Selection for Ethanol Consumption and Withdrawal: Genetic and Transcriptional Network Effects SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Consumption and Withdrawal; Weighted Gene Co-Expression Network Analysis; Dual-Trait Selective Breeding; Mouse; Microarray ID MAP KINASE PATHWAY; ALCOHOL-WITHDRAWAL; VOLUNTARY CONSUMPTION; C57BL/6J MICE; MOUSE LINES; DRINKING; LOCI; DEPENDENCE; SUSCEPTIBILITY; PREFERENCE AB BackgroundData from C57BL/6J (B6)xDBA/2J (D2) F-2 intercrosses (B6xD2F(2)), standard and recombinant inbred strains, and heterogeneous stock mice indicate that a reciprocal (or inverse) genetic relationship exists between alcohol consumption and withdrawal severity. Furthermore, some genetic studies have detected reciprocal quantitative trait loci (QTLs) for these traits. We used a novel mouse model developed by simultaneous selection for both high alcohol consumption/low withdrawal and low alcohol consumption/high withdrawal and analyzed the gene expression and genome-wide genotypic differences. MethodsRandomly chosen third selected generation (S-3) mice (N=24/sex/line), bred from a B6xD2F(2), were genotyped using the Mouse Universal Genotyping Array, which provided 2,760 informative markers. QTL analysis used a marker-by-marker strategy with the threshold for a significant log of the odds (LOD) set at 10. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene co-expression network analysis (WGCNA) were implemented. ResultsSignificant QTLs for consumption/withdrawal were detected on chromosomes (Chr) 2, 4, 9, and 12. A suggestive QTL mapped to Chr 6. Some of the QTLs overlapped with known QTLs mapped for 1 of the traits individually. One thousand seven hundred and forty-five transcripts were detected as being differentially expressed between the lines; there was some overlap with known withdrawal genes (e.g., Mpdz) located within QTL regions. WGCNA revealed several modules of co-expressed genes showing significant effects in both differential expression and intramodular connectivity; a module richly annotated with kinase-related annotations was most affected. ConclusionsMarked effects of selection on expression and network structure were detected. QTLs overlapping with differentially expressed genes on Chr 2 (distal) and 4 suggest that these are cis-eQTLs (Chr 2: Kif3b, Kcnq2; Chr 4: Mpdz, Snapc3). Other QTLs identified were on Chr 2 (proximal), 9, and 12. Network results point to involvement of kinase-related mechanisms and outline the need for further efforts such as interrogation of noncoding RNAs. C1 [Metten, Pamela; Iancu, Ovidiu D.; Spence, Stephanie E.; Walter, Nicole A. R.; Oberbeck, Denesa; Colville, Alexandre; McWeeney, Shannon; Phillips, Tamara J.; Buck, Kari J.; Crabbe, John C.; Belknap, John K.; Hitzemann, Robert J.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Metten, Pamela; Iancu, Ovidiu D.; Spence, Stephanie E.; Walter, Nicole A. R.; Oberbeck, Denesa; Colville, Alexandre; Phillips, Tamara J.; Buck, Kari J.; Crabbe, John C.; Belknap, John K.; Hitzemann, Robert J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Harrington, Christina A.] Oregon Hlth & Sci Univ, Integrated Genom Lab, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Biostat Publ Hlth & Preventat Med, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol Med Informat & Cl, Portland, OR 97201 USA. RP Metten, P (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 12, Portland, OR 97239 USA. EM mettenp@ohsu.edu FU Department of Veterans Affairs [P60 AA010760, R01 AA011034, R01 AA013484, R01 AA006243, R01 AA011114, 5UL1 RR024140, U01 AA013519, R24 AA020245]; Department of the Army/Department of Defense-TATRC [10245005.05] FX The authors are grateful for the assistance of Mr. Jason Schlumbohm, Mr. Larry Huang, Ms. Karen Shepherdson, Mr. Jason Erk, Mr. Andy-Jade Cameron, and Dr. Mark Rutledge-Gorman in performance of these experiments, sample preparation, assistance with data presentation, and manuscript submission. This study was supported by P60 AA010760, R01 AA011034, R01 AA013484, R01 AA006243, R01 AA011114, 5UL1 RR024140, U01 AA013519, R24 AA020245, grants from the Department of Veterans Affairs, and grant 10245005.05 from the Department of the Army/Department of Defense-TATRC. NR 44 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2915 EP 2924 DI 10.1111/acer.12574 PG 10 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500007 PM 25581648 ER PT J AU Fortier, CB Leritz, EC Salat, DH Lindemer, E Maksimovskiy, AL Shepel, J Williams, V Venne, JR Milberg, WP McGlinchey, RE AF Fortier, Catherine B. Leritz, Elizabeth C. Salat, David H. Lindemer, Emily Maksimovskiy, Arkadiy L. Shepel, Juli Williams, Victoria Venne, Jonathan R. Milberg, William P. McGlinchey, Regina E. TI Widespread Effects of Alcohol on White Matter Microstructure SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Brain; Addiction; Diffusion Magnetic Resonance; White Matter; Alcoholism ID PREFRONTAL CORTEX; CIGARETTE-SMOKING; DIFFUSION MRI; BRAIN-DAMAGE; DISRUPTION; ADDICTION; DRINKING; CONSUMPTION; PERFORMANCE; BEHAVIORS AB BackgroundEvidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence. MethodsGlobal and regional WM microstructure was assessed using diffusion magnetic resonance measures of fractional anisotropy (FA) for 31 abstinent alcoholics (ALC) with an average of 25years of abuse and approximately 5years of sobriety and 20 nonalcoholic control (NC) participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using tract-based spatial statistics. Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxelwise analysis. ResultsWidespread, bilateral reductions in FA were observed in ALC as compared to NC participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity. ConclusionsThis study found widespread reductions in WM integrity in a group of ALC compared to NC participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety. C1 [Fortier, Catherine B.; Leritz, Elizabeth C.; Salat, David H.; Maksimovskiy, Arkadiy L.; Shepel, Juli; Williams, Victoria; Venne, Jonathan R.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Fortier, Catherine B.; Leritz, Elizabeth C.; Salat, David H.; Lindemer, Emily; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Neuroimaging Res Ctr Vet, Boston, MA 02130 USA. [Fortier, Catherine B.; Venne, Jonathan R.; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA USA. [Leritz, Elizabeth C.; Salat, David H.; Shepel, Juli; Williams, Victoria] Anthinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Maksimovskiy, Arkadiy L.] Boston Univ, Sch Med, Dept Behav Neurosci, Boston, MA 02118 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, GRECC 182, 150 South Huntington Ave, Boston, MA 02130 USA. EM Catherine_Fortier@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS) VA RRD [B6796-C]; NIH NIAAA [14205]; NIH [AG08796]; NIH NINR [R01NR010827]; NIH NIA [K23AG034258]; NINDS [K23NS062148]; VA Merit Review Awards FX This research was support by Translational Research Center for TBI and Stress Disorders (TRACTS) VA RR&D B6796-C, NIH NIAAA 14205, NIH AG08796, NIH NINR R01NR010827, NIH NIA K23AG034258, NINDS K23NS062148, and VA Merit Review Awards to CBF and REM. NR 56 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2925 EP 2933 DI 10.1111/acer.12568 PG 9 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500008 PM 25406797 ER PT J AU Valmas, MM Ruiz, SM Gansler, DA Sawyer, KS Oscar-Berman, M AF Valmas, Mary M. Ruiz, Susan Mosher Gansler, David A. Sawyer, Kayle S. Oscar-Berman, Marlene TI Social Cognition Deficits and Associations with Drinking History in Alcoholic Men and Women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Social Cognition; Emotion; Alcoholism; Gender; Advanced Clinical Solutions ID FACIAL EXPRESSION RECOGNITION; AFFECTIVE STIMULI; BRAIN; PERCEPTION; DEPENDENCE; DYSFUNCTION; DISORDERS; PROSODY; AUTISM; CORTEX AB BackgroundPrevious studies have demonstrated the presence of a social cognition factor as an element of general cognition in healthy control and clinical populations. Recently developed measures of social cognition include the social perception and faces subtests of the Wechsler Advanced Clinical Solutions (ACS) Social Cognition module. While these measures have been validated on various clinical samples, they have not been studied in alcoholics. Alcoholism has been associated with emotional abnormalities and diminished social cognitive functioning as well as neuropathology of brain areas underlying social processing abilities. We used the ACS Social Perception and Faces subtests to assess alcoholism-related impairments in social cognition. MethodsSocial cognitive functioning was assessed in 77 abstinent alcoholic individuals (37 women) and 59 nonalcoholic control participants (29 women), using measures of the ACS Social Cognition module and subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) that contain a social cognition component (Picture Completion and Comprehension). Group and gender differences in ACS and WAIS-IV performance were assessed, as well as relationships between measures of alcoholism severity and social cognitive functioning. ResultsAlcoholics performed significantly worse than nonalcoholics on the ACS measures of Affect Naming and Faces Content. Alcoholic men were impaired relative to alcoholic women on Prosody Face Matching and Faces Content scores. Among alcoholics, longer durations of heavy drinking were associated with poorer performance on Affect Naming, and a greater number of daily drinks were associated with lower Prosody Face Matching performance. For alcoholic women, a longer duration of abstinence was associated with better performance on Affect Naming. ConclusionsAlcoholic men and women showed different patterns of associations between alcoholism indices and clinically validated social cognition assessments. These findings extend into the social cognition domain, previous literature demonstrating the presence of cognitive deficits in alcoholism, their association with alcoholism severity, and variability by gender. Moreover, because impairments in social cognition can persist despite extended abstinence, they have important implications for relapse prevention. C1 [Valmas, Mary M.; Ruiz, Susan Mosher; Sawyer, Kayle S.; Oscar-Berman, Marlene] VA Boston Healthcare Syst, Psychol Res Serv, Boston, MA USA. [Valmas, Mary M.; Gansler, David A.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Valmas, Mary M.; Ruiz, Susan Mosher; Sawyer, Kayle S.; Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, 72 East Concord St L-815, Boston, MA 02118 USA. EM oscar@bu.edu OI Sawyer, Kayle/0000-0001-7767-5688 FU National Institutes of Health, NIAAA [R01-AA07112, K05-AA00219]; Medical Research Service of the U.S. Department of Veterans Affairs FX This research was supported by grants from the National Institutes of Health, NIAAA R01-AA07112 and K05-AA00219, and the Medical Research Service of the U.S. Department of Veterans Affairs. NR 54 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2998 EP 3007 DI 10.1111/acer.12566 PG 10 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500016 PM 25581654 ER PT J AU Martinu, T Gowdy, KM Nugent, JL Sun, J Kinnier, CV Nelson, ME Lyes, MA Kelly, FL Foster, WM Gunn, MD Palmer, SM AF Martinu, Tereza Gowdy, Kymberly M. Nugent, Julia L. Sun, Jesse Kinnier, Christine V. Nelson, Margaret E. Lyes, Matthew A. Kelly, Francine L. Foster, W. Michael Gunn, Michael D. Palmer, Scott M. TI Role of C-C Motif Ligand 2 and C-C Motif Receptor 2 in Murine Pulmonary Graft-versus-Host Disease after Lipopolysaccharide Inhalations SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE graft-versus-host disease; lipopolysaccharide; dendritic cells; C-C motif ligand 2; C-C motif receptor 2 ID CHEMOATTRACTANT PROTEIN-1 MCP-1; IDIOPATHIC PNEUMONIA SYNDROME; STEM-CELL TRANSPLANTATION; INNATE IMMUNE ACTIVATION; DENDRITIC CELLS; LUNG INJURY; AIRWAY HYPERRESPONSIVENESS; INHALED LIPOPOLYSACCHARIDE; CHEMOKINE RECEPTOR-2; CCR2(-/-) MICE AB Environmental exposures are a potential trigger of chronic pulmonary graft-versus-host disease (pGVHD) after successful recovery from hematopoietic cell transplant (HCT). We hypothesized that inhalations of LPS, a prototypic environmental stimulus, trigger pGVHD via increased pulmonary recruitment of donor-derived antigen-presenting cells (APCs) through the C-C motif ligand 2 (CCL2)-C-C motif receptor 2 (CCR2) chemokine axis. B10.BR(H2(k)) and C57BL/6(H2(b)) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with wild-type (WT) C57BL/6, CCL2(-/-), or CCR2(-/-) donors. After 4 weeks, recipient mice received daily inhaled LPS for 5 days and were killed at multiple time points. Allo mice exposed to repeated inhaled LPS developed prominent lymphocytic bronchiolitis, similar to human pGVHD. The increase in pulmonary T cells in Allo mice after LPS exposures was accompanied by increased CCL2, CCR2, and Type-1 T-helper cytokines as well as by monocytes and monocytederived dendritic cells (moDCs) compared with Syn and nontransplanted controls. Using CCL2(-/-) donors leads to a significant decrease in lungDCs but to only mildly reduced CD4 T cells. Using CCR2(-/-) donors significantly reduces lung DCs and moDCs but does not change T cells. CCL2 or CCR2 deficiency does not alter pGVHD pathology but increases airway hyperreactivity and IL-5 or IL-13 cytokines. Our results show that hematopoietic donor- derived CCL2 and CCR2 regulate recruitment of APCs to the Allo lung after LPS exposure. Although they do not alter pathologic pGVHD, their absence is associated with increased airway hyperreactivity and IL-5 and IL-13 cytokines. These results suggest that the APC changes that result from CCL2-CCR2 blockade may have unexpected effects on T cell differentiation and physiologic outcomes in HCT. C1 [Martinu, Tereza; Nelson, Margaret E.; Lyes, Matthew A.; Kelly, Francine L.; Foster, W. Michael; Gunn, Michael D.; Palmer, Scott M.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Palmer, Scott M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Gowdy, Kymberly M.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Nugent, Julia L.; Sun, Jesse] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Martinu, T (reprint author), Duke Univ, Med Ctr, DUMC Box 3221, Durham, NC 27710 USA. EM tereza.martinu@duke.edu FU National Institutes of Health [S10RR019145] FX The authors thank Mr. Robert F. Beasley for help with lung DC isolation. Flow cytometric sorting was performed in the Duke Human Vaccine Institute Research Flow Cytometry Shared Resource Facility (Durham, NC) supported by National Institutes of Health grant S10RR019145. NR 36 TC 1 Z9 1 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2014 VL 51 IS 6 BP 810 EP 821 DI 10.1165/rcmb.2013-0451OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AY2KS UT WOS:000347419700010 PM 24921973 ER PT J AU Chalmers, JR Schmitt, J Apfelbacher, C Dohil, M Eichenfield, LF Simpson, EL Singh, J Spuls, P Thomas, KS Admani, S Aoki, V Ardeleanu, M Barbarot, S Berger, T Bergman, JN Block, J Borok, N Burton, T Chamlin, SL Deckert, S DeKlotz, CC Graff, LB Hanifin, JM Hebert, AA Humphreys, R Katoh, N Kisa, RM Margolis, DJ Merhand, S Minnillo, R Mizutani, H Nankervis, H Ohya, Y Rodgers, P Schram, ME Stalder, JF Svensson, A Takaoka, R Teper, A Tom, WL von Kobyletzki, L Weisshaar, E Zelt, S Williams, HC AF Chalmers, J. R. Schmitt, J. Apfelbacher, C. Dohil, M. Eichenfield, L. F. Simpson, E. L. Singh, J. Spuls, P. Thomas, K. S. Admani, S. Aoki, V. Ardeleanu, M. Barbarot, S. Berger, T. Bergman, J. N. Block, J. Borok, N. Burton, T. Chamlin, S. L. Deckert, S. DeKlotz, C. C. Graff, L. B. Hanifin, J. M. Hebert, A. A. Humphreys, R. Katoh, N. Kisa, R. M. Margolis, D. J. Merhand, S. Minnillo, R. Mizutani, H. Nankervis, H. Ohya, Y. Rodgers, P. Schram, M. E. Stalder, J. F. Svensson, A. Takaoka, R. Teper, A. Tom, W. L. von Kobyletzki, L. Weisshaar, E. Zelt, S. Williams, H. C. TI Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME) SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID B-VIRUS-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; VARICELLA-ZOSTER VIRUS; STRONGYLOIDES-STERCORALIS INFECTION; EPIDERMOLYSIS-BULLOSA-ACQUISITA; FORCE RECOMMENDATION STATEMENT; MODIFYING ANTIRHEUMATIC DRUGS; DOSE METHOTREXATE THERAPY; HEPATITIS-B; PEMPHIGUS-VULGARIS AB This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure. C1 [Chalmers, J. R.; Thomas, K. S.; Burton, T.; Nankervis, H.; Williams, H. C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Schmitt, J.; Deckert, S.] Univ Dresden, Ctr Evidence Based Healthcare, Dresden, Germany. [Apfelbacher, C.] Univ Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany. [Dohil, M.; Eichenfield, L. F.; Admani, S.; Borok, N.; DeKlotz, C. C.; Tom, W. L.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Simpson, E. L.; Hanifin, J. M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Singh, J.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Spuls, P.; Schram, M. E.] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, NL-1105 AZ Amsterdam, Netherlands. [Aoki, V.; Takaoka, R.] Univ Sao Paulo, Dept Dermatol, Sao Paulo, Brazil. [Ardeleanu, M.] Regeneron Pharmaceut Inc, Immunol & Inflammat, Clin Sci, Tarrytown, NY 10591 USA. [Barbarot, S.] CHU Nantes, Dept Dermatol, F-44035 Nantes 01, France. [Berger, T.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Bergman, J. N.] Univ British Columbia, Pediat Allergy & Dermatol Ctr, Vancouver, BC V5Z 1M9, Canada. [Block, J.] Natl Eczema Assoc, San Rafael, CA USA. [Chamlin, S. L.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Graff, L. B.] LEO Pharma AS, Ballerup, Denmark. [Hebert, A. A.] Univ Texas Houston, Sch Med, Dept Dermatol, Houston, TX USA. [Humphreys, R.] Natl Eczema Soc, London, England. [Katoh, N.] Kyoto Prefectural Univ Med, Dept Dermatol, Kyoto, Japan. [Kisa, R. M.] Pierre Fabre Pharmaceut, New York, NY USA. [Margolis, D. J.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Merhand, S.] French Assoc Eczema, Redon, France. [Minnillo, R.] Soc Investigat Dermatol, Cleveland, OH USA. [Mizutani, H.] Mie Univ, Dept Dermatol, Tsu, Mie 514, Japan. [Ohya, Y.] Natl Ctr Child Hlth & Dev, Div Allergy, Tokyo, Japan. [Rodgers, P.] LEO Pharma, Parsippany, NJ USA. [Stalder, J. F.] Nantes Univ Hosp, Dept Dermatol, Nantes, France. [Svensson, A.] Malmo Univ Hosp, Dept Dermatol, Malmo, Sweden. [Teper, A.] Sanofi Aventis, Hastings On Hudson, NY USA. [von Kobyletzki, L.] Lund Univ, Dept Dermatol & Venerol, Lund, Sweden. [Weisshaar, E.] Univ Heidelberg Hosp, Dept Clin Social Med, Heidelberg, Germany. [Zelt, S.] Stiefel Labs, Res Triangle Pk, NC USA. RP Chalmers, JR (reprint author), Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. EM Joanne.Chalmers@nottingham.ac.uk RI Aoki, Valeria/H-1415-2012; OI Schram, Miranda/0000-0003-0515-4124; Chalmers, Joanne/0000-0002-2281-7367; Apfelbacher, Christian/0000-0003-3805-8219; DeKlotz, Cynthia/0000-0002-6410-8710 FU National Institute for Health Research (NIHR) [RP-PG-0407-10177] FX This report represents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (RP-PG-0407-10177). The views expressed in this report are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. NR 100 TC 22 Z9 22 U1 2 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 DEC PY 2014 VL 171 IS 6 BP 1318 EP 1325 DI 10.1111/bjd.13237 PG 8 WC Dermatology SC Dermatology GA AX9QD UT WOS:000347236100172 PM 24980543 ER PT J AU Pascoe, V Kimball, A AF Pascoe, V. Kimball, A. TI Seasonal variation in psoriasis: a 3-year study utilizing the Physician's Global Assessment psoriasis severity scale SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT 7th International Congress of Psoriasis - From Gene to Clinic CY DEC 11-13, 2014 CL London, ENGLAND C1 [Pascoe, V.; Kimball, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2014 VL 171 IS 6 MA P03 BP E122 EP E123 PG 2 WC Dermatology SC Dermatology GA AX9QD UT WOS:000347236100037 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Brain peptides and the modulation of postoperative gastric ileus SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PLASMA GHRELIN LEVELS; GENE-RELATED PEPTIDE; INCREASES FOOD-INTAKE; BODY-MASS INDEX; ABDOMINAL-SURGERY; GROWTH-HORMONE; GASTROINTESTINAL MOTILITY; INSULIN-SECRETION; ACYLATED PEPTIDE AB Postoperative ileus (POI) develops after abdominal surgery irrespective of the site of surgery. When prolonged, POI can lead to longer hospitalization times and higher healthcare costs. Moreover, it is associated with complaints for the patient. In order to develop new strategies to treat this condition, a deeper understanding of the pathophysiology of the POI is necessary. This review will focus on brain peptides (ghrelin, nesfatin-1, somatostatin, corticotropin-releasing factor, thyrotropin-releasing hormone and calcitonin gene-related peptide) involved in the mediation of POI and the possible modulation of these pathways to shorten the time of POI. Lastly, the role of vagal signaling or chewing gum as potential treatment strategies of alleviating symptoms of POI is discussed. C1 [Stengel, Andreas] Charite, Campus Benjamin Franklin, Div Gen Internal & Psychosomat Med, Charite Ctr Internal Med & Dermatol, D-13353 Berlin, Germany. [Tache, Yvette] Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth,Dept Med, Los Angeles, CA 90073 USA. [Tache, Yvette] VA Greater Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth,Dept Med, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIH [R01 DK-33061]; NIH Center [DK-41301]; VA Research Career Scientist; German Research Foundation [STE 1765/3-1]; Charite University Funding [UFF 89-441-176] FX This work was supported by NIH R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), VA Research Career Scientist (Y.T.), VA Merit Award (Y.T.) German Research Foundation STE 1765/3-1 (A.S.) and Charite University Funding UFF 89-441-176 (AS.). NR 85 TC 4 Z9 5 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2014 VL 19 BP 31 EP 37 DI 10.1016/j.coph.2014.06.006 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3UO UT WOS:000347508000008 PM 24999843 ER PT J AU Ronnestad, I Akiba, Y Kaji, I Kaunitz, JD AF Ronnestad, Ivar Akiba, Yasutada Kaji, Izumi Kaunitz, Jonathan D. TI Duodenal luminal nutrient sensing SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID CHAIN FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR; INTESTINAL GLUCOSE-ABSORPTION; RAT SMALL-INTESTINE; ENTEROENDOCRINE CELLS; PEPTIDE-1 SECRETION; TASTE RECEPTOR; AMINO-ACID; GASTROINTESTINAL-TRACT; BICARBONATE SECRETION AB The gastrointestinal mucosa is exposed to numerous chemical substances and microorganisms, including macronutrients, micronutrients, bacteria, endogenous ions, and proteins. The regulation of mucosal protection, digestion, absorption and motility is signaled in part by luminal solutes. Therefore, luminal chemosensing is an important mechanism enabling the mucosa to monitor luminal conditions, such as pH, ion concentrations, nutrient quantity, and microflora. The duodenal mucosa shares luminal nutrient receptors with lingual taste receptors in order to detect the five basic tastes, in addition to essential nutrients, and unwanted chemicals. The recent 'de-orphanization' of nutrient sensing G protein-coupled receptors provides an essential component of the mechanism by which the mucosa senses luminal nutrients. In this review, we will update the mechanisms of and underlying physiological and pathological roles in luminal nutrient sensing, with a main focus on the duodenal mucosa. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. [Ronnestad, Ivar; Akiba, Yasutada; Kaji, Izumi; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaji, Izumi; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Ronnestad, Ivar] Univ Bergen, Dept Biol, N-5020 Bergen, Norway. RP Kaunitz, JD (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. EM jake@ucla.edu RI Ronnestad, Ivar/A-1774-2013; OI Ronnestad, Ivar/0000-0001-8789-0197; Akiba, Yasutada/0000-0001-5731-1019 FU Ajinomoto, Inc., Japan; Department of Veterans Affairs Merit Review Award; Research Council of Norway [208352, 199482]; University of Bergen; Department of Veterans Affairs Merit Review Award, NIH-NIDDK [R01 DK54221] FX Supported by a research grant from Ajinomoto, Inc., Japan (Y Akiba), Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 (J Kaunitz), the funding from a Grant-in-Aid for Japan Society for the Promotion of Science Fellow (I Kaji), and funding from Research Council of Norway, 208352; 199482, and University of Bergen, Sabbatical Grant (I Ronnestad). NR 60 TC 5 Z9 5 U1 1 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2014 VL 19 BP 67 EP 75 DI 10.1016/j.coph.2014.07.010 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3UO UT WOS:000347508000013 PM 25113991 ER PT J AU Struzyna, LA Katiyar, K Cullen, DK AF Struzyna, Laura A. Katiyar, Kritika Cullen, D. Kacy TI Living scaffolds for neuroregeneration SO CURRENT OPINION IN SOLID STATE & MATERIALS SCIENCE LA English DT Review DE Tissue engineering; Cell transplant; Biomaterials; Regeneration; Neurotrauma; Neurodegeneration; Axon pathfinding; Cell migration ID PERIPHERAL-NERVE REGENERATION; NEURAL STEM-CELLS; LONG-TERM SURVIVAL; NEURITE OUTGROWTH; IN-VITRO; NEURONAL MIGRATION; NEUROTROPHIC FACTOR; GRASSHOPPER EMBRYOS; SUBSTRATE CURVATURE; FUNCTIONAL RECOVERY AB Neural tissue engineers are exploiting key mechanisms responsible for neural cell migration and axonal pathfinding during embryonic development to create living scaffolds for neuroregeneration following injury and disease. These mechanisms involve the combined use of haptotactic, chemotactic, and mechanical cues to direct cell movement and re-growth. Living scaffolds provide these cues through the use of cells engineered in a predefined architecture, generally in combination with biomaterial strategies. Although several hurdles exist in the implementation of living regenerative scaffolds, there are considerable therapeutic advantages to using living cells in conjunction with biomaterials. The leading contemporary living scaffolds for neurorepair are utilizing aligned glial cells and neuronal/axonal tracts to direct regenerating axons across damaged tissue to appropriate targets, and in some cases to directly replace the function of lost cells. Future advances in technology, including the use of exogenous stimulation and genetically engineered stem cells, will further the potential of living scaffolds and drive a new era of personalized medicine for neuroregeneration. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Struzyna, Laura A.; Katiyar, Kritika; Cullen, D. Kacy] Univ Penn, Dept Neurosurg, Perelman Sch Med, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. [Struzyna, Laura A.; Cullen, D. Kacy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Katiyar, Kritika] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), 105E Hayden Hall 3320 Smith Walk, Philadelphia, PA 19104 USA. EM lstruz@mail.med.upenn.edu; kritikak@mail.med.upenn.edu; dkacy@mail.med.upenn.edu FU U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]; Congressionally Directed Medical Research Program [W81XWH-10-1-0941]; Axonia Medical, Inc.; Department of Veterans Affairs (RRD Merit Review) [B1097-I]; National Institutes of Health/NINDS [T32-NS043126]; National Science Foundation (Graduate Research Fellowship) [DGE-1321851] FX This work was made possible due to financial support provided by the U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine (#W81XWH-08-2-0034) and the Congressionally Directed Medical Research Program (#W81XWH-10-1-0941); Axonia Medical, Inc., through a sponsored research agreement; Department of Veterans Affairs (RR&D Merit Review #B1097-I); National Institutes of Health/NINDS (T32-NS043126); and the National Science Foundation (Graduate Research Fellowship DGE-1321851). NR 101 TC 7 Z9 8 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-0286 EI 1879-0348 J9 CURR OPIN SOLID ST M JI Curr. Opin. Solid State Mat. Sci. PD DEC PY 2014 VL 18 IS 6 BP 308 EP 318 DI 10.1016/j.cossms.2014.07.004 PG 11 WC Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Materials Science; Physics GA AY3QU UT WOS:000347498600002 ER PT J AU Rieken, M Schubert, T Xylinas, E Kluth, L Roupret, M Trinh, QD Lee, RK Al Awamlh, BAH Fajkovic, H Novara, G Margulis, V Lotan, Y Martinez-Salamanca, JI Matsumoto, K Seitz, C Remzi, M Karakiewicz, PI Scherr, DS Briganti, A Bachmann, A Shariat, SF AF Rieken, M. Schubert, T. Xylinas, E. Kluth, L. Roupret, M. Trinh, Q-D Lee, R. K. Al Awamlh, B. Al Hussein Fajkovic, H. Novara, G. Margulis, V. Lotan, Y. Martinez-Salamanca, J. I. Matsumoto, K. Seitz, C. Remzi, M. Karakiewicz, P. I. Scherr, D. S. Briganti, A. Bachmann, A. Shariat, S. F. CA UTUC Collaboration TI Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma SO EJSO LA English DT Article DE Upper tract urothelial carcinoma; Radical nephroureterectomy; Blood transfusion; Surgery outcomes; Disease recurrence ID CANCER PROGRESSION; RECURRENCE; CYSTECTOMY; SURVIVAL; BLADDER; SERIES; IMPACT; MORTALITY AB Background: To test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality. Results: A total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92-1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89-1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93-1.28, p = 0.29). Conclusions: In patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rieken, M.; Schubert, T.; Xylinas, E.; Kluth, L.; Lee, R. K.; Al Awamlh, B. Al Hussein; Scherr, D. S.; Shariat, S. F.] New York Presbyterian Hosp, Dept Urol, Weill Cornell Med Coll, New York, NY USA. [Rieken, M.; Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Xylinas, E.] Paris Descartes Univ, AP HP, Dept Urol, Cochin Hosp, Paris, France. [Kluth, L.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Roupret, M.] Hop La Pitie Salpetriere, AP HP, Dept Urol, Serv Urol, Paris, France. [Roupret, M.] Univ Paris 06, GRC5, ONCOTYPE Uro, Inst Univ Cancerol, Paris, France. [Trinh, Q-D] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg,Med Sch, Boston, MA 02115 USA. [Trinh, Q-D] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Med Sch, Boston, MA 02115 USA. [Fajkovic, H.; Seitz, C.; Shariat, S. F.] Med Univ Vienna, Dept Urol, A-1090 Vienna, Austria. [Novara, G.] Univ Padua, Urol Clin, Dept Surg Oncol & Gastroenterol Sci, I-35100 Padua, Italy. [Margulis, V.; Lotan, Y.; Shariat, S. F.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Martinez-Salamanca, J. I.] Univ Autonoma Madrid, Dept Urol, Hosp Univ Puerta Hierro Majadahonda, Madrid, Spain. [Matsumoto, K.] Kitasato Univ, Sch Med, Dept Urol, Sagamihara, Kanagawa 228, Japan. [Remzi, M.] Landesklinikum Korneuburg, Dept Urol, Korneuburg, Austria. [Karakiewicz, P. I.] Univ Montreal, Dept Urol, Montreal, PQ, Canada. [Briganti, A.] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy. RP Shariat, SF (reprint author), Med Univ Vienna, Dept Urol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM sfshariat@gmail.com NR 24 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD DEC PY 2014 VL 40 IS 12 BP 1693 EP 1699 DI 10.1016/j.ejso.2014.03.018 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA AY5AJ UT WOS:000347585600015 PM 24780094 ER PT J AU Gandaglia, G Karakiewicz, PI Abdollah, F Becker, A Roghmann, F Sammon, JD Kim, SP Perrotte, P Briganti, A Montorsi, F Trinh, QD Sun, M AF Gandaglia, G. Karakiewicz, P. I. Abdollah, F. Becker, A. Roghmann, F. Sammon, J. D. Kim, S. P. Perrotte, P. Briganti, A. Montorsi, F. Trinh, Q. -D. Sun, M. TI The effect of age at diagnosis on prostate cancer mortality: A grade-for-grade and stage-for-stage analysis SO EJSO LA English DT Article DE Prostate cancer; Radical prostatectomy; Cancer-specific survival; Competing-risks; Age at diagnosis ID RADICAL RETROPUBIC PROSTATECTOMY; LONG-TERM SURVIVAL; PATHOLOGICAL STAGE; COMPETING RISK; GLEASON SCORE; PATIENT AGE; MEN; OUTCOMES; IMPACT; THERAPY AB Objective: To evaluate the effect of advancing age on cancer-specific mortality (CSM) after radical prostatectomy (RP). Materials and methods: Overall, 205,551 patients with PCa diagnosed between 1988 and 2009 within the Surveillance Epidemiology and End Results (SEER) database were included in the study. Patients were stratified according to age at diagnosis: <= 50, 51-60, 61-70, and >= 71 years. The 15-year cumulative incidence CSM rates were computed. Competing-risks regression models were performed to test the effect of age on CSM in the entire cohort, and for each grade (Gleason score 2-4, 5-7, and 8-10) and stage (pT2, pT3a, and pT3b) subcohorts. Results: Advancing age was associated with higher 15-year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged <= 50 vs. 51-60 vs. 61-70 vs. >= 71 years, respectively; P < 0.001). In multivariable analyses, age at diagnosis was a significant predictor of CSM. This relationship was also observed in sub-analyses focusing on patients with Gleason score 5-7, and/or pT2 disease (all P <= 0.05). Conversely, age failed to reach the independent predictor status in men with Gleason score 2-4, 8-10, pT3a, and/or pT3b disease. Conclusions: Advancing age increases the risk of CSM. However, when considering patients affected by more aggressive disease, age was not significantly associated with higher risk of dying from PCa. In high-risk patients, tumor characteristics rather than age should be considered when making treatment decisions. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Gandaglia, G.; Karakiewicz, P. I.; Becker, A.; Roghmann, F.; Trinh, Q. -D.; Sun, M.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Gandaglia, G.; Abdollah, F.; Briganti, A.; Montorsi, F.] IRCCS Osped San Raffaele, URI, Div Oncol, Unit Urol, Milan, Italy. [Becker, A.] Univ Med Ctr Hamburg Eppendorf, Martiniclin, Hamburg, Germany. [Roghmann, F.] Ruhr Univ Bochum, Dept Urol, Bochum, Germany. [Sammon, J. D.] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Kim, S. P.] Mayo Clin, Dept Urol, Rochester, NY USA. [Perrotte, P.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada. [Trinh, Q. -D.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM giorgio.gandaglia@gmail.com FU University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX Pierre I Karakiewicz is partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. NR 34 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD DEC PY 2014 VL 40 IS 12 BP 1706 EP 1715 DI 10.1016/j.ejso.2014.05.001 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA AY5AJ UT WOS:000347585600017 PM 24915856 ER PT J AU Shaughnessy, DT McAllister, K Worth, L Haugen, AC Meyer, JN Domann, FE Van Houten, B Mostoslavsky, R Bultman, SJ Baccarelli, AA Begley, TJ Sobol, RW Hirschey, MD Ideker, T Santos, JH Copeland, WC Tice, RR Balshaw, DM Tyson, FL AF Shaughnessy, Daniel T. McAllister, Kimberly Worth, Leroy Haugen, Astrid C. Meyer, Joel N. Domann, Frederick E. Van Houten, Bennett Mostoslavsky, Raul Bultman, Scott J. Baccarelli, Andrea A. Begley, Thomas J. Sobol, Robert W. Hirschey, Matthew D. Ideker, Trey Santos, Janine H. Copeland, William C. Tice, Raymond R. Balshaw, David M. Tyson, Frederick L. TI Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID DNA COPY NUMBER; PLURIPOTENT STEM-CELLS; COLON-CARCINOMA CELLS; ENERGY-METABOLISM; EXCISION-REPAIR; OXIDATIVE-PHOSPHORYLATION; ATAXIA-TELANGIECTASIA; HISTONE ACETYLATION; BUTYRATE METABOLISM; CANCER METABOLISM AB Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria-nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25-26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria-cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. C1 [Shaughnessy, Daniel T.; McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Balshaw, David M.; Tyson, Frederick L.] NIEHS, Div Extramural Res & Training, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Domann, Frederick E.] Univ Iowa, Carver Coll Med, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA. [Van Houten, Bennett; Sobol, Robert W.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA USA. [Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Lab Environm Epigenet, Boston, MA 02115 USA. [Begley, Thomas J.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12222 USA. [Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Hirschey, Matthew D.] Duke Univ, Med Ctr, Durham, NC USA. [Ideker, Trey] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Santos, Janine H.] NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Copeland, William C.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Tice, Raymond R.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Shaughnessy, DT (reprint author), NIEHS, Div Extramural Res & Training, MD K3-12,POB 12233, Res Triangle Pk, NC 27709 USA. EM shaughn1@niehs.nih.gov OI Baccarelli, Andrea/0000-0002-3436-0640; Domann, Frederick/0000-0002-0489-2179 FU NIA NIH HHS [R01 AG045351]; NIEHS NIH HHS [R01 ES017540, P30 ES005605, P42 ES010356] NR 105 TC 35 Z9 35 U1 7 U2 55 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 DEC PY 2014 VL 122 IS 12 BP 1271 EP 1278 DI 10.1289/ehp.1408418 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AY1YC UT WOS:000347384600012 PM 25127496 ER PT J AU Nadol, JB O'Malley, JT Burgess, BJ Galler, D AF Nadol, Joseph B., Jr. O'Malley, Jennifer T. Burgess, Barbara J. Galler, Donald TI Cellular immunologic responses to cochlear implantation in the human SO HEARING RESEARCH LA English DT Article ID FOREIGN-BODY REACTION; SILICONE ALLERGY; HISTOPATHOLOGY; REMOVAL AB A cochlear implant array consists of biomaterials, including metal and polymeric in type which are biocompatible, but not necessarily bio-inert. Histologic evidence of a foreign body reaction has been described in temporal bones in patients who in life had undergone cochlear implantation. In the current study, the cellular immune response was characterized using immunohistochemical stains for B-cell lymphocytes (CD20), T-cell lymphocytes (CD3), and macrophages (CD68). In addition, energy dispersive spectroscopy by scanning electron microscopy (EDS-SEM) was performed to characterize the nature of particulate foreign material seen near the electrode array. Infiltrations of B-cell and Tcell lymphocytes and macrophages were identified immunohistochemically. The track of the electrode array was frequently lined by multi-nucleated foreign body giant cells. Energy dispersive X-ray spectroscopy identified the particulate material found in the fibrous sheeth surrounding the cochlear implant to be consistent with platinum. In conclusion, a cochlear implant generates a vigorous cellular immune response consisting of B and T lymphocytes, foreign body giant cells, and macrophages. Platinum was identified as one of the antigens likely responsible for this cellular response. This foreign body response may in certain cases result in migration or even extrusion of an implant device. (C) 2014 Elsevier B.V. All rights reserved. C1 [Nadol, Joseph B., Jr.; O'Malley, Jennifer T.; Burgess, Barbara J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Galler, Donald] MIT, Dept Mat Sci & Engn, Cambridge, MA 02138 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Joseph_nadol@meei.harvard.edu FU NIDCD NIH HHS [U24 DC013983] NR 31 TC 5 Z9 5 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD DEC PY 2014 VL 318 BP 11 EP 17 DI 10.1016/j.heares.2014.09.007 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AY6FT UT WOS:000347663400002 PM 25285622 ER PT J AU Mancuso, JJ Halaney, DL Elahi, S Ho, D Wang, TY Ouyang, YJ Dijkstra, J Milner, TE Feldman, MD AF Mancuso, J. Jacob Halaney, David L. Elahi, Sahar Ho, Derek Wang, Tianyi Ouyang, Yongjian Dijkstra, Jouke Milner, Thomas E. Feldman, Marc D. TI Intravascular optical coherence tomography light scattering artifacts: merry-go-rounding, blooming, and ghost struts SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE imaging; lasers; stents; tomography ID ACCURACY; REPRODUCIBILITY AB We sought to elucidate the mechanisms underlying two common intravascular optical coherence tomography (IV-OCT) artifacts that occur when imaging metallic stents: "merry-go-rounding" (MGR), which is an increase in strut arc length (SAL), and "blooming," which is an increase in the strut reflection thickness (blooming thickness). Due to uncontrollable variables that occur in vivo, we performed an in vitro assessment of MGR and blooming in stented vessel phantoms. Using Xience V and Driver stents, we examined the effects of catheter offset, intimal strut coverage, and residual blood on SAL and blooming thickness in IV-OCT images. Catheter offset and strut coverage both caused minor MGR, while the greatest MGR effect resulted from light scattering by residual blood in the vessel lumen, with 1% hematocrit (Hct) causing a more than fourfold increase in SAL compared with saline (p < 0.001). Residual blood also resulted in blooming, with blooming thickness more than doubling when imaged in 0.5% Hct compared with saline (p < 0.001). We demonstrate that a previously undescribed mechanism, light scattering by residual blood in the imaging field, is the predominant cause of MGR. Light scattering also results in blooming, and a newly described artifact, three-dimensional-MGR, which results in " ghost struts" in B-scans. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE). C1 [Mancuso, J. Jacob; Halaney, David L.; Ouyang, Yongjian; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Mancuso, J. Jacob; Halaney, David L.; Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Elahi, Sahar; Ho, Derek; Wang, Tianyi; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Dijkstra, Jouke] Leiden Univ, Med Ctr, Dept Radiol, Div Image Proc, NL-2333 ZA Leiden, Netherlands. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu OI Halaney, David/0000-0003-4437-0516 FU South Texas Veterans Health Care System (VA Merit Grant, San Antonio, Texas); Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas); Volcano Corporation (San Diego, California); Clayton Foundation for Biomedical Research (Houston, Texas) FX This work was supported by the South Texas Veterans Health Care System (VA Merit Grant, San Antonio, Texas), the Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas), Volcano Corporation (San Diego, California), and the Clayton Foundation for Biomedical Research (Houston, Texas). Disclosures: None. NR 17 TC 0 Z9 0 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD DEC PY 2014 VL 19 IS 12 AR 126017 DI 10.1117/1.JBO.19.12.126017 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AY2TS UT WOS:000347442600022 PM 25545341 ER PT J AU Merchant, RM Ha, YP Wong, CA Schwartz, HA Sap, M Ungar, LH Asch, DA AF Merchant, Raina M. Ha, Yoonhee P. Wong, Charlene A. Schwartz, H. Andrew Sap, Maarten Ungar, Lyle H. Asch, David A. TI The 2013 US Government Shutdown (#Shutdown) and Health: An Emerging Role for Social Media SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID EMERGENCY-PREPAREDNESS AB In October 2013, multiple United States (US) federal health departments and agencies posted on Twitter, "We're sorry, but we will not be tweeting or responding to @ replies during the shutdown. We'll be back as soon as possible!" These "last tweets" and the millions of responses they generated revealed social media's role as a forum for sharing and discussing information rapidly. Social media are now among the few dominant communication channels used today. We used social media to characterize the public discourse and sentiment about the shutdown. The 2013 shutdown represented an opportunity to explore the role social media might play in events that could affect health. C1 [Merchant, Raina M.; Ha, Yoonhee P.; Wong, Charlene A.] Univ Penn, Penn Med Social Media & Hlth Innovat Lab, Penn Med Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Schwartz, H. Andrew; Sap, Maarten; Ungar, Lyle H.] Univ Penn, Dept Comp & Informat Sci, Posit Psychol Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Penn Med Social Media & Hlth Innovat Lab, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM Raina.Merchant@uphs.upenn.edu FU NHLBI NIH HHS [K23 HL109083] NR 11 TC 2 Z9 2 U1 1 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2248 EP 2250 DI 10.2105/AJPH.2014.302118 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500027 PM 25322303 ER PT J AU Arya, M Kumar, D Patel, S Street, RL Giordano, TP Viswanath, K AF Arya, Monisha Kumar, Disha Patel, Sajani Street, Richard L., Jr. Giordano, Thomas Peter Viswanath, Kasisomayajula TI Mitigating HIV Health Disparities: The Promise of Mobile Health for a Patient-Initiated Solution SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN-AMERICAN MEN; MISSED OPPORTUNITIES; CARE SETTINGS; BEHAVIOR-CHANGE; INTERVENTIONS; ADOLESCENTS; PREVENTION; INFECTION; BARRIERS AB The HIV epidemic is an ongoing public health problem fueled, in part, by undertesting for HIV. When HIV-infected people learn their status, many of them decrease risky behaviors and begin therapy to decrease viral load, both of which prevent ongoing spread of HIV in the community. Some physicians face barriers to testing their patients for HIV and would rather their patients ask them for the HIV test. A campaign prompting patients to ask their physicians about HIV testing could increase testing. A mobile health (mHealth) campaign would be a low-cost, accessible solution to activate patients to take greater control of their health, especially populations at risk for HIV. This campaign could achieve Healthy People 2020 objectives: improve patient-physician communication, improve HIV testing, and increase use of mHealth. C1 [Arya, Monisha; Street, Richard L., Jr.; Giordano, Thomas Peter] Michael E Debakey VA Med Ctr, IQuESt, Houston, TX USA. [Arya, Monisha] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kumar, Disha; Patel, Sajani] Rice Univ, Weiss Sch Nat Sci, Houston, TX USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Arya, M (reprint author), Baylor Coll Med, Infect Dis Sect, Dept Med, One Baylor Plaza, Houston, TX 77030 USA. EM monishaa@bcm.edu FU NIMH NIH HHS [K23 MH094235, MH094235-01A1] NR 55 TC 2 Z9 2 U1 1 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2251 EP 2255 DI 10.2105/AJPH.2014.302120 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500028 PM 25322292 ER PT J AU Merchant, RM Griffis, HM Ha, YP Kilaru, AS Sellers, AM Hershey, JC Hill, SS Kramer-Golinkoff, E Nadkarni, L Debski, MM Padrez, KA Becker, LB Asch, DA AF Merchant, Raina M. Griffis, Heather M. Ha, Yoonhee P. Kilaru, Austin S. Sellers, Allison M. Hershey, John C. Hill, Shawndra S. Kramer-Golinkoff, Emily Nadkarni, Lindsay Debski, Margaret M. Padrez, Kevin A. Becker, Lance B. Asch, David A. TI Hidden in Plain Sight: A Crowdsourced Public Art Contest to Make Automated External Defibrillators More Visible SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HOSPITAL CARDIAC-ARREST; AMERICAN-HEART-ASSOCIATION; ACCESS DEFIBRILLATION; IMPROVING SURVIVAL; UNITED-STATES; HEALTH; PROFESSIONALS; SURVEILLANCE; CHALLENGE; COMMUNITY AB Objectives. We sought to explore the feasibility of using a crowdsourcing study to promote awareness about automated external defibrillators (AEDs) and their locations. Methods. The Defibrillator Design Challenge was an online initiative that asked the public to create educational designs that would enhance AED visibility, which took place over 8 weeks, from February 6, 2014, to April 6, 2014. Participants were encouraged to vote for AED designs and share designs on social media for points. Using a mixed-methods study design, we measured participant demographics and motivations, design characteristics, dissemination, and Web site engagement. Results. Over 8 weeks, there were 13 992 unique Web site visitors; 119 submitted designs and 2140 voted. The designs were shared 48 254 times on Facebook and Twitter. Most designers-voters reported that they participated to contribute to an important cause (44%) rather than to win money (0.8%). Design themes included: empowerment, location awareness, objects (e.g., wings, lightning, batteries, life-buoys), and others. Conclusions. The Defibrillator Design Challenge engaged a broad audience to generate AED designs and foster awareness. This project provides a framework for using design and contest architecture to promote health messages. C1 [Merchant, Raina M.; Griffis, Heather M.; Ha, Yoonhee P.; Kilaru, Austin S.; Sellers, Allison M.; Hershey, John C.; Hill, Shawndra S.; Kramer-Golinkoff, Emily; Nadkarni, Lindsay; Debski, Margaret M.; Padrez, Kevin A.] Univ Penn, Social Media & Hlth Innovat Lab, Penn Med Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Becker, Lance B.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Social Media & Hlth Innovat Lab, 1022 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM Raina.Merchant@uphs.upenn.edu FU Leonard Davis Institute of Health Economics Pilot Grant, Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; Heartsine, Belfast, Northern Ireland; National Institutes of Health [10714038]; Physio-Control, Seattle, WA; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; National Institutes of Health, Bethesda, MD; Medtronic Foundation, Minneapolis, MN FX This work was supported by Leonard Davis Institute of Health Economics Pilot Grant, Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; and Heartsine, Belfast, Northern Ireland. R. M. Merchant was supported by the National Institutes of Health (K23 grant 10714038); Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; and Heartsine, Belfast, Northern Ireland. L. B. Becker was supported by Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; the National Institutes of Health, Bethesda, MD; Cardiac Science, Bothell, WA; and Medtronic Foundation, Minneapolis, MN. NR 34 TC 4 Z9 4 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2306 EP 2312 DI 10.2105/AJPH.2014.302211 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500037 PM 25320902 ER PT J AU Benzer, JK Creech, SK Mohr, DC Charns, MP AF Benzer, Justin K. Creech, Suzannah K. Mohr, David C. Charns, Martin P. TI LEARNING GOALS MAY PREVENT "GOALS GONE WILD" SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID HEALTH-CARE C1 [Benzer, Justin K.; Mohr, David C.; Charns, Martin P.] VA Boston Healthcare Syst, CHOIR, Boston, MA 02130 USA. [Benzer, Justin K.; Mohr, David C.; Charns, Martin P.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Creech, Suzannah K.] Providence VA Med Ctr, Vulnerable Veteran Populat Res Grp, Providence, RI USA. [Creech, Suzannah K.] Brown Univ, Dept Psychiat, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Benzer, JK (reprint author), VA Boston Healthcare Syst, CHOIR, 150 S Huntington Ave 152-M, Boston, MA 02130 USA. EM justin.benzer@va.gov OI Benzer, Justin/0000-0001-5151-2127; Creech, Suzannah/0000-0002-6582-1673 NR 10 TC 1 Z9 1 U1 2 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP E1 EP E1 DI 10.2105/AJPH.2014.302264 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500001 PM 25320875 ER PT J AU Whetstine, JR AF Whetstine, Johnathan R. TI Methylation: A multifaceted modification - Looking at transcription and beyond Preface SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Editorial Material C1 [Whetstine, Johnathan R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Whetstine, Johnathan R.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Bldg 149,13th St,Room 7-213, Charlestown, MA 02129 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 EI 0006-3002 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD DEC PY 2014 VL 1839 IS 12 SI SI BP 1351 EP 1352 DI 10.1016/j.bbagrm.2014.09.005 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AX7ZC UT WOS:000347129100001 PM 25225044 ER PT J AU Joh, RI Palmieri, CM Hill, IT Motamedi, M AF Joh, Richard I. Palmieri, Christina M. Hill, Ian T. Motamedi, Mo TI Regulation of histone methylation by noncoding RNAs SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE Noncoding RNA; Histone methylation; Epigenetics; IncRNA; siRNA; piRNA ID X-CHROMOSOME INACTIVATION; NEWLY SYNTHESIZED HISTONES; FISSION YEAST CENTROMERES; GENE-EXPRESSION; DNA-REPLICATION; C-ELEGANS; HETEROCHROMATIN FORMATION; EPIGENETIC INHERITANCE; CHROMATIN STATE; TRANSCRIPTIONAL REPRESSION AB Cells can adapt to their environment and develop distinct identities by rewiring their transcriptional networks to regulate the output of key biological pathways without concomitant mutations to the underlying genes. These alterations, called epigenetic changes, persist stably through mitotic or, in some instances, meiotic cell divisions. In eukaryotes, heritable changes to chromatin structure are a prominent, but not exclusive, mechanism by which epigenetic changes are mediated. These changes are initiated by sequence-specific events, which trigger a cascade of molecular interactions resulting in feedback mechanisms, alterations in chromatin structure, histone posttranslational modifications (PTMs), and ultimately establishment of distinct transcriptional states. In recent years, advances in next generation sequencing have led to the discovery of several novel classes of noncoding RNAs (ncRNAs). In addition to their well-established cytoplasmic roles in posttranscriptional regulation of gene expression, ncRNAs have emerged as key regulators of epigenetic changes via chromatin-dependent mechanisms in organisms ranging from yeast to man. They function by affecting chromatin structure, histone PTMs, and the recruitment of transcriptional activating or repressing complexes. Among histone PTMs, lysine methylation serves as the binding substrate for the recruitment of key protein complexes involved in the regulation of genome architecture, stability, and gene expression. In this review, we will outline the known mechanisms by which ncRNAs of different origins regulate histone methylation, and in doing so contribute to a variety of genome regulatory functions in eukaryotes. This article is part of a Special Issue entitled: Methylation: A Multifaceted Modification looking at transcription and beyond. (C) 2014 Elsevier B.V. All rights reserved. C1 [Joh, Richard I.; Palmieri, Christina M.; Hill, Ian T.; Motamedi, Mo] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Joh, Richard I.; Palmieri, Christina M.; Hill, Ian T.; Motamedi, Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hill, Ian T.] Harvard Univ, Sch Med, PhD Program Biol & Biomed Sci, Boston, MA 02115 USA. RP Motamedi, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM mmotamedi@hms.harvard.edu OI Joh, Richard/0000-0003-0583-8032 FU NCI Proton Beam [C06 CA059267]; V Scholar Award FX We thank the members of the lab for discussion and critical reading of the manuscript. Research in the lab is supported by NCI Proton Beam Grant (C06 CA059267) and a V Scholar Award to MM. NR 174 TC 5 Z9 5 U1 4 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 EI 0006-3002 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD DEC PY 2014 VL 1839 IS 12 SI SI BP 1385 EP 1394 DI 10.1016/j.bbagrm.2014.06.006 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AX7ZC UT WOS:000347129100005 PM 24954181 ER PT J AU Van Rechem, C Whetstine, JR AF Van Rechem, Capucine Whetstine, Johnathan R. TI Examining the impact of gene variants on histone lysine methylation SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE Somatic mutation; SNP; KMT; KDM; EZH2; Histone ID LINKED MENTAL-RETARDATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; CHROMATIN REMODELING GENES; ACUTE LYMPHOBLASTIC-LEUKEMIA; CLEFT LIP/CLEFT PALATE; B-CELL LYMPHOMAS; ZINC-FINGER GENE; SOMATIC MUTATIONS; SOTOS-SYNDROME; MICROSATELLITE INSTABILITY AB In recent years, there has been a boom in the amount of genome-wide sequencing data that has uncovered important and unappreciated links between certain genes, families of genes and enzymatic processes and diseases such as cancer. Such studies have highlighted the impact that chromatin modifying enzymes could have in cancer and other genetic diseases. In this review, we summarize characterized mutations and single nucleotide polymorphisms (SNPs) in histone lysine methyltransferases (KMTs), histone lysine demethylases (KDMs) and histones. We primarily focus on variants with strong disease correlations and discuss how they could impact histone lysine methylation dynamics and gene regulation. This article is part of a Special Issue entitled: Methylation: A Multifaceted Modification looking at transcription and beyond. (C) 2014 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp Canc Ctr, Bldg 149,Room 7-213,13th St, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu FU American Cancer Society Basic Scholar Grant; MGH Proton Beam Federal Share Grant [CA059267]; NIH [R01GM097360]; Medical Discovery; Marsha Rivkin Center for Ovarian Cancer Research FX We are grateful to Dr. Joshua C. Black for his comments and suggestions. The studies conducted in this manuscript were funded by the following agencies: American Cancer Society Basic Scholar Grant, MGH Proton Beam Federal Share Grant (CA059267) and NIH R01GM097360 to J.R.W. A post-doctoral fellowship was provided by the Fund for Medical Discovery (C.V.R.). This research was supported in part by a grant from the Marsha Rivkin Center for Ovarian Cancer Research (C.V.R.). NR 136 TC 12 Z9 12 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 EI 0006-3002 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD DEC PY 2014 VL 1839 IS 12 SI SI BP 1463 EP 1476 DI 10.1016/j.bbagrm.2014.05.014 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AX7ZC UT WOS:000347129100012 PM 24859469 ER PT J AU Sewastianik, T Prochorec-Sobieszek, M Chapuy, B Juszczynski, P AF Sewastianik, Tomasz Prochorec-Sobieszek, Monika Chapuy, Bjoern Juszczynski, Przemyslaw TI MYC deregulation in lymphoid tumors: molecular mechanisms, clinical consequences and therapeutic implications SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE MYC; Burkitt lymphoma; Diffuse large B-cell lymphoma; Double hit lymphoma; Targeted therapy ID B-CELL LYMPHOMAS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BET BROMODOMAIN INHIBITION; GENE-EXPRESSION SIGNATURES; ACUTE MYELOID-LEUKEMIA; HEAVY-CHAIN LOCUS; C-MYC; BURKITT-LYMPHOMA; MULTIPLE-MYELOMA AB MYC is one of the most frequently deregulated oncogenes in human malignancies. It encodes a leucine zipper transcription factor that modulates a broad spectrum of cellular genes responsible for enhancing cell proliferation, cellular metabolism, growth, angiogenesis, metastasis, genomic instability, stem cell self-renewal and reduced differentiation. MYC functions predominantly as an amplifier of expression of already active genes, potentiating the pre-existing transcriptional program, although it can also repress certain transcriptional targets. In mouse models, MYC induces lymphomas, but requires cooperation with other lesions, including inactivation of the p53 pathway, structural alterations of BCL2 family members, or increased PI3K activity. In human B-cell tumors, MYC rearrangements involving the 8q24 region and immunoglobulin heavy or light genes are a hallmark of Burkitt lymphoma (BL), but can also occur in other lymphoid malignancies, that include diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU), plasma cell myeloma (PCM), mantle cell lymphoma (MCL) and plasmablastic lymphoma. For non-BL lymphoid malignancies, MYC fusions represent secondary genetic events and exist in the context of complex karyotypes. Regardless of the mechanism deregulating MYC, lymphomas over-expressing MYC are addicted to this oncogene, highlighting the potential clinical utility of MYC targeting strategies. Several promising approaches for pharmaceutical intervention have been suggested which are now in preclinical or clinical development. Herein, we therefore review the molecular pathogenetic mechanisms associated with MYC deregulation in human B-cell lymphomas and their implications for therapies targeting MYC. (C) 2014 Elsevier B.V. All rights reserved. C1 [Sewastianik, Tomasz; Prochorec-Sobieszek, Monika; Juszczynski, Przemyslaw] Inst Hematol & Transfus Med, Dept Diagnost Hematol, PL-02776 Warsaw, Poland. [Chapuy, Bjoern] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Juszczynski, P (reprint author), Inst Hematol & Transfus Med, Dept Diagnost Hematol, Indiry Gandhi Str 14, PL-02776 Warsaw, Poland. EM pjuszczynski@ihit.waw.pl FU Foundation for Polish Science [TEAM/2011-7/4]; European Regional Development Fund; Operational Program Innovative Economy FX This work and T.S. PhD scholarship are supported by a Foundation for Polish Science grant TEAM/2011-7/4, co-financed by the European Regional Development Fund and Operational Program Innovative Economy 2007-2013. NR 159 TC 14 Z9 14 U1 4 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC PY 2014 VL 1846 IS 2 BP 457 EP 467 DI 10.1016/j.bbcan.2014.08.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AY0BQ UT WOS:000347263400015 PM 25199984 ER PT J AU Shaknovich, R De, S Michor, F AF Shaknovich, Rita De, Subhajyoti Michor, Franziska TI Epigenetic diversity in hematopoietic neoplasms SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Epigenetics; Heterogeneity; Cancer; Lymphoma ID INDUCED CYTIDINE DEAMINASE; ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMAS; CHRONIC MYELOPROLIFERATIVE NEOPLASMS; POLYCYTHEMIA VERA MYELOFIBROSIS; DNA METHYLTRANSFERASE 1; SOMATIC HYPERMUTATION; GENE-EXPRESSION; DEACETYLASE INHIBITOR; HUMAN COLON AB Tumor cell populations display a remarkable extent of variability in non-genetic characteristics such as DNA methylation, histone modification patterns, and differentiation levels of individual cells. It remains to be elucidated whether non-genetic heterogeneity is simply a byproduct of tumor evolution or instead a manifestation of a higher-order tissue organization that is maintained within the neoplasm to establish a differentiation hierarchy, a favorable microenvironment, or a buffer against changing selection pressures during tumorigenesis. Here, we review recent findings on epigenetic diversity, particularly heterogeneity in DNA methylation patterns in hematologic malignancies. We also address the implications of epigenetic heterogeneity for the clonal evolution of tumors and discuss its effects on gene expression and other genome functions in cancer. (C) 2014 Published by Elsevier B.V. C1 [Shaknovich, Rita] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10021 USA. [Shaknovich, Rita] Weill Cornell Med Coll, Dept Pathol, Div Immunopathol, New York, NY 10021 USA. [De, Subhajyoti] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [De, Subhajyoti] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu FU Dana-Farber Cancer Institute Physical Sciences Oncology Center [U54CA143798] FX We would like to thank Nils Weinhold for discussions and assistance. This work was supported by the Dana-Farber Cancer Institute Physical Sciences Oncology Center (U54CA143798) to F.M. NR 123 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC PY 2014 VL 1846 IS 2 BP 477 EP 484 DI 10.1016/j.bbcan.2014.09.003 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AY0BQ UT WOS:000347263400017 PM 25240947 ER PT J AU Wurdinger, T Deumelandt, K van der Vliet, HJ Wesseling, P de Gruijl, TD AF Wurdinger, Thomas Deumelandt, Katrin van der Vliet, Hans J. Wesseling, Pieter de Gruijl, Tanja D. TI Mechanisms of intimate and long-distance cross-talk between glioma and myeloid cells: How to break a vicious cycle SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Glioblastoma; Cross-talk; Immune response; Monocytes; Glioma-associated macrophages and microglia; Myeloid-derived suppressor cells ID CENTRAL-NERVOUS-SYSTEM; TUMOR-ASSOCIATED MACROPHAGES; NEWLY-DIAGNOSED GLIOBLASTOMA; REGULATORY T-CELLS; ANTITUMOR IMMUNE-RESPONSES; MALIGNANT BRAIN-TUMORS; HLA-DR EXPRESSION; SUPPRESSOR-CELLS; IN-VITRO; EXTRACELLULAR VESICLES AB Glioma-associated microglia and macrophages (GAMs) and myeloid-derived suppressor cells (MDSCs) condition the glioma microenvironment to generate an immunosuppressed niche for tumour expansion. This immunosuppressive microenvironment is considered to be shaped through a complex multi-step interactive process between glioma cells, GAMs and MDSCs. Glioma cells recruit GAMs and MDSCs to the tumour site and block their maturation. Glioma cell-derived factors subsequently skew these cells towards an immunosuppressive, tumour-promoting phenotype. Finally, GAMs and MDSCs enhance immune suppression in the glioma microenvironment and promote glioma growth, invasiveness, and neovascularization. The local and distant cross-talk between glioma cells and GAMs and MDSCs is regulated by a plethora of soluble proteins and cell surface-bound factors, and possibly via extracellular vesicles and platelets. Importantly, GAMs and MDSCs have been reported to impair the efficacy of glioma therapy, in particular immunotherapeutic approaches. Therefore, advancing our understanding of the function of GAMs and MDSCs in brain tumours and targeted intervention of their immunosuppressive function may benefit the treatment of glioma. (C) 2014 Elsevier B.V. All rights reserved. C1 [Wurdinger, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Wurdinger, Thomas; Deumelandt, Katrin] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, Dept Neurosurg, Amsterdam, Netherlands. [Deumelandt, Katrin; van der Vliet, Hans J.; de Gruijl, Tanja D.] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. [Wesseling, Pieter] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, Dept Pathol, Amsterdam, Netherlands. [Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. RP Wurdinger, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02138 USA. EM twurdinger@mgh.harvard.edu; td.degruijl@vumc.nl RI Wesseling, P./H-8114-2014 OI Wesseling, P./0000-0001-5453-5201 FU VIDI from the Dutch Organization of Scientific Research (NWO) [91711366, 91756321]; European Research Council [336540]; Netherlands Organization for Health Research and Development (ZonMw) [90700309]; Dutch Cancer Society [VU 2010-4728] FX This work was supported by the VIDI fellowships 91711366 (T.W.) and 91756321 (T.D.d.G) from the Dutch Organization of Scientific Research (NWO), and European Research Council Starting Researchers Grant 336540 (T.W), by The Netherlands Organization for Health Research and Development (ZonMw) grant 90700309and the Dutch Cancer Society (grant VU 2010-4728), both to H.J.v.d.V. NR 243 TC 13 Z9 13 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC PY 2014 VL 1846 IS 2 BP 560 EP 575 DI 10.1016/j.bbcan.2014.10.003 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AY0BQ UT WOS:000347263400024 PM 25453365 ER PT J AU Orup, HI Deutsch, CK Holmes, LB AF Orup, H. Ivan, Jr. Deutsch, Curtis K. Holmes, Lewis B. TI Laser Light Scan Analysis of the " Anticonvulsant Face" SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE laser light scanner; structured light scanner; anticonvulsants; the "anticonvulsant face" ID FETAL HYDANTOIN SYNDROME; EXPOSED IN-UTERO; ANTIEPILEPTIC DRUGS; PRENATAL EXPOSURE; PREGNANCY; CHILDREN; MALFORMATIONS; CARBAMAZEPINE; LAMOTRIGINE; VALPROATE AB BackgroundThe anticonvulsant face, with a short nose, broad nasal bridge, epicanthal folds, and wide mouth, was described in the 1970s in children who had been exposed during pregnancy to the anticonvulsant drugs phenytoin and phenobarbital. The laser light scan makes it possible to establish three-dimensional positions of physical features and to determine more objectively the changes in the size and shape of the affected soft tissues of the faces of children exposed to these anticonvulsant drugs during pregnancy. MethodsThirteen individuals, exposed throughout pregnancy to phenytoin as either monotherapy or polytherapy, were identified in a previous analysis as having significant changes in their craniofacial features based on measurements of cephalometric radiographs. Those changes were associated with midface hypoplasia and a short nose, features of the anticonvulsant face. The soft tissues of their faces have been evaluated with laser light scans. ResultsThe notable changes in soft tissues identified by laser light scans were a wide philtrum (cph-cph), narrow mouth (ch-ch), short nasal bridge (n-prn), shortened nose height (n-sn), and flattened orbits (orbital protrusion index). ConclusionThis analysis of the facial features of phenytoin-exposed individuals, selected because of changes in their craniofacial bony structures, showed that there were several significant changes, two of which, widening of the philtrum and a small mouth, have not been described previously as part of this phenotype. Birth Defects Research (Part A), 2014. (c) 2014 Wiley Periodicals, Inc. Birth Defects Research (Part A) 100:905-911, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Orup, H. Ivan, Jr.] Harvard Univ, Sch Dent Med, Dept Orthodont, Boston, MA 02115 USA. [Deutsch, Curtis K.] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA USA. [Holmes, Lewis B.] MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. [Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu FU NICHD NIH HHS [P30 HD004147] NR 34 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD DEC PY 2014 VL 100 IS 12 BP 905 EP 911 DI 10.1002/bdra.23250 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AX4RB UT WOS:000346918000001 PM 24863698 ER PT J AU Gandaglia, G Sun, M Trinh, QD Becker, A Schiffmann, J Hu, JC Briganti, A Montorsi, F Perrotte, P Karakiewicz, PI Abdollah, F AF Gandaglia, Giorgio Sun, Maxine Quoc-Dien Trinh Becker, Andreas Schiffmann, Jonas Hu, Jim C. Briganti, Alberto Montorsi, Francesco Perrotte, Paul Karakiewicz, Pierre I. Abdollah, Firas TI Survival benefit of definitive therapy in patients with clinically advanced prostate cancer: estimations of the number needed to treat based on competing-risks analysis SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; locally-advanced; radical prostatectomy; observation; radiotherapy; survival benefit ID PROPENSITY SCORE METHODS; RADICAL PROSTATECTOMY; MEN; EXPERIENCE; SURGERY; TRIAL AB ObjectiveTo describe the survival benefit associated with radical prostatectomy (RP), as compared with initial observation, in patients with locally advanced prostate cancer (PCa). Patients and MethodsOverall, 1382 patients with locally advanced PCa treated with RP or initial observation between 1995 and 2009 were identified from the Surveillance, Epidemiology and End Results Medicare insurance programme-linked database. Patients were matched using propensity-score methodology, then 10-year cancer-specific mortality (CSM) rates were estimated and the number needed to treat (NNT) was calculated. Competing-risks regression analyses tested the relationship between treatment type and CSM. ResultsOverall, the 10-year CSM rates were 11.8 and 19.3% for patients treated with RP and initial observation, respectively (P < 0.001). The corresponding 10-year NNT was 13. The 10-year CSM rates for the same treatment groups were 8.9 vs 13.9%, respectively, for Gleason score 7, 16.8 vs 27.8%, respectively, for Gleason score 8-10, 10.1 vs 15.8%, respectively, for clinical stage T3a, and 17.0 vs 29.3%, respectively, for T3b/T4, respectively (all P 0.04). The corresponding NNTs were 20, 9, 17 and 8, respectively. In multivariable analyses, RP was an independent predictor of more favourable CSM rates in all categories (all P 0.04). In separate sensitivity analyses, no differences were recorded when patients treated with radiotherapy were compared with those receiving RP (P = 0.4). Conversely, patients undergoing initial observation had a higher risk of CSM compared with those treated with radiotherapy (P = 0.03). ConclusionsRP leads to a significant survival advantage compared with observation in patients with locally advanced disease. The highest benefit was observed in patients with T3b/T4 and Gleason score 8-10 disease. C1 [Gandaglia, Giorgio; Sun, Maxine; Becker, Andreas; Schiffmann, Jonas; Karakiewicz, Pierre I.; Abdollah, Firas] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 1P1, Canada. [Gandaglia, Giorgio; Briganti, Alberto; Montorsi, Francesco; Abdollah, Firas] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Urol Res Inst, Dept Urol, Milan, Italy. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Urol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Becker, Andreas; Schiffmann, Jonas] Univ Med Ctr Hamburg Eppendorf, Martiniclin, Hamburg, Germany. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Perrotte, Paul; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 1P1, Canada. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 264 Blvd Rene Levesque E 228, Montreal, PQ H2X 1P1, Canada. EM Giorgio.gandaglia@gmail.com OI , Jonas/0000-0002-0654-5920 FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX P.I.K. is partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. NR 31 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2014 VL 114 IS 6B BP E62 EP E69 DI 10.1111/bju.12645 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AX5ST UT WOS:000346988300009 PM 24467651 ER PT J AU Gandaglia, G Sun, M Popa, I Schiffmann, J Abdollah, F Trinh, QD Saad, F Graefen, M Briganti, A Montorsi, F Karakiewicz, PI AF Gandaglia, Giorgio Sun, Maxine Popa, Ioana Schiffmann, Jonas Abdollah, Firas Quoc-Dien Trinh Saad, Fred Graefen, Markus Briganti, Alberto Montorsi, Francesco Karakiewicz, Pierre I. TI The impact of androgen-deprivation therapy (ADT) on the risk of cardiovascular (CV) events in patients with non-metastatic prostate cancer: a population-based study SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; androgen-deprivation therapy; cardiovascular events; side-effects ID RADICAL PROSTATECTOMY; HORMONE AGONISTS; MEN; DISEASE; SURVIVAL; RADIOTHERAPY; SUPPRESSION; GNRH AB ObjectiveTo examine and quantify the contemporary association between androgen-deprivation therapy (ADT) and three separate endpoints: coronary artery disease (CAD), acute myocardial infarction (AMI), and sudden cardiac death (SCD), in a large USA contemporary cohort of patients with prostate cancer. Patients and MethodsIn all, 140474 patients diagnosed with non-metastatic prostate cancer between 1995 and 2009 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database were abstracted. Patients treated with ADT and those not receiving ADT were matched using propensity score methodology. The 10-year CAD, AMI, and SCD rates were estimated. Competing-risks regression analyses tested the association between the type of ADT (GnRH agonists vs bilateral orchidectomy) and CAD, AMI, and SCD, after adjusting for the risk of dying during follow-up. ResultsOverall, the 10-year rates of CAD, AMI, and SCD were 25.9%, 15.6%, and 15.8%, respectively. After stratification according to ADT status (ADT-naive vs GnRH agonists vs bilateral orchidectomy), the CAD rates were 25.1% vs 26.9% vs 23.2%, the AMI rates were 14.8% vs 16.6% vs 14.8%, and the SCD rates were 14.2% vs 17.7% vs 16.4%, respectively. In competing-risks multivariable regression analyses, the administration of GnRH agonists (all P < 0.001), but not bilateral orchidectomy (all P 0.7), was associated with higher risk of CAD, AMI, and SCD. ConclusionsThe administration of GnRH agonists, but not orchidectomy, is still associated with a significantly increased risk of CAD, AMI, and, especially, SCD in patients with non-metastatic prostate cancer. Alternative forms of ADT should be considered in patients at higher risk of CV events. C1 [Gandaglia, Giorgio; Sun, Maxine; Popa, Ioana; Schiffmann, Jonas; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Gandaglia, Giorgio; Abdollah, Firas; Briganti, Alberto; Montorsi, Francesco] Univ Vita Salute San Raffaele, Hosp San Raffaele, San Raffaele Sci Inst, Urol Res Inst, Milan, Italy. [Popa, Ioana; Saad, Fred; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada. [Schiffmann, Jonas; Graefen, Markus] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany. [Quoc-Dien Trinh] Harvard Univ, Div Urol Surg, Sch Med, Boston, MA USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM giorgio.gandaglia@gmail.com OI , Jonas/0000-0002-0654-5920 NR 32 TC 20 Z9 20 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2014 VL 114 IS 6B BP E82 EP E89 DI 10.1111/bju.12732 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AX5ST UT WOS:000346988300012 PM 24612110 ER PT J AU Sonpavde, G Pond, GR Armstrong, AJ Galsky, MD Leopold, L Wood, BA Wang, SL Paolini, J Chen, I Chow-Maneval, E Mooney, DJ Lechuga, M Smith, MR Michaelson, MD AF Sonpavde, Guru Pond, Gregory R. Armstrong, Andrew J. Galsky, Matthew D. Leopold, Lance Wood, Brian A. Wang, Shaw-Ling Paolini, Jolanda Chen, Isan Chow-Maneval, Edna Mooney, David J. Lechuga, Mariajose Smith, Matthew R. Michaelson, M. Dror TI Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer SO BJU INTERNATIONAL LA English DT Article DE metastatic; castration-resistant prostate cancer; radiographic progression; Prostate Cancer Working Group (PCWG)-2; overall survival (OS) ID SOLID TUMORS; 2ND-LINE CHEMOTHERAPY; BONE METASTASES; PLUS PREDNISONE; SURVIVAL; MEN; ANTIGEN; ASSOCIATION; SURROGACY; PLACEBO AB ObjectiveTo investigate the association of radiographic progression defined by Prostate Cancer Working Group (PCWG)-2 guidelines and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). Patients and MethodsTwo trials that used PCWG-2 guidelines to define progression were analysed: a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone plus AT-101 or placebo, and a phase III trial (n = 873) comparing prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox proportional hazards regression models were used to estimate the association of radiographic progression with OS. Landmark analyses compared progressing patients with those who had not progressed. Sub-analyses compared patients removed from trial for progression vs other reasons. ResultsAn increased risk of death was seen for radiographic progression at landmark times from 6 to 12 months with docetaxel-based therapy (hazard ratio [HR] >1.7 at all time-points). An increased risk of death was also seen with post-docetaxel prednisone alone or with sunitinib for progression at landmark times from 2 to 8 months (HR >2.7 at all time-points). Kendall's was 0.50 (P < 0.001) in the setting of docetaxel-based therapy and 0.34 (P < 0.001) in the post-docetaxel setting for association between radiographic progression and death amongst patients with both events. Removal from study due to radiographic progression was associated with a significantly lower OS compared with removal for other reasons in both trials. Limitations of a retrospective analysis apply and there was no central radiology review. ConclusionsRadiographic progression by PCWG-2 criteria was significantly associated with OS in patients with mCRPC receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. With external validation as a surrogate endpoint in trials showing survival benefits, the use of radiographic progression-free survival may expedite drug development in mCRPC, which has been hampered by the lack of intermediate endpoints. C1 [Sonpavde, Guru; Mooney, David J.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Pond, Gregory R.] McMaster Univ, Dept Biostat, Hamilton, ON, Canada. [Armstrong, Andrew J.] Duke Prostate Ctr, Div Hematol Oncol, Dept Med, Durham, NC USA. [Galsky, Matthew D.] Mt Sinai Tisch Canc Inst, Div Hematol Oncol, Dept Med, New York, NY USA. [Leopold, Lance; Wood, Brian A.] Ascenta Therapeut, Malvern, PA USA. [Wang, Shaw-Ling; Paolini, Jolanda; Chen, Isan; Chow-Maneval, Edna; Lechuga, Mariajose] Pfizer Inc, Madison, NJ USA. [Wang, Shaw-Ling] ICON Clin Res Inc, San Diego, CA USA. [Chen, Isan; Chow-Maneval, Edna] Seragon Pharmaceut, San Diego, CA USA. [Smith, Matthew R.; Michaelson, M. Dror] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Smith, Matthew R.; Michaelson, M. Dror] Harvard Univ, Sch Med, Boston, MA USA. RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Ctr Comprehens Canc, 1802 6th Ave S NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer FX G.S.: Research support from Pfizer NR 22 TC 9 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2014 VL 114 IS 6B BP E25 EP E31 DI 10.1111/bju.12589 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AX5ST UT WOS:000346988300004 PM 24298897 ER PT J AU Emerton, BC Gansler, DA Sandberg, EH Jerram, M AF Emerton, Britt C. Gansler, David A. Sandberg, Elisabeth H. Jerram, Matthew TI Functional anatomic dissociation of description and picture naming in the left temporal lobe SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Description naming; Picture naming; Anterior temporal lobectomy; Pre-surgical epilepsy evaluation ID CEREBRAL-BLOOD-FLOW; EPILEPSY PATIENTS; LANGUAGE; WORD; ACTIVATION; LOBECTOMY; BRAIN; FMRI; HEMISPHERE; OUTCOMES AB Functional magnetic resonance imaging (fMRI) was used in a non-patient experimental sample to assess the neuroanatomical dissociation of picture and description naming (PN and DN) in temporal lobe (TL). The purpose was to determine the generalizability of findings in semantic organization in the epilepsy patient population to the broader population. It was hypothesized that, akin to patient derived findings, DN would uniquely activate left TL regions anterior to those associated with PN, while overlapping in middle and posterior left TL. Participants (n = 16) underwent fMRI while silently naming target words during a picture naming task (PNT; line drawings) and description naming task (DNT; orthographic phrases). Analysis was a priori restricted to the left TL. Group results of direct contrasts (DNT > PNT and PNT > DNT) confirmed the hypothesized dissociation with DNT > PNT activating anterior left TL. Within-condition contrasts (DNT and PNT alone) yielded additional support, revealing areas of shared and unique activation in each condition. This is the first imaging study to contrast DN and PN in the same sample. The results suggest DN and PN are meaningfully different constructs subserved by converging and diverging TL neuroanatomy and may be differentially affected by disease. C1 [Emerton, Britt C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Emerton, Britt C.] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. [Gansler, David A.; Sandberg, Elisabeth H.; Jerram, Matthew] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Sandberg, Elisabeth H.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. RP Gansler, DA (reprint author), Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. EM dgansler@suffolk.edu NR 40 TC 3 Z9 3 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2014 VL 8 IS 4 BP 570 EP 578 DI 10.1007/s11682-013-9281-9 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA AX4SA UT WOS:000346920400010 PM 24357099 ER PT J AU Attia, EF Akgun, KM Wongtrakool, C Goetz, MB Rodriguez-Barradas, MC Rimland, D Brown, ST Hoo, GWS Kim, J Lee, PJ Schnapp, LM Sharafkhaneh, A Justice, AC Crothers, K AF Attia, Engi F. Akguen, Kathleen M. Wongtrakool, Cherry Goetz, Matthew Bidwell Rodriguez-Barradas, Maria C. Rimland, David Brown, Sheldon T. Hoo, Guy W. Soo Kim, Joon Lee, Patty J. Schnapp, Lynn M. Sharafkhaneh, Amir Justice, Amy C. Crothers, Kristina TI Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4 SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LIPOPOLYSACCHARIDE-BINDING PROTEIN; RESOLUTION COMPUTED-TOMOGRAPHY; AIRWAY WALL THICKNESS; ANTIRETROVIRAL THERAPY; DIFFUSING-CAPACITY; LUNG-FUNCTION; INFECTION; INFLAMMATION; SMOKERS AB BACKGROUND: The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema. METHODS: We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semi-quantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as >10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection. RESULTS: Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for >10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/mu L (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of >10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV. CONCLUSIONS: HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/mu L and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema. C1 [Attia, Engi F.; Schnapp, Lynn M.; Crothers, Kristina] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Akguen, Kathleen M.; Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. [Akguen, Kathleen M.; Lee, Patty J.; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Wongtrakool, Cherry; Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Wongtrakool, Cherry; Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Goetz, Matthew Bidwell; Hoo, Guy W. Soo] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell; Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rodriguez-Barradas, Maria C.; Sharafkhaneh, Amir] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.; Sharafkhaneh, Amir] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Brown, Sheldon T.; Kim, Joon] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Brown, Sheldon T.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. RP Crothers, K (reprint author), Univ Washington, Harborview Med Ctr, 325 Ninth Ave,Campus Box 359762, Seattle, WA 98104 USA. EM crothk@uw.edu OI Attia, Engi/0000-0002-5044-9602; Justice, Amy/0000-0003-0139-5502; Crothers, Kristina/0000-0001-9702-0371 FU National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [R21 HL120391, R01 HL090342]; University of Washington Center for AIDS Research; NIH [P30-AI-027757]; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of Mental Health; National Institute on Drug Abuse; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NHLBI; National Institute on Aging FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [R21 HL120391 to Dr Schnapp and R01 HL090342 to Dr Crothers]. This research was funded in part by a 2012 developmental grant from the University of Washington Center for AIDS Research, an NIH-funded program under award number P30-AI-027757, which is supported by the following NIH institutes and centers: National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NHLBI, and National Institute on Aging. NR 54 TC 23 Z9 23 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2014 VL 146 IS 6 BP 1543 EP 1553 DI 10.1378/chest.14-0543 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AX9IU UT WOS:000347217600042 PM 25080158 ER PT J AU Kawashiri, M Nomura, A Konno, T Hayashi, K AF Kawashiri, Masa-aki Nomura, Akihiro Konno, Tetsuo Hayashi, Kenshi TI Can Next-Generation Sequencing Replace Sanger Sequencing for Screening Genetic Variants? SO CIRCULATION JOURNAL LA English DT Editorial Material ID HYPERTROPHIC CARDIOMYOPATHY; PERSPECTIVES; MUTATION C1 [Kawashiri, Masa-aki; Nomura, Akihiro; Konno, Tetsuo; Hayashi, Kenshi] Kanazawa Univ, Grad Sch Med, Div Cardiovasc Med, Kanazawa, Ishikawa 9208641, Japan. [Konno, Tetsuo] Kanazawa Univ, Res & Educ Ctr Innovat & Prevent Med, Kanazawa, Ishikawa 9208641, Japan. [Nomura, Akihiro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Kawashiri, M (reprint author), Kanazawa Univ, Grad Sch Med, Div Cardiovasc Med, 13-1 Takara Machi, Kanazawa, Ishikawa 9208641, Japan. EM mk@med.kanazawa-u.ac.jp NR 15 TC 1 Z9 1 U1 0 U2 10 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 EI 1347-4820 J9 CIRC J JI Circ. J. PD DEC PY 2014 VL 78 IS 12 BP 2845 EP 2847 DI 10.1253/circj.CJ-14-1144 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX1HL UT WOS:000346698300010 PM 25366809 ER PT J AU Taghian, NR Miller, CL Jamrnallo, LS O'Toole, J Skolny, MN AF Taghian, Nadine R. Miller, Cynthia L. Jamrnallo, Lauren S. O'Toole, Jean Skolny, Melissa N. TI Lymphedema following breast cancer treatment and impact on quality of life: A review SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Lymphedema; Breast cancer; Quality of life ID STANDARD AXILLARY TREATMENT; SENTINEL NODE BIOPSY; RISK-FACTORS; OPTOELECTRONIC VOLUMETRY; EARLY-DIAGNOSIS; ARM LYMPHEDEMA; LIMB VOLUME; GROUP TRIAL; SURGERY; DISSECTION AB Lymphedema resulting from breast cancer treatment is a chronic condition which can significantly compromise quality of life. We sought to review various aspects of breast-cancer related lymphedema including measurement techniques, definitions, risk factors, and specifically, impact on physical, psychological, and emotional well-being of women treated for breast cancer. For the purpose of this review, we performed a literature search using PubMed for articles on lymphedema secondary to breast cancer treatment published since 1997. While improvements in breast cancer therapy have contributed to a decrease in the incidence of lymphedema, the overall negative impact the condition has on patients and survivors has remained unchanged. The development of lymphedema results in physical impairments including compromised function, diminished strength, fatigue, and pain in the affected arm. Affected women may have decreased self-confidence resulting from a distorted body image. Negative emotions reported by women with lymphedema include anxiety, frustration, sadness, anger, fear, and increased self-consciousness. Lymphedema secondary to breast cancer treatment remains a significant quality of life issue, with known consequences related to a woman's physical, psychological, and emotional well-being. 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Taghian, Nadine R.; Miller, Cynthia L.; Jamrnallo, Lauren S.; Skolny, Melissa N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [O'Toole, Jean] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA. RP Skolny, MN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3 55 Fruit St, Boston, MA 02114 USA. EM mskolny@partners.org FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema FX The project described was supported by award numbers R01CA139118 (AGT), P50CA089393 (AGT) from the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 73 TC 15 Z9 17 U1 4 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD DEC PY 2014 VL 92 IS 3 BP 227 EP 234 DI 10.1016/j.critrevonc.2014.06.004 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA AX7ZL UT WOS:000347130000007 PM 25085806 ER PT J AU Sollid, LM Pos, W Wucherpfennig, KW AF Sollid, Ludvig M. Pos, Wouter Wucherpfennig, Kai W. TI Molecular mechanisms for contribution of MHC molecules to autoimmune diseases SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CHRONIC BERYLLIUM DISEASE; SEROPOSITIVE RHEUMATOID-ARTHRITIS; PSORIASIS SUSCEPTIBILITY LOCI; GENOME-WIDE ASSOCIATION; HUMAN-LEUKOCYTE ANTIGEN; CD4(+) T-CELLS; CELIAC-DISEASE; ANKYLOSING-SPONDYLITIS; MULTIPLE-SCLEROSIS; CLASS-I AB It will soon be 50 years since the first MHC associations with human disease were described. These seminal studies opened a flourishing area of research, yet much remains to be discovered. Genome-wide association studies of autoimmune diseases have demonstrated that the MHC region has effect sizes that supersede those for any non-MHC locus for most diseases. Thus, an understanding of how particular MHC alleles confer susceptibility will be essential for a comprehensive understanding of autoimmune disease pathogenesis. Here we review recent exciting findings in this important field. C1 [Sollid, Ludvig M.] Univ Oslo, Dept Immunol, Ctr Immune Regulat, N-0372 Oslo, Norway. [Sollid, Ludvig M.] Natl Hosp Norway, Oslo Univ Hosp, N-0372 Oslo, Norway. [Pos, Wouter; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Sollid, LM (reprint author), Univ Oslo, Dept Immunol, Ctr Immune Regulat, N-0372 Oslo, Norway. EM l.m.sollid@medisin.uio.no; kai_wucherpfennig@dfci.harvard.edu RI Sollid, Ludvig/N-9691-2015 OI Sollid, Ludvig/0000-0001-8860-704X FU Research Council of Norway; European Research Council; South-East Norway Regional Health Authority; NIH [PO1 AI045757]; American Diabetes Association FX This work was supported by grants from the Research Council of Norway, the European Research Council and the South-East Norway Regional Health Authority (to L.M.S.), a NIH grant (PO1 AI045757 to K.W.W.) and a postdoctoral fellowship award by the American Diabetes Association (to W.P.). NR 50 TC 18 Z9 18 U1 0 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2014 VL 31 BP 24 EP 30 DI 10.1016/j.coi.2014.08.005 PG 7 WC Immunology SC Immunology GA AX8BS UT WOS:000347136200006 PM 25216261 ER PT J AU Kumar, V Wijmenga, C Xavier, RJ AF Kumar, Vinod Wijmenga, Cisca Xavier, Ramnik J. TI Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID LONG NONCODING RNAS; SEROPOSITIVE RHEUMATOID-ARTHRITIS; CELIAC-DISEASE; SUSCEPTIBILITY LOCI; AUTOIMMUNE-DISEASES; INFECTIOUS-DISEASE; MULTIPLE COMMON; IDENTIFICATION; EXPRESSION; INTERFERON AB Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents. We propose that the interdisciplinary studies (genetics genomics immunology infection bioinformatics) are the future post-GWAS approaches to advance our understanding of the pathogenesis of immune-mediated diseases. C1 [Kumar, Vinod; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Kumar, V (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. EM v.kumar@umcg.nl RI Wijmenga, Cisca/D-2173-2009; OI Wijmenga, Cisca/0000-0002-5635-1614 FU European Research Council Advanced Grant [ERC-671274]; Dutch Digestive Diseases Foundation [MLDS WO11-30]; European Union's Seventh Framework Programme (EU FP7) TANDEM project [HEALTH-F3-2012-305279]; CCFA; Helmsley Charitable Trust; National Institutes of Health [DK43351] FX This work was supported by the European Research Council Advanced Grant (ERC-671274 to CW), the Dutch Digestive Diseases Foundation (MLDS WO11-30 to CW and VK), the European Union's Seventh Framework Programme (EU FP7) TANDEM project (HEALTH-F3-2012-305279 to CW and VK) and CCFA, Helmsley Charitable Trust and National Institutes of Health (DK43351 to RJX). We thank Jackie Senior and Kate Mc Intyre for editing this paper. NR 60 TC 11 Z9 12 U1 3 U2 27 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2014 VL 31 BP 51 EP 57 DI 10.1016/j.coi.2014.09.007 PG 7 WC Immunology SC Immunology GA AX8BS UT WOS:000347136200010 PM 25458995 ER PT J AU Li, SC Rieckmann, A AF Li, Shu-Chen Rieckmann, Anna TI Neuromodulation and aging: implications of aging neuronal gain control on cognition SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; DIRECT-CURRENT STIMULATION; AGE-RELATED-CHANGES; LIVING HUMAN-BRAIN; LONG-TERM-MEMORY; WORKING-MEMORY; OLD-AGE; ALZHEIMERS-DISEASE; RECEPTOR-BINDING; LIFE-SPAN AB The efficacy of various transmitter systems declines with advancing age. Of particular interest, various pre-synaptic and post-synaptic components of the dopaminergic system change across the human lifespan; impairments in these components play important roles in cognitive deficits commonly observed in the elderly. Here, we review evidence from recent multimodal neuroimaging, pharmacological and genetic studies that have provided new insights for the associations among dopamine functions, aging, functional brain activations and behavioral performance across key cognitive functions, ranging from working memory and episodic memory to goal-directed learning and decision making. Specifically, we discuss these empirical findings in the context of an established neurocomputational theory of aging neuronal gain control. We also highlight gaps in the current understanding of dopamine neuromodulation and aging brain functions and suggest avenues for future research. C1 [Li, Shu-Chen] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. [Li, Shu-Chen] Max Planck Inst Human Dev & Educ, Ctr Lifespan Psychol, D-14195 Berlin, Germany. [Rieckmann, Anna] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Rieckmann, Anna] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. RP Li, SC (reprint author), Tech Univ Dresden, Dept Psychol, Zellescher Weg 17, D-01062 Dresden, Germany. EM shu-chen.li@tu-dresden.de RI Li, Shu-Chen/K-7838-2012 OI Li, Shu-Chen/0000-0002-5520-5789 FU Max Planck Society; German Science Foundation [DFG LI 878/12-2]; Ministry for Education and Research [BMBF 0Q0913, 01GQ1313]; Max Planck Institute for Human Development [M.FE.A.BILD0005]; European Commission FX Shu-Chen Li's research has been supported by fundings from the Max Planck Society (1996-2012), German Science Foundation (DFG LI 878/12-2), and the Ministry for Education and Research (BMBF 0Q0913, 01GQ1313). She gives special thanks to all collaborators in the Neuromodulation of Lifespan Cognition Project, which was sponsored by the Max Planck Institute for Human Development (2005-2012; M.FE.A.BILD0005). Anna Rieckmann was supported by a Marie Curie International Outgoing Fellowship from the European Commission. NR 94 TC 11 Z9 11 U1 2 U2 16 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD DEC PY 2014 VL 29 BP 148 EP 158 DI 10.1016/j.conb.2014.07.009 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AX7YS UT WOS:000347128200021 PM 25064177 ER PT J AU Mirzamohammadi, F Papaioannou, G Kobayashi, T AF Mirzamohammadi, Fatemeh Papaioannou, Garyfallia Kobayashi, Tatsuya TI microRNAs in Cartilage Development, Homeostasis, and Disease SO CURRENT OSTEOPOROSIS REPORTS LA English DT Article DE Chondrocyte; microRNA; Growth plate; Articular cartilage; Osteoarthritis ID MESENCHYMAL STEM-CELLS; REGULATES CHONDROGENIC DIFFERENTIATION; HUMAN OSTEOARTHRITIC CHONDROCYTES; HUMAN ARTICULAR CHONDROCYTES; IN-VITRO; SKELETAL DEVELOPMENT; EXPRESSION; SOX9; MIR-140; GROWTH AB microRNAs (miRNAs) regulate gene expression mainly at the posttranscriptional level. Many different miRNAs are expressed in chondrocytes, and each individual miRNA can regulate hundreds of target genes, creating a complex gene regulatory network. Experimental evidence suggests that miRNAs play significant roles in various aspects of cartilage development, homeostasis, and pathology. The possibility that miRNAs can be novel therapeutic targets for cartilage diseases led to vigorous investigations to understand the role of individual miRNAs in skeletal tissues. Here, we summarize our current understanding of miRNAs in chondrocytes and cartilage. In the first part, we discuss roles of miRNAs in growth plate development and chondrocyte differentiation. In the second part, we put a particular focus on articular cartilage and discuss the significance of variety of findings in the context of osteoarthritis, the most common degenerative joint disease. C1 [Mirzamohammadi, Fatemeh; Papaioannou, Garyfallia; Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mirzamohammadi, Fatemeh; Papaioannou, Garyfallia; Kobayashi, Tatsuya] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kobayashi, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM tkobayashi1@mgh.harvard.edu FU National Institutes of Health [AR054500, AR056645] FX We thank Dr. Marc Wein for helpful discussion. This work was supported by the National Institutes of Health [AR054500 and AR056645 to T.K.] NR 77 TC 14 Z9 17 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA EI 1544-2241 J9 CURR OSTEOPOROS REP JI Curr. Osteoporos. Rep. PD DEC PY 2014 VL 12 IS 4 BP 410 EP 419 DI 10.1007/s11914-014-0229-9 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY0KB UT WOS:000347284400004 PM 25091054 ER PT J AU Schomer, AC Nearing, BD Schachter, SC Verrier, RL AF Schomer, Andrew C. Nearing, Bruce D. Schachter, Steven C. Verrier, Richard L. TI Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy SO EPILEPSIA LA English DT Article DE Vagus nerve stimulation; T-wave alternans; Heart rate variability; Sudden unexpected death in epilepsy ID HEART-RATE-VARIABILITY; LEFT-VENTRICULAR FUNCTION; ANTIEPILEPTIC DRUGS; REFRACTORY EPILEPSY; STELLATE GANGLION; UNEXPLAINED DEATH; SEIZURES; THERAPY; SUDDEN; SUDEP AB ObjectiveThe cardiac component of risk for sudden unexpected death in epilepsy (SUDEP) and alterations in cardiac risk by vagus nerve stimulation (VNS) are not well understood. We determined changes in T-wave alternans (TWA), a proven noninvasive marker of risk for sudden cardiac death in patients with cardiovascular disease, and heart rate variability (HRV), an indicator of autonomic function, in association with VNS in patients with drug-resistant focal epilepsy. MethodsAmbulatory 24-h electrocardiograms (N=9: ages 29-63, six males) were analyzed. ResultsMean TWA during the interictal period was 373.1V (mean +/- SEM) in lead V-1 for nine patients monitored following implantation of the VNS system (n=7) or battery change (n=2). Of these, six patients also monitored prior to implantation (n=5) or battery change (n=1) showed abnormally high TWA levels pre-VNS (60.0 +/- 4.3V), which were significantly reduced by 24.3V (to 35.7 +/- 4.8V, p=0.02) after VNS settings were adjusted for desired clinical response. TWA in four (67%) of the six patients was reduced in association with VNS to levels below the 47-V cut point of abnormality. The decrease in TWA was correlated with VNS intensity (r=0.88, p<0.02). In addition, low-frequency HRV was reduced by 60% (805.61 +/- 253.96 to 323.49 +/- 102.74msec(2), p=0.05) and low-to high-frequency HRV ratio by 32% (3.34 +/- 0.57 to 2.26 +/- 0.31, p=0.025), indicating a change in autonomic balance in favor of parasympathetic dominance. SignificanceThis is the first report that elevated levels of TWA in patients with drug-refractory partial-onset seizures were reduced in association with VNS, potentially by improving sympathetic/parasympathetic balance. VNS may have a cardioprotective role at stimulation settings typically used for seizure control. These findings indicate the utility of TWA for tracking improvement in cardiac status in this population. C1 [Schomer, Andrew C.; Schachter, Steven C.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Schomer, Andrew C.; Nearing, Bruce D.; Schachter, Steven C.; Verrier, Richard L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Nearing, Bruce D.; Verrier, Richard L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Verrier, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Div Cardiovasc Med,Dept Med,Med Sch, 99 Brookline Ave,RN 301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu OI Verrier, Richard/0000-0001-5602-6793 FU Cyberonics, Inc. (Houston, TX) FX Drs. Verrier and Nearing receive royalty from Georgetown University (Washington, DC) and Beth Israel Deaconess Medical Center (Boston, MA) for Modified Moving Average T-Wave Alternans algorithms licensed to GE Healthcare (Milwaukee, WI). Drs. Schachter and Schomer disclose no conflicts of interest. Beth Israel Deaconess Medical Center received funding for this study from Cyberonics, Inc. (Houston, TX), Dr. Verrier, Principal Investigator. The sponsor had no input into study design, data analysis, or conclusions. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 40 TC 15 Z9 15 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD DEC PY 2014 VL 55 IS 12 BP 1996 EP 2002 DI 10.1111/epi.12855 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AX5OE UT WOS:000346975200020 PM 25470430 ER PT J AU Alvarez, V Westover, MB Drislane, FW Dworetzky, BA Curley, D Lee, JW Rossetti, AO AF Alvarez, Vincent Westover, M. Brandon Drislane, Frank W. Dworetzky, Barbara A. Curley, David Lee, Jong Woo Rossetti, Andrea O. TI Evaluation of a clinical tool for early etiology identification in status epilepticus SO EPILEPSIA LA English DT Article DE Epilepsy; Diagnostic test assessment; Critical care; Coma; Neurologic emergency ID CONVULSIVE STATUS EPILEPTICUS; PROGNOSIS; MANAGEMENT; MORTALITY; ADULTS; GUIDELINES; DIAGNOSIS; COHORT; DRUGS AB ObjectivesBecause early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. MethodsThis prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. ResultsTwo hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4-89.8) (=0.88). Interrater agreement was 83.3% (95% CI 80.4-96) (=0.81). SignificanceThis tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment. C1 [Alvarez, Vincent; Dworetzky, Barbara A.; Lee, Jong Woo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Alvarez, Vincent; Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Alvarez, Vincent; Drislane, Frank W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Curley, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Emergency Dept, Boston, MA 02115 USA. [Rossetti, Andrea O.] CHU Vaudois, Dept Clin Neurosci, Lausanne, Switzerland. [Rossetti, Andrea O.] Univ Lausanne, Lausanne, Switzerland. [Alvarez, Vincent] Hop Valais, Dept Internal Med, Neurol Serv, CH-19501 Sion, Switzerland. RP Alvarez, V (reprint author), Hop Sion, Serv Neurol Etage C, Ave Grand Champsec 80, CH-19501 Sion, Switzerland. EM vincent.alvarez@hopitalvs.ch RI Rossetti, Andrea/A-6712-2008; OI Rossetti, Andrea/0000-0002-7878-172X; Dworetzky, Barbara/0000-0002-3364-2347 FU Swiss National Science Foundation [P2GEP3_148510]; Gottfried und Julia Bangerter-Rhyner Foundation; American Brain Foundation; FDA; Epilepsy Foundation; American Epilepsy Society; UCB, Inc; Duke Clinical Research Institute; Sunovion, Inc.; Sage; UCB; Eisai FX Dr. Alvarez in funded by the Swiss National Science Foundation, grant: P2GEP3_148510 and the Gottfried und Julia Bangerter-Rhyner Foundation. Dr. M Brandon Westover has received research funding from the American Brain Foundation. Dr. Frank W. Drislane has received royalties form UpToDate and from Lippincott Williams & Wilkins. Dr. Barbara A. Dworetzky has received research funding from the FDA, the Epilepsy Foundation, and the American Epilepsy Society. She is a consultant for SleepMed and Best Doctors. Dr. David Curley has nothing to disclose. Dr. Jong Woo Lee has received research funding from UCB, Inc, the Duke Clinical Research Institute, and Sunovion, Inc. He is a consultant for SleepMed. Dr. Andrea O. Rossetti received research support from Sage, UCB, and Eisai. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 33 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD DEC PY 2014 VL 55 IS 12 BP 2059 EP 2068 DI 10.1111/epi.12852 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AX5OE UT WOS:000346975200026 PM 25385281 ER PT J AU Guerrero-Berroa, E Schmeidler, J Beeri, MS AF Guerrero-Berroa, Elizabeth Schmeidler, James Beeri, Michal Schnaider TI Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Type 2 diabetes; Cerebrovascular disease; Alzheimer's disease; Neuropathology; Review ID ADVANCED GLYCATION ENDPRODUCTS; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; DEGRADING ENZYME; COGNITIVE DECLINE; OXIDATIVE STRESS; ANIMAL-MODELS; MOUSE MODEL; MELLITUS; BETA AB Postmortem studies have shown that cerebrovascular disease (CVD) neuropathology occurs frequently in type 2 diabetes (T2D) through mechanisms associated with chronic hyperglycemia such as advanced glycation end-products (AGES). The involvement of T2D in Alzheimer's disease (AD)-type neuropathology has been more controversial. While postmortem data from animal studies have supported the involvement of T2D in AD-type neuropathology through insulin mechanism that may affect the development of neuritic plaques and neurofibrillary tangles (NFTs), findings from postmortem studies in humans, of the association of T2D with AD, have been mainly negative. To complicate matters, medications to treat T2D have been implicated in reduced AD-type neuropathology. In this review we summarize the literature on animal and human postmortem studies of T2D neuropathology, mainly the mechanisms involved in hyperglycemiarelated CVD neuropathology and hyperinsulinemia-related AD-type neuropathology. (C) 2014 Elsevier B.V. and ECNR All rights reserved. C1 [Guerrero-Berroa, Elizabeth; Schmeidler, James; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Beeri, Michal Schnaider] Chaim Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. RP Guerrero-Berroa, E (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd,Room 1F-01, Bronx, NY 10468 USA. EM elizabeth.guerrero-berroa@mssm.edu FU NIA [R01 AG034087, P50 AG005138]; Helen Bader Foundation; Irma T. Hirschl Scholar award FX This study was supported by NIA Grants R01 AG034087 to Dr. Beeni and P50 AG005138 to Dr. Sano, the Helen Bader Foundation and the Irma T. Hirschl Scholar award to Dr. Been. NR 58 TC 0 Z9 0 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD DEC PY 2014 VL 24 IS 12 BP 1961 EP 1966 DI 10.1016/j.euroneuro.2014.01.019 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AX7LJ UT WOS:000347097200011 PM 24529419 ER PT J AU Kim, SY Le Rademacher, J Antin, JH Anderlini, P Ayas, M Battiwalla, M Carreras, J Kurtzberg, J Nakamura, R Eapen, M Deeg, HJ AF Kim, Sung-Yong Le Rademacher, Jennifer Antin, Joseph H. Anderlini, Paolo Ayas, Mouhab Battiwalla, Minoo Carreras, Jeanette Kurtzberg, Joanne Nakamura, Ryotaro Eapen, Mary Deeg, H. Joachim TI Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation SO HAEMATOLOGICA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; UNRELATED DONOR TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; TELOMERE LENGTH; RISK-FACTORS; CYCLOSPORINE; ASSOCIATION; KARYOTYPE; RECIPIENT; CHILDREN AB A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. C1 [Kim, Sung-Yong; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kim, Sung-Yong] KonKuk Univ, Sch Med, Med Ctr, Seoul, South Korea. [Le Rademacher, Jennifer; Carreras, Jeanette; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Le Rademacher, Jennifer] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia. [Carreras, Jeanette] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Dept Pediat Pediat Blood & Marrow Transplant, Durham, NC USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Deeg, HJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. EM jdeeg@fhcrc.org FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-10039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; [HL036444]; [HL095999]; [CA015704] FX The CIBMTR which is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-10039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members. SY K and HJD were supported by grants HL036444, HL095999 and CA015704. NR 28 TC 3 Z9 3 U1 2 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD DEC PY 2014 VL 99 IS 12 BP 1868 EP 1875 DI 10.3324/haematol.2014.108977 PG 8 WC Hematology SC Hematology GA AX6EP UT WOS:000347016400013 PM 25107891 ER PT J AU Perrin, JM Anderson, LE Van Cleave, J AF Perrin, James M. Anderson, L. Elizabeth Van Cleave, Jeanne TI The Rise In Chronic Conditions Among Infants, Children, And Youth Can Be Met With Continued Health System Innovations SO HEALTH AFFAIRS LA English DT Article ID CARE NEEDS; MENTAL-HEALTH; UNITED-STATES; US CHILDREN; SPECIALTY CARE; PREVALENCE; CHILDHOOD; ACCESS; TRENDS; DISABILITY AB Since the early twentieth century, medical and public health innovations have led to dramatic changes in the epidemiology of health conditions among infants, children, and youth. Infectious diseases have substantially diminished, and survival rates for children with cancer, congenital heart disease, leukemia, and other conditions have greatly improved. However, over the past fifty years chronic health conditions and disabilities among children and youth have steadily risen, primarily from four classes of common conditions: asthma, obesity, mental health conditions, and neurodevelopmental disorders. In this article we describe the epidemiological shift among infants, children, and youth and examine sociodemographic and other factors contributing to it. We describe how health systems are responding by reorganizing and innovating. For children with rare complex conditions, concentrating subspecialty care at regional centers has been effective. For the much larger numbers of children with common chronic conditions, primary care providers have expanded diagnosis, treatment, and management options in promising ways. C1 [Perrin, James M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Perrin, James M.; Van Cleave, Jeanne] MassGen Hosp Children, Boston, MA USA. [Anderson, L. Elizabeth] Univ Tennessee, Coll Med, Memphis, TN USA. RP Perrin, JM (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM JPERRIN@mgh.harvard.edu FU American Pediatric Society/Society for Pediatric Research [T35 HD 7446] FX L. Elizabeth Anderson's time was supported by a grant to the American Pediatric Society/Society for Pediatric Research (Grant No. T35 HD 7446). This work is solely the responsibility of the authors and does not represent the official views of the American Pediatric Society/Society for Pediatric Research. NR 45 TC 13 Z9 13 U1 2 U2 16 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 DEC PY 2014 VL 33 IS 12 BP 2099 EP 2105 DI 10.1377/hlthaff.2014.0832 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AX9NR UT WOS:000347229800003 PM 25489027 ER PT J AU Wang, Y Wang, H Ren, LQ Weng, QY Bao, YY Tian, HS Yang, YG Li, XK AF Wang, Yi Wang, Hui Ren, Luqing Weng, Qiaoyou Bao, Yuyan Tian, Haishan Yang, Yong-Guang Li, Xiaokun TI Non-mitogenic form of acidic fibroblast growth factor protects against graft-versus-host disease without accelerating leukemia SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE GVHD; GVL; Acidic fibroblast growth factor; Mitogenic activity ID BONE-MARROW-TRANSPLANTATION; EXPRESSION; CANCER; ANGIOGENESIS; CARCINOMA; ISCHEMIA; EPITHELIUM; RECEPTORS; THERAPY; AFGF AB Acid fibroblast growth factor (aFGF) has been shown to prevent epithelial damage under various conditions, suggesting its potential to inhibit GVHD. However, because aFGF receptors are expressed on tumor cells, it may possibly offset the graft-vs.-tumor (GVT) effects of allogeneic bone marrow transplantation (allo-BMT). Here, we addressed these questions in a B6 -> B6D2F1 allo-BMT model. Although aFGF administration attenuated GVHD in non-leukemic recipients, aFGF treatment markedly accelerated death in mice that received recipient-type tumor (P815) cells along with allo- or syngeneic-BMT. Similar protection against GVHD was achieved by administration of a non-mitogenic form of aFGF (naFGF). Importantly, GVT effects were fully preserved in naFGF-treated recipients. Furthermore, aFGF, but not naFGF, significantly enhanced P815 cell proliferation both in vitro and in vivo. Our data indicate that the tumor-promoting, but not GVHD-protecting, effect of aFGF largely depends on its mitogenic activity, and suggest that naFGF may provide a safer approach to inhibiting GVHD in patients with malignancies. (C) 2014 Elsevier B.V. All rights reserved. C1 [Wang, Yi; Ren, Luqing; Weng, Qiaoyou; Bao, Yuyan; Tian, Haishan] Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China. [Wang, Yi; Wang, Hui; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wang, Hui; Yang, Yong-Guang] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10027 USA. [Yang, Yong-Guang] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. [Li, Xiaokun] Wenzhou Med Univ, Sch Pharmaceut Sci, Key Lab Biotechnol Pharmaceut Engn, Wenzhou 325035, Peoples R China. RP Yang, YG (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10027 USA. EM yy2324@cumc.columbia.edu; profixk@163.com FU Natural Science Funding of China [81102452]; Natural Science Funding of Zhejiang [2011RCB025, 2012R10042] FX The study was supported by grants from the Natural Science Funding of China (81102452 to Y. Wang), and the Natural Science Funding of Zhejiang (2011RCB025 to Y. Wang, and 2012R10042 to X. Li). NR 30 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2014 VL 23 IS 2 BP 395 EP 399 DI 10.1016/j.intimp.2014.09.006 PG 5 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA AX5GF UT WOS:000346954000004 PM 25239811 ER PT J AU Ramsey, H Wu, MX AF Ramsey, Haley Wu, Mei X. TI Mitochondrial anti-oxidant protects IEX-1 deficient mice from organ damage during endotoxemia SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE IEX-1; Reactive oxygen species; Mitoquinone; Sepsis ID NEUTROPHIL RESPIRATORY BURST; OXIDATIVE STRESS; SEPTIC SHOCK; SEPSIS; DYSFUNCTION; PHAGOCYTOSIS; SEVERITY; MITOQ; GENE; GLY96/IEX-1 AB Sepsis, a leading cause of mortality in intensive care units worldwide, is often a result of overactive and systemic inflammation following serious infections. We found that mice lacking immediate early responsive gene X-1 (IEX-1) were prone to lipopolysaccharide (LPS) -induced endotoxemia. A nonlethal dose of LPS provoked numerous aberrations in lEX-1 knockout (1(0) mice including pancytopenia, increased serum aspartate aminotransferase (AST), and lung neutrophilia, concurrent with liver and kidney damage, followed by death. Given these results, in conjunction with a proven role for lEX-1 in the regulation of reactive oxygen species (ROS) homeostasis during stress, we pre-treated IEX-1 KO mice with Mitoquinone (MitoQ), a mitochondrion-based antioxidant prior to LPS injection. The treatment significantly reduced ROS formation in circulatory cells and protected against pancytopenia and multiple organ failure, drastically increasing the survival rate of IEX-1 KO mice challenged by this low dose of LPS. This study confirms significant contribution of mitochondrial ROS to the etiology of sepsis. Published by Elsevier B.V. C1 [Ramsey, Haley; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM MWU5@mgh.harvard.edu FU National Institutes of Health [CA158756, AI089779, DA028378] FX We thank Michael P. Murphy for the generous gift of MitoQ used in this study. This work is supported by the National Institutes of Health Grants CA158756, AI089779, and DA028378 to M.X.W. NR 30 TC 3 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2014 VL 23 IS 2 BP 658 EP 663 DI 10.1016/j.intimp.2014.10.019 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA AX5GF UT WOS:000346954000039 PM 25466275 ER PT J AU Anderson, RE Ahn, R Nelson, BD Chavez, J de Redon, E Burke, T AF Anderson, R. Eleanor Ahn, Roy Nelson, Brett D. Chavez, Jean de Redon, Emily Burke, Thomas TI Defining the anesthesia gap for reproductive health procedures in resource-limited settings SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Review DE Anesthesia; Low-income countries; Reproductive health ID DEVELOPING-COUNTRIES; MATERNAL MORTALITY; CESAREAN-SECTION; SURGERY; CARE; INFRASTRUCTURE; HOSPITALS; SERVICES; AFRICA; RATES AB Background: In resource-limited settings, severe shortages of anesthetists and anesthesiologists lead to surgical delays that increase maternal and neonatal mortality and morbidity. Objectives: To more clearly understand the individual components of the anesthesia gap pertaining to reproductive health surgeries and procedures in resource-limited settings. Search strategy: Medline, the Cochrane Library, CINAHL, Embase, and POPLINE were systematically searched for reports published before December 31, 2013. Search terms were related to obstetric surgery, resource-limited settings, and anesthesia. Selection criteria: Studies that addressed the use of anesthesia in reproductive procedures in resource-limited settings were included. Data collection and analysis: Reviewers independently evaluated the full text of identified studies, extracted information related to study objectives and conclusions, and identified the anesthesia gap. Main results: Overall, 14 publications met the inclusion criteria. A significant lack of infrastructure, equipment and supplies, and trained personnel were identified as key factors responsible for a lack of anesthesia services. Conclusions: A shortage of trained anesthesia providers, equipment, supplies, medications, and infrastructure, along with limitations in transportation in resource-limited settings have produced a wide gap between available anesthesia services and the demand for them for reproductive health surgeries and procedures. Safe, affordable, and scalable solutions to address the anesthesia gap are urgently needed. (C) 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Anderson, R. Eleanor; Ahn, Roy; Nelson, Brett D.; Chavez, Jean; de Redon, Emily; Burke, Thomas] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. [Anderson, R. Eleanor; Ahn, Roy; Nelson, Brett D.; Burke, Thomas] Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, RE (reprint author), Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM randerson3@partners.org OI Nelson, Brett/0000-0002-5049-1798 NR 42 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 EI 1879-3479 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD DEC PY 2014 VL 127 IS 3 BP 229 EP 233 DI 10.1016/j.ijgo.2014.06.023 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX7ZI UT WOS:000347129700002 PM 25179170 ER PT J AU Ko, BJ Kim, SM Park, KH Park, HS Mantzoros, CS AF Ko, B-J Kim, S. M. Park, K. H. Park, H. S. Mantzoros, C. S. TI Levels of circulating selenoprotein P, fibroblast growth factor (FGF) 21 and FGF23 in relation to the metabolic syndrome in young children SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE selenoprotein P; fibroblast growth factor 21; fibroblast growth factor 23; metabolic syndrome; child ID CARDIOVASCULAR RISK; INSULIN-RESISTANCE; GLUCOSE-HOMEOSTASIS; SELENIUM; ADOLESCENTS; EXPRESSION; PROTEIN; OBESITY; ATHEROSCLEROSIS; INFLAMMATION AB BACKGROUND/OBJECTIVES: Circulating selenoprotein P (SeP), fibroblast growth factor (FGF) 21 and FGF23 have been associated with metabolic syndrome (MetS) in adults but not in children. We sought to evaluate the association among SeP, FGF21, FGF23 and MetS in young children. SUBJECTS/METHODS: A cross-sectional study conducted during a school health examination on 210 children aged 9 years. We measured serum SeP, FGF21 and FGF23 levels, and assessed anthropometric and cardiometabolic variables. MetS was defined as the presence of. 3 of the following five criteria: high blood pressure, low high-density lipoprotein cholesterol (HDL-C), high triglyceride, high fasting glucose and abdominal obesity. RESULTS: SeP was correlated positively with HDL-C and negatively with body mass index, waist circumference (WC), blood pressure, transaminases, triglyceride and homeostasis model assessment of insulin resistance (HOMA-IR). FGF21 was directly correlated with WC, triglyceride and HOMA-IR, and FGF23 was inversely correlated with fasting glucose and alanine aminotransferase. Children with MetS had lower SeP and FGF23 levels and higher HOMA-IR than children without MetS. The highest tertile of SeP had decreased odds for MetS (odds ratio 0.05, 95% confidence interval (CI) 0.00-0.96, P for trend = 0.042), whereas FGF21 and FGF23 did not relate to the risk for MetS after controlling for confounders. CONCLUSIONS: Elevated SeP concentrations are independently associated with a reduced risk of MetS in children. The associations between FGF21, FGF23 and metabolic parameters are not of comparable significance. C1 [Ko, B-J; Park, K. H.; Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Ko, B-J; Kim, S. M.] Korea Univ, Coll Med, Dept Family Med, Seoul 136705, South Korea. [Park, K. H.] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do, South Korea. [Park, H. S.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Family Med, Seoul 138736, South Korea. [Mantzoros, C. S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. RP Park, HS (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Family Med, Seoul 138736, South Korea. EM hyesoon@amc.seoul.kr; cmantzor@bidmc.harvard.edu OI Park, Kyung Hee/0000-0001-9806-0076 FU National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [2012-004869] FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science, and Technology (2012-004869). NR 41 TC 10 Z9 10 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2014 VL 38 IS 12 BP 1497 EP 1502 DI 10.1038/ijo.2014.45 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AX7PL UT WOS:000347107400003 PM 24638201 ER PT J AU Huh, JY Dincer, F Mesfum, E Mantzoros, CS AF Huh, J. Y. Dincer, F. Mesfum, E. Mantzoros, C. S. TI Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE irisin; myokine; muscle hypertrophy; adipocyte browning ID SKELETAL-MUSCLE; ADIPOSE-TISSUE; EXERCISE; ASSOCIATION; RESISTANCE; EXPRESSION; GLUCOSE; OBESITY; PLASMA; CELLS AB BACKGROUND: Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated. METHODS: Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes. RESULTS: In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1 alpha and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1 alpha 4, a newly discovered PGC1a isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass. CONCLUSIONS: These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans. C1 [Huh, J. Y.; Dincer, F.; Mesfum, E.; Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, C. S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, 330 Brookline Ave,Feldberg 876, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu FU Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX This study was supported by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 32 TC 31 Z9 36 U1 2 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2014 VL 38 IS 12 BP 1538 EP 1544 DI 10.1038/ijo.2014.42 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AX7PL UT WOS:000347107400009 PM 24614098 ER PT J AU Bujakowska, KM Consugar, M Place, E Harper, S Lena, J Taub, DG White, J Navarro-Gomez, D DiFranco, CW Farkas, MH Gai, XW Berson, EL Pierce, EA AF Bujakowska, Kinga M. Consugar, Mark Place, Emily Harper, Shyana Lena, Jaclyn Taub, Daniel G. White, Joseph Navarro-Gomez, Daniel DiFranco, Carol Weigel Farkas, Michael H. Gai, Xiaowu Berson, Eliot L. Pierce, Eric A. TI Targeted Exon Sequencing in Usher Syndrome Type I SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Usher syndrome; retinitis pigmentosa; hearing loss; retina; genetics; next-generation; sequencing; selective exon capture; molecular diagnostic ID LEBER CONGENITAL AMAUROSIS; BARDET-BIEDL-SYNDROME; SYNDROME TYPE 1D; SYNDROME TYPE 1B; RETINAL DEGENERATION; RETINITIS-PIGMENTOSA; MOUSE MODEL; USH1C GENE; HAIR-CELLS; MUTATIONS AB PURPOSE. Patients with Usher syndrome type I (USH1) have retinitis pigmentosa, profound congenital hearing loss, and vestibular ataxia. This syndrome is currently thought to be associated with at least six genes, which are encoded by over 180 exons. Here, we present the use of state-of-the-art techniques in the molecular diagnosis of a cohort of 47 USH1 probands. METHODS. The cohort was studied with selective exon capture and next-generation sequencing of currently known inherited retinal degeneration genes, comparative genomic hybridization, and Sanger sequencing of new USH1 exons identified by human retinal transcriptome analysis. RESULTS. With this approach, we were able to genetically solve 14 of the 47 probands by confirming the biallelic inheritance of mutations. We detected two likely pathogenic variants in an additional 19 patients, for whom family members were not available for cosegregation analysis to confirm biallelic inheritance. Ten patients, in addition to primary disease-causing mutations, carried rare likely pathogenic USH1 alleles or variants in other genes associated with deaf-blindness, which may influence disease phenotype. Twenty-one of the identified mutations were novel among the 33 definite or likely solved patients. Here, we also present a clinical description of the studied cohort at their initial visits. CONCLUSIONS. We found a remarkable genetic heterogeneity in the studied USH1 cohort with multiplicity of mutations, of which many were novel. No obvious influence of genotype on phenotype was found, possibly due to small sample sizes of the genotypes under study. C1 [Bujakowska, Kinga M.; Consugar, Mark; Place, Emily; Lena, Jaclyn; Taub, Daniel G.; White, Joseph; Navarro-Gomez, Daniel; Farkas, Michael H.; Gai, Xiaowu; Berson, Eliot L.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA USA. [Harper, Shyana; DiFranco, Carol Weigel; Berson, Eliot L.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Pierce, EA (reprint author), Massachusetts Eye & Ear, 243 Charles St, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 FU National Eye Institute [EY012910]; Foundation Fighting Blindness (USA); Fleming Family Foundation FX Supported by grants from the National Eye Institute (EY012910), the Foundation Fighting Blindness (USA) and the Fleming Family Foundation. NR 55 TC 5 Z9 5 U1 3 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2014 VL 55 IS 12 BP 8488 EP 8496 DI 10.1167/iovs.14-15169 PG 9 WC Ophthalmology SC Ophthalmology GA AX9KR UT WOS:000347222300094 PM 25468891 ER PT J AU Castro, VM Apperson, WK Gainer, VS Ananthakrishnan, AN Goodson, AP Wang, TWD Herrick, CD Murphy, SN AF Castro, Victor M. Apperson, W. Kay Gainer, Vivian S. Ananthakrishnan, Ashwin N. Goodson, Alyssa P. Wang, Taowei D. Herrick, Christopher D. Murphy, Shawn N. TI Evaluation of matched control algorithms in EHR-based phenotyping studies: A case study of inflammatory bowel disease comorbidities SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE EHR; Controls; Matching; Comorbidity; Inflammatory bowel disease ID ELECTRONIC HEALTH RECORDS; INFORMATICS; BIAS AB The success of many population studies is determined by proper matching of cases to controls. Some of the confounding and bias that afflict electronic health record (EHR)-based observational studies may be reduced by creating effective methods for finding adequate controls. We implemented a method to match case and control populations to compensate for sparse and unequal data collection practices common in EHR data. We did this by matching the healthcare utilization of patients after observing that more complete data was collected on high healthcare utilization patients vs. low healthcare utilization patients. In our results, we show that many of the anomalous differences in population comparisons are mitigated using this matching method compared to other traditional age and gender-based matching. As an example, the comparison of the disease associations of ulcerative colitis and Crohn's disease show differences that are not present when the controls are chosen in a random or even a matched age/gender/race algorithm. In conclusion, the use of healthcare utilization-based matching algorithms to find adequate controls greatly enhanced the accuracy of results in EHR studies. Full source code and documentation of the control matching methods is available at https://community.i2b2.org/wiki/display/conmat/. (C) 2014 Elsevier Inc. All rights reserved. C1 [Castro, Victor M.; Apperson, W. Kay; Gainer, Vivian S.; Goodson, Alyssa P.; Wang, Taowei D.; Herrick, Christopher D.; Murphy, Shawn N.] Partners HealthCare, Partners Res Informat Syst & Comp, Boston, MA 02129 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Comp Sci Lab, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Castro, VM (reprint author), Partners HealthCare, Res Comp, Constitut Ctr 1, 260U, Boston, MA 02129 USA. EM vcastro@partners.org FU Foundation of the National Institutes of Health [FNIH - MURPHY09OMOP0]; National Institutes of Health [K23 DK091742] FX This study was supported by The Foundation of the National Institutes of Health (FNIH - MURPHY09OMOP0). Ashwin N. Ananthakrishnan is supported by a grant from the National Institutes of Health (K23 DK091742). NR 19 TC 3 Z9 3 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 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD DEC PY 2014 VL 52 BP 105 EP 111 DI 10.1016/j.jbi.2014.08.012 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AY0HC UT WOS:000347277000012 PM 25196084 ER PT J AU Franco, W Jimenez-Lozano, JN Tam, J Purschke, M Wang, Y Sakamoto, FH Farinelli, WA Doukas, AG Anderson, RR AF Franco, Walfre Jimenez-Lozano, Joel N. Tam, Joshua Purschke, Martin Wang, Ying Sakamoto, Fernanda H. Farinelli, William A. Doukas, Apostolos G. Anderson, R. Rox TI Fractional Skin Harvesting: Device Operational Principles and Deployment Evaluation SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article ID DEEP PENETRATION; SOFT SOLIDS; RESISTANCE AB As an alternative method to conventional split-thickness skin grafts (STSGs), we recently proposed fractional skin grafting (FSG), which consists in harvesting hundreds of microscopic skin tissue columns (MSTCs) to place them directly into the skin wound (Tam et al., 2013, "Fractional Skin Harvesting: Autologous Skin Graft Without Donor Site Morbidity,"Plast. Reconstructive Surgery-Global Open, 1(6)). This paper (i) introduces the concept and operational principles of a simple but robust fractional skin harvesting (FSH) device and (ii) presents the quantitative evaluation of the deployment of the FSH device with respect to different harvesting-needle sizes. The device utilizes a hypodermic needle with a specific cutting-geometry to core skin tissue mechanically. The tissue core is removed from the donor site into a collecting basket by air and fluid flows. The air flow transports the tissue core, while the fluid flow serves the purpose of lubrication for tissue transport and wetting for tissue preservation. The design and functionality of the device were validated in an animal study conducted to establish preclinical feasibility, safety and efficacy of the proposed FSH device and FSG method. The FSH device, operating at 55.16 kPa (8 psi) gauge pressure and 208 ml/min saline flow rate, cored 800 mu m diameter x 2.5 mm length skin columns using a 1.05/0.81 mm outer/inner diameter needle. The MSTC harvesting rate was established by the user at 1 column/sec. For this columns size, about 50 MSTCs are required to cover a 1.5 cm x 1.5 cm wound. In comparison to STSGs, the proposed FSG method results in superior healing outcomes on the donor and wound sites. Most important, the donor site heals without morbidity by remodeling tissue, as opposed to scarring. The FSH device has the capability of extracting full-thickness skin columns while preserving its viability and eliminating the donor site morbidity associated with skin grafting. C1 [Franco, Walfre; Jimenez-Lozano, Joel N.; Tam, Joshua; Purschke, Martin; Wang, Ying; Sakamoto, Fernanda H.; Farinelli, William A.; Doukas, Apostolos G.; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Franco, W (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM wfranco@mgh.harvard.edu FU DARPA; ARO [W911NF-11-1-0122, W911NF-12-1-0086] FX The authors are grateful to Ms. Maura Williams and Ms. Deanna Cavallaro for their experimental support. Animal studies and device development were funded by DARPA and ARO (Contract Nos. W911NF-11-1-0122 and W911NF-12-1-0086). NR 12 TC 1 Z9 1 U1 2 U2 4 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 EI 1932-619X J9 J MED DEVICES JI J. Med. Devices PD DEC PY 2014 VL 8 IS 4 AR 041005 DI 10.1115/1.4027427 PG 9 WC Engineering, Biomedical SC Engineering GA AX1HA UT WOS:000346697200005 ER PT J AU Krummenacher, P Kossowsky, J Schwarz, C Brugger, P Kelley, JM Meyer, A Gaab, J AF Krummenacher, Peter Kossowsky, Joe Schwarz, Caroline Brugger, Peter Kelley, John M. Meyer, Andrea Gaab, Jens TI Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking SO JOURNAL OF PAIN LA English DT Article DE Placebo analgesia; expectation; children; magical thinking; pain ID INDIVIDUAL-DIFFERENCES; COGNITIVE-DEVELOPMENT; INDUCED EXPECTATIONS; PARANORMAL-BELIEF; DOPAMINE RELEASE; PAIN; BRAIN; RESPONSES; NOCEBO; AGE AB Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned stratified for MT and gender to either an analgesia-expectation or a control-expectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearm side: Low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. Perspective: The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children aged 6 to 9 years (girls > boys). Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. (C) 2014 by the American Pain Society C1 [Krummenacher, Peter; Kossowsky, Joe; Schwarz, Caroline; Gaab, Jens] Univ Basel, Dept Psychol Clin Psychol & Psychotherapy, Basel, Switzerland. [Krummenacher, Peter] Univ Zurich, Coll Helveticum, CH-8092 Zurich, Switzerland. [Krummenacher, Peter] Swiss Fed Inst Technol, CH-8092 Zurich, Switzerland. [Krummenacher, Peter] Brainabil LLC, Zurich, Switzerland. [Kossowsky, Joe] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Kossowsky, Joe; Kelley, John M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02115 USA. [Brugger, Peter] Univ Zurich Hosp, Dept Neurol, Neuropsychol Unit, CH-8091 Zurich, Switzerland. [Kelley, John M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Meyer, Andrea] Univ Basel, Dept Psychol Clin Psychol & Epidemiol, CH-4003 Basel, Switzerland. RP Krummenacher, P (reprint author), Swiss Fed Inst Technol, Schmelzbergstr 25, CH-8092 Zurich, Switzerland. EM krummenacher@collegium.ethz.ch OI Gaab, Jens/0000-0002-9194-8491 FU University of Basel; brainability LLC; Swiss National Science Foundation [P2BSP1_148628] FX This research was supported by the University of Basel. P.K. was also supported by brainability LLC. J.K.'s contributions to this study were supported by the Swiss National Science Foundation, grant project (P2BSP1_148628). NR 81 TC 7 Z9 7 U1 2 U2 14 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2014 VL 15 IS 12 BP 1282 EP 1293 DI 10.1016/j.jpain.2014.09.005 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX4HC UT WOS:000346893100008 PM 25261340 ER PT J AU Jensen, KB Petzke, F Carville, S Choy, E Fransson, P Gracely, RH Vitton, O Marcus, H Williams, SCR Ingvar, M Kosek, E AF Jensen, Karin B. Petzke, Frank Carville, Serena Choy, Ernest Fransson, Peter Gracely, Richard H. Vitton, Olivier Marcus, Hanke Williams, Steven C. R. Ingvar, Martin Kosek, Eva TI Segregating the Cerebral Mechanisms of Antidepressants and Placebo in Fibromyalgia SO JOURNAL OF PAIN LA English DT Article DE Antidepressive agents; fibromyalgia; milnacipran; magnetic resonance imaging; placebos ID DEFAULT-MODE NETWORK; CONTROLLED TRIAL; DOUBLE-BLIND; PAIN MODULATION; BRAIN-FUNCTION; DULOXETINE; DISORDER; OSTEOARTHRITIS; SENSITIVITY; EFFICACY AB Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology. Perspective: This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain. (C) 2014 by the American Pain Society C1 [Jensen, Karin B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Jensen, Karin B.] Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. [Petzke, Frank] Univ Hosp, Ctr Anesthesiol Emergency & Intens Care Med, Gottingen, Germany. [Carville, Serena] Royal Coll Physicians, Natl Clin Guideline Ctr, London NW1 4LE, England. [Choy, Ernest] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [Fransson, Peter; Ingvar, Martin; Kosek, Eva] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Gracely, Richard H.] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [Vitton, Olivier] Pierre Fabre, Boulogne, France. [Marcus, Hanke] Univ Cologne, Dept Anesthesiol & Postoperat Intens Care Med, Cologne, Germany. [Williams, Steven C. R.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, London WC2R 2LS, England. [Ingvar, Martin; Kosek, Eva] Karolinska Inst, Osher Ctr Integrat Med, Stockholm, Sweden. RP Jensen, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Bldg,120 Second Ave, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu RI Williams, Steve/D-6979-2011; OI Williams, Steve/0000-0003-4299-1941; Jensen, Karin/0000-0003-2521-3160; Ingvar, Martin/0000-0002-9041-5714 FU Department of Health via the National Institute for Health Research (NIHR); COFAS Marie Curie Fellowship; Osher Center for Integrative Medicine at Karolinska Institutet; Swedish Rheumatism Association FX The study was sponsored by and performed in collaboration with Pierre Fabre. E.C. acknowledges financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. K.B.J. receives support from the COFAS Marie Curie Fellowship and Osher Center for Integrative Medicine at Karolinska Institutet. E.K. received support from the Swedish Rheumatism Association. NR 47 TC 1 Z9 1 U1 1 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2014 VL 15 IS 12 BP 1328 EP 1337 DI 10.1016/j.jpain.2014.09.011 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX4HC UT WOS:000346893100012 PM 25283470 ER PT J AU Manning, DC Alexander, G Arezzo, JC Cooper, A Harden, RN Oaklander, AL Raja, SN Rauck, R Schwartzman, R AF Manning, Donald C. Alexander, Guillermo Arezzo, Joseph C. Cooper, Alyse Harden, R. Norman Oaklander, Anne Louise Raja, Srinivasa N. Rauck, Richard Schwartzman, Robert TI Lenalidomide for Complex Regional Pain Syndrome Type 1: Lack of Efficacy in a Phase II Randomized Study SO JOURNAL OF PAIN LA English DT Article DE Complex regional pain syndrome; cytokines; immunomodulation; lenalidomide; thalidomide; clinical trial ID REFLEX SYMPATHETIC DYSTROPHY; NEUROPATHIC PAIN; THALIDOMIDE; TRIAL; INFLAMMATION; CYTOKINES; CELLS; SERUM; CRPS AB Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1. The study comprised 12 weeks of treatment followed by a long-term extension. The primary efficacy outcome was reduced pain in the index limb, defined as >= 30% improvement from baseline using an 11-point numeric rating scale. One hundred eighty-four subjects enrolled. The primary endpoint was not met because equal proportions of treated (16.1%) and control (16.1%) subjects achieved the outcome; however, lenalidomide was well tolerated, with no evidence of neuropathy or major adverse effects. This study is the largest controlled, blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria. It demonstrates the feasibility of conducting high-quality clinical trials in CRPS type 1 and provides considerations for designing future trials. Perspective: This article reports an adequately powered, controlled clinical trial in subjects with CRPS. Treatment and placebo were equally effective, but the study demonstrated that lenalidomide treatment is feasible in this population. The study provides examples to consider in designing future CRPS trials. (C) 2014 by the American Pain Society C1 [Manning, Donald C.] Univ Virginia Hlth Syst, Dept Anesthesiol, Charlottesville, VA USA. [Manning, Donald C.] Adynxx Inc, San Francisco, CA USA. [Alexander, Guillermo; Schwartzman, Robert] Drexel Univ, Dept Neurol, Philadelphia, PA 19104 USA. [Arezzo, Joseph C.] Albert Einstein Coll Med, Dept Neurosci & Neurol, Bronx, NY 10467 USA. [Cooper, Alyse] Celgene Corp, Summit, NJ USA. [Harden, R. Norman] Rehabil Inst Chicago, Ctr Pain Studies, Chicago, IL 60611 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raja, Srinivasa N.] Johns Hopkins Univ, Div Pain Med, Baltimore, MD USA. [Rauck, Richard] Clin Res Ctr, Salem, NC USA. RP Manning, DC (reprint author), 16 Johnston Dr, Bloomsbury, NJ 08804 USA. EM donaldcmanning@gmail.com FU Celgene Corporation; Celgene; Reflex Sympathetic Dystrophy Syndrome Association; Medtronic Inc FX This study was sponsored by Celgene Corporation. Celgene developed the protocol in conjunction with the clinical investigators. Celgene was solely responsible for investigative site selection, data collection and storage methods and technology, clinical monitoring of protocol and Good Clinical Practice guidelines compliance, statistical analysis plan and execution, reporting of safety data to regulatory agencies, and the provision of study drug and matching control. The authors received editorial support for manuscript preparation from Amy Zannikos, PharmD, of Peloton Advantage, LLC, funded by Celgene Corporation. The authors, however, directed and are fully responsible for all content and editorial decisions for this manuscript. D.C.M. was an employee of Celgene Corporation during the execution of the reported study, an owner of Celgene stock, and a former member of the Board of Directors for Reflex Sympathetic Dystrophy Syndrome Association-USA. G.A. received standard compensation for participating as an investigator in this study. J.C.A. received standard compensation for assisting with the design and analysis of the electrophysiology data from this study. A.C. is an employee of Celgene Corporation. R.N.H. received standard compensation for participating as an investigator in this study and also had an unrestricted grant from Celgene at the time of this study. He also has received research support from the Reflex Sympathetic Dystrophy Syndrome Association. A.L.O. reports no conflicts of interest. S.N.R. received standard compensation for participating as an investigator in this study and reports a research grant from Medtronic Inc for studies on the mechanisms of spinal cord stimulation induced analgesia. R.R. received standard compensation for participating as an investigator in this study. R.S. received standard compensation for participating as an investigator in this study. NR 41 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2014 VL 15 IS 12 BP 1366 EP 1376 DI 10.1016/j.jpain.2014.09.013 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX4HC UT WOS:000346893100015 PM 25283471 ER PT J AU Sudore, RL Casarett, D Smith, D Richardson, DM Ersek, M AF Sudore, Rebecca L. Casarett, David Smith, Dawn Richardson, Diane M. Ersek, Mary TI Family Involvement at the End-of-Life and Receipt of Quality Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE End-of-life care; communication; quality assessment; veterans ID SURROGATE DECISION-MAKING; HOSPITALIZED ADULTS; ADVANCE DIRECTIVES; ETHNIC-DIFFERENCES; CANCER; NATIONWIDE; VETERANS; COMORBIDITY; CAPACITY; IMPACT AB Context. Most patients will lose decision-making capacity at the end of life. Little is known about the quality of care received by patients who have family involved in their care. Objectives. To evaluate differences in the receipt of quality end-of-life care for patients who died with and without family involvement. Methods. We retrospectively reviewed the charts of 34,290 decedents from 146 acute and long-term care Veterans Affairs facilities between 2010 and 2011. Outcomes included: 1) palliative care consult, 2) chaplain visit, and 3) death in an inpatient hospice or palliative care unit. We also assessed "do not resuscitate" (DNR) orders. Family involvement was defined as documented discussions with the health care team in the last month of life. We used logistic regression adjusted for demographics, comorbidity, and clustered by facility. For chaplain visit, hospice or palliative care unit death, and DNR, we additionally adjusted for palliative care consults. Results. Mean (SD) age was 74 (+/- 12) years, 98% were men, and 19% were nonwhite. Most decedents (94.2%) had involved family. Veterans with involved family were more likely to have had a palliative care consult, adjusted odds ratio (AOR) 4.31 (95% CI 3.90-4.76); a chaplain visit, AOR 1.18 (95% CI 1.07-1.31); and a DNR order, AOR 4.59 (95% CI 4.08-5.16) but not more likely to die in a hospice or palliative care unit. Conclusion. Family involvement at the end of life is associated with receipt of palliative care consultation and a chaplain visit and a higher likelihood of a DNR order. Clinicians should support early advance care planning for vulnerable patients who may lack family or friends. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Sudore, Rebecca L.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. [Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Casarett, David] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Smith, Dawn; Richardson, Diane M.; Ersek, Mary] Dept Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. RP Sudore, RL (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM rebecca.sudore@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSRD FX The authors have no conflicts of interest to disclose. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSR&D, which had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 33 TC 5 Z9 5 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1108 EP 1116 DI 10.1016/j.jpainsymman.2014.04.001 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300010 PM 24793077 ER PT J AU Goldstein, NE Kalman, J Kutner, JS Fromme, EK Hutchinson, MD Lipman, HI Matlock, DD Swetz, KM Lampert, R Herasme, O Morrison, RS AF Goldstein, Nathan E. Kalman, Jill Kutner, Jean S. Fromme, Erik K. Hutchinson, Mathew D. Lipman, Hannah I. Matlock, Daniel D. Swetz, Keith M. Lampert, Rachel Herasme, Omarys Morrison, R. Sean TI A Study to Improve Communication Between Clinicians and Patients With Advanced Heart Failure: Methods and Challenges Behind the Working to Improve Discussions About Defibrillator Management Trial SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Heart failure; communication; randomized controlled trial; palliative care; methods; intervention; IRB ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; QUALITY-OF-LIFE; EXPERT CONSENSUS STATEMENT; VENTRICULAR ASSIST DEVICES; SERIOUSLY-ILL PATIENTS; PATIENTS NEARING END; PALLIATIVE CARE; REQUESTING WITHDRAWAL; TREATMENT PREFERENCES; ELECTRONIC DEVICES AB We report the challenges of the Working to Improve Discussions About Defibrillator Management trial, our novel, multicenter trial aimed at improving communication between cardiology clinicians and their patients with advanced heart failure (HF) who have implantable cardioverter defibrillators (ICDs). The study objectives are (1) to increase ICD deactivation conversations, (2) to increase the number of ICDs deactivated, and (3) to improve psychological outcomes in bereaved caregivers. The unit of randomization is the hospital, the intervention is aimed at HF clinicians, and the patient and caregiver are the units of analysis. Three hospitals were randomized to usual care and three to intervention. The intervention consists of an interactive educational session, clinician reminders, and individualized feedback. We enroll patients with advanced HF and their caregivers, and then we regularly survey them to evaluate whether the intervention has improved communication between them and their HF providers. We encountered three implementation barriers. First, there were institutional review board concerns at two sites because of the palliative nature of the study. Second, we had difficulty in creating entry criteria that accurately identified an HF population at high risk of dying. Third, we had to adapt our entry criteria to the changing landscape of ventricular assist devices and cardiac transplant eligibility. Here we present our novel solutions to the difficulties we encountered. Our work has the ability to enhance conduct of future studies focusing on improving care for patients with advanced illness. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Goldstein, Nathan E.; Herasme, Omarys; Morrison, R. Sean] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kalman, Jill] Icahn Sch Med Mt Sinai, Div Cardiol, Samuel Bronfman Dept Med, New York, NY 10029 USA. [Goldstein, Nathan E.; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Nursing, Portland, OR USA. [Hutchinson, Mathew D.] Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Div Geriatr, Bronx, NY 10467 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Div Cardiol, Bronx, NY 10467 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Montefiore Einstein Ctr Bioeth, Bronx, NY 10467 USA. [Swetz, Keith M.] Mayo Clin, Sect Palliat Med, Dept Med, Div Gen Internal Med, Rochester, MN USA. [Lampert, Rachel] Yale Univ, Sch Med, Dept Internal Med, Cardiol Sect, New Haven, CT 06510 USA. RP Goldstein, NE (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, Box 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM nathan.goldstein@mssm.edu FU National Heart, Lung, and Blood Institute [R01HL102084] FX Research reported in this publication was supported by a grant from the National Heart, Lung, and Blood Institute (R01HL102084). The content is solely the responsibility of the authors and does not represent the views of the National Institutes of Health or the Department of Veterans Affairs. The investigators have no conflicts of interest to disclose. NR 52 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1236 EP 1246 DI 10.1016/j.jpainsymman.2014.03.005 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300021 PM 24768595 ER PT J AU Janne, PA Ou, SHI Kim, DW Oxnard, GR Martins, R Kris, MG Dunphy, F Nishio, M O'Connell, J Paweletz, C Taylor, I Zhang, H Goldberg, Z Mok, T AF Jaenne, Pasi A. Ou, Sai-Hong I. Kim, Dong-Wan Oxnard, Geoffrey R. Martins, Renato Kris, Mark G. Dunphy, Frank Nishio, Makoto O'Connell, Joseph Paweletz, Cloud Taylor, Ian Zhang, Hui Goldberg, Zelanna Mok, Tony TI Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: a multicentre, open-label, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; EGFR MUTATIONS; GEFITINIB; ERLOTINIB; AFATINIB; ADENOCARCINOMA; CHEMOTHERAPY; RESISTANCE; INHIBITOR; THERAPY AB Background Patients with EGFR-mutant non-small-cell lung cancer generally have a progression-free survival of 9-13 months while being treated with the EGFR tyrosine-kinase inhibitors gefitinib or erlotinib. However, resistance inevitably develops, and more effective EGFR inhibitors are needed. Dacomitinib is a covalent pan-HER inhibitor that has shown clinical activity in patients previously treated with gefitinib or erlotinib. We did a trial of dacomitinib as initial systemic therapy in clinically and molecularly selected patients with advanced non-small-cell lung cancer. Methods In this open-label, multicentre, phase 2 trial, we enrolled treatment-naive patients with advanced lung cancer who had clinical (never-smokers [<100 cigarettes per lifetime] or former light smokers [<10 pack-years per lifetime] and >= 15 years since last cigarette) or molecular (EGFR mutation, regardless of smoking status) characteristics associated with response to EGFR inhibitors. We gave dacomitinib orally once daily (45 mg or 30 mg) until progressive disease, unacceptable toxicity, or patient withdrawal. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.0) to investigate the activity of dacomitinib in all patients with a baseline scan and at least one post-treatment scan, with investigator assessment of response and progression. The primary endpoint was progression-free survival at 4 months in the as-enrolled population, with a null hypothesis of progression-free survival at 4 months of 50% or less. The study is registered with ClinicalTrials. gov, number NCT00818441, and is no longer accruing patients. Findings Between March 11, 2009, and April 1, 2011, we enrolled 89 patients from 25 centres, including 45 (51%) with EGFR-activating mutations in exon 19 (n=25) or exon 21 (n=20). Progression-free survival at 4 months was 76.8% (95% CI 66.4-84.4) in the as-enrolled population, and was 95.5% (95% CI 83.2-98.9) in the EGFR-mutant population. The most common all-grade treatment-related adverse events were diarrhoea in 83 (93%) patients, dermatitis acneiform in 69 (78%) patients, dry skin in 39 (44%) patients, and stomatitis in 36 (40%) patients. Two patients (2%) had grade 4 treatment-related events (one with hypokalaemia and one with dyspnoea). No grade 5 toxicities were recorded. Interpretation Dacomitinib had encouraging clinical activity as initial systemic treatment in clinically or molecularly selected patients with advanced non-small-cell lung cancer. C1 [Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.; Paweletz, Cloud] Dana Farber Canc Inst, Belfer Inst Appl Canc, Boston, MA 02115 USA. [Ou, Sai-Hong I.] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Martins, Renato] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. [Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Dunphy, Frank] Duke Univ, Med Ctr, Durham, NC USA. [Nishio, Makoto] Hosp JFCR, Inst Canc, Dept Thorac Med Oncol, Tokyo, Japan. [O'Connell, Joseph] Pfizer Oncol, New York, NY USA. [Taylor, Ian] Pfizer Oncol, Groton, CT USA. [Zhang, Hui] Pfizer China Res & Dev Co Ltd, Shanghai, Peoples R China. [Goldberg, Zelanna] Pfizer Oncol, San Diego, CA USA. [Mok, Tony] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong Canc Inst, Dept Clin Oncol,State Key Lab Oncol South China, Shatin, Hong Kong, Peoples R China. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, HIM 223, Boston, MA 02115 USA. EM pasi_janne@dfci.harvard.edu OI Kris, Mark/0000-0002-7317-5341 FU Pfizer FX We thank all of the patients, their families, the investigators, research nurses, study coordinators, and operations staff who participated in this trial. The study was sponsored by Pfizer. Medical writing support was provided by Rachel Mason at ACUMED (Tytherington, UK) and Joanne Fitz-Gerald, a freelance medical writer, and was funded by Pfizer. NR 24 TC 29 Z9 31 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2014 VL 15 IS 13 BP 1433 EP 1441 DI 10.1016/S1470-2045(14)70461-9 PG 9 WC Oncology SC Oncology GA AX4OT UT WOS:000346912300042 PM 25456362 ER PT J AU Kumar, SK Berdeja, JG Niesvizky, R Lonial, S Laubach, JP Hamadani, M Stewart, AK Hari, P Roy, V Vescio, R Kaufman, JL Berg, D Liao, E Di Bacco, A Estevam, J Gupta, N Hui, AM Rajkumar, V Richardson, PG AF Kumar, Shaji K. Berdeja, Jesus G. Niesvizky, Ruben Lonial, Sagar Laubach, Jacob P. Hamadani, Mehdi Stewart, A. Keith Hari, Parameswaran Roy, Vivek Vescio, Robert Kaufman, Jonathan L. Berg, Deborah Liao, Eileen Di Bacco, Alessandra Estevam, Jose Gupta, Neeraj Hui, Ai-Min Rajkumar, Vincent Richardson, Paul G. TI Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study SO LANCET ONCOLOGY LA English DT Article ID DOSE DEXAMETHASONE; BORTEZOMIB; THERAPY; THALIDOMIDE; TRIAL; MAINTENANCE; PREDNISONE; MLN9708; MODELS; CELL AB Background The combination of bortezomib, lenalidomide, and dexamethasone is a highly effective therapy for newly diagnosed multiple myeloma. Ixazomib is an investigational, oral, proteasome inhibitor with promising anti-myeloma effects and low rates of peripheral neuropathy. In a phase 1/2 trial we aimed to assess the safety, tolerability, and activity of ixazomib in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma. Methods We enrolled patients newly diagnosed with multiple myeloma aged 18 years or older with measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and no grade 2 or higher peripheral neuropathy, and treated them with oral ixazomib (days 1, 8, 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, 22) for up to 12 28-day cycles, followed by maintenance therapy with ixazomib alone. In phase 1, we gave patients escalating doses of ixazomib (1.68-3.95 mg/m(2) ) to establish the recommended dose for phase 2. The primary endpoints were maximum tolerated dose for phase 1, and the rate of very good partial response or better for phase 2. Safety analyses were done in all patients who received at least one dose of study drug; efficacy analyses were done in all patients who received at least one dose of study drug at the phase 2 dose, had measurable disease at baseline, and had at least one post-baseline response assessment. This study is registered at ClinicalTrials. gov, number NCT01217957. Findings Between Nov 22, 2010, and Feb 28, 2012, we enrolled 65 patients (15 to phase 1 and 50 to phase 2). Four doselimiting toxic events were noted in phase 1: one at a dose of ixazomib of 2.97 mg/m(2) and three at 3.95 mg/m(2). The maximum tolerated dose of ixazomib was established as 2.97 mg/m(2) and the recommended phase 2 dose was 2.23 mg/m(2), which was converted to a 4.0 mg fixed dose based on population pharmacokinetic results. Grade 3 or higher adverse events related to any drug were reported in 41 (63%) patients, including skin and subcutaneous tissue disorders (11 patients, 17%), neutropenia (eight patients, 12%), and thrombocytopenia (five patients, 8%); drug-related peripheral neuropathy of grade 3 or higher occurred in four (6%) patients. Five patients discontinued because of adverse events. In 64 response-evaluable patients, 37 (58%, 95% CI 45-70) had a very good partial response or better. Interpretation The all-oral combination of weekly ixazomib plus lenalidomide and dexamethasone was generally well tolerated and appeared active in newly diagnosed multiple myeloma. These results support the phase 3 trial development of this combination for multiple myeloma. C1 [Kumar, Shaji K.; Rajkumar, Vincent] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Niesvizky, Ruben] New York Presbyterian Hosp, Weill Cornell Med Coll, Myeloma Ctr, New York, NY USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Laubach, Jacob P.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamadani, Mehdi] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Stewart, A. Keith] Mayo Clin, Coll Med, Scottsdale, AZ USA. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Vescio, Robert] Samuel Oschin Comprehens Canc, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Berg, Deborah; Liao, Eileen; Di Bacco, Alessandra; Estevam, Jose; Gupta, Neeraj; Hui, Ai-Min] Takeda Pharmaceut Int Co, Cambridge, MA USA. RP Kumar, SK (reprint author), Mayo Clin, Div Hematol, Rochester, MN 55905 USA. EM kumar.shaji@mayo.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Hari, Parameswaran/0000-0002-8800-297X FU Millennium Pharmaceuticals FX Millennium Pharmaceuticals, wholly owned subsidiary of Takeda Pharmaceutical International Company. NR 27 TC 58 Z9 60 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2014 VL 15 IS 13 BP 1503 EP 1512 DI 10.1016/S1470-2045(14)71125-8 PG 10 WC Oncology SC Oncology GA AX4OT UT WOS:000346912300049 PM 25456369 ER PT J AU Dumitrascu, DL Shampo, M Kyle, RA Steensma, DP AF Dumitrascu, Dan L. Shampo, Marc Kyle, Robert A. Steensma, David P. TI Nicolae Testemitanu-Moldovan Surgeon, Scientist, and Politician SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Dumitrascu, Dan L.] Iuliu Hatieganu Univ Med & Pharm, Cluj Napoca, Romania. [Shampo, Marc; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Boston Med Sch, Boston, MA USA. RP Dumitrascu, DL (reprint author), Iuliu Hatieganu Univ Med & Pharm, Cluj Napoca, Romania. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 2014 VL 89 IS 12 BP E131 EP E131 DI 10.1016/j.mayocp.2014.02.023 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AX7NN UT WOS:000347102600003 PM 25468521 ER PT J AU Gather, MC Yun, SH AF Gather, Malte C. Yun, Seok Hyun TI Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers SO NATURE COMMUNICATIONS LA English DT Article ID SEMICONDUCTOR-LASERS; SPONTANEOUS-EMISSION; CONJUGATED POLYMER; CRYSTAL-STRUCTURE; WAVE-GUIDES; GREEN; AEQUOREA; FILMS; BIOLUMINESCENCE; DENDRIMERS AB Bioluminescent organisms are likely to have an evolutionary drive towards high radiance. As such, bio-optimized materials derived from them hold great promise for photonic applications. Here, we show that biologically produced fluorescent proteins retain their high brightness even at the maximum density in solid state through a special molecular structure that provides optimal balance between high protein concentration and low resonance energy transfer self-quenching. Dried films of green fluorescent protein show low fluorescence quenching (-7 dB) and support strong optical amplification (g(net) = 22 cm(-1); 96 dB cm(-1)). Using these properties, we demonstrate vertical cavity surface emitting micro-lasers with low threshold (<100 pJ, outperforming organic semiconductor lasers) and self-assembled all-protein ring lasers. Moreover, solid-state blends of different proteins support efficient Forster resonance energy transfer, with sensitivity to intermolecular distance thus allowing all-optical sensing. The design of fluorescent proteins may be exploited for bio-inspired solid-state luminescent molecules or nanoparticles. C1 [Gather, Malte C.; Yun, Seok Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Gather, Malte C.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Gather, Malte C.] Univ St Andrews, SUPA, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Gather, MC (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St UP 5, Cambridge, MA 02139 USA. EM mcg6@st-andrews.ac.uk; syun@hms.harvard.edu OI Gather, Malte/0000-0002-4857-5562 FU US National Science Foundation [ECCS-1101947]; National Institutes of Health [P41EB015903, R21EB013761]; Department of Defense [FA9550-11-1-0331]; Korea National Research Foundation [R31-2008-000-10071-0]; Bullock-Wellman Fellowship; Daimler and Benz Fellowship; Marie Curie Career Integration Grant [PCIG12-GA-2012-334407] FX We thank J.-J. Song (Korea Advanced Institute of Science and Technology) for providing recombinant eGFP solution, R. Tsien (University of California, San Diego) for donating the tdTomato construct and K. Leosson (University of Iceland) for support with topography measurements. This work was supported by the US National Science Foundation (ECCS-1101947), National Institutes of Health (P41EB015903, R21EB013761), Department of Defense (FA9550-11-1-0331) and the Korea National Research Foundation (R31-2008-000-10071-0). M.C.G. acknowledges support from the Bullock-Wellman Fellowship, the Daimler and Benz Fellowship and the Marie Curie Career Integration Grant (PCIG12-GA-2012-334407). NR 44 TC 22 Z9 22 U1 10 U2 49 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 DEC PY 2014 VL 5 AR 5722 DI 10.1038/ncomms6722 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9NP UT WOS:000347229600005 PM 25483850 ER PT J AU Herter-Sprie, GS Korideck, H Christensen, CL Herter, JM Rhee, K Berbeco, RI Bennett, DG Akbay, EA Kozono, D Mak, RH Makrigiorgos, GM Kimmelman, AC Wong, KK AF Herter-Sprie, Grit S. Korideck, Houari Christensen, Camilla L. Herter, Jan M. Rhee, Kevin Berbeco, Ross I. Bennett, David G. Akbay, Esra A. Kozono, David Mak, Raymond H. Makrigiorgos, G. Mike Kimmelman, Alec C. Wong, Kwok-Kin TI Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models SO NATURE COMMUNICATIONS LA English DT Article ID BODY RADIATION-THERAPY; EXPRESSION; RESISTANCE; BIOLOGY; TRIAL AB Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small-cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Owing to development of multifocal disease, however, these models have not been usable in studies of outcomes following focal radiotherapy (RT). We report the development of a preclinical platform to deliver state-of-the-art image-guided RT in these models. Presence of a single tumour as usually diagnosed in patients is modelled by confined injection of adenoviral Cre recombinase. Furthermore, three-dimensional conformal planning and state-of-the-art image-guided dose delivery are performed as in humans. We evaluate treatment efficacies of two different radiation regimens and find that Kras-driven tumours can temporarily be stabilized upon RT, whereas additional loss of either Lkb1 or p53 renders these lesions less responsive to RT. C1 [Herter-Sprie, Grit S.; Christensen, Camilla L.; Rhee, Kevin; Akbay, Esra A.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Herter-Sprie, Grit S.; Christensen, Camilla L.; Rhee, Kevin; Akbay, Esra A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Herter-Sprie, Grit S.; Christensen, Camilla L.; Rhee, Kevin; Akbay, Esra A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Korideck, Houari; Berbeco, Ross I.; Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Div Med Phys & Biophys, Dept Radiat Oncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02215 USA. [Herter, Jan M.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol,Med Sch, Boston, MA 02215 USA. [Bennett, David G.] Harvard Univ, Sch Med, Dept Radiol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kozono, David; Mak, Raymond H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02215 USA. [Kimmelman, Alec C.] Harvard Univ, Brigham & Womens Hosp, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02215 USA. RP Kimmelman, AC (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst,Med Sch, 450 Brookline Ave, Boston, MA 02215 USA. EM alec_kimmelman@dfci.harvard.edu; kwong1@partners.org FU Deutsche Forschungsgemeinschaft [HE 6897/1-1, HE 6810/1-1]; National Cancer Institute [R01CA157490, K08CA172354, U01CA141576, P01CA120964, CA122794, R01CA140594, P01CA154303, CA163896, CA166480]; LUNGevity Foundation [CDA 2013-02]; ACS Research Scholar Grant [RSG-13-298-01-TBG]; Lustgarten Foundation; Susan Spooner Research Fund FX We thank Y. Guo, P. Gao and J. Cavanaugh for technical assistance; K. Labbe for administrative assistance; the members of the Wong, Kimmelman and Makrigiorgos laboratories for helpful discussions. This work was supported by the Deutsche Forschungsgemeinschaft (HE 6897/1-1 to G.S.H.-S. and HE 6810/1-1 to J.M.H.), the National Cancer Institute (R01CA157490 to A.C.K., K08CA172354 to D.K., U01CA141576, P01CA120964, CA122794, R01CA140594, P01CA154303, CA163896 and CA166480 to K.-K.W.), the LUNGevity Foundation (CDA 2013-02 to D.K.), ACS Research Scholar Grant (RSG-13-298-01-TBG to A.C.K.), the Lustgarten Foundation (to A.C.K.) and Susan Spooner Research Fund (to K.-K.W.). NR 25 TC 9 Z9 9 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2014 VL 5 AR 5870 DI 10.1038/ncomms6870 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX8RM UT WOS:000347176200003 PM 25519892 ER PT J AU Porichis, F Hart, MG Griesbeck, M Everett, HL Hassan, M Baxter, AE Lindqvist, M Miller, SM Soghoian, DZ Kavanagh, DG Reynolds, S Norris, B Mordecai, SK Nguyen, Q Lai, CF Kaufmann, DE AF Porichis, Filippos Hart, Meghan G. Griesbeck, Morgane Everett, Holly L. Hassan, Muska Baxter, Amy E. Lindqvist, Madelene Miller, Sara M. Soghoian, Damien Z. Kavanagh, Daniel G. Reynolds, Susan Norris, Brett Mordecai, Scott K. Quan Nguyen Lai, Chunfai Kaufmann, Daniel E. TI High-throughput detection of miRNAs and gene-specific mRNA at the single-cell level by flow cytometry SO NATURE COMMUNICATIONS LA English DT Article ID IN-SITU HYBRIDIZATION; T-CELLS; EXPRESSION; SEQ; MICRORNAS; PCR; DNA AB Fluorescent in situ hybridization (FISH) is a method that uses fluorescent probes to detect specific nucleic acid sequences at the single-cell level. Here we describe optimized protocols that exploit a highly sensitive FISH method based on branched DNA technology to detect mRNA and miRNA in human leukocytes. This technique can be multiplexed and combined with fluorescent antibody protein staining to address a variety of questions in heterogeneous cell populations. We demonstrate antigen-specific upregulation of IFN gamma and IL-2 mRNAs in HIV- and CMV-specific T cells. We show simultaneous detection of cytokine mRNA and corresponding protein in single cells. We apply this method to detect mRNAs for which flow antibodies against the corresponding proteins are poor or are not available. We use this technique to show modulation of a microRNA critical for T-cell function, miR-155. We adapt this assay for simultaneous detection of mRNA and proteins by ImageStream technology. C1 [Porichis, Filippos; Hart, Meghan G.; Griesbeck, Morgane; Everett, Holly L.; Hassan, Muska; Lindqvist, Madelene; Miller, Sara M.; Soghoian, Damien Z.; Kavanagh, Daniel G.; Kaufmann, Daniel E.] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Porichis, Filippos; Hart, Meghan G.; Griesbeck, Morgane; Everett, Holly L.; Hassan, Muska; Lindqvist, Madelene; Miller, Sara M.; Soghoian, Damien Z.; Kavanagh, Daniel G.; Kaufmann, Daniel E.] Harvard Univ, Cambridge, MA 02139 USA. [Baxter, Amy E.; Kaufmann, Daniel E.] Ctr Hosp Univ Montreal, Ctr Rech, Quebec City, PQ, Canada. [Baxter, Amy E.; Kaufmann, Daniel E.] Univ Montreal, Montreal, PQ, Canada. [Reynolds, Susan; Norris, Brett; Quan Nguyen; Lai, Chunfai] Affymetrix Inc, Santa Clara, CA 95051 USA. [Mordecai, Scott K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Porichis, F (reprint author), MIT, Ragon Inst MGH, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM fporichis@mgh.harvard.edu; daniel.kaufmann@umontreal.ca OI Baxter, Amy/0000-0002-1555-0713 FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [PO1 AI-080192, UM1AI100663, 1R56AI095088-01]; National Heart Lung and Blood Institute of the National Institutes of Health [RO1 HL-092565]; Office of the Director, National Institutes of Health [NIH 1S10OD012027-01A1]; Research Scholar Career Award of the Quebec Health Research Fund (FRQS); Massachusetts General Hospital Executive Committee on Research; Harvard Global Health Institute (HGHI); Grand Challenges Exploration award from Bill and Melinda Gates Foundation FX We thank the clinical and laboratory staff at the Massachusetts General Hospital and all the study participants for their invaluable role in this project. We would like to thank Dr Frederic Preffer for his input on this manuscript. This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (PO1 AI-080192 and UM1AI100663 (CHAVI-ID); D.E.K.; 1R56AI095088-01 to D.G.K.), the National Heart Lung and Blood Institute of the National Institutes of Health (RO1 HL-092565; D.E.K.) and The Office of the Director, National Institutes of Health (NIH 1S10OD012027-01A1; Dr Frederic Preffer). D.E.K. is supported by a Research Scholar Career Award of the Quebec Health Research Fund (FRQS). F.P. was supported by a fellowship grant of the Massachusetts General Hospital Executive Committee on Research and the Harvard Global Health Institute (HGHI). D.G.K. was supported by a Grand Challenges Exploration award from Bill and Melinda Gates Foundation. NR 27 TC 23 Z9 23 U1 7 U2 46 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 DEC PY 2014 VL 5 AR 5641 DI 10.1038/ncomms6641 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9MQ UT WOS:000347227200001 PM 25472703 ER PT J AU Shen, K Luk, S Hicks, DF Elman, JS Bohr, S Iwamoto, Y Murray, R Pena, K Wang, FJ Seker, E Weissleder, R Yarmush, ML Toner, M Sgroi, D Parekkadan, B AF Shen, Keyue Luk, Samantha Hicks, Daniel F. Elman, Jessica S. Bohr, Stefan Iwamoto, Yoshiko Murray, Ryan Pena, Kristen Wang, Fangjing Seker, Erkin Weissleder, Ralph Yarmush, Martin L. Toner, Mehmet Sgroi, Dennis Parekkadan, Biju TI Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays SO NATURE COMMUNICATIONS LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; GENE-EXPRESSION; CELL-INTERACTIONS; PROSTATE-CANCER; STEM-CELLS; IN-VITRO; MICROENVIRONMENT; REVERSINE; GROWTH AB Tumour-stromal interactions are a determining factor in cancer progression. In vivo, the interaction interface is associated with spatially resolved distributions of cancer and stromal phenotypes. Here, we establish a micropatterned tumour-stromal assay (mu TSA) with laser capture microdissection to control the location of co-cultured cells and analyse bulk and interfacial tumour-stromal signalling in driving cancer progression. mu TSA reveals a spatial distribution of phenotypes in concordance with human oestrogen receptor-positive (ER+) breast cancer samples, and heterogeneous drug activity relative to the tumour-stroma interface. Specifically, an unknown mechanism of reversine is shown in targeting tumour-stromal interfacial interactions using ER+ MCF-7 breast cancer and bone marrow-derived stromal cells. Reversine suppresses MCF-7 tumour growth and bone metastasis in vivo by reducing tumour stromalization including collagen deposition and recruitment of activated stromal cells. This study advocates mu TSA as a platform for studying tumour microenvironmental interactions and cancer field effects with applications in drug discovery and development. C1 [Shen, Keyue; Luk, Samantha; Elman, Jessica S.; Bohr, Stefan; Murray, Ryan; Wang, Fangjing; Seker, Erkin; Yarmush, Martin L.; Toner, Mehmet; Parekkadan, Biju] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Shen, Keyue; Luk, Samantha; Elman, Jessica S.; Bohr, Stefan; Murray, Ryan; Wang, Fangjing; Seker, Erkin; Yarmush, Martin L.; Toner, Mehmet; Parekkadan, Biju] Shriners Hosp Children, Boston, MA 02114 USA. [Hicks, Daniel F.; Sgroi, Dennis] Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Charlestown, MA 02129 USA. [Iwamoto, Yoshiko; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Pena, Kristen] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Parekkadan, Biju] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shen, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM keyue.shen@usc.edu; biju_parekkadan@hms.harvard.edu OI Seker, Erkin/0000-0003-2401-3562 FU Shriners Hospitals for Children; National Institutes of Health Grants [R01EB012521, K01DK087770]; Massachusetts General Hospital Fund for Medical Discovery FX We thank Dr Robert A. Weinberg for the MDA-MB-231/GFP cells; Dr Akira Orimo for the normal breast fibroblasts and cancer-associated fibroblasts; Daniel Datorre and Drs Jack M. Milwid and William McCarty for assistance with animal work; Patricia Della Pelle and Anna Levitz for assistance with histology. This work was supported in part by the Shriners Hospitals for Children (B.P.), National Institutes of Health Grants R01EB012521 (B.P.) and K01DK087770 (B.P.), and also by Massachusetts General Hospital Fund for Medical Discovery (K.S.). NR 70 TC 8 Z9 8 U1 3 U2 22 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 DEC PY 2014 VL 5 AR 5662 DI 10.1038/ncomms6662 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9NA UT WOS:000347228100005 PM 25489927 ER PT J AU Muller, M Hess, L Tardivo, A Lajmanovich, R Attademo, A Poletta, G Simoniello, MF Yodice, A Lavarello, S Chialvo, D Scremin, O AF Muller, Marie Hess, Leonardo Tardivo, Agostina Lajmanovich, Rafael Attademo, Andres Poletta, Gisela Fernanda Simoniello, Maria Yodice, Agustina Lavarello, Simona Chialvo, Dante Scremin, Oscar TI Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos SO NEUROTOXICOLOGY LA English DT Article DE Acetylcholinesterase inhibitors; Evoked potentials; Comet assay; Auditory startle; EEG ID ACETYLCHOLINESTERASE INHIBITOR CHLORPYRIFOS; SOMATOSENSORY-EVOKED-POTENTIALS; HIPPOCAMPAL THETA-RHYTHM; ACOUSTIC STARTLE REFLEX; ANESTHETIZED RAT; CHOLINERGIC MODULATION; SENSORY-INTERFERENCE; PREPULSE INHIBITION; REPEATED EXPOSURES; BEHAVIORAL STATES AB Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10 mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia. In another group of conscious animals, auditory startle reflex (ASR) was evaluated followed, after euthanasia, with measurements of plasma B-esterases, and genotoxicity with the alkaline comet assay (ACA) at the same CPF doses. The results indicated a CPF dose related inhibition of B-esterases. Enhanced inhibition of the ASR by a subthreshold pre-pulse was observed at all doses and ACA showed a significant higher DNA damage than vehicle controls in animals exposed to 10 mg/kg CPF. A trend to higher frequencies of EEGp and an increase in amplitude of the first negative wave of the SEP were found at all doses. The first positive wave of the SEP decreased at the CPF dose of 10 mg/kg. In summary, a shift to higher EEG frequencies and alterations of somatosensory and auditory input to the central nervous system were sensitive manifestations of CPF toxicity, associated with depression of B-esterases. The changes in electrical activity of the cerebral cortex and DNA damage observed at doses that do not elicit overt toxicity may be useful in the detection of CPF exposure before clinical signs appear. Published by Elsevier Inc. C1 [Muller, Marie; Hess, Leonardo; Tardivo, Agostina; Yodice, Agustina; Lavarello, Simona; Chialvo, Dante; Scremin, Oscar] Univ Natl Rosario, Fac Ciencias Med, PROFISIO, RA-3100 Rosario, Argentina. [Lajmanovich, Rafael; Attademo, Andres; Poletta, Gisela; Fernanda Simoniello, Maria] Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Santa Fe, Argentina. [Lajmanovich, Rafael; Attademo, Andres; Poletta, Gisela; Chialvo, Dante; Scremin, Oscar] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina. [Scremin, Oscar] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. [Scremin, Oscar] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Scremin, O (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Bldg, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 FU National Research Council of Argentina (CONICET); Capacitacion e Investigacion para la Medicina Argentina (CIMA) FX The work was supported by the National Research Council of Argentina (CONICET) and funds from Capacitacion e Investigacion para la Medicina Argentina (CIMA) a non-profit academic organization. NR 83 TC 6 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2014 VL 45 BP 22 EP 30 DI 10.1016/j.neuro.2014.08.012 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100003 PM 25196089 ER PT J AU Bae, J Samur, M Munshi, A Hideshima, T Keskin, D Kimmelman, A Lee, AH Dranoff, G Anderson, KC Munshi, NC AF Bae, Jooeun Samur, Mehmet Munshi, Aditya Hideshima, Teru Keskin, Derin Kimmelman, Alec Lee, Ann-Hwee Dranoff, Glen Anderson, Kenneth C. Munshi, Nikhil C. TI Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells SO ONCOIMMUNOLOGY LA English DT Article DE breast / colon / pancreatic cancer; cancer vaccine; heteroclitic peptides; XBP1 ID UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR EOMESODERMIN; POTENTIAL THERAPEUTIC APPLICATION; ENDOPLASMIC-RETICULUM; MULTIPLE-MYELOMA; ER STRESS; BONE-MARROW; EFFECTOR; BET; EXPRESSION AB XBP1 is a critical transcriptional activator of the unfolded protein response (UPR), which increases tumor cell survival under prolonged endoplasmic reticulum (ER) stress and hypoxic conditions. This study was designed to evaluate the immunogenicity of heteroclitic XBP1 unspliced (US)(184-192) (YISPWILAV) and heteroclictic XBP1 spliced (SP)(367-375) (YLFPQLISV) HLA-A2 peptides, and to characterize the specific activities of XBP1 peptides-specific cytotoxic T lymphocytes (XBP1-CTL) against breast cancer, colon cancer, and pancreatic cancer cells. The XBP1-CTL had upregulated expression of critical T cell markers and displayed HLA-A2-restricted and antigen-specific activities against breast cancer, colon cancer and pancreatic cancer cells. XBP1-CTL were enriched withCD45ROC memory CTL, which showed high expression of critical T cell markers (CD28, ICOS, CD69, CD40L), cell proliferation and antitumor activities as compared to CD45RO(-) non-memory CTL. The effector memory (EM: CD45RO(+)CCR7(-)) subset had the highest level of cell proliferation while the central memory (CM: CD45RO(+)CCR7(+)) subset demonstrated enhanced functional activities (CD107a degranulation, IFN gamma/IL-2 production) upon recognition of the respective tumor cells. Furthermore, both the EM and CM XBP1-CTL subsets expressed high levels of Th1 transcription regulators Tbet and Eomes. The highest frequencies of IFN gamma or granzyme B producing cells were detected within CM XBP1-CTL subset that were either Tbet(+) or Eomes(+) in responding to the tumor cells. These results demonstrate the immunotherapeutic potential of a cocktail of immunogenic HLA-A2 specific heteroclitic XBP1 US184-192 and heteroclictic XBP1 SP367-375 peptides to induce CD3(+)CD8(+) CTL enriched for CM and EM cells with specific antitumor activities against a variety of solid tumors. C1 [Bae, Jooeun; Samur, Mehmet; Munshi, Aditya; Hideshima, Teru; Keskin, Derin; Kimmelman, Alec; Dranoff, Glen; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bae, Jooeun; Samur, Mehmet; Munshi, Aditya; Hideshima, Teru; Keskin, Derin; Kimmelman, Alec; Dranoff, Glen; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Ann-Hwee] Weill Cornell Med Coll, New York, NY USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. RP Bae, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jooeun_bae@dfci.harvard.edu OI Munshi, Aditya/0000-0002-9111-7495 FU National Institutes of Health [RO1-124929, P50-100007, PO1-78378, PO1155258, RO1-50947] FX This work was supported in part by grants from the National Institutes of Health Grants RO1-124929 to Dr. Nikhil C. Munshi, P50-100007, PO1-78378 and PO1155258 to Drs. Kenneth C. Anderson and Nikhil C. Munshi, and RO1-50947 to Dr. Kenneth C. Anderson. This research was also supported in part by a generous donation from Mr. and Mrs. Stewart Nagler. Dr. Kenneth C. Anderson is an American Cancer Society Clinical Research Professor. NR 66 TC 2 Z9 2 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD DEC PY 2014 VL 3 IS 12 AR e970914 DI 10.4161/21624011.2014.970914 PG 22 WC Oncology; Immunology SC Oncology; Immunology GA AY6MH UT WOS:000347679800012 ER PT J AU Wouters, MCA Dijkgraaf, EM Kuijjer, ML Jordanova, ES Hollema, H Welters, MJP van der Hoeven, JJM Daemen, T Kroep, JR Nijman, HW van der Burg, S AF Wouters, M. C. A. Dijkgraaf, E. M. Kuijjer, M. L. Jordanova, E. S. Hollema, H. Welters, M. J. P. van der Hoeven, J. J. M. Daemen, T. Kroep, J. R. Nijman, H. W. van der Burg, S. H. TI Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer SO ONCOIMMUNOLOGY LA English DT Article DE epithelial ovarian cancer; IL-6, interleukin-6; IL-6R; interleukin-6 receptor; pSTAT3; tumor-infiltrating myeloid cells ID T-CELLS; PROGNOSTIC-SIGNIFICANCE; DENDRITIC CELLS; M2 MACROPHAGES; POOR-PROGNOSIS; CARCINOMA; EXPRESSION; THERAPY; TARGET; DIFFERENTIATION AB An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL-6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color immunofluorescence confocal microscopy was used to identify myeloid cell populations by CD14, CD33, and CD163. The relationship between these markers, tumor-infiltrating immune cells, clinical-pathological characteristics and survival was investigated. EOC displayed a dense infiltration with myeloid cells, in particular of the CD163(+) type. The distribution pattern of all myeloid subtypes was comparable among the different histological subtypes. Analysis of the tumor cells revealed a high expression of IL-6R in 15% and of IL-6 in 23% of patients. Interestingly, tumors expressing IL-6 or IL-6R formed two different groups. Tumors with a high expression of IL-6R displayed low mature myeloid cell infiltration and a longer disease-specific survival (DSS), especially in late stage tumors. High expression of IL-6R was an independent prognostic factor for survival by multivariate analyses (hazard ratio = 0.474, p = 0.011). In contrast, tumors with high epithelial IL-6 expression displayed a dense infiltration of mature myeloid cells and were correlated with a shorter DSS. Furthermore, in densely CD8(+) T-cell infiltrated tumors, the ratio between these lymphoid cells and CD163(+) myeloid cells was predictive for survival. Thus, IL-6 and IL-6R are opposite markers for myeloid cell infiltration and survival. C1 [Wouters, M. C. A.; Nijman, H. W.] Univ Groningen, Univ Med Ctr Groningen, Dept Gynecol Oncol, Groningen, Netherlands. [Dijkgraaf, E. M.; Welters, M. J. P.; van der Hoeven, J. J. M.; Kroep, J. R.; van der Burg, S. H.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Wouters, M. C. A.; Daemen, T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol, Groningen, Netherlands. [Kuijjer, M. L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kuijjer, M. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jordanova, E. S.] Vrije Univ Amsterdam Med Ctr, Ctr Gynaecol Oncol Amsterdam, Amsterdam, Netherlands. [Hollema, H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands. RP van der Burg, S (reprint author), Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. EM shvdburg@lumc.nl RI Wouters, Maartje/A-6431-2016; OI Wouters, Maartje/0000-0001-5829-6973; Jordanova, Ekaterina S./0000-0002-8121-1322 FU Dutch Cancer Society [2009-4400] FX MJPW was financially supported by a grant from the Dutch Cancer Society 2009-4400 NR 41 TC 4 Z9 4 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD DEC PY 2014 VL 3 IS 12 AR UNSP e962397 DI 10.4161/21624011.2014.962397 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA AY6MH UT WOS:000347679800007 ER PT J AU Canellos, GP AF Canellos, George P. TI Advanced DLBCL: As Systemic Therapy Improves, the Need for RT Diminishes SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID B-CELL LYMPHOMA; LOCALIZED AGGRESSIVE LYMPHOMA; INVOLVED FIELD RADIOTHERAPY; CHOP PLUS RADIOTHERAPY; NON-HODGKINS-LYMPHOMA; STAGE III-IV; ELDERLY-PATIENTS; INTERMEDIATE-GRADE; RADIATION-THERAPY; RITUXIMAB THERAPY C1 [Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Canellos, George P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2014 VL 28 IS 12 BP 1085 EP 1086 PG 2 WC Oncology SC Oncology GA AX8CM UT WOS:000347138100007 PM 25510807 ER PT J AU Gustafson, GS Nguyen, PL Assimos, DG D'Amico, AV Gottschalk, AR Hsu, ICJ Lloyd, S Mclaughlin, PW Merrick, G Showalter, TN Taira, AV Vapiwala, N Yamada, Y Davis, BJ AF Gustafson, Gary S. Nguyen, Paul L. Assimos, Dean G. D'Amico, Anthony V. Gottschalk, Alexander R. Hsu, I-Chow Joe Lloyd, Shane Mclaughlin, Patrick W. Merrick, Gregory Showalter, Timothy N. Taira, Al V. Vapiwala, Neha Yamada, Yoshiya Davis, Brian J. TI ACR Appropriateness Criteria (R) Postradical Prostatectomy Irradiation in Prostate Cancer SO ONCOLOGY-NEW YORK LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; SALVAGE RADIATION-THERAPY; POSITIVE SURGICAL MARGINS; PSA DOUBLING TIME; INTENSITY-MODULATED RADIOTHERAPY; TERM-FOLLOW-UP; ANDROGEN DEPRIVATION THERAPY; BIOCHEMICAL DISEASE-FREE; ADJUVANT RADIOTHERAPY; ANTIGEN RECURRENCE AB The purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectonny prostate cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Recent and relevant literature reviewed by the panel led to establishment of criteria for appropriate use of radiation therapy in postprostatectomy prostate cancer. The discussion includes treatment technique, appropriate dose, field design, and the role of prostate-specific antigen (PSA). Ratings and commentary of the panel on multiple treatment parameters were used to reach consensus. Patients with high-risk pathologic features benefit from postprostatectomy radiation therapy. C1 [Gustafson, Gary S.] William Beaumont Hosp, Troy, MI 48085 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Assimos, Dean G.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Assimos, Dean G.] Amer Urol Assoc, New Orleans, LA USA. [D'Amico, Anthony V.] Joint Ctr Radiat Therapy, Boston, MA 02115 USA. [Gottschalk, Alexander R.; Hsu, I-Chow Joe] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lloyd, Shane] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Mclaughlin, Patrick W.] Univ Michigan, Novi, MI USA. [Merrick, Gregory] Schiffler Canc Ctr, Wheeling, WV USA. [Merrick, Gregory] Wheeling Jesuit Univ, Wheeling, WV USA. [Showalter, Timothy N.] Univ Virginia, Charlottesville, VA USA. [Taira, Al V.] Dorothy Schneider Canc Ctr, San Mateo, CA USA. [Vapiwala, Neha] Univ Penn, Philadelphia, PA 19104 USA. [Yamada, Yoshiya] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Davis, Brian J.] Mayo Clin, Rochester, MN USA. RP Gustafson, GS (reprint author), William Beaumont Hosp, Troy, MI 48085 USA. NR 130 TC 0 Z9 0 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2014 VL 28 IS 12 BP 1125 EP + PG 11 WC Oncology SC Oncology GA AX8CM UT WOS:000347138100012 PM 25510812 ER PT J AU Woo, SB Grammer, RL Lerman, MA AF Woo, Sook-Bin Grammer, Rebecca L. Lerman, Mark A. TI Keratosis of unknown significance and leukoplakia: a preliminary study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID PROLIFERATIVE VERRUCOUS LEUKOPLAKIA; ORAL EPITHELIAL DYSPLASIA; MALIGNANT-TRANSFORMATION; CLINICAL-IMPLICATIONS; FIELD CANCERIZATION; PROGRESSION MODEL; INCISIONAL BIOPSY; NECK-CANCER; LESIONS; CLASSIFICATION AB Objective. The objectives were to (1) determine the frequency of specific diagnoses in a series of white lesions, and (2) describe the nature of keratotic lesions that are neither reactive nor dysplastic. Study Design. White lesions were analyzed and diagnosed as reactive keratoses, dysplastic/malignant, or keratoses of unknown significance (KUS). Results. Of the 1251 specimens that were evaluated, 703 met criteria for inclusion, and approximately 75% were reactive, 10% dysplastic/malignant, and 14% KUS. Excluding reactive keratoses, 43% were dysplastic/malignant and 57% were KUS. Conclusions. Reactive keratoses were the most common white lesions followed by lichen planus. Dysplastic/ malignant lesions constituted almost 50% of all true leukoplakias. KUS constituted the remaining cases and do not show typical reactive histopathology as well as clear dysplasia. They may represent evolving or devolving reactive keratoses but may also represent the very earliest dysplasia phenotype. Clinical findings may be helpful in differentiating the two. C1 [Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Grammer, Rebecca L.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lerman, Mark A.] Tufts Univ, Sch Dent Med, Dept Oral Pathol Oral Med & Craniofacial Pain, Boston, MA 02111 USA. [Woo, Sook-Bin] StrataDx, Lexington, MA USA. [Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. RP Lerman, MA (reprint author), Tufts Univ, Sch Dent Med, Dept Oral Pathol Oral Med & Craniofacial Pain, Boston, MA 02111 USA. EM Mark.Lerman@tufts.edu NR 45 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 EI 1528-395X J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD DEC PY 2014 VL 118 IS 6 BP 715 EP 726 DI 10.1016/j.oooo.2014.09.016 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AX9WB UT WOS:000347248900021 PM 25457889 ER PT J AU Jensen, MP Sherlin, LH Fregni, F Gianas, A Howe, JD Hakimian, S AF Jensen, Mark P. Sherlin, Leslie H. Fregni, Felipe Gianas, Ann Howe, Jon D. Hakimian, Shahin TI Baseline Brain Activity Predicts Response to Neuromodulatory Pain Treatment SO PAIN MEDICINE LA English DT Article DE Spinal Cord Injury; Chronic Pain; Electroencephalography; Nonpharmacological Treatments ID SPINAL-CORD-INJURY; HYPNOTIC-SUSCEPTIBILITY; PSYCHOLOGICAL INTERVENTIONS; EEG; HYPNOSIS; RELAXATION; STIMULATION; BIOFEEDBACK; STATES; THETA AB ObjectivesThe objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. DesignRandomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. MethodsThirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). ResultsAs hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. ConclusionsThe findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. C1 [Jensen, Mark P.; Gianas, Ann] Univ Washington, Dept Rehabil Med, Seattle, WA 98104 USA. [Sherlin, Leslie H.] Southwest Coll Naturopath Med, Dept Mind Body Med, Tempe, AZ USA. [Sherlin, Leslie H.] Nova Tech EEG, Mesa, AZ USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil,Spaulding Rehabil Hosp, Boston, MA USA. [Howe, Jon D.] Univ Washington, Dept Psychol, Seattle, WA 98104 USA. [Hakimian, Shahin] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. RP Jensen, MP (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Box 359612,325 Ninth Ave, Seattle, WA 98104 USA. EM mjensen@uw.edu FU National Institutes of Health [R21 HD058049]; National Institute of Child Health and Human Development; National Center for Medical Rehabilitation Research FX This research was supported by grant number R21 HD058049 from the National Institutes of Health, National Institute of Child Health and Human Development, and National Center for Medical Rehabilitation Research. NR 58 TC 6 Z9 6 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD DEC PY 2014 VL 15 IS 12 BP 2055 EP 2063 DI 10.1111/pme.12546 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AX9QO UT WOS:000347237200013 PM 25287554 ER PT J AU Liachko, NF McMillan, PJ Strovas, TJ Loomis, E Greenup, L Murrell, JR Ghetti, B Raskind, MA Montine, TJ Bird, TD Leverenz, JB Kraemer, BC AF Liachko, Nicole F. McMillan, Pamela J. Strovas, Timothy J. Loomis, Elaine Greenup, Lynne Murrell, Jill R. Ghetti, Bernardino Raskind, Murray A. Montine, Thomas J. Bird, Thomas D. Leverenz, James B. Kraemer, Brian C. TI The Tau Tubulin Kinases TTBK1/2 Promote Accumulation of Pathological TDP-43 SO PLOS GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE BRAIN; HELICAL FILAMENT-TAU; CAENORHABDITIS-ELEGANS; PHOSPHORYLATION SITES; INDUCED NEUROTOXICITY; TARDBP MUTATIONS; DNA-BINDING; IN-VIVO AB Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP. C1 [Liachko, Nicole F.; Strovas, Timothy J.; Loomis, Elaine; Bird, Thomas D.; Leverenz, James B.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Liachko, Nicole F.; Raskind, Murray A.; Bird, Thomas D.; Kraemer, Brian C.] Univ Washington, Dept Med, Seattle, WA USA. [McMillan, Pamela J.; Greenup, Lynne; Raskind, Murray A.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [McMillan, Pamela J.; Leverenz, James B.; Kraemer, Brian C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Murrell, Jill R.; Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Montine, Thomas J.; Bird, Thomas D.; Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Montine, Thomas J.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Liachko, NF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs [1147891, I01BX007080]; National Institutes of Health [R01NS064131, AG 000057-31, 2P50AG005136-27, 5P50NS2062684-02] FX This work was supported by grants from the Department of Veterans Affairs [Merit Review Grant #1147891 to BCK and CDA2 Award #I01BX007080 to NFL] and National Institutes of Health [R01NS064131 to BCK, AG 000057-31 to NFL, 2P50AG005136-27 and 5P50NS2062684-02 to JBL]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 14 Z9 14 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2014 VL 10 IS 12 AR e1004803 DI 10.1371/journal.pgen.1004803 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900015 PM 25473830 ER PT J AU Ulirsch, JC Lacy, JN An, XL Mohandas, N Mikkelsen, TS Sankaran, VG AF Ulirsch, Jacob C. Lacy, Jessica N. An, Xiuli Mohandas, Narla Mikkelsen, Tarjei S. Sankaran, Vijay G. TI Altered Chromatin Occupancy of Master Regulators Underlies Evolutionary Divergence in the Transcriptional Landscape of Erythroid Differentiation SO PLOS GENETICS LA English DT Article ID CONGENITAL DYSERYTHROPOIETIC ANEMIA; DIAMOND-BLACKFAN ANEMIA; EMBRYONIC STEM-CELLS; MODEL-BASED ANALYSIS; CHIP-SEQ REVEALS; FACTOR-BINDING; GENE-EXPRESSION; HISTONE MODIFICATIONS; HUMAN GENOME; DNA AB Erythropoiesis is one of the best understood examples of cellular differentiation. Morphologically, erythroid differentiation proceeds in a nearly identical fashion between humans and mice, but recent evidence has shown that networks of gene expression governing this process are divergent between species. We undertook a systematic comparative analysis of six histone modifications and four transcriptional master regulators in primary proerythroblasts and erythroid cell lines to better understand the underlying basis of these transcriptional differences. Our analyses suggest that while chromatin structure across orthologous promoters is strongly conserved, subtle differences are associated with transcriptional divergence between species. Many transcription factor (TF) occupancy sites were poorly conserved across species (similar to 25% for GATA1, TAL1, and NFE2) but were more conserved between proerythroblasts and cell lines derived from the same species. We found that certain cis-regulatory modules co-occupied by GATA1, TAL1, and KLF1 are under strict evolutionary constraint and localize to genes necessary for erythroid cell identity. More generally, we show that conserved TF occupancy sites are indicative of active regulatory regions and strong gene expression that is sustained during maturation. Our results suggest that evolutionary turnover of TF binding sites associates with changes in the underlying chromatin structure, driving transcriptional divergence. We provide examples of how this framework can be applied to understand epigenomic variation in specific regulatory regions, such as the beta-globin gene locus. Our findings have important implications for understanding epigenomic changes that mediate variation in cellular differentiation across species, while also providing a valuable resource for studies of hematopoiesis. C1 [Ulirsch, Jacob C.; Lacy, Jessica N.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res,Div Hematol Oncol, Boston, MA 02163 USA. [Ulirsch, Jacob C.; Lacy, Jessica N.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ulirsch, Jacob C.; Lacy, Jessica N.; Mikkelsen, Tarjei S.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA USA. [An, Xiuli; Mohandas, Narla] New York Blood Ctr, New York, NY 10021 USA. [Mikkelsen, Tarjei S.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Ulirsch, JC (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res,Div Hematol Oncol, Boston, MA 02163 USA. EM sankaran@broadinstitute.org FU National Institutes of Health [U01 HL117720, R21 HL120791, R01 DK103794]; Diamond Blackfan Anemia Foundation; March of Dimes Basil O'Connor Scholar Award FX This work was supported by National Institutes of Health grants U01 HL117720, R21 HL120791, and R01 DK103794, a grant from the Diamond Blackfan Anemia Foundation, and a March of Dimes Basil O'Connor Scholar Award (to VGS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 10 Z9 10 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2014 VL 10 IS 12 AR e1004890 DI 10.1371/journal.pgen.1004890 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900075 PM 25521328 ER PT J AU Doppler, SA Werner, A Barz, M Lahm, H Deutsch, MA Dressen, M Schiemann, M Voss, B Gregoire, S Kuppusamy, R Wu, SM Lange, R Krane, M AF Doppler, Stefanie A. Werner, Astrid Barz, Melanie Lahm, Harald Deutsch, Marcus-Andre Dressen, Martina Schiemann, Matthias Voss, Bernhard Gregoire, Serge Kuppusamy, Rajarajan Wu, Sean M. Lange, Ruediger Krane, Markus TI Myeloid Zinc Finger 1 (Mzf1) Differentially Modulates Murine Cardiogenesis by Interacting with an Nkx2.5 Cardiac Enhancer SO PLOS ONE LA English DT Article ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; SMOOTH-MUSCLE; GENE-EXPRESSION; PROTEIN MZF1; IN-VITRO; HEART; MOUSE; MESODERM; TRANSCRIPTION AB Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown. Mzf1 expression was significantly enriched in CPCs from in vitro differentiated ES cells and in mouse embryonic hearts. To examine the effect of Mzf1 overexpression on CPC formation, we generated a double transgenic, inducible, tetOMzf1-Nkx2.5 CE eGFP ES line. During in vitro differentiation an early and continuous Mzf1 overexpression inhibited CPC formation and cardiac gene expression. A late Mzf1 overexpression, coincident with a second physiological peak of Mzf1 expression, resulted in enhanced cardiogenesis. These findings implicate a novel, temporal-specific role of Mzf1 in embryonic heart development. Thereby we add another piece of puzzle in understanding the complex mechanisms of vertebrate cardiac development and progenitor cell differentiation. Consequently, this knowledge will be of critical importance to guide efficient cardiac regenerative strategies and to gain further insights into the molecular basis of congenital heart malformations. C1 [Doppler, Stefanie A.; Werner, Astrid; Barz, Melanie; Lahm, Harald; Deutsch, Marcus-Andre; Dressen, Martina; Voss, Bernhard; Lange, Ruediger; Krane, Markus] Tech Univ Munich, Dept Expt Surg, Dept Cardiovasc Surg, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Schiemann, Matthias] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-80290 Munich, Germany. [Schiemann, Matthias] TUM, Clin Cooperat Grp Antigen Specif Immunotherapy &, Helmholtz Ctr Munich Neuherberg, Munich, Germany. [Gregoire, Serge] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Div Cardiol,Dept Med, Boston, MA USA. [Kuppusamy, Rajarajan; Wu, Sean M.] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Div Cardiovasc Med, Stanford, CA 94305 USA. [Kuppusamy, Rajarajan; Wu, Sean M.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Lange, Ruediger; Krane, Markus] DZHK German Ctr Cardiovasc Res Partner Site Munic, Munich, Germany. RP Doppler, SA (reprint author), Tech Univ Munich, Dept Expt Surg, Dept Cardiovasc Surg, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. EM doppler@dhm.mhn.de FU Deutsche Gesellschaft fur Thorax-, Herz- und Gefasschirurgie; DSHF; DGTHG; Bayerische Forschungsstiftung [AZ-1012-12]; Deutsche Stiftung fur Herzforschung [F/37/11]; Deutsches Zentrum fur Herz Kreislauf Forschung [DZHK B 13-050A, DZHK B 14-013SE]; Deutsche Forschungsgemeinschaft - Sachmittelantrag [KR3770/7-1, KR3770/9-1] FX This work was supported by the Dr. Rusche Forschungspreis 2011 of the Deutsche Gesellschaft fur Thorax-, Herz- und Gefasschirurgie (http://www.dshf.de/dr_rusche_forschungsprojekt_projekte.php). Grant Support (Doppler et al.): The study was supported by Dr. Rusche Forschungsprojekt (2011) of the DSHF and DGTHG. Marcus-Andre Deutsch (MAD) is supported by Dr. Rusche Forschungsprojekt (2014) of the DSHF and DGTHG. Rudiger Lange (RL) is supported by Bayerische Forschungsstiftung (AZ-1012-12). Markus Krane (MK) is supported by Deutsche Stiftung fur Herzforschung (F/37/11), Deutsches Zentrum fur Herz Kreislauf Forschung (DZHK B 13-050A), Deutsche Forschungsgemeinschaft - Sachmittelantrag (KR3770/7-1), Deutsches Zentrum fur Herz Kreislauf Forschung (DZHK B 14-013SE), and Deutsche Forschungsgemeinschaft - Sachmittelantrag (KR3770/9-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 1 Z9 1 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 1 PY 2014 VL 9 IS 12 AR e113775 DI 10.1371/journal.pone.0113775 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7SK UT WOS:000347114900078 PM 25436607 ER PT J AU LaPlante, RA Douw, L Tang, W Stufflebeam, SM AF LaPlante, Roan A. Douw, Linda Tang, Wei Stufflebeam, Steven M. TI The Connectome Visualization Utility: Software for Visualization of Human Brain Networks SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; SMALL-WORLD NETWORKS; GRAPH-THEORETICAL ANALYSIS; FUNCTIONAL CONNECTIVITY; ELECTROPHYSIOLOGICAL DATA; ANATOMICAL NETWORKS; COMMUNITY STRUCTURE; DIFFUSION MRI; EEG DATA; MEG AB In analysis of the human connectome, the connectivity of the human brain is collected from multiple imaging modalities and analyzed using graph theoretical techniques. The dimensionality of human connectivity data is high, and making sense of the complex networks in connectomics requires sophisticated visualization and analysis software. The current availability of software packages to analyze the human connectome is limited. The Connectome Visualization Utility (CVU) is a new software package designed for the visualization and network analysis of human brain networks. CVU complements existing software packages by offering expanded interactive analysis and advanced visualization features, including the automated visualization of networks in three different complementary styles and features the special visualization of scalar graph theoretical properties and modular structure. By decoupling the process of network creation from network visualization and analysis, we ensure that CVU can visualize networks from any imaging modality. CVU offers a graphical user interface, interactive scripting, and represents data uses transparent neuroimaging and matrix-based file types rather than opaque application-specific file formats. C1 [LaPlante, Roan A.; Douw, Linda; Tang, Wei; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Douw, Linda] Vrije Univ Amsterdam Med Ctr, Dept Anat & Clin Neurosci, Amsterdam, Netherlands. [Stufflebeam, Steven M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Stufflebeam, Steven M.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP LaPlante, RA (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM rlaplant@nmr.mgh.harvard.edu FU National Institute of Health [R01-NS069696, U01-MH093765, P41-RR14075]; Defense Advanced Research Projects Agency FX This work was supported by National Institute of Health (http://www.nih.gov/) grants R01-NS069696, U01-MH093765, and P41-RR14075 provided to SMS, and by the Defense Advanced Research Projects Agency (http://www.darpa.mil/) provided to SMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 88 TC 4 Z9 4 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 1 PY 2014 VL 9 IS 12 AR e113838 DI 10.1371/journal.pone.0113838 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7SK UT WOS:000347114900084 PM 25437873 ER PT J AU Campbell, JH Ratai, EM Autissier, P Nolan, DJ Tse, S Miller, AD Gonzalez, RG Salemi, M Burdo, TH Williams, KC AF Campbell, Jennifer H. Ratai, Eva-Maria Autissier, Patrick Nolan, David J. Tse, Samantha Miller, Andrew D. Gonzalez, R. Gilberto Salemi, Marco Burdo, Tricia H. Williams, Kenneth C. TI Anti-alpha 4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection SO PLOS PATHOGENS LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CENTRAL-NERVOUS-SYSTEM; ACUTE SIV INFECTION; ACUTE HIV-INFECTION; MULTIPLE-SCLEROSIS; T-CELLS; MICROBIAL TRANSLOCATION; ANTIRETROVIRAL THERAPY; CD8(+) LYMPHOCYTES; LYMPHOID-TISSUE AB Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-alpha 4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28(+), RNA(+)) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity. C1 [Campbell, Jennifer H.; Autissier, Patrick; Tse, Samantha; Burdo, Tricia H.; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Ratai, Eva-Maria; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ratai, Eva-Maria] Massachusetts Gen Hosp, Dept Neurosci, Boston, MA 02114 USA. [Nolan, David J.; Salemi, Marco] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Miller, Andrew D.] Cornell Univ, Coll Vet Med, Sect Anat Pathol, Dept Biomed Sci, Ithaca, NY 14853 USA. RP Williams, KC (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. EM kenneth.williams.3@bc.edu FU NIH [R01 NS040237, R01 NS082116] FX This work was supported by NIH grants R01 NS040237 (KWC) and R01 NS082116 (THB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 10 Z9 10 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2014 VL 10 IS 12 AR e1004533 DI 10.1371/journal.ppat.1004533 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400021 PM 25502752 ER PT J AU Deng, LQ Bensing, BA Thamadilok, S Yu, H Lau, K Chen, X Ruhl, S Sullam, PM Varki, A AF Deng, Lingquan Bensing, Barbara A. Thamadilok, Supaporn Yu, Hai Lau, Kam Chen, Xi Ruhl, Stefan Sullam, Paul M. Varki, Ajit TI Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood SO PLOS PATHOGENS LA English DT Article ID VIRIDANS GROUP STREPTOCOCCI; SUBMANDIBULAR-SUBLINGUAL SALIVA; SURFACE GLYCOPROTEINS GSPB; SIALIC-ACID DIVERSITY; INFECTIVE ENDOCARDITIS; STAPHYLOCOCCAL ENDOCARDITIS; CARDIOVASCULAR-DISEASE; ANTIMICROBIAL THERAPY; CONTAINING RECEPTORS; HEART-ASSOCIATION AB Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis. C1 [Deng, Lingquan; Varki, Ajit] Univ Calif San Diego, Dept Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. [Deng, Lingquan; Varki, Ajit] Univ Calif San Diego, Dept Cellular & Mol Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. [Bensing, Barbara A.; Sullam, Paul M.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Bensing, Barbara A.; Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Thamadilok, Supaporn; Ruhl, Stefan] SUNY Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14260 USA. [Yu, Hai; Lau, Kam; Chen, Xi] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. RP Varki, A (reprint author), Univ Calif San Diego, Dept Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. EM a1varki@ucsd.edu OI Ruhl, Stefan/0000-0003-3888-4908 FU G. Harold and Leila Y. Mathers foundation; NIH [P01HL107150, R01-AI41513, R01-AI106987, R01HD065122]; NIH/NIDCR [DE019807]; Department of Veterans Affairs; Northern California Institute for Research and Education, VA Merit Review Award FX This work was supported by grants from the G. Harold and Leila Y. Mathers foundation and NIH P01HL107150 (to AV), R01-AI41513 and R01-AI106987 (to PMS), NIH/NIDCR DE019807 (to SR), NIH R01HD065122 (to XC), and in part by the Department of Veterans Affairs and the Northern California Institute for Research and Education, in particular a VA Merit Review Award to PMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 11 Z9 11 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2014 VL 10 IS 12 AR e1004540 DI 10.1371/journal.ppat.1004540 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400027 PM 25474103 ER PT J AU Sowd, GA Mody, D Eggold, J Cortez, D Friedman, KL Fanning, E AF Sowd, Gregory A. Mody, Dviti Eggold, Joshua Cortez, David Friedman, Katherine L. Fanning, Ellen TI SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products SO PLOS PATHOGENS LA English DT Article ID DOUBLE-STRAND-BREAK; DEPENDENT PROTEIN-KINASE; TELANGIECTASIA-MUTATED ATM; REPAIR PATHWAY CHOICE; HOMOLOGY-DIRECTED REPAIR; COMMON FRAGILE SITES; S-PHASE CHECKPOINT; LARGE T-ANTIGEN; ATAXIA-TELANGIECTASIA; CELL-CYCLE AB Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PKcs kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PKcs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication. C1 [Sowd, Gregory A.; Mody, Dviti; Eggold, Joshua; Friedman, Katherine L.; Fanning, Ellen] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. [Cortez, David] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. RP Sowd, GA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM gregorya_sowd@dfci.harvard.edu; katherine.friedman@vanderbilt.edu FU National Institutes of Health [GM52948, T32 AI089554, P30 CA068485]; Vanderbilt University; Vanderbilt Beckman Scholar Program FX This work was supported by National Institutes of Health (http://www.nih.gov/) grants (GM52948 to EF, T32 AI089554 to JE Crowe, P30 CA068485 to the Vanderbilt-Ingram Cancer Center), Vanderbilt University (http://www.vanderbilt.edu/), and the Vanderbilt Beckman Scholar Program (http://www.vanderbilt.edu/chemistry/beckman/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 9 Z9 9 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2014 VL 10 IS 12 AR e1004536 DI 10.1371/journal.ppat.1004536 PG 20 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400024 PM 25474690 ER PT J AU Yang, JA Yeom, J Hwang, BW Hoffman, AS Hahn, SK AF Yang, Jeong-A. Yeom, Junseok Hwang, Byung Woo Hoffman, Allan S. Hahn, Sei Kwang TI In situ-forming injectable hydrogels for regenerative medicine SO PROGRESS IN POLYMER SCIENCE LA English DT Editorial Material DE Artificial extracellular matrix; Cell therapy; Injectable hydrogel; Regenerative medicine; Tissue regeneration ID MESENCHYMAL STEM-CELLS; CHITOSAN-BASED HYDROGELS; BIOMEDICAL APPLICATIONS; CLICK CHEMISTRY; HYALURONIC-ACID; DRUG-DELIVERY; SUPRAMOLECULAR HYDROGELS; BIODEGRADABLE HYDROGELS; INCLUSION COMPLEXES; CEREBRAL ORGANOIDS AB Regenerative medicine involves interdisciplinary biomimetic approaches for cell therapy and tissue regeneration, employing the triad of cells, signals, and/or scaffolds. Remarkably, the field of therapeutic cells has evolved from the use of embryonic and adult stem cells to the use of induced pluripotent stem cells. For application of these cells in regenerative medicine, cell fate needs to be carefully controlled via external signals, such as the physical properties of an artificial extracellular matrix (ECM) and biologically active molecules in the form of small molecules, peptides, and proteins. It is therefore crucial to develop biomimetic scaffolds, reflecting the nanoenvironment of three-dimensional (3D) ECM in the body. Here, we describe in situ-forming injectable hydrogel systems, prepared using a variety of chemical crosslinkers and/or physical interactions, for application in regenerative medicine. Selective and fast chemical reactions under physiological conditions are prerequisites for in situ formation of injectable hydrogels. These hydrogels are attractive for regenerative medicine because of their ease of administration, facile encapsulation of cells and biomolecules without severe toxic effects, minimally invasive treatment, and possibly enhanced patient compliance. Recently, the Michael addition reaction between thiol and vinyl groups, the click reaction between bis(yne) molecules and multiarm azides, and the Schiff base reaction have been investigated for generation of injectable hydrogels, due to the high selectivity and biocompatibility of these reactions. Noncovalent physical interactions have also been proposed as crosslinking mechanisms for in situ forming injectable hydrogels. Hydrophobic interactions, ionic interactions, stereocomplex formation, complementary pair formation, and host-guest interactions drive the formation of 3D polymeric networks. In particular, supramolecular hydrogels have been developed using the host-guest chemistry of cyclodextrin (CD) and cucurbituril (CB), which allows highly selective, simple, and biocompatible crosslinking. Molecular recognition and complex formation of supramolecules, without the need for additional additives, have been successfully applied to the 3D network formation of polymer chains. Finally, we revieliv the current state of the art of injectable hydrogel systems for application in regenerative medicine, including cell therapy and tissue regeneration. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Yang, Jeong-A.; Yeom, Junseok; Hwang, Byung Woo; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Hoffman, Allan S.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Hahn, Sei Kwang] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Hahn, Sei Kwang] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, San 31 Hyoja Dong, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr NR 128 TC 70 Z9 70 U1 40 U2 254 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6700 J9 PROG POLYM SCI JI Prog. Polym. Sci. PD DEC PY 2014 VL 39 IS 12 BP 1973 EP 1986 DI 10.1016/j.progpolymsci.2014.07.006 PG 14 WC Polymer Science SC Polymer Science GA AX8AY UT WOS:000347134000001 ER PT J AU Keane, TM Rubin, A Lachowicz, M Brief, D Enggasser, JL Roy, M Hermos, J Helmuth, E Rosenbloom, D AF Keane, Terence M. Rubin, Amy Lachowicz, Mark Brief, Deborah Enggasser, Justin L. Roy, Monica Hermos, John Helmuth, Eric Rosenbloom, David TI Temporal Stability of DSM-5 Posttraumatic Stress Disorder Criteria in a Problem-Drinking Sample SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE PTSD; CFA; DSM-5; problem drinkers; longitudinal invariance ID CONFIRMATORY FACTOR-ANALYSIS; ADMINISTERED PTSD SCALE; SUBSTANCE USE DISORDERS; WORLD-TRADE-CENTER; VA HEALTH-CARE; MEASUREMENT INVARIANCE; IDENTIFICATION TEST; SYMPTOMS; VETERANS; AUDIT AB The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reformulated posttraumatic stress disorder (PTSD) based partially on research showing there were 4 main factors that underlie the symptoms of the disorder. The primary aim of this study was to examine the temporal stability of the DSM-5 factors as measured by the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5; Weathers et al., 2010). Confirmatory factor analyses were conducted to examine the structure of DSM-5 PTSD, and temporal stability over 3 time points was examined to determine if the measure reflects a consistent construct over time. Our sample was 507 combat-exposed veterans of Iraq and Afghanistan who enrolled in an online intervention for problem drinking and combat-related stress (Brief et al., 2013). We administered the PCL-5 at baseline, 8-week postintervention, and 3-month follow-up assessments. The DSM-5 model provided an adequate fit to the data at baseline. Tests of equality of form and equality of factor loadings demonstrated stability of the factor structure over time, indicating temporal stability. This study confirmed the results of previous research supporting the DSM-5 model of PTSD symptoms (Elhai et al., 2012; Miller et al., 2013). This is the 1st study to demonstrate the temporal stability of the PCL-5, indicating its use in longitudinal studies measures the same construct over time. C1 [Keane, Terence M.; Rubin, Amy; Lachowicz, Mark; Brief, Deborah; Enggasser, Justin L.; Roy, Monica; Hermos, John] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Rubin, Amy; Hermos, John] BUSM, Dept Med, Boston, MA 02118 USA. [Lachowicz, Mark; Brief, Deborah; Enggasser, Justin L.; Roy, Monica] BUSM, Dept Psychiat, Boston, MA USA. [Helmuth, Eric; Rosenbloom, David] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Keane, TM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 151, Boston, MA 02130 USA. EM Terry.Keane@va.gov FU NIAAA NIH HHS [RC1 AA019248, RC1AA019248] NR 53 TC 9 Z9 9 U1 3 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2014 VL 26 IS 4 BP 1138 EP 1145 DI 10.1037/a0037133 PG 8 WC Psychology, Clinical SC Psychology GA AX1HK UT WOS:000346698200008 PM 24932642 ER PT J AU LaMotte, AD Taft, CT Reardon, AF Miller, MW AF LaMotte, Adam D. Taft, Casey T. Reardon, Annemarie F. Miller, Mark W. TI Agreement Between Veteran and Partner Reports of Intimate Partner Aggression SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE intimate partner aggression; concordance; veteran; PTSD; relationship ID POSTTRAUMATIC-STRESS-DISORDER; CONFLICT-TACTICS-SCALES; RETURNING VETERANS; VIOLENCE; RELIABILITY; CONCORDANCE; KAPPA AB We examined intimate partner aggression (IPA) reporting concordance between veterans and their partners and investigated relationship satisfaction, posttraumatic stress disorder (PTSD) symptoms, and relationship attributions as correlates of IPA reporting discrepancies. The sample consisted of 239 veterans of different service eras and their intimate partners. Veterans and partners reported their physical and psychological IPA perpetration and victimization over the past 6 months. Methodological improvements over prior concordance studies included the use of clinician-assessed PTSD symptoms and the assessment of relationship attributions via observational coding of couples' conflict interactions. Results suggested low to moderate levels of agreement between veterans and partners and indicated that relationship satisfaction was associated with reporting less IPA than one's partner reported, replicating prior concordance findings. Previous concordance findings with self-reported PTSD symptoms were also reproduced in the current study using clinician-assessed PTSD symptoms. Veterans' PTSD symptoms were associated with reporting less IPA than their partners reported and partners' PTSD symptoms were associated with reporting more IPA than the veterans reported. Additionally, we found an association between relationship attributions and reporting discrepancies. For both dyad members, making more positive and less negative relationship attributions was associated with reporting less IPA than one's partner reported. Findings underscore the difficulty of obtaining objective self-reports of adverse behavior and highlight factors that may influence such reports. Clinically, this information could be used to better identify cases in which obtaining collateral reports of IPA are particularly warranted. C1 [LaMotte, Adam D.; Taft, Casey T.; Reardon, Annemarie F.; Miller, Mark W.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Taft, Casey T.; Reardon, Annemarie F.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU NIMH NIH HHS [R01 MH079806] NR 25 TC 1 Z9 1 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2014 VL 26 IS 4 BP 1369 EP 1374 DI 10.1037/pas0000018 PG 6 WC Psychology, Clinical SC Psychology GA AX1HK UT WOS:000346698200029 PM 25265413 ER PT J AU Allen, JD Caspi, C Yang, M Leyva, B Stoddard, AM Tamers, S Tucker-Seeley, RD Sorensen, GC AF Allen, Jennifer Dacey Caspi, Caitlin Yang, May Leyva, Bryan Stoddard, Anne M. Tamers, Sara Tucker-Seeley, Reginald D. Sorensen, Glorian C. TI Pathways between acculturation and health behaviors among residents of low-income housing: The mediating role of social and contextual factors SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE United States; Acculturation; Health behavior; Immigrant; Public housing; Social context ID FOOD FREQUENCY QUESTIONNAIRE; SELF-REPORTED SMOKING; UNITED-STATES; PHYSICAL-ACTIVITY; HISPANIC IMMIGRANTS; US HISPANICS; LIFE-COURSE; VALIDITY; DISCRIMINATION; MODEL AB Acculturation may influence health behaviors, yet mechanisms underlying its effect are not well understood. In this study, we describe relationships between acculturation and health behaviors among low-income housing residents, and examine whether these relationships are mediated by social and contextual factors. Residents of 20 low-income housing sites in the Boston metropolitan area completed surveys that assessed acculturative characteristics, social/contextual factors, and health behaviors. A composite acculturation scale was developed using latent class analysis, resulting in four distinct acculturative groups. Path analysis was used to examine interrelationships between acculturation, health behaviors, and social/contextual factors, specifically self-reported social ties, social support, stress, material hardship, and discrimination. Of the 828 respondents, 69% were born outside of the U.S. Less acculturated groups exhibited healthier dietary practices and were less likely to smoke than more acculturated groups. Acculturation had a direct effect on diet and smoking, but not physical activity. Acculturation also showed an indirect effect on diet through its relationship with material hardship. Our finding that material hardship mediated the relationship between acculturation and diet suggests the need to explicate the significant role of financial resources in interventions seeking to promote healthy diets among low-income immigrant groups. Future research should examine these social and contextual mediators using larger, population-based samples, preferably with longitudinal data. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Allen, Jennifer Dacey; Tamers, Sara; Tucker-Seeley, Reginald D.; Sorensen, Glorian C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Caspi, Caitlin] Univ Minnesota, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA. [Yang, May; Stoddard, Anne M.] New England Res Inst, Watertown, MA USA. [Leyva, Bryan] NCI, NIH, Bethesda, MD 20892 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Phyllis Cantor Ctr Nursing Res & Patient Care Ser, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer.allen@tufts.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [R01 CA111310-01A1, K05 CA108663-05]; Centers for Disease Control and Prevention the NIH/NCI Harvard Education Program in Cancer Prevention and Control [U48DP001946, R25 CA057713]; NIH/NCI Cancer Related Health Disparities Education and Career Development Program [R25 CA163184]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663- 05]; NCI K01 career development award [CA169041-01] FX This research was supported by the National Cancer Institute (grant numbers R01 CA111310-01A1; K05 CA108663-05), Cooperative Agreement Number U48DP001946 from the Centers for Disease Control and Prevention the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713), the NIH/NCI Cancer Related Health Disparities Education and Career Development Program (R25 CA163184), the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663- 05), and an NCI K01 career development award (Grant# CA169041-01).The findings and conclusions in this journal article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors would like to thank the 20 low-income housing sites that participated in this research, and the assistance from the Cambridge, Somerville and Chelsea Public Housing Authorities. The authors also acknowledge the administrative and field staff at the Harvard School of Public Health and Dana-Farber Cancer Institute, and the study participants for their contributions to this project. They also thank Gary Adamkiewicz, Marty Alvarez-Reeves, Amy Harley, Ruth Lederman, Samuel Lipson, Carol Lowenstein, Hannah L Mills, Laura Tom, Brianna Wadler, and Lorraine Wallace for their contributions to the overall study design and implementation. NR 69 TC 10 Z9 10 U1 8 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2014 VL 123 BP 26 EP 36 DI 10.1016/j.socscimed.2014.10.034 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AX6GT UT WOS:000347021800004 PM 25462602 ER PT J AU Gardner, AJ Iverson, GL Williams, WH Baker, S Stanwell, P AF Gardner, Andrew J. Iverson, Grant L. Williams, W. Huw Baker, Stephanie Stanwell, Peter TI A Systematic Review and Meta-Analysis of Concussion in Rugby Union SO SPORTS MEDICINE LA English DT Review ID CHRONIC TRAUMATIC ENCEPHALOPATHY; VISUAL SCREENING TOOL; WORLD-CUP; INJURY SURVEILLANCE; NEW-ZEALAND; PERFORMANCE PROJECT; SPORTS INJURIES; BRAIN-INJURY; FOLLOW-UP; PROTECTIVE HEADGEAR AB Background Rugby Union, a popular full-contact sport played throughout the world, has one of the highest rates of concussion of all full-contact sports. Objective The aim of the current review was to systematically evaluate the available evidence on concussion in Rugby Union and to conduct a meta-analysis of findings regarding the incidence of concussion. Methods Articles were retrieved via a number of online databases. The current review examined all articles published in English up to May 2014 pertaining to concussion in Rugby Union players. The key search terms included 'Rugby Union', 'rugby', 'union', and 'football', in combination with the injury terms 'athletic injuries', 'concussion', 'sports concussion', 'sports-related concussion', 'brain concussion', 'brain injury', 'brain injuries', 'mild traumatic brain injury', 'mTBI', 'traumatic brain injury', 'TBI', 'craniocerebral trauma', 'head injury', and 'brain damage'. Results The final search outcome following the eligibility screening process resulted in the inclusion of 96 articles for this review. The meta-analysis included a total of 37 studies. The results of the meta-analysis revealed an overall incidence of match-play concussion in men's rugby-15s of 4.73 per 1,000 player match hours. The incidence of concussion during training was 0.07 per 1,000 practice hours. The incidence of concussion in women's rugby-15s was 0.55 per 1,000 player match hours. In men's rugby-7s match-play, concussion incidence was 3.01 per 1,000 player match hours. The incidence of concussion varied considerably between levels of play, with elite level play recording a rate of 0.40 concussions per 1,000 player match hours, schoolboy level 0.62 concussions per 1,000 player match hours, and the community or sub-elite level recording a rate of 2.08 concussions per 1,000 player match hours. The incidence of concussion in men's rugby-15s as a function of playing position (forwards vs. backs) was 4.02 and 4.85 concussions per 1,000 player match hours, respectively. Conclusions Concussion is a common injury sustained and reported in match play and to a lesser extent during practice by Rugby Union players. Based on the available published data, there appears to be a variation in risk of concussion across level of play, with the sub-elite level having the greatest incidence of injury. Future research focused on studying the acute consequences and best management strategies in current players, and the potential longer term outcomes of concussion in retired players, is needed. A focus on the areas of prevention, injury identification, and medical management, and risk for long-term outcomes will be of benefit to current athletes. C1 [Gardner, Andrew J.; Stanwell, Peter] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Gardner, Andrew J.] Calvary Mater Hosp, Ctr Translat Neurosci & Mental Hlth, Waratah, NSW 2298, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Sport Concuss Clin, Boston, MA 02114 USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Williams, W. Huw] Univ Exeter, Sch Psychol, Exeter, Devon, England. [Baker, Stephanie] Cardiff Univ, Sch Psychol, Cardiff CF10 3AX, S Glam, Wales. [Stanwell, Peter] Univ Newcastle, Fac Hlth & Med, Sch Hlth Sci, Callaghan, NSW 2308, Australia. RP Gardner, AJ (reprint author), Calvary Mater Hosp, Ctr Translat Neurosci & Mental Hlth, Level 5,McAuley Bldg, Waratah, NSW 2298, Australia. EM andrew.gardner@neurogard.com.au; giverson@mgh.harvard.edu; w.h.williams@exeter.ac.uk; BakerS4@cardiff.ac.uk; peter.stanwell@newcastle.edu.au RI Gardner, Andrew/J-5162-2013; Stanwell, Peter/F-9136-2012; OI Stanwell, Peter/0000-0002-4780-0393; williams, huw/0000-0003-0670-2620 FU Brain Foundation, Australia; NSW Sporting Injuries Committee; Hunter Medical Research Institute (HMRI) FX The authors thank Debbie Booth from the University of Newcastle for her assistance with the initial database search and Sarah Hiles from the University of Newcastle for her assistance with methodology regarding meta-analysis. Funding was provided by the Brain Foundation, Australia; NSW Sporting Injuries Committee; and Hunter Medical Research Institute (HMRI) funded by Jennie Thomas. NR 135 TC 8 Z9 8 U1 8 U2 65 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0112-1642 EI 1179-2035 J9 SPORTS MED JI Sports Med. PD DEC PY 2014 VL 44 IS 12 BP 1717 EP 1731 DI 10.1007/s40279-014-0233-3 PG 15 WC Sport Sciences SC Sport Sciences GA AX4TY UT WOS:000346925300007 PM 25138311 ER PT J AU De Jesus, DF Kulkarni, RN AF De Jesus, Dario F. Kulkarni, Rohit N. TI Epigenetic modifiers of islet function and mass SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID BETA-CELL DYSFUNCTION; ENDOPLASMIC-RETICULUM STRESS; DNA DEMETHYLATION DYNAMICS; ALTERED GENE-EXPRESSION; IN-UTERO UNDERNUTRITION; DIABETES-MELLITUS; PANCREATIC-ISLETS; OXIDATIVE STRESS; INSULIN-RESISTANCE; HIGH GLUCOSE AB Type 2 diabetes (T2D) is associated with insulin resistance in target tissues including the beta-cell, leading to significant beta-cell loss and secretory dysfunction. T2D is also associated with aging, and the underlying mechanisms that increase susceptibility of an individual to develop the disease implicate epigenetics: interactions between susceptible loci and the environment. In this review, we discuss the effects of aging on beta-cell function and adaptation, besides the significance of mitochondria in islet bioenergetics and epigenome. We highlight three important modulators of the islet epigenome, namely: metabolites, hormones, and the nutritional state. Unraveling the signaling pathways that regulate the islet epigenome during aging will help to better understand the development of disease progression and to design novel therapies for diabetes prevention. C1 [De Jesus, Dario F.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [De Jesus, Dario F.] Univ Porto, Abdel Salazar Biomed Sci Inst, Grad Program Areas Basic & Appl Biol GABBA, P-5000 Oporto, Portugal. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU Portuguese Foundation for Science and Technology FCT [SFRH/BD/51699/2011]; NIH [R01 DK 67536] FX We thank Amelia M. Silva, Carmen Jeronimo, Ines S. Lima, and the Kulkarni lab members Anders Molven and Ivan Valdez for their helpful discussions and critical reading of the manuscript. We regret that several reports could not be cited due to space constraints. D.F.DJ. is supported by the Portuguese Foundation for Science and Technology FCT (SFRH/BD/51699/2011), and R.N.K. is supported by NIH R01 DK 67536. NR 111 TC 6 Z9 6 U1 1 U2 17 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2014 VL 25 IS 12 BP 628 EP 636 DI 10.1016/j.tem.2014.08.006 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX8DL UT WOS:000347140500003 PM 25246382 ER PT J AU Prentice, JC Conlin, PR Gellad, WF Edelman, D Lee, TA Pizer, SD AF Prentice, Julia C. Conlin, Paul R. Gellad, Walid F. Edelman, David Lee, Todd A. Pizer, Steven D. TI Capitalizing on Prescribing Pattern Variation to Compare Medications for Type 2 Diabetes SO VALUE IN HEALTH LA English DT Article DE comparative effectiveness research; instrumental variables; provider prescribing variation; type 2 diabetes ID ACUTE MYOCARDIAL-INFARCTION; AFFAIRS HEALTH-CARE; INSTRUMENTAL VARIABLES; ADMINISTRATIVE DATA; CLINICAL-TRIALS; GLUCOSE CONTROL; MELLITUS; RISK; ROSIGLITAZONE; MORTALITY AB Background: Clinical trials often compare hypoglycemic medications on the basis of glycemic control but do not examine long-term outcomes (e.g., mortality). This study demonstrates an alternative approach to lengthening clinical trials to assess these long-term outcomes. Objective: To use observational quasi-experimental methods using instrumental variables (lVs) to compare the effect of two hypoglycemic medications, sulfonylureas (SUs) and thiazolidinediones (TZDs), on long-term outcomes. Methods: This study used administrative data from the Veterans Health Administration and Medicare from 2000 to 2010. The study population included US veterans dually enrolled in Medicare who received a prescription for metformin and then initiated SUs or TZDs. Patients could either continue on or discontinue metformin after the initiation of the second agent. Treatment was defined as starting either a SD or a TZD. Local variations in SD prescribing rates were used as instruments in IV models to control for selection bias. Survival models predicted all cause mortality, ambulatory care sensitive condition hospitalizations, and stroke or heart attack (acute myocardial infarction). Results: Starting on SUs compared to TZDs significantly increased the likelihood of experiencing mortality and ACSC hospitalization. The estimated hazard ratio for the effect of starting on SUs compared to TZDs was 1.50 (95% confidence interval [CIJ 1.09-2.09) for all-cause mortality, 1.68 (95% Cl 1.31-2.15) for ambulatory care sensitive condition hospitalization, and 1.15 (95% CI 0.80-1.66) for acute myocardial infarction or stroke. Conclusions: Our findings suggest increased risk of major adverse events associated with SUs as a second-line agent Quasi-experimental IV methods may be an important alternative to lengthening clinical trials to assess long-term outcomes. C1 [Prentice, Julia C.; Conlin, Paul R.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Prentice, Julia C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Conlin, Paul R.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Gellad, Walid F.] VA Pittsburgh Med Ctr, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Pittsburgh, PA USA. [Edelman, David] Durham VA Med Ctr, Durham, NC USA. [Edelman, David] Duke Univ, Sch Med, Durham, NC USA. [Lee, Todd A.] Univ Illinois, Chicago, IL USA. [Pizer, Steven D.] Northeastern Univ, Boston, MA 02115 USA. RP Prentice, JC (reprint author), VA Boston Healthcare Syst, Hlth Care Financing & Econ, 150 South Huntington Ave 152H, Boston, MA 02130 USA. EM jprentic@bu.edu OI Edelman, David/0000-0001-7112-6151 FU Health Services Research and Development Service of the U.S. Department of Veterans Affairs [IIR 10-136]; Agency for Healthcare Research and Quality [R01 HS019708]; National Institute of Health [K24 DK63214] FX Health Services Research and Development Service of the U.S. Department of Veterans Affairs (grant no. IIR 10-136), Agency for Healthcare Research and Quality (grant no. R01 HS019708), and the National Institute of Health (grant no. K24 DK63214) supported this study. NR 56 TC 5 Z9 5 U1 1 U2 4 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 DEC PY 2014 VL 17 IS 8 BP 854 EP 862 DI 10.1016/j.jval.2014.08.2674 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AX4RC UT WOS:000346918100012 PM 25498781 ER PT J AU Safdar, B Nagurney, JT Anise, A DeVon, HA D'Onofrio, G Hess, EP Hollander, JE Legato, MJ McGregor, AJ Scott, J Tewelde, S Diercks, DB AF Safdar, Basmah Nagurney, John T. Anise, Ayodola DeVon, Holli A. D'Onofrio, Gail Hess, Erik P. Hollander, Judd E. Legato, Mariane J. McGregor, Alyson J. Scott, Jane Tewelde, Semhar Diercks, Deborah B. TI Gender-specific Research for Emergency Diagnosis and Management of Ischemic Heart Disease: Proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; SYNDROME EVALUATION WISE; QUANTITATIVE PRETEST PROBABILITY; ELEVATION MYOCARDIAL-INFARCTION; TAKO-TSUBO CARDIOMYOPATHY; ACUTE CHEST-PAIN; DEPARTMENT PATIENTS; ANGINA-PECTORIS; SEX-DIFFERENCES; TAKOTSUBO CARDIOMYOPATHY AB Coronary artery disease (CAD) is the most common cause of death for both men and women. However, over the years, emergency physicians, cardiologists, and other health care practitioners have observed varying outcomes in men and women with symptomatic CAD. Women in general are 10 to 15 years older than men when they develop CAD, but suffer worse postinfarction outcomes compared to age-matched men. This article was developed by the cardiovascular workgroup at the 2014 Academic Emergency Medicine (AEM) consensus conference to identify sex- and gender-specific gaps in the key themes and research questions related to emergency cardiac ischemia care. The workgroup had diverse stakeholder representation from emergency medicine, cardiology, critical care, nursing, emergency medical services, patients, and major policy-makers in government, academia, and patient care. We implemented the nominal group technique to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and Web-based surveys between June 2013 and May 2014. Through three rounds of nomination and refinement, followed by an in-person meeting on May 13, 2014, we achieved consensus on five priority themes and 30 research questions. The overarching themes were as follows: 1) the full spectrum of sex-specific risk as well as presentation of cardiac ischemia may not be captured by our standard definition of CAD and needs to incorporate other forms of ischemic heart disease (IHD); 2) diagnosis is further challenged by sex/gender differences in presentation and variable sensitivity of cardiac biomarkers, imaging, and risk scores; 3) sex-specific pathophysiology of cardiac ischemia extends beyond conventional obstructive CAD to include other causes such as microvascular dysfunction, takotsubo, and coronary artery dissection, better recognized as IHD; 4) treatment and prognosis are influenced by sex-specific variations in biology, as well as patient-provider communication; and 5) the changing definitions of pathophysiology call for looking beyond conventionally defined cardiovascular outcomes to patient-centered outcomes. These emergency care priorities should guide future clinical and basic science research and extramural funding in an area that greatly influences patient outcomes. C1 [Safdar, Basmah; D'Onofrio, Gail] Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hess, Erik P.] Mayo Clin, Dept Emergency Med, Rochester, MN USA. Thomas Jefferson Univ, Dept Emergency Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [McGregor, Alyson J.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Tewelde, Semhar] Univ Maryland, Dept Emergency Med, College Pk, MD 20742 USA. [Diercks, Deborah B.] Univ Calif Davis, Med Ctr, Dept Emergency Med, Davis, CA 95616 USA. [Anise, Ayodola] Patient Ctr Outcomes Res Inst, Washington, DC USA. [DeVon, Holli A.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Legato, Mariane J.] Columbia Univ, Cardiol Sect, Dept Med, New York, NY USA. [Scott, Jane] NHLBI, Washington, DC USA. RP Safdar, B (reprint author), Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. EM basmah.safdar@yale.edu OI Hollander, Judd/0000-0002-1318-2785; D'Onofrio, Gail/0000-0002-3833-1871 FU National Institute of Neurological Disorders and Stroke [1R13NS087861-01]; Office of Research on Women's Health at the National Institutes of Health FX The consensus conference was supported by grant 1R13NS087861-01 from the National Institute of Neurological Disorders and Stroke and the Office of Research on Women's Health at the National Institutes of Health. Additional funding was provided by several organizational, institutional, and individual donors. Non-CME events were supported by Janssen Pharmaceuticals and Besins Critical Care/BH Pharma. See the executive summary elsewhere in this issue for full funding information. NR 76 TC 4 Z9 5 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2014 VL 21 IS 12 BP 1350 EP 1360 DI 10.1111/acem.12527 PG 11 WC Emergency Medicine SC Emergency Medicine GA AW9KS UT WOS:000346576700009 PM 25413468 ER PT J AU Musey, PI Linnstaedt, SD Platts-Mills, TF Miner, JR Bortsov, AV Safdar, B Bijur, P Rosenau, A Tsze, DS Chang, AK Dorai, S Engel, KG Feldman, JA Fusaro, AM Lee, DC Rosenberg, M Keefe, FJ Peak, DA Nam, CS Patel, RG Fillingim, RB McLean, SA AF Musey, Paul I., Jr. Linnstaedt, Sarah D. Platts-Mills, Timothy F. Miner, James R. Bortsov, Andrey V. Safdar, Basmah Bijur, Polly Rosenau, Alex Tsze, Daniel S. Chang, Andrew K. Dorai, Suprina Engel, Kirsten G. Feldman, James A. Fusaro, Angela M. Lee, David C. Rosenberg, Mark Keefe, Francis J. Peak, David A. Nam, Catherine S. Patel, Roma G. Fillingim, Roger B. McLean, Samuel A. TI Gender Differences in Acute and Chronic Pain in the Emergency Department: Results of the 2014 Academic Emergency Medicine Consensus Conference Pain Section SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID STRESS-INDUCED ANALGESIA; LOW-BACK-PAIN; CAPSAICIN-INDUCED HYPERALGESIA; MOTOR-VEHICLE COLLISION; VISUAL ANALOG PAIN; SEX-DIFFERENCES; PSYCHOLOGICAL DISTRESS; MENSTRUAL-CYCLE; OLDER-ADULTS; FUNCTIONAL OUTCOMES AB Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings. C1 [Musey, Paul I., Jr.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Linnstaedt, Sarah D.; McLean, Samuel A.] Univ N Carolina, TRYUMPH Res Program, Chapel Hill, NC USA. [Linnstaedt, Sarah D.; Bortsov, Andrey V.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. [Platts-Mills, Timothy F.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Miner, James R.] Univ Minnesota, Dept Emergency Med, Minneapolis, MN USA. [Safdar, Basmah] Yale Univ, Dept Emergency Med, New Haven, CT USA. [Bijur, Polly] Albert Einstein Coll Med, Dept Emergency Med, Bronx, NY 10467 USA. [Rosenau, Alex; Dorai, Suprina] Lehigh Valley Hlth Network, Dept Emergency Med, Allentown, PA USA. [Rosenau, Alex] Univ S Florida, Morsani Sch Med, Tampa, FL USA. Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. [Chang, Andrew K.] Montefiore Med Ctr, Dept Emergency Med, Bronx, NY 10467 USA. [Engel, Kirsten G.] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Feldman, James A.; Nam, Catherine S.] Boston Univ, Sch Med, Dept Emergency Med, Boston Med Ctr, Boston, MA 02118 USA. [Fusaro, Angela M.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Rosenberg, Mark] St Josephs Reg Med Ctr, Dept Emergency Med, Paterson, NJ USA. [Rosenberg, Mark] New York Med Coll, Valhalla, NY 10595 USA. [Keefe, Francis J.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Patel, Roma G.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Fillingim, Roger B.] Univ Florida, Coll Dent, Gainesville, FL USA. RP Musey, PI (reprint author), Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. EM Pmusey@IU.edu OI Tsze, Daniel/0000-0002-7567-8743; McLean, Samuel/0000-0001-9482-3582 FU National Institute of Neurological Disorders and Stroke [1R13NS087861-01]; Office of Research on Women's Health at the National Institutes of Health FX The consensus conference was supported by grant 1R13NS087861-01 from the National Institute of Neurological Disorders and Stroke and the Office of Research on Women's Health at the National Institutes of Health. Several organizational, institutional, and individual donors provided additional funding. Janssen Pharmaceuticals and Besins Critical Care/BH Pharma supported non-CME events. See the executive summary elsewhere in this issue for full funding information. NR 93 TC 7 Z9 7 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2014 VL 21 IS 12 BP 1421 EP 1430 DI 10.1111/acem.12529 PG 10 WC Emergency Medicine SC Emergency Medicine GA AW9KS UT WOS:000346576700017 PM 25422152 ER PT J AU Bernstein, J Bernstein, E Belanoff, C Cabral, HJ Babakhanlou-Chase, H Derrington, TM Diop, H Douriez, C Evans, SR Jacobs, H Kotelchuck, M AF Bernstein, Judith Bernstein, Edward Belanoff, Candice Cabral, Howard J. Babakhanlou-Chase, Hermik Derrington, Taletha M. Diop, Hafsatou Douriez, Carole Evans, Stephen R. Jacobs, Hilary Kotelchuck, Milton TI The Association of Injury With Substance Use Disorder Among Women of Reproductive Age: An Opportunity to Address a Major Contributor to Recurrent Preventable Emergency Department Visits? SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID UNITED-STATES; YOUNG-ADULTS; DRUG-USE; SCREENING-TEST; RISK-FACTORS; ALCOHOL-USE; ABUSE; GENDER; PREVALENCE; VIOLENCE AB ObjectivesSubstance use disorder (SUD) among women of reproductive age is a complex public health problem affecting a diverse spectrum of women and their families, with potential consequences across generations. The goals of this study were 1) to describe and compare the prevalence of patterns of injury requiring emergency department (ED) visits among SUD-positive and SUD-negative women and 2) among SUD-positive women, to investigate the association of specific categories of injury with type of substance used. MethodsThis study was a secondary analysis of a large, multisource health care utilization data set developed to analyze SUD prevalence, and health and substance abuse treatment outcomes, for women of reproductive age in Massachusetts, 2002 through 2008. Sources for this linked data set included diagnostic codes for ED, inpatient, and outpatient stay discharges; SUD facility treatment records; and vital records for women and for their neonates. ResultsInjury data (ICD-9-CM E-codes) were available for 127,227 SUD-positive women. Almost two-thirds of SUD-positive women had any type of injury, compared to 44.8% of SUD-negative women. The mean (SD) number of events also differed (2.274.1 for SUD-positive women vs. 0.731.3 for SUD-negative women, p<0.0001). For four specific injury types, the proportion injured was almost double for SUD-positive women (49.3% vs 23.4%), and the mean (SD) number of events was more than double (0.720.9 vs. 0.26 +/- 0.5, p<0.0001). The numbers and proportions of motor vehicle incidents and falls were significantly higher in SUD-positive women (22.5% vs. 12.5% and 26.6% vs. 11.0%, respectively), but the greatest differences were in self-inflicted injury (11.5% vs. 0.8%; mean +/- SD events= 0.19 +/- 0.9 vs. 0.009 +/- 0.2, p<0.0001) and purposefully inflicted injury (11.5% vs 1.9%, mean +/- SD events= 0.18 +/- 0.1 vs. 0.02 +/- 0.2, p<0.0001). In each of the injury categories that we examined, injury rates among SUD-positive women were lowest for alcohol disorders only and highest for alcohol and drug disorders combined. Among 33,600 women identified as using opioids, 2,132 (6.3%) presented to the ED with overdose. Multiple overdose visits were common (mean +/- SD= 3.67 +/- 6.70 visits). After adjustment for sociodemographic characteristics, psychiatric history, and complex/chronic illness, SUD remained a significant risk factor for all types of injury, but for the suicide/self-inflicted injury category, psychiatric history was by far the stronger predictor. ConclusionsThe presence of SUD increases the likelihood that women in the 15- to 49-year age group will present to the ED with injury. Conversely, women with injury may be more likely to be involved in alcohol abuse or other substance use. The high rates of injury that we identified among women with SUD suggest the utility of including a brief, validated screen for substance use as part of an ED injury treatment protocol and referring injured women for assessment and/or treatment when scores indicate the likelihood of SUD. C1 [Bernstein, Judith; Belanoff, Candice; Cabral, Howard J.; Evans, Stephen R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Douriez, Carole] Boston Med Ctr, Boston, MA USA. [Derrington, Taletha M.] SRI Int, Educ Div, Ctr Educ & Human Serv, Menlo Pk, CA 94025 USA. [Kotelchuck, Milton] MassGen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Bernstein, Edward; Jacobs, Hilary] Massachusetts Dept Publ Hlth, Bur Subst Abuse Serv, Boston, MA USA. [Diop, Hafsatou] Massachusetts Dept Publ Hlth, Bur Family Hlth & Nutr, Off Data Translat, Boston, MA USA. RP Bernstein, J (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. EM jbernste@bu.edu FU NIH NIAAA [R21AA018395]; NIH NIDA [R21DA027181]; Massachusetts Department of Public Health; Department of Emergency Medicine, Boston University School of Medicine FX Supported in part by NIH NIAAA R21AA018395, NIH NIDA R21DA027181 and supplemental funding from the Massachusetts Department of Public Health and the Department of Emergency Medicine, Boston University School of Medicine. NR 38 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2014 VL 21 IS 12 BP 1459 EP 1468 DI 10.1111/acem.12548 PG 10 WC Emergency Medicine SC Emergency Medicine GA AW9KS UT WOS:000346576700022 PM 25491709 ER PT J AU Gurrera, RJ Dismukes, R Edwards, M Feroze, U Nakshabandi, F Tanaka, G Tang, M AF Gurrera, Ronald J. Dismukes, Rodney Edwards, Matthew Feroze, Usama Nakshabandi, Firas Tanaka, Gen Tang, Michael TI Preparing Residents in Training to Become Health-Care Leaders: A Pilot Project SO ACADEMIC PSYCHIATRY LA English DT Editorial Material DE Residents; Professional development; Teaching methods AB Objective The aim of this study is to describe a successful and exportable training module that addresses Next Accreditation System (NAS) behavioral milestones for leadership competencies. Methods A novel leadership training module, which required the creation of original business plans by teams of residents, was incorporated into a psychiatry PGY-2 training curriculum. Results In the creation and presentation of their business plans, the residents demonstrated competencies in the NAS functional domains of interpersonal and communication skills, professionalism, practice-based learning and improvement, and systems-based practice. Residents who responded with feedback after completing the course were very positive about their experience. Conclusions The leadership training module described here allowed residents to acquire and demonstrate many of the competencies specified in leadership-oriented NAS milestones. The module did not require additional funding or a formal rotation or "track," is scalable to accommodate any number of residents and can be modified based on available local teaching resources. C1 [Gurrera, Ronald J.; Dismukes, Rodney; Edwards, Matthew; Feroze, Usama; Nakshabandi, Firas; Tanaka, Gen; Tang, Michael] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Gurrera, Ronald J.; Dismukes, Rodney; Edwards, Matthew; Feroze, Usama; Nakshabandi, Firas; Tanaka, Gen; Tang, Michael] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. RP Gurrera, RJ (reprint author), VA Boston Healthcare Syst, Brockton, MA 02301 USA. EM ronald.gurrera@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD DEC PY 2014 VL 38 IS 6 BP 701 EP 705 DI 10.1007/s40596-014-0162-3 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA AX2SI UT WOS:000346794100010 PM 25026945 ER PT J AU Gonzalez, DA Jenkins, SR AF Gonzalez, David Andres Jenkins, Sharon Rae TI Cross-Measure Equivalence and Communicability in the Assessment of Depression: A Focus on Factor-Based Scales SO ASSESSMENT LA English DT Article DE depression assessment; factors; BDI-II; CES-D; IDAS; IDS ID INVENTORY-II; ANXIETY DISORDERS; DSM-V; BECK; SYMPTOMATOLOGY; SYMPTOMS; QUESTIONNAIRES; DIMENSIONALITY; VALIDITY; HAMILTON AB All measures of depression yield a global summary scale indicating the severity of depressive symptoms, implicitly conceptualized as a homogeneous construct. However, depression is a heterogeneous construct, with different presentations, subtypes, correlates, and responses to interventions. In response, the National Institute of Mental Health (NIMH) has suggested changes in the way depression is assessed, moving the focus to specific factors, such as cognitive, somatic, or affective symptoms. Still, there is little factor overlap between measures, and shared factors are weighted differently. To help fulfill NIMH's strategic plan, this study used canonical correlation analysis (CCA) to explore shared latent variables and redundancy across the measures. It also analyzed the psychometric properties of factor-based subscales in the Beck Depression Inventory-2nd edition (BDI-II), Center for Epidemiologic Studies Depression scale (CES-D), Inventory for Depression and Anxiety Symptoms (IDAS), and Inventory of Depressive Symptomatology (IDS). Using a diverse sample of 218 students who reported at least mild depressive symptoms, this study found that the IDAS was best aligned with NIMH's strategic plan; it has complete DSM-IV/DSM-5 symptom coverage and content-valid, psychometrically sound subscales. The BDI-II, CES-D, and IDS did not have consistent subscales, nor had incomplete or incongruent coverage of DSM criteria. Furthermore, CCA revealed low redundancy across measures (23% to 41% shared variance). These results suggest that different measures of depression do not measure the same construct. As a partial solution, empirical conversion tables were provided for researchers and clinicians to empirically compare total scores from different measures. C1 [Gonzalez, David Andres; Jenkins, Sharon Rae] Univ N Texas, Denton, TX 76203 USA. [Gonzalez, David Andres] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gonzalez, DA (reprint author), Univ N Texas, Dept Psychol, 1155 Union Circle 311280, Denton, TX 76203 USA. EM davidgonzalez@my.unt.edu NR 44 TC 1 Z9 1 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 EI 1552-3489 J9 ASSESSMENT JI Assessment PD DEC PY 2014 VL 21 IS 6 BP 731 EP 741 DI 10.1177/1073191114524018 PG 11 WC Psychology, Clinical SC Psychology GA AX0LS UT WOS:000346644500010 PM 24586091 ER PT J AU Zhao, F Li, JY Zhou, N Sakai, J Gao, Y Shi, JF Goldman, B Browdy, HM Luo, HBR Xu, B AF Zhao, Fan Li, Jingyu Zhou, Ning Sakai, Jiro Gao, Yuan Shi, Junfeng Goldman, Bronia Browdy, Hayley M. Luo, Hongbo R. Xu, Bing TI De Novo Chemoattractants Form Supramolecular Hydrogels for Immunomodulating Neutrophils In Vivo SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PEPTIDE RECEPTORS; IMMUNE ADJUVANT; INFLAMMATION; CHEMOTAXIS; SPECIFICITY; RECRUITMENT; LEUKOCYTES; EXPRESSION; AGONISTS; BINDING AB Most immunomodulatory materials (e.g., vaccine adjuvants such as alum) modulate adaptive immunity, and yet little effort has focused on developing materials to regulate innate immunity, which get mentioned only when inflammation affects the biocompatibility of biomaterials. Traditionally considered as short-lived effector cells from innate immunity primarily for the clearance of invading microorganisms without specificity, neutrophils exhibit a key role in launching and shaping the immune response. Here we show that the incorporation of unnatural amino acids into a well-known chemoattractant-N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-offers a facile approach to create a de novo, multifunctional chemoattractant that self-assembles to form supramolecular nanofibrils and hydrogels. This de novo chemoattractant not only exhibits preserved cross-species chemoattractant activity to human and murine neutrophils, but also effectively resists proteolysis. Thus, its hydrogel, in vivo, releases the chemoattractant and attracts neutrophils to the desired location in a sustainable manner. As a novel and general approach to generate a new class of biomaterials for modulating innate immunity, this work offers a prolonged acute inflammation model for developing various new applications. C1 [Zhao, Fan; Zhou, Ning; Gao, Yuan; Shi, Junfeng; Goldman, Bronia; Browdy, Hayley M.; Xu, Bing] Brandeis Univ, Dept Chem, Waltham, MA 02454 USA. [Li, Jingyu; Sakai, Jiro; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Li, Jingyu; Sakai, Jiro; Luo, Hongbo R.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Li, Jingyu; Sakai, Jiro; Luo, Hongbo R.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Li, Jingyu] Sichuan Univ, West China Sch Preclin & Forens Med, Dept Pathophysiol, Chengdu 610041, Peoples R China. RP Xu, B (reprint author), Brandeis Univ, Dept Chem, 415 South St MS015, Waltham, MA 02454 USA. EM bxu@brandeis.edu RI XU, Bing/A-7828-2008; Zhao, Fan/A-3686-2012; OI XU, Bing/0000-0002-4639-387X; Zhao, Fan/0000-0002-6103-5608; Sakai, Jiro/0000-0002-2526-2766 FU NCI NIH HHS [CA142746, R01 CA142746]; NHLBI NIH HHS [HL092020, HL085100, R01 HL085100, R01 HL092020]; NIAID NIH HHS [AI076471, R01 AI076471]; NIGMS NIH HHS [GM076084, R01 GM076084] NR 44 TC 2 Z9 2 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD DEC PY 2014 VL 25 IS 12 BP 2116 EP 2122 DI 10.1021/bc5004923 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA AX1BB UT WOS:000346682300005 PM 25398017 ER PT J AU Budde, KS Barron, DS Fox, PT AF Budde, Kristin S. Barron, Daniel S. Fox, Peter T. TI Stuttering, induced fluency, and natural fluency: A hierarchical series of activation likelihood estimation meta-analyses SO BRAIN AND LANGUAGE LA English DT Article DE Persistent developmental stuttering; Functional neuroimaging; Meta-analysis; Activation likelihood estimation; ALE ID POSITRON-EMISSION-TOMOGRAPHY; NONSTUTTERING ADULTS; SPEECH PRODUCTION; ALE METAANALYSIS; SINGLE; AREAS; SUPPLEMENTARY; CONNECTIVITY; VALIDATION; PATTERNS AB Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). (C) 2014 Elsevier Inc. All rights reserved. C1 [Budde, Kristin S.; Barron, Daniel S.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Budde, Kristin S.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Barron, Daniel S.] Yale Univ, Sch Med, New Haven, CT USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Fox, Peter T.] Univ Hong Kong, Dept Linguist, Hong Kong, Hong Kong, Peoples R China. RP Budde, KS (reprint author), 300 George St,Suite 901, New Haven, CT 06511 USA. EM kristin.budde@yale.edu FU National Institute of Health (NIMH) [RO1 MH074457] FX We thank Juan Saenz, Michaela Robertson and P. Mickle Fox for technical assistance. This study was supported by funds from the National Institute of Health (NIMH: RO1 MH074457), P. Fox PI. NR 50 TC 12 Z9 12 U1 1 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD DEC PY 2014 VL 139 BP 99 EP 107 DI 10.1016/j.bandl.2014.10.002 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA AX4FK UT WOS:000346888900009 PM 25463820 ER PT J AU Hayes, FJ AF Hayes, Frances J. TI Widespread Use of Performance-Enhancing Drugs-An Inconvenient Truth SO ENDOCRINE REVIEWS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 511,55 Fruit St, Boston, MA 02114 USA. EM hayes.frances@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 2014 VL 35 IS 6 BP E1 EP E2 DI 10.1210/er.2014-1047 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1HU UT WOS:000346699200001 PM 25423333 ER PT J AU Qureshi, S Galiveeti, S Bichet, DG Roth, J AF Qureshi, Sana Galiveeti, Sneha Bichet, Daniel G. Roth, Jesse TI Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy SO ENDOCRINOLOGY LA English DT Article ID CYCLIC ADENINE RIBONUCLEOTIDE; HUMAN ANTIDIURETIC-HORMONE; ISOLATED TOAD BLADDER; WATER-CHANNEL; ARGININE-VASOPRESSIN; SYNTHETIC ANALOG; PLASMA-MEMBRANE; RECEPTOR GENE; RAT-KIDNEY; PHARMACOLOGICAL CHAPERONES AB Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI. C1 [Qureshi, Sana; Galiveeti, Sneha; Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Lab Diabet & Diabet Related Disorders, Manhasset, NY 11030 USA. [Qureshi, Sana; Roth, Jesse] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA. [Galiveeti, Sneha] Mt Sinai Med Ctr Hlth Syst, James J Peters VA Med Ctr, Bronx, NY 10029 USA. [Bichet, Daniel G.] Univ Montreal, Hop Sacre Coeur Montreal, Grp Prot Membranaires, Montreal, PQ H4J 1C5, Canada. [Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Hofstra North Shore Long Isl Jewish Sch Med, Hempstead, NY 11549 USA. RP Roth, J (reprint author), Yeshiva Univ, Feinstein Inst Med Res North Shore Long Isl Jewis, Albert Einstein Coll Med, 149-37 Powells Cove Blvd, Whitestone, NY 11357 USA. EM jesserothmd@hotmail.com FU Feinstein Institute for Medical Research, Manhasset, NY; Russell Berrie Foundation, Teaneck, NJ; Alan and Tatyana Forman family FX J.R.'s academic program receives support from the Feinstein Institute for Medical Research, Manhasset, NY, Russell Berrie Foundation, Teaneck, NJ, and the Alan and Tatyana Forman family. NR 201 TC 9 Z9 9 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2014 VL 155 IS 12 BP 4605 EP 4621 DI 10.1210/en.2014-1385 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX0UN UT WOS:000346668000002 PM 25211589 ER PT J AU Schnabolk, G Stauffer, K O'Quinn, E Coughlin, B Kunchithapautham, K Rohrer, B AF Schnabolk, Gloriane Stauffer, Kimberly O'Quinn, Elizabeth Coughlin, Beth Kunchithapautham, Kannan Rohrer, Baerbel TI A comparative analysis of C57BL/6J and 6N substrains; chemokine/cytokine expression and susceptibility to laser-induced choroidal neovascularization SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE rd8 mutation; Choroidal neovascularization; Age-related macular degeneration; Para-inflammation; Pre-conditioning ID DIET-INDUCED OBESITY; MACULAR DEGENERATION; MOUSE MODEL; MUTATION; GENE; INFLAMMATION; COMPLEMENT; THERAPY; RETINA; CELLS AB Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly. To study potential underlying mechanisms of AMD, animal models are utilized, focusing mostly on mice. Recently, genomic and phenotypic differences between the so-called control substrains, C57BL/6J and C57BL/6N, have been described in models of ocular and non-ocular diseases. In particular, the rd8 mutation of the Crb 1 gene present in the C57BL/6N has been shown to impact certain ocular phenotypes and appears to augment phenotypes generally associated with inflammation. Here, we investigated angiogenic factor and cytokine expression using pathway arrays as well as the susceptibility to laser-induced choroidal neovascularization (CNV), a model of wet AMD, in the two substrains. Age-matched 3-month-old C57BL/ 6J and C57BL/6N animals differed in gene expression levels for angiogenic factors and cytokines, with 6N animals expressing higher levels of inflammatory markers than 6Js. Yet laser-induced CNV was comparable in size between the two substrains. This lack of difference in CNV size was correlated with a gene expression profile that was comparable between the two substrains, due to the fact that the degree of change in gene expression of inflammatory markers after CNV was blunted in 6N mice. In summary, significant gene expression differences exist between C57BL/6J and C57BL/6N animals, reinforcing the notion that appropriate litter-mate controls or genetic background controls need to be used. Contrary to our expectation, CNV was not augmented in 6N animals, suggesting that low chronic inflammation in the RPE might provide a level of pre-conditioning and protection against stress. Published by Elsevier Ltd. C1 [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [Stauffer, Kimberly; O'Quinn, Elizabeth; Coughlin, Beth; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320]; Department for Veteran Affairs [RX000444]; Beckman Initiative for Macular Research [1202]; Research to Prevent Blindness (PRB), New York, NY,; Foundation Fighting Blindness, Columbia, MD; Wofford College to K.S. (John Rampey Fund); NIH [C06RR015455] FX We thank Luanna Bartholomew for critical review. This work was supported in the laboratory of B.R. in part by the National Institutes of Health (NIH R01EY019320), a Department for Veteran Affairs merit award RX000444, the Beckman Initiative for Macular Research (1202), an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY, Foundation Fighting Blindness, Columbia, MD, and a summer undergraduate stipend from Wofford College to K.S. (John Rampey Fund). Animal studies were conducted in a facility constructed with support from the NIH C06RR015455. NR 29 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2014 VL 129 BP 18 EP 23 DI 10.1016/j.exer.2014.10.005 PG 6 WC Ophthalmology SC Ophthalmology GA AX4HJ UT WOS:000346893800004 PM 25305577 ER PT J AU Santagata, S Ince, TA AF Santagata, Sandro Ince, Tan A. TI Normal cell phenotypes of breast epithelial cells provide the foundation of a breast cancer taxonomy SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE biomarkers; breast cancer diagnostics; heterogeneity; Nurses' Health Study; -omics; pathology ID CLASSIFICATION; TUMORS AB The current classification system for breast cancer is based on expression of empirical prognostic and predictive biomarkers. As an alternative, we propose a hypothesis-based ontological breast cancer classification modeled after the taxonomy of species in evolutionary biology. This approach uses normal breast epithelial cell types and differentiation lineages as the gold standard to classify tumors. We show that there are at least eleven previously undefined normal cell types in human breast epithelium and that each breast carcinoma is related to one of these normal cell types. We find that triple negative breast cancers do not have a 'basal-like' phenotype. Normal breast epithelial cells conform to four novel hormonal differentiation states and almost all human breast tumors duplicate one of these hormonal differentiation states which have significant survival differences. This ontological classification scheme provides actionable treatment strategies and provides an alternative approach for understanding tumor biology with wide-ranging implications for tumor taxonomy. C1 [Santagata, Sandro] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Santagata, Sandro] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ince, Tan A.] Univ Miami, Sylvester Comprehens Canc Ctr, Braman Family Breast Canc Inst, Dept Pathol,Miller Sch Med, Miami, FL 33136 USA. [Ince, Tan A.] Univ Miami, Interdisciplinary Stem Cell Inst, Miller Sch Med, Miami, FL 33136 USA. RP Ince, TA (reprint author), Univ Miami, Sylvester Comprehens Canc Ctr, Braman Family Breast Canc Inst, Dept Pathol,Miller Sch Med, BRB Room 907, Miami, FL 33136 USA. EM TInce@med.miami.edu FU NCI NIH HHS [R01 CA146445, R01-CA146445-01]; NINDS NIH HHS [K08NS064168] NR 16 TC 3 Z9 3 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD DEC PY 2014 VL 14 IS 12 BP 1385 EP 1389 DI 10.1586/14737140.2014.956096 PG 5 WC Oncology SC Oncology GA AX0JP UT WOS:000346639100001 PM 25263303 ER PT J AU Hsu, RY VanValkenburg, S Tanriover, A DiGiovanni, CW AF Hsu, Raymond Y. VanValkenburg, Scott Tanriover, Altug DiGiovanni, Christopher W. TI Surgical Techniques of Gastrocnemius Lengthening SO FOOT AND ANKLE CLINICS LA English DT Article DE Gastrocnemius contracture; Silfverskiold; Baumann; Vulpius; Baker; Strayer ID NONINSERTIONAL ACHILLES TENDINOPATHY; RECALCITRANT PLANTAR FASCIITIS; LOWER-EXTREMITY KINEMATICS; CEREBRAL-PALSY; EQUINUS DEFORMITY; BAUMANN PROCEDURE; STRAYER PROCEDURE; RECESSION; CONTRACTURE; RELEASE AB This article summarizes the various alternatives for direct gastrocnemius lengthening and elucidates the relative strengths and tradeoffs of each as a means of providing balanced perspective in selecting the appropriate procedure for any given patient. C1 [Hsu, Raymond Y.] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Orthopaed Surg, Providence, RI 02903 USA. [VanValkenburg, Scott; DiGiovanni, Christopher W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Tanriover, Altug] Cankaya Hosp, Dept Orthopaed Surg, TR-06700 Ankara, Turkey. RP VanValkenburg, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM s.vanvalkenburg22@gmail.com NR 60 TC 2 Z9 2 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1083-7515 EI 1558-1934 J9 FOOT ANKLE CLIN JI Foot Ankle Clin. PD DEC PY 2014 VL 19 IS 4 BP 745 EP + DI 10.1016/j.fcl.2014.08.007 PG 22 WC Orthopedics SC Orthopedics GA AX1CZ UT WOS:000346687100013 PM 25456720 ER PT J AU Willauer, P Sangeorzan, BJ Whittaker, EC Shofer, JB Ledoux, WR AF Willauer, Patrick Sangeorzan, Bruce J. Whittaker, Eric C. Shofer, Jane B. Ledoux, William R. TI The Sensitivity of Standard Radiographic Foot Measures to Misalignment SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE foot; X-ray; radiograph; misalignment ID ALIGNMENT; RELIABILITY; FLATFOOT; HINDFOOT AB Background: The purpose of this study was to identify the effects that X-ray source misalignment has on common measurements made from anterior-poster (AP) and medial-lateral (ML) view foot radiographs. Methods: A cadaveric foot model was used to obtain ML radiographs with +/- 25 degree transverse plane misalignment. From these images the calcaneal pitch angle (CPA) and lateral talometatarsal angle (LTMA) were measured. AP images were captured with up to 30 degree sagittal plane misalignment as well as +/- 15 degree misalignment in the transverse plane at each sagittal angle. From these images the talonavicular coverage angle (TNCA) and talometatarsal angle (TMA) were measured. Results: On the ML images, the CPA was sensitive to transverse plane misalignment from -10 to -25 degrees and from 15 to 25 degrees (P < .005). The LTMA was a more reliable measurement than the CPA and did not demonstrate sensitivity to transverse plane misalignment. On the AP images, the TNCA and TMA were not sensitive to sagittal plane misalignment alone. However, at 0, 10, and 15 degrees sagittal misalignment the TNCA showed sensitivity to transverse plane misalignment (P < .0083). Conclusion: Misalignment of an X-ray source can lead to errors in the measurement of foot radiographic parameters, especially the CPA when there is transverse plane misalignment and the TNCA when there is both sagittal and transverse plane misalignment. The LTMA and TMA can be measured reliably, even with significant misalignment present. C1 [Willauer, Patrick; Sangeorzan, Bruce J.; Whittaker, Eric C.; Shofer, Jane B.; Ledoux, William R.] RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA USA. [Willauer, Patrick] Univ Washington, Sch Med, Seattle, WA USA. [Sangeorzan, Bruce J.; Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM bsangeor@uw.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs [A4843C]; University of Washington Medical Student Research and Training Program FX The author(s) received the following financial support for the research, authorship, and/or publication of this article: his research was partially supported by the Department of Veterans Affairs, RR&D grant A4843C and the University of Washington Medical Student Research and Training Program. NR 19 TC 2 Z9 2 U1 1 U2 2 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 DEC PY 2014 VL 35 IS 12 BP 1334 EP 1340 DI 10.1177/1071100714549188 PG 7 WC Orthopedics SC Orthopedics GA AX1FL UT WOS:000346693300016 PM 25237177 ER PT J AU Luz, J Johnson, AH Kohler, MJ AF Luz, Jennifer Johnson, A. Holly Kohler, Minna J. TI Point-of-Care Ultrasonography in the Diagnosis and Management of Superficial Peroneal Nerve Entrapment: Case Series SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE sports; nerve entrapment; chronic lower extremity pain; musculoskeletal ultrasound ID EXERTIONAL COMPARTMENT SYNDROME; FOOT; DECOMPRESSION; SONOGRAPHY; ANKLE; LEG C1 [Luz, Jennifer] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Johnson, A. Holly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. [Kohler, Minna J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Yawkey Ctr Outpat, Boston, MA 02114 USA. RP Kohler, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM MKohler@partners.org NR 25 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD DEC PY 2014 VL 35 IS 12 BP 1362 EP 1366 DI 10.1177/1071100714548198 PG 5 WC Orthopedics SC Orthopedics GA AX1FL UT WOS:000346693300020 PM 25249318 ER PT J AU Dizon, DS Sill, MW Schilder, JM McGonigle, KF Rahman, Z Miller, DS Mutch, DG Leslie, KK AF Dizon, Don S. Sill, Michael W. Schilder, Jeanne M. McGonigle, Kathryn F. Rahman, Zia Miller, David S. Mutch, David G. Leslie, Kimberly K. TI A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Angiogenesis inhibitor; Clinical trial ID ANGIOGENESIS; TRIAL AB Introduction. Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR alpha and beta, FGFR 1/3, and VEGFR 1-3, in this population. Objectives. The primary objectives were to estimate event-free survival (EFS) at 6 months and the proportion of patients who have an objective tumor response. In addition, we sought to determine the nature and degree of toxicity. Secondary objectives were to estimate progression-free and overall survival. Methods. This was a two-stage, single-arm phase II study. Eligible patients were treated with single-agent nintedanib at a dose of 200 mg twice daily. Results. Of 37 patients enrolled, 32 were eligible. There were zero complete and three partial responses for an overall response rate of 9.4% (90%2-sided CI = 2.6-22.5%). Seven patients (21.9%; 90%2-sided CI = 10.7-37.2%) were EFS at 6 months, with one patient continuing on study at the time of this writing. Serious toxicity included the following grade 3 events: gastrointestinal toxicity (5), neutropenia (1), edema (1), hypertension (1), and liver function abnormalities (5). Conclusions. Nintedanib lacked sufficient activity as a single agent to warrant enrollment to second stage. However, predinical data indicate it may be synergistic with paclitaxel in a population of patients enriched for specific p53 mutations that result in loss of function. Subsequent studies may evaluate this agent in combination with paclitaxel. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dizon, Don S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Sill, Michael W.] Roswell Pk Canc Inst, Stat & Data Ctr, NRG Oncol Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Schilder, Jeanne M.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Schilder, Jeanne M.] Univ Washington, Womens Canc Care Seattle, Seattle, WA 98195 USA. [Rahman, Zia] St Francis Hosp & Med Ctr, Hartford, CT USA. [Miller, David S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Mutch, David G.] Washington Univ, Sch Med, St Louis, MO USA. [Leslie, Kimberly K.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. RP Dizon, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM ddizon@partners.org; msill@gogstats.org; jschilde@iupui.edu; kathryn.mcgonigle@nwhsea.org; zrahman@stfranciscare.org; David.Miller@utsouthwestem.edu; mutchd@wudosis.wustl.edu; kimberly-leslie@uiowa.edu RI Miller, David/H-4604-2011; OI Miller, David/0000-0002-8215-5887; Mutch, David/0000-0002-6921-1581 FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group Statistical Office [CA 37517]; NRG Oncology [1 U10 CA180822] FX This study was supported by the National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical Office (CA 37517), and the NRG Oncology (1 U10 CA180822). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: Abington Memorial Hospital, Walter Reed National Military Medical Center, Women's Cancer Care of Seattle; University of Washington, University of Texas Southwestern Medical Center, Indiana University Hospital, University of California Medical Center at Irvine-Orange Campus, Rush University Medical Center, Cleveland Clinic Foundation, Washington University School of Medicine, Memorial Sloan Kettering Cancer Center, University of Oklahoma Health Sciences Center, Women and Infants Hospital, Georgia Core, Carolina Medical Center/Levine Cancer Institute, and Community Clinical Oncology Programs. NR 13 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2014 VL 135 IS 3 BP 441 EP 445 DI 10.1016/j.ygyno.2014.10.001 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500006 PM 25312396 ER PT J AU Moore, RG Hawkins, DM Miller, MC Landrum, LM Gajewski, W Ball, JJ Allard, WJ Skates, SJ AF Moore, Richard G. Hawkins, Douglas M. Miller, M. Craig Landrum, Lisa M. Gajewski, Walter Ball, John J. Allard, W. Jeffery Skates, Steven J. TI Combining clinical assessment and the Risk of Ovarian Malignancy Algorithm for the prediction of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ROMA; Ovarian cancer; Pelvic mass; Risk assessment ID PELVIC MASS; ADNEXAL MASS; CA 125; HE-4; WOMEN; MULTIPLE; MARKERS; CA-125; ROMA; BIOMARKERS AB Objectives. AGOG guidelines for the evaluation of women with a pelvic mass employ a combination of physical exam, imaging, and CA125 to guide physicians in the triage of women to gynecologic oncologists. We studied the use of ROMA with clinical assessment for cancer risk assessment in women with a pelvic mass. Methods. This was a prospective, multicenter trial evaluating women with a pelvic mass who had an initial clinical risk assessment (ICRA) performed by a generalist. ROMA scores were calculated and sensitivity, specificity, PPV and NPV were determined for ICRA and ICRA + ROMA. Results. A total of 461 women were entered into the study. There were 375 benign tumors, 48 EOC, 18 LMP tumors and 20 non-ovarian malignancies. For detection of ovarian cancer alone, ICRA had a sensitivity of 85.4%, a specificity of 84.3%, and a NPV of 97.8%. Adding ROMA to ICRA produced a significant improvement of 8.4% in sensitivity, achieving a sensitivity of 93.8% with a specificity of 67.2% and a NPV of 98.8%. Examination of all malignancies (ovarian & non-ovarian) provided a sensitivity of 89.7% for ROMA + ICRA in comparison to 77.9% for ICRA alone, a significant increase in sensitivity of 11.8%. The NPV also significantly increased from 95.5% to 97.3%. Overall, ROMA detected 13 additional malignancies missed by ICRA. Conclusions. Adjunctive use of ROMA with clinical assessment improves the stratification of women with a pelvic mass into low and high risk groups for ovarian cancer. The combination is particularly effective in ruling out malignant disease. (C) 2014 Elsevier Inc. All rights reserved. C1 [Moore, Richard G.; Miller, M. Craig] Brown Univ, Women & Infants Hosp, Program Womens Oncol, Dept Obstet & Gynecol,Alpert Med Sch, Providence, RI 02925 USA. [Hawkins, Douglas M.] Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. [Landrum, Lisa M.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Gynecol Oncol Sect, Oklahoma City, OK 73190 USA. [Gajewski, Walter] New Hanover Reg Med Ctr, Zimmer Canc Ctr, Wilmington, NC USA. [Ball, John J.] Jackson Clin, Jackson, TN USA. [Allard, W. Jeffery] Medivice Consulting, New Durham, NH USA. [Skates, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Moore, RG (reprint author), Brown Univ, Women & Infants Hosp, Program Womens Oncol, Dept Obstet & Gynecol,Alpert Med Sch, Providence, RI 02925 USA. EM rmoore@wihri.org FU Fujirebio Diagnostics, Inc.; Abbott Diagnostics, Inc. FX Richard G. Moore has received research funding from Fujirebio Diagnostics, Inc. and Abbott Diagnostics, Inc. Doug M. Hawkin is a Statistical Consultant for Fujirebio Diagnostics, Inc. M. Craig Miller is a Database design consultant for Fujirebio Diagnostics, Inc. W. Jeffrey Allard is a consultant for Fujirebio Diagnostics, Inc. Lisa M. Landrum, Walter Gajewski, John J. Ball and Steven J. Skates have no conflicts to report NR 33 TC 2 Z9 2 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2014 VL 135 IS 3 BP 547 EP 551 DI 10.1016/j.ygyno.2014.10.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500023 PM 25449569 ER PT J AU Chuang, L Moore, KN Creasman, WT Goodman, A Cooper, HH Price, FV Conner, MG Gupta, V Gallion, HH Husseinzadeh, N Duarte, J Vu, QHN Sanchez, JA Kanis, MJ AF Chuang, Linus Moore, Kathleen N. Creasman, William Thomas Goodman, Annekathryn Cooper, Hoover Henriquez Price, Fredric V. Conner, Michael G. Gupta, Vishal Gallion, Holly H. Husseinzadeh, Nader Duarte, Jose Quoc Huy Nguyen Vu Sanchez, Jose Angel Kanis, Margaux J. TI Teaching gynecologic oncology in Low resource settings: A collaboration of health volunteers overseas and the society of gynecologic oncology SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID COUNTRIES C1 [Chuang, Linus; Kanis, Margaux J.] Mt Sinai Sch Med, New York, NY 10029 USA. [Moore, Kathleen N.] Univ Oklahoma, Norman, OK 73019 USA. [Creasman, William Thomas] Med Univ S Carolina, Charleston, SC USA. [Goodman, Annekathryn] Massachusetts Gen Hosp Univ, Boston, MA USA. [Goodman, Annekathryn; Husseinzadeh, Nader] Univ Honduras, Tegucigalpa, Honduras. [Price, Fredric V.] West Penn Allegheny Hlth Syst, Pittsburgh, PA USA. [Conner, Michael G.] Univ Alabama Birmingham, Birmingham, AL USA. [Gupta, Vishal] Mt Sinai Med Ctr, Miami Beach, FL USA. [Gallion, Holly H.] Pikeville Med Ctr, Pikeville, KY USA. [Husseinzadeh, Nader] Univ Cincinnati, Cincinnati, OH 45221 USA. [Duarte, Jose] Natl Canc Inst, Asuncion, Paraguay. [Quoc Huy Nguyen Vu] Hue Univ Med & Pharm, New York, NY USA. RP Kanis, MJ (reprint author), Mt Sinai Sch Med, 1176 Fifth Ave,Ninth Floor, New York, NY 10029 USA. EM Linus.chuang@mssm.edu; kathleen-moore@ouhsc.edu; creasman@musc.edu; agoodman@partners.org; drhenriquezcooper@yahoo.com; fprice@wpahs.org; mgconner@uab.edu; vishal.gupta@mountsinai.org; hollygallion@yahoo.com; nader.husseinzadeh@uc.edu; jlduarte7@hotmail.com; nhuy@dng.vnn.vn; jose.skiro@gmail.com OI NGUYEN, VU QUOC HUY/0000-0002-4744-7059 NR 7 TC 2 Z9 2 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 DEC PY 2014 VL 135 IS 3 BP 580 EP 582 DI 10.1016/j.ygyno.2014.10.002 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500028 PM 25308928 ER PT J AU Schorge, JO Clark, RM Lee, SI Penson, RT AF Schorge, John O. Clark, Rachel M. Lee, Susanna I. Penson, Richard T. TI Primary debulking surgery for advanced ovarian cancer: Are you a believer or a dissenter? SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Primary debulking surgery; Neoadjuvant chemotherapy; Advanced ovarian cancer ID ADVANCED-STAGE OVARIAN; ADVANCED EPITHELIAL OVARIAN; PRIMARY CYTOREDUCTIVE SURGERY; GYNECOLOGIC-ONCOLOGY-GROUP; HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; COMPUTED-TOMOGRAPHY SCAN; PET/CONTRAST-ENHANCED CT; GROSS RESIDUAL DISEASE; NEOADJUVANT CHEMOTHERAPY; SURGICAL CYTOREDUCTION AB Nothing stirs the collective soul of primary debulking surgery (PDS) advocates like hard data suggesting equivalent outcomes of neoadjuvant chemotherapy (NAC). These opposing views have even metaphorically come to blows at the highly entertaining "SGO Fight Night" that took place during the 2008 Annual Meeting on Women's Cancer, replete with teams supporting each of the would-be gladiators. Decades of retrospective data supporting the clinical benefit of PDS has recently been challenged by the publication in 2010 of a randomized phase III trial conducted in Europe supporting the clinical efficacy of NAC. Naturally, a firestorm of criticism among believers ensued, yet practice patterns within the United States did slowly change, suggesting an emerging block of dissenters. Another randomized phase III European trial, as presented in abstract form in 2013, showed similar findings. Few other topics within the field of gynecologic oncology have participants so entrenched in the "corners" of their existing practice patterns. This review attempts to consolidate the current evidence supporting both sides so that the patient can be declared the winner. (C) 2014 Elsevier Inc. All rights reserved. C1 [Schorge, John O.; Clark, Rachel M.] Massachusetts Gen Hosp, Vincent Gynecol Oncol Serv, Boston, MA 02114 USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Div Abdominal Imaging, Boston, MA 02114 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Div Med Gynecol Oncol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Gynecol Oncol Serv, Yawkey-9E,55 Fruit St, Boston, MA 02114 USA. EM jschorge@partners.org NR 117 TC 18 Z9 18 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2014 VL 135 IS 3 BP 595 EP 605 DI 10.1016/j.ygyno.2014.10.007 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500031 PM 25316177 ER PT J AU Campos, SM Brady, WE Moxley, KM O'Cearbhaill, RE Lee, PS DiSilvestro, PA Rotmensch, J Rose, PG Thaker, PH O'Malley, DM ParvizHanjani Zuna, RE Hensley, ML AF Campos, Susana M. Brady, William E. Moxley, Katherine M. O'Cearbhaill, Roisin E. Lee, Paula S. DiSilvestro, Paul A. Rotmensch, Jacob Rose, Peter G. Thaker, Premal H. O'Malley, David M. ParvizHanjani Zuna, Rosemary E. Hensley, Martee L. TI A phase II evaluation of Pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A Gynecologic Oncology Group Study (vol 133, pg 537, 2014) SO GYNECOLOGIC ONCOLOGY LA English DT Correction C1 [Campos, Susana M.] Dana Farber Canc Inst, Dana Farber Partners Canc Care, Boston, MA 02115 USA. [Brady, William E.] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Moxley, Katherine M.; Zuna, Rosemary E.] Univ Oklahoma, Ctr Sci, Oklahoma City, OK 73104 USA. [O'Cearbhaill, Roisin E.; Hensley, Martee L.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Lee, Paula S.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [DiSilvestro, Paul A.] Brown Univ, Women & Infants Hosp, Providence, RI 02905 USA. [Rotmensch, Jacob] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Rose, Peter G.] Cleveland Clin, Cleveland, OH 44195 USA. [Thaker, Premal H.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [O'Malley, David M.] Ohio State Univ, Columbus Canc Council, Hilliard, OH 43026 USA. [ParvizHanjani] Abington Mem Hosp, Abington, PA 19001 USA. RP Campos, SM (reprint author), Dana Farber Canc Inst, Dana Farber Partners Canc Care, Boston, MA 02115 USA. EM Susana_Campos@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2014 VL 135 IS 3 BP 624 EP 624 DI 10.1016/j.ygyno.2014.08.011 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500035 ER PT J AU Burke, WM Orr, J Leitao, M Salom, E Gehrig, P Olawaiye, AB Brewer, M Boruta, D Villella, J Herzog, T Abu Shahin, F AF Burke, William M. Orr, James Leitao, Mario Salom, Emery Gehrig, Paola Olawaiye, Alexander B. Brewer, Molly Boruta, Dave Villella, Jeannine Herzog, Tom Abu Shahin, Fadi CA SGO Clinical Practice Endometrial Soc Gynecologic Oncology Clinical TI Endometrial cancer: A review and current management strategies: Part I (vol 134, pg 385, 2014) SO GYNECOLOGIC ONCOLOGY LA English DT Correction C1 [Burke, William M.] Valley Hosp, Div Gynecol Oncol, Paramus, NJ USA. [Burke, William M.] Columbia Univ, Med Ctr, New York, NY USA. [Orr, James; Abu Shahin, Fadi] Florida Gynecol Oncol, Ft Myers, FL USA. [Leitao, Mario] Mem Sloan Kettering Canc Ctr, Gynecol Serv, New York, NY 10021 USA. [Salom, Emery] Florida Int Univ, Div Gynecol Oncol, Miami, FL 33199 USA. [Gehrig, Paola] Univ N Carolina, Div Gynecol Oncol, Chapel Hill, NC USA. [Olawaiye, Alexander B.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Brewer, Molly] Univ Connecticut, Ctr Hlth, Carole & Ray Neag Comprehens Canc Ctr, Div Gynecol Oncol, Farmington, CT USA. [Boruta, Dave] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Villella, Jeannine] Winthrop Univ Hosp, Div Gynecol Oncol, Long Isl City, NY USA. [Herzog, Tom] SUNY Stony Brook, Sch Med, Div Gynecol Oncol, Long Isl City, NY USA. [Herzog, Tom] Columbia Univ, Med Ctr, Div Gynecol Oncol, New York, NY USA. RP Burke, WM (reprint author), One Valley Hlth Plaza, Paramus, NJ 07652 USA. EM wmb7@columbia.edu NR 1 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2014 VL 135 IS 3 BP 625 EP 625 DI 10.1016/j.ygyno.2014.08.035 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AX3DA UT WOS:000346819500036 ER PT J AU Shanmugarajah, K Villani, V Madariaga, MLL Shalhoub, J Michel, SG AF Shanmugarajah, Kumaran Villani, Vincenzo Madariaga, Maria Lucia L. Shalhoub, Joseph Michel, Sebastian G. TI Current progress in public health models addressing the critical organ shortage SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Organ shortage; Policy; Donation; Presumed consent; Explicit consent; Mandated choice ID PRESUMED CONSENT LEGISLATION; MANDATED CHOICE; KIDNEY SALES; DONATION; INCREASE; ISRAEL; DONORS; TRANSPLANTATION; PROCUREMENT; EXPERIENCE AB Since its inauguration in 1954, the field of modern transplantation has made great strides in surgical technique, the prevention of acute and chronic rejection, the minimization of immunosuppression-related side-effects and transplant tolerance. As such, organ transplantation is used worldwide as a curative, life-saving treatment for people with end-stage organ failure. However, the successes of organ transplantation have resulted in the number of patients on transplant waiting lists far exceeding the number of organs available, with growing numbers of patients dying while awaiting transplants. In order to address this critical organ shortage, a number of legislative changes have been implemented worldwide to increase the number of individuals registering as organ donors. These have included presumed consent donation, incentivized organ donation, commercial organ transplantation and mandated choice models. This article will address these public health policies in turn. The implementation of these strategies and the evidence for their efficacy will be evaluated. Based on this, we have identified that well-supported transplant coordinators approaching next-of-kin, incentives and public health campaigns are key factors that increase organ donation. Finally we propose a modified mandated choice model that may be an alternative option to maximize the number of available organs for transplantation. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Shanmugarajah, Kumaran; Villani, Vincenzo; Madariaga, Maria Lucia L.; Michel, Sebastian G.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Michel, Sebastian G.] Univ Munich, Dept Cardiac Surg, D-81377 Munich, Germany. [Madariaga, Maria Lucia L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. [Shanmugarajah, Kumaran; Shalhoub, Joseph] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England. RP Shanmugarajah, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM kumaran.shanmugarajah@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766; Shalhoub, Joseph/0000-0003-1011-7440 NR 33 TC 1 Z9 1 U1 1 U2 12 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 DEC PY 2014 VL 12 IS 12 BP 1363 EP 1368 DI 10.1016/j.ijsu.2014.11.011 PG 6 WC Surgery SC Surgery GA AX0MO UT WOS:000346646600024 PM 25463765 ER PT J AU Levine, AR Laliberte, B Lin, H Stan, K Ladha, KS Kaafarani, HMA Lee, J AF Levine, Alexander R. Laliberte, Benjamin Lin, Hsin Stan, Kimberleigh Ladha, Karim S. Kaafarani, Haytham M. A. Lee, Jarone TI Weight based heparin dosing for thromboembolic disease is associated with earlier anticoagulation in surgical patients SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Article DE Anticoagulants; Heparin; Drug safety; Cardiology ID INTENSIVE-CARE-UNIT; VENOUS THROMBOEMBOLISM; MANAGEMENT; THROMBOSIS AB Introduction: Achievement of early therapeutic anticoagulation with unfractionated heparin (UFH) is associated with improved outcomes in thromboembolic disease. Weight based UFH expedites time to therapeutic anticoagulation. Treatment with UFH is challenging in surgical patients due to their high propensity for bleeding. We sought to test the hypothesis that an initial weight based UFH infusion in surgical patients increases the percentage of patients who achieve early therapeutic anticoagulation without increasing the risk of hemorrhagic events. Methods: Using a non-concurrent retrospective cohort study design, adult surgical patients receiving UFH for venous thromboembolism (VTE) at a tertiary care center were included. Two groups were identified: the weight based (WB) and the under-dosed (UD) heparin groups. For our primary outcome, we compared percentage of patients in each group that achieved a therapeutic PTT within 24 h. Secondary outcomes included the incidence of supratherapeutic PTT levels, hemorrhagic events, and complications associated with VTE. Results: 73 subjects met study criteria, which included 8 subjects in the WB group and 65 in the UD group. The demographic, baseline laboratory, admitting service and type of VTE were similar between the 2 groups. The percentages of WB and UD subjects who achieved a therapeutic PTT within 24 h were 75% and 28%, respectively (p < 0.01). There was no difference in the incidence of supratherapeutic PTT or hemorrhagic events. Conclusion: Surgical patients who received an initial weight based UFH infusion achieved earlier therapeutic anticoagulation compared to under-dosed UFH without increasing the occurrence of supratherapeutic PTT levels or hemorrhagic events. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Levine, Alexander R.; Lin, Hsin; Stan, Kimberleigh] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02214 USA. [Laliberte, Benjamin] Univ Maryland, Med Ctr, Dept Pharm, College Pk, MD USA. [Ladha, Karim S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02214 USA. [Kaafarani, Haytham M. A.; Lee, Jarone] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02214 USA. RP Levine, AR (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02214 USA. EM arlevine@partners.org RI Ladha, Karim/K-7170-2015; OI Ladha, Karim/0000-0001-7303-2458; Lee, Jarone/0000-0002-4532-8523 NR 14 TC 0 Z9 1 U1 0 U2 2 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 DEC PY 2014 VL 12 IS 12 BP 1416 EP 1419 DI 10.1016/j.ijsu.2014.10.022 PG 4 WC Surgery SC Surgery GA AX0MO UT WOS:000346646600032 PM 25448664 ER PT J AU Salcone, EM Hamdy, S Melki, S Hunter, DG AF Salcone, Erin M. Hamdy, Shaden Melki, Samir Hunter, David G. TI Scleral perforations during routine traction test in a patient with osteogenesis imperfecta SO JOURNAL OF AAPOS LA English DT Article AB Osteogenesis imperfecta comprises a rare group of genetic disorders caused by abnormal collagen that results in increased bone fragility and other sequelae. We describe a 37-year-old woman with osteogenesis imperfecta in whom two full-thickness scleral perforations were created by adjacent teeth of 0.5 mm forceps during traction testing while undergoing routine strabismus surgery. This case reviews the ocular findings of osteogenesis imperfecta and highlights the potential risk of ocular surgical complications in these patients. C1 [Salcone, Erin M.; Hamdy, Shaden; Hunter, David G.] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02155 USA. [Salcone, Erin M.] Dartmouth Hitchcock Med Ctr, Sect Ophthalmol, Lebanon, NH 03766 USA. [Hamdy, Shaden] Res Inst Ophthalmol, Cairo, Egypt. [Melki, Samir] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. [Melki, Samir; Hunter, David G.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Hunter, DG (reprint author), Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02155 USA. EM David.Hunter@childrens.harvard.edu FU Children's Hospital Ophthalmology Foundation, Boston, MA (DGH) FX Financial support provided by the Children's Hospital Ophthalmology Foundation, Boston, MA (DGH). NR 11 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD DEC PY 2014 VL 18 IS 6 BP 610 EP 612 DI 10.1016/j.jaapos.2014.07.166 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA AX2EE UT WOS:000346755600024 PM 25448153 ER PT J AU Wang, JP Lau, ME Gulur, P AF Wang, Jingping Lau, Mary E. Gulur, Padma TI Delayed Spinal Epidural Hematoma After Epidural Catheter Removal With Reinitiation of Warfarin SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE epidural hematoma; lumbar epidural; thoracic epidural; delayed hematoma; cathater removal; warfarin; spinal epidural hematoma; epidural analgesia ID REGIONAL-ANESTHESIA; GUIDELI 3RD-EDITION; PATIENT C1 [Wang, Jingping; Lau, Mary E.; Gulur, Padma] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Wang, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,WACC,Suite 330, Boston, MA 02114 USA. EM pgulur@partners.org NR 9 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 1053-0770 EI 1532-8422 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2014 VL 28 IS 6 BP 1566 EP 1569 DI 10.1053/j.jvca.2013.05.023 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA AX2FK UT WOS:000346758800022 PM 24075636 ER PT J AU Fitzsimons, MG Ichinose, F Vagefi, PA Marknnann, JF Pierce, ET MacGillivray, TE Herd, M Gauran, C Madsen, JC Baker, J AF Fitzsimons, Michael G. Ichinose, Funnito Vagefi, Parsia A. Marknnann, James F. Pierce, Eric T. MacGillivray, Thomas E. Herd, Martin Gauran, Cosmin Madsen, Joren C. Baker, Joshua TI Successful Right Ventricular Mechanical Support After Combined Heart-Liver Transplantation SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE right ventricle; right ventricular failure; heart failure; right ventricular assist device (RVAD); heart and liver transplantation; heart failure; organ transplantation ID POSTREPERFUSION SYNDROME; FAILURE C1 [Fitzsimons, Michael G.; Ichinose, Funnito; Pierce, Eric T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Cardiac Anesthesia, Boston, MA 02114 USA. [Vagefi, Parsia A.; Marknnann, James F.; Herd, Martin; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Transplant Surg Div, Boston, MA 02114 USA. [MacGillivray, Thomas E.; Baker, Joshua] Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Div, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Cardiac Anesthesia, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 15 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 1053-0770 EI 1532-8422 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2014 VL 28 IS 6 BP 1583 EP 1585 DI 10.1053/j.jvca.2013.10.013 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA AX2FK UT WOS:000346758800026 PM 24462515 ER PT J AU Bachmann, KN Fazeli, PK Lawson, EA Russell, BM Riccio, AD Meenaghan, E Gerweck, AV Eddy, K Holmes, T Goldstein, M Weigel, T Ebrahimi, S Mickley, D Gleysteen, S Bredella, MA Klibanski, A Miller, KK AF Bachmann, Katherine Neubecker Fazeli, Pouneh K. Lawson, Elizabeth A. Russell, Brian M. Riccio, Ariana D. Meenaghan, Erinne Gerweck, Anu V. Eddy, Kamryn Holmes, Tara Goldstein, Mark Weigel, Thomas Ebrahimi, Seda Mickley, Diane Gleysteen, Suzanne Bredella, Miriam A. Klibanski, Anne Miller, Karen K. TI Comparison of Hip Geometry, Strength, and Estimated Fracture Risk in Women With Anorexia Nervosa and Overweight/Obese Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; TROCHANTERIC SOFT-TISSUES; BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; FAT MASS; ASSOCIATION; MEN; OSTEOPOROSIS; PREDICTION; IMPACT AB Context: Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry datato estimate hip geometry and femoral strength. Factor of risk (phi) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. Objective: The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. Design: This was a cross-sectional study. Setting: The study was conducted at a Clinical Research Center. Patients: Patients included 368 women (aged 19-45 y): 246 AN, 53 over weight/obese, and 69 lean controls. Main Outcome Measures: HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (phi(attenuated)) were measured. Results: Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P <= .03). The phi(attenuated) was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and phi(attenuated) (P < .05). Mean phi(attenuated) (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. Conclusions: Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD. C1 [Bachmann, Katherine Neubecker; Fazeli, Pouneh K.; Lawson, Elizabeth A.; Russell, Brian M.; Riccio, Ariana D.; Meenaghan, Erinne; Gerweck, Anu V.; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eddy, Kamryn] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Goldstein, Mark; Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Holmes, Tara] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. [Goldstein, Mark] Massachusetts Gen Hosp Children, Div Adolescent Med, Boston, MA 02114 USA. [Weigel, Thomas] McLean Hosp, Klarman Ctr, Belmont, MA 02478 USA. [Weigel, Thomas] Harvard Univ, Sch Med, Belmont, MA 02478 USA. [Ebrahimi, Seda] Cambridge Eating Disorders Ctr, Cambridge, MA 02138 USA. [Mickley, Diane] Wilkins Ctr Eating Disorders, Greenwich, CT 06831 USA. [Gleysteen, Suzanne] Beth Israel Deaconess Med Ctr, Boston, MA 02446 USA. [Gleysteen, Suzanne] Harvard Univ, Sch Med, Boston, MA 02446 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@mgh.harvard.edu FU National Institutes of Health [R01 HL 077674, K24 HL092902, R01 DK052625, R24 DK092759, K23 DK094820, K23 MH092560, K23 RR-23090, T32 DK 007028, UL1 RR025758, K12 HD051959] FX This work was supported by National Institutes of Health Grants R01 HL 077674, K24 HL092902, R01 DK052625, R24 DK092759, K23 DK094820, K23 MH092560, K23 RR-23090, T32 DK 007028, UL1 RR025758, and K12 HD051959. NR 33 TC 5 Z9 5 U1 0 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP 4664 EP 4673 DI 10.1210/jc.2014-2104 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300039 PM 25062461 ER PT J AU Dichtel, LE Yuen, KCJ Bredella, MA Gerweck, AV Russell, BM Riccio, AD Gurel, MH Sluss, PM Biller, BMK Miller, KK AF Dichtel, Laura E. Yuen, Kevin C. J. Bredella, Miriam A. Gerweck, Anu V. Russell, Brian M. Riccio, Ariana D. Gurel, Michelle H. Sluss, Patrick M. Biller, Beverly M. K. Miller, Karen K. TI Overweight/Obese Adults With Pituitary Disorders Require Lower Peak Growth Hormone Cutoff Values on Glucagon Stimulation Testing to Avoid Overdiagnosis of Growth Hormone Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FATTY-ACID DEPRESSION; BODY-MASS INDEX; GH DEFICIENCY; ENDOCRINE-SOCIETY; PROVOCATIVE TESTS; OBESE SUBJECTS; SECRETION; DIAGNOSIS; ARGININE; RELEASE AB Context: Obesity is associated with diminished GH secretion, which may result in the over-diagnosis of adult GH deficiency (GHD) in overweight/obese pituitary patients. However, there are no body mass index (BMI)-specific peak GH cutoffs for the glucagon stimulation test (GST), the favored dynamic test for assessing adult GHD in the United States. Objective: The objective of the study was to determine a peak GH cutoff level for the diagnosis of adult GHD in overweight/obese individuals using the GST. Design: This was a retrospective, cross-sectional study. Setting: The study was conducted at Massachusetts General Hospital and Oregon Health and Science University. Methods: A total of 108 subjects with a BMI >= 25kg/m(2)were studied: healthy controls (n = 47), subjects with total pituitary deficiency (TPD) (n = 20, >= 3 non-GH pituitary hormone deficiencies), and subjects with partial pituitary deficiency (PPD) (n = 41, 1-2 non-GH pituitary hormone deficiencies). Intervention: The intervention consisted of a standard 4-hour GST. Main Outcome Measures: The main outcome measure was peak GH level on GST. Results: Using the standard peak GH cutoff of 3 ng/mL, 95% of TPD cases (19 of 20), 80% of PPD (33 of 41), and 45% of controls (21 of 47) were classified as GHD. In receiver-operator characteristic curve analysis (controls vs TPD), a peak GH value of 0.94 ng/mL provided the greatest sensitivity (90%) and specificity (94%). Using a peak GH cutoff of 1 ng/mL, 6% of controls (3 of 47), 59% of PPDs (24 of 41), and 90% of TPDs (18 of 20) were classified as GHD. BMI (R = -0.35, P =.02) and visceral adipose tissue (R = -0.32, P = .03) negatively correlated with peak GH levels in controls. Conclusion: A large proportion of healthy overweight/obese individuals (45%) failed the GST using the standard 3 ng/mL GH cutoff. Overweight/obese pituitary patients are at risk of being misclassified as GHD using this cutoff level. A 1-ng/mL GH cutoff may reduce the overdiagnosis of adult GHD in overweight/obese patients. C1 [Dichtel, Laura E.; Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Biller, Beverly M. K.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Clin Pathol Core Lab, Boston, MA 02114 USA. [Yuen, Kevin C. J.] Oregon Hlth & Sci Univ,Portland, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL457B,55 Fruit St, Boston, MA 02114 USA. EM kkmiller@mgh.harvard.edu FU National Institutes of Health Grants [R01 HL077674, K24 HL092902, K23 RR023090, T32 DK007028]; Harvard Clinical and Translational Science Center [UL1 RR025758] FX This work was supported by National Institutes of Health Grants R01 HL077674, K24 HL092902, K23 RR023090, and T32 DK007028 as well as the Harvard Clinical and Translational Science Center Grant UL1 RR025758. NR 38 TC 18 Z9 19 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP 4712 EP 4719 DI 10.1210/jc.2014-2830 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300045 PM 25210883 ER PT J AU Chan, YM Lippincott, MF Butler, JP Sidhoum, VF Li, CX Plummer, L Seminara, SB AF Chan, Yee-Ming Lippincott, Margaret F. Butler, James P. Sidhoum, Valerie F. Li, Cindy X. Plummer, Lacey Seminara, Stephanie B. TI Exogenous Kisspeptin Administration as a Probe of GnRH Neuronal Function in Patients With Idiopathic Hypogonadotropic Hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; SEX STEROID CONTROL; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; MENSTRUAL-CYCLE; DEFICIENT MEN; IN-VIVO; MUTATIONS; SECRETION; RECEPTOR AB Context: Idiopathic hypogonadotropic hypogonadism (IHH) results from defective synthesis, secretion, or action of GnRH. Kisspeptin is a potent stimulus for GnRH secretion. Objective: We probed the functional capacity of the GnRH neuronal network in patients with IHH. Participants: Eleven subjects with congenital IHH (9 men and 2 women) and one male subject who underwent reversal of IHH were studied. Six of the twelve subjects had an identified genetic cause of their IHH: KAL1 (n = 1), FGFR1 (n = 3), PROKR2 (n = 1), GNRHR (n = 1). Intervention: Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to intravenous boluses of kisspeptin (0.24 nmol/kg) andGnRH(75 ng/kg) both pre- and post-six days of treatment with exogenous GnRH (25 ng/kg sc every 2 h). Results: All subjects with abiding IHH failed to demonstrate a GnRH-induced LH response to exogenous kisspeptin. In contrast, the subject who achieved reversal of his hypogonadotropism demonstrated a robust response to kisspeptin. Conclusions: The functional capacity of the GnRH neuronal network in IHH patients is impaired, as evidenced by their inability to respond to the same dose of kisspeptin that effects a robust GnRH-induced LH response in healthy men and luteal- phase women. This impairment is observed across a range of genotypes, suggesting that it reflects a fundamental property of GnRH neuronal networks that have not been properly engaged during pubertal development. In contrast, a patient who had experienced reversal of his hypogonadotropism responded to exogenous kisspeptin. C1 [Chan, Yee-Ming; Lippincott, Margaret F.; Sidhoum, Valerie F.; Li, Cindy X.; Plummer, Lacey; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Chan, Yee-Ming; Lippincott, Margaret F.; Sidhoum, Valerie F.; Li, Cindy X.; Plummer, Lacey; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Butler, James P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Butler, James P.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Seminara, SB (reprint author), 55 Fruit St,BHX 5, Boston, MA 02214 USA. EM Seminara.Stephanie@mgh.harvard.edu OI Lippincott, Margaret/0000-0002-3533-1999 FU Doris Duke Charitable Foundation [2013110]; NCATS NIH HHS [UL1 TR000170, UL1TR000170]; NCRR NIH HHS [UL1 RR025758, UL1 RR 025758]; NHLBI NIH HHS [UC2 HL102926, UC2 HL102924, RC2 HL102923, HL-102923, HL-295102925, UC2 HL102923, RC2 HL102926, RC2 HL102924, HL-296 103010, HL-102926, HL-102924]; NICHD NIH HHS [P50 HD028138, K24 HD067388, F32 HD078083, U54 HD028138, R01 HD043341, K12 HD052896, HD052896]; NIDDK NIH HHS [T32 DK007028] NR 55 TC 2 Z9 2 U1 1 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP E2762 EP E2771 DI 10.1210/jc.2014-2233 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300089 PM 25226293 ER PT J AU Farr, OM Fiorenza, C Papageorgiou, P Brinkoetter, M Ziemke, F Koo, BB Rojas, R Mantzoros, CS AF Farr, Olivia M. Fiorenza, Christina Papageorgiou, Panagiotis Brinkoetter, Mary Ziemke, Florencia Koo, Bang-Bon Rojas, Rafael Mantzoros, Christos S. TI Leptin Therapy Alters Appetite and Neural Responses to Food Stimuli in Brain Areas of Leptin-Sensitive Subjects Without Altering Brain Structure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOTHALAMIC AMENORRHEA; PREFRONTAL CORTEX; OBESE GENE; DB/DB MICE; OB/OB MICE; REWARD; ACTIVATION; RESISTANCE; BEHAVIOR; LESIONS AB Context: Leptin is a key regulator of energy intake and expenditure. Individuals with congenital leptin deficiency demonstrate structural and functional brain changes when given leptin. However, whether acquired leptin deficiency may operate similarly is unclear. Objective: We set out to determine whether the brains of individuals with acquired leptin deficiency may react to leptin in a similar manner. Design: We used functional magnetic resonance imaging before and after short-and long-term metreleptin treatment in three leptin-sensitive patients with acquired hypoleptinemia. Nine healthy women were scanned as normoleptinemic controls. Setting: The setting was an academic medical center. Patients or Other Participants: The participants were 3 hypoleptinemic women and nine normoleptinemic, matched women. Interventions: We used metreleptin, recombinant leptin, therapy for 24 weeks in hypoleptinemic women only. Main Outcome Measure: We measured neural changes in response to viewing food as compared to nonfood images. We hypothesized that metreleptin treatment would increase brain activity in areas related to cognitive control and inhibition and would decrease brain activity in areas related to reward processing, as compared to the normoleptinemic counterparts. Results: Unlike patients with congenital leptin deficiency, hypoleptinemic patients demonstrated no structural brain differences from healthy controls and/or structural changes in response to treatment. Short-term metreleptin treatment in leptin-sensitive hypoleptinemic subjects enhances areas involved in detecting the salience and rewarding value of food during fasting, whereas long-term treatment decreases attention to food and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment, and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. Conclusions: Leptin replacement in acutely hypoleptinemic women did not alter brain structure but did alter functional cortical activity to food cues in key feeding and reward-related areas. C1 [Farr, Olivia M.; Fiorenza, Christina; Papageorgiou, Panagiotis; Brinkoetter, Mary; Ziemke, Florencia; Mantzoros, Christos S.] VA Boston Healthcare Syst, Div Endocrinol, Boston, MA 02130 USA. [Farr, Olivia M.; Fiorenza, Christina; Papageorgiou, Panagiotis; Brinkoetter, Mary; Ziemke, Florencia; Rojas, Rafael; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Koo, Bang-Bon] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), VA Boston Healthcare Syst, Div Endocrinol, 9-B,150 South Huntington Ave, Boston, MA 02130 USA. EM Christos.Mantzoros@va.gov OI Farr, Olivia/0000-0002-5182-3432 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1]; National Institutes of Health-National Center for Research Resources (Harvard Clinical and Translational Science Center) [M01-RR-01032] FX These studies at the Mantzoros group were supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants 58785, 79929, and 81913 and Award 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. Funding was also received from the National Institutes of Health-National Center for Research Resources Grant M01-RR-01032 (Harvard Clinical and Translational Science Center). NR 54 TC 12 Z9 12 U1 0 U2 7 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP E2529 EP E2538 DI 10.1210/jc.2014-2774 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300059 PM 25279500 ER PT J AU Wisco, BE Marx, BP Wolf, EJ Miller, MW Southwick, SM Pietrzak, RH AF Wisco, Blair E. Marx, Brian P. Wolf, Erika J. Miller, Mark W. Southwick, Steven M. Pietrzak, Robert H. TI Posttraumatic Stress Disorder in the US Veteran Population: Results From the National Health and Resilience in Veterans Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; COMORBIDITY SURVEY-REPLICATION; TRAUMA EXPOSURE; DSM-IV; MILITARY PERSONNEL; SUICIDAL IDEATION; SOCIAL SUPPORT; WAR VETERANS; PTSD; AFGHANISTAN AB Objective: To describe the prevalence of posttraumatic stress disorder (PTSD) and comorbid psychiatric disorders and identify correlates of PTSD in a contemporary, nationally representative sample of US veterans. Method: Data were analyzed from Wave 1 of the National Health and Resilience in Veterans Study, a cross-sectional, retrospective, web-based survey of a population-based sample of 3,157 US veterans conducted between October and December 2011. The main outcome measure was probable lifetime PTSD, which was assessed by using a DSM-IV version of the PTSD Checklist (PCL), the PCL-Specific Stressor version. Results: The weighted lifetime and current prevalence of probable PTSD was 8.0% (standard error [SE] = 0.48) and 4.8% (SE = 0.40), respectively. 87.0% of veterans reported exposure to at least 1 potentially traumatic event (PTE); veterans reported a mean of 3.4 (SD = 2.8) different PTE types in their lifetime. Sudden death of a loved one was the most frequently endorsed PTE (61.3%), and sexual abuse in adulthood had the highest conditional probability of PTSD (37.3%). PTSD was associated with increased odds of mood, anxiety, and substance use disorders (odds ratios [ORs] = 2.2-19.1, P values < .001); suicidal ideation (OR = 9.7, P < .001); and suicide attempts (OR = 11.8, P < .001). Psychosocial factors, including resilience, community integration, and secure attachment, were associated with decreased odds of PTSD (ORs = 0.5-0.7, P values < .05). Conclusions: In a nationally representative sample of US veterans, the prevalence of lifetime and current PTSD was 8.0% and 4.8%, respectively, and PTSD was associated with elevated risk for several psychiatric conditions and suicidality. Veterans reported exposure to many PTE types in addition to combat, and conditional risk for PTSD was high for noncombat-related trauma. Prevention and treatment efforts designed to bolster protective psychosocial factors may help mitigate PTSD risk in this population. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Wisco, Blair E.] Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA. [Marx, Brian P.; Wolf, Erika J.; Miller, Mark W.] Boston Univ, Sch Med, Natl Ctr PTSD, US Dept Vet Affairs VA,Boston Healthcare Syst, Boston, MA 02118 USA. [Marx, Brian P.; Wolf, Erika J.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Natl Ctr PTSD, VA Connecticut Healthcare Syst, New Haven, CT 06516 USA. [Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06516 USA. RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder,Dept Psychia, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU VA National Center for Posttraumatic Stress Disorder; National Institute of Mental Health [1R01MH095737-01A1]; Department of Defense [W81XWH-10-2-0181, W81XWH-12-2-0117-PTSD-IIRA-INT]; Defense Advanced Research Programs Agency [N66001-11-C-4006]; VA (Cooperative Studies Program) [591]; VA Clinical Science Research and Development Program; VA Clinical Science Research and Development Merit Review Award FX This study was funded by the VA National Center for Posttraumatic Stress Disorder and a private donation. Dr Marx was supported by funding from the National Institute of Mental Health (1R01MH095737-01A1), Department of Defense (W81XWH-10-2-0181, W81XWH-12-2-0117-PTSD-IIRA-INT), Defense Advanced Research Programs Agency (N66001-11-C-4006), and the VA (Cooperative Studies Program #591). This work was supported by a Career Development Award to Dr Wolf from the VA Clinical Science Research and Development Program. Dr Miller's contribution was supported by a VA Clinical Science Research and Development Merit Review Award. NR 55 TC 37 Z9 37 U1 11 U2 36 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP 1338 EP 1346 DI 10.4088/JCP.14m09328 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500010 PM 25551234 ER PT J AU Evans, VC Iverson, GL Yatham, LN Lam, RW AF Evans, Vanessa C. Iverson, Grant L. Yatham, Lakshmi N. Lam, Raymond W. TI The Relationship Between Neurocognitive and Psychosocial Functioning in Major Depressive Disorder: A Systematic Review SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID QUALITY-OF-LIFE; FORM HEALTH SURVEY; COGNITIVE DEFICITS; BIPOLAR DISORDER; IMPAIRMENT; UNIPOLAR; DISABILITY; OUTCOMES; METAANALYSIS; ASSOCIATION AB Objective: Neurocognitive deficits are demonstrated in major depressive disorder (MDD) and most likely contribute to the functional impairment experienced by affected individuals. We systematically reviewed the evidence on neurocognitive deficits and their relationship(s) to psychosocial functioning in MDD. Data Sources: English-language literature was searched in MEDLINE, EMBASE, Science Direct, and PsycInfo databases for the years 1980-October 15, 2013, with the following terms: (depressive disorder or depressive disorder, major) and permutations of (cognitive, neurocognitive, neuropsych*) with (impairment, deficit, performance, test) and (quality of life; functional outcomes; outcome assessment, health care) or (assessment, outcomes; assessment, patient outcomes; outcomes assessment; outcomes assessments, patient). Study Selection: Inclusion criteria were (1) nongeriatric adults (<60 years) with a primary diagnosis of MDD by DSM-IV, ICD-9, or ICD-10 criteria; (2) use of neuropsychological tests; and (3) use of a specific measure of social, occupational, or daily functioning. Of 488 articles identified in the initial search, 10 met the inclusion criteria. Data Extraction: Two independent appraisers assessed eligibility of the studies. Substantial heterogeneity in the samples and methods precluded a quantitative meta-analysis, so we performed a narrative descriptive review. Results: The included studies employed a variety of neurocognitive tests and assessments of psychosocial functioning. Overall, depressed samples had neurocognitive deficits in various domains that were associated with different measures of psychosocial functioning. However, these findings were constrained by methodological limitations of studies. Conclusions: The limited evidence base suggests that neurocognitive functioning appears to be broadly associated with functional impairment in individuals with MDD, but the quality of evidence is weak. Further studies to clarify the relationship(s) between neurocognitive and psychosocial functioning in MDD will benefit from larger and more homogeneous samples, prospective designs with multivariate analyses, and use of comprehensive assessments of psychosocial functioning that are validated in depressed populations. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Evans, Vanessa C.; Iverson, Grant L.; Yatham, Lakshmi N.; Lam, Raymond W.] Univ British Columbia, Dept Psychiat, Mood & Anxiety Disorders Program, Vancouver, BC V6T 2A1, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Lam, RW (reprint author), Univ British Columbia, Dept Psychiat, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. EM r.lam@ubc.ca OI Lam, Raymond W./0000-0001-7142-4669 FU Alcohol Beverage Medical Research Council; AstraZeneca Canada; Canadian Institutes of Health Research; CNS Vital Signs; ImPACT Applications; Lundbeck Canada; Pfizer Canada; Psychological Assessment Resources (PAR); Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs; AstraZeneca; Bristol-Myers Squibb; Eli Lilly; GlaxoSmithKline; Johnson Johnson; Novartis; Pfizer; Abbott; Servier; Wyeth; Stanley Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD); Canadian Psychiatric Foundation; Canadian Psychiatric Association Foundation; Litebook; Lundbeck; Merck; St Jude Medical; UBC Institute of Mental Health/Coast Capital Savings FX Dr Iverson has received research support or honoraria from Alcohol Beverage Medical Research Council, AstraZeneca Canada, Canadian Institutes of Health Research, CNS Vital Signs, ImPACT Applications, Lundbeck Canada, Pfizer Canada, Psychological Assessment Resources (PAR), and Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs. Dr Yatham has been an advisory board member for and received honoraria and grant/research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Abbott, Servier, and Wyeth; has been an advisory board member for Forest; and has received grant/research support from the Stanley Foundation, the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Canadian Institutes of Health Research, and the Canadian Psychiatric Foundation. Dr Lam has received ad hoc speaker honoraria from AstraZeneca, Canadian Psychiatric Association, Canadian Network for Mood and Anxiety Treatments, Lundbeck, Lundbeck Institute, Mochida, Pfizer, and Servier; has served on ad hoc consulting/advisory boards of AstraZeneca, Bristol-Myers Squibb, Canadian Network for Mood and Anxiety Treatments, Eli Lilly, Litebook, Lundbeck, Pfizer, and Takeda; has received research funds (through University of British Colombia) from Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Psychiatric Association Foundation, Litebook, Lundbeck, Merck, Pfizer, St Jude Medical, and UBC Institute of Mental Health/Coast Capital Savings; has received patents/copyrights from Lam Employment Absence and Productivity Scale (LEAPS); and has received book royalties from Cambridge University Press and Oxford University Press. Ms Evans has no disclosures to report. NR 65 TC 26 Z9 27 U1 6 U2 26 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP 1359 EP 1370 DI 10.4088/JCP.13r08939 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500012 PM 25551235 ER PT J AU Tsai, J Pilver, CE Hoff, RA AF Tsai, Jack Pilver, Corey E. Hoff, Rani A. TI Potential Mental Health Needs of US Adult Residents Under Different Provisions of the Affordable Care Act SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; PERSONALITY-DISORDER; UNITED-STATES; MEDICAID; PREVALENCE; DISABILITY; ALCOHOL; POVERTY; INDIVIDUALS; COMORBIDITY AB Objective: This study examined different groups of the US population who may be affected by the expansion of Medicaid and creation of health insurance exchanges under the Affordable Care Act (ACA). Method: Data were based on structured interviews with a nationally representative sample of 34,587 adults from the 2004-2005 Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Psychiatric diagnoses were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Results: Of the total sample, 6.4% were currently on Medicaid; 3.9% were uninsured and likely eligible for the Medicaid expansion (LEME); 8.6% were uninsured and not LEME but likely to participate in the health insurance exchanges; 4.6% were insured and LEME; and 76.6% were insured and not LEME. Among those uninsured, those LEME had a significantly higher prevalence of mood and anxiety disorders than those not LEME (odds ratios = 1.26-1.41). Among those insured, those LEME had a higher prevalence of mood, anxiety, substance use, and personality disorders than those not LEME (odds ratios = 1.78-2.41). Although there were few clinical differences between those currently on Medicaid and those LEME, those currently on Medicaid were more likely to use all types of services for mood, anxiety, and substance use disorders. Conclusions: The ACA may directly affect the 12.5% of the US adult population who are uninsured by requiring them to obtain insurance coverage. Given the high prevalence for various psychiatric disorders among those uninsured, state plans to expand Medicaid and create health insurance exchanges have potential to offer coverage to many adults with mental health needs, and states should carefully plan for comprehensive services. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Hoff, Rani A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pilver, Corey E.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Hoff, Rani A.] US Dept Vet Affairs, Northeast Program Evaluat Ctr, West Haven, CT USA. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM jack.tsai@yale.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This work was supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. Role of the sponsor: The funding agencies had no role in the conduct or publication of the study. NR 28 TC 5 Z9 5 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP 1402 EP 1410 DI 10.4088/JCP.13m08885 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500017 PM 25271598 ER PT J AU Papakostas, GI Ionescu, DF AF Papakostas, George I. Ionescu, Dawn F. TI Updates and Trends in the Treatment of Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; ANTIDEPRESSANT EFFICACY; CHANNEL BLOCKER; VORTIOXETINE; THERAPY; SAFETY; LEVOMILNACIPRAN; AUGMENTATION; KETAMINE AB Mental illness accounts for 7.4% of the total disease burden worldwide-more than HIV/AIDS, tuberculosis, or diabetes-making it the leading cause of years lost to disability. 1 Depressive disorders make up 40.5% of that disability, the most of all mental illnesses. Despite the devastating global effects of depression, a report on approval trends by the US Food and Drug Administration (FDA) found that new molecular entities (NMEs) approved for targeting psychiatric illness peaked in the 1960s and have been declining since.(2) Indeed, of the 27 NMEs approved by the FDA in 2013, only 1 had psychiatric indications,(3) highlighting the slow pace of psychiatric drug discovery.(4) Despite this, recent progress has been made. In this article, our aim is to (1) describe recently FDA-approved medications for major depressive disorder (MDD), as well as adjunctive therapies studied during the period 2013 to 2014 (study completion, publication, or meeting reports), and (2) discuss the current trends in novel antidepressant therapies. C1 [Papakostas, George I.; Ionescu, Dawn F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Clin Trials Network, 1 Bowdoin Sq,6th Fl, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Ionescu, Dawn/K-5675-2015 FU AstraZeneca; Bristol-Myers Squibb; Forest; National Institute of Mental Health; Pamlab; Pfizer; Ridge Diagnostics; Sunovion; Theracos, Inc FX Dr Papakostas has served as a consultant for Abbott, AstraZeneca, Avanir, Brainsway, Bristol-Myers Squibb, Cephalon, Dey, Eli Lilly, GlaxoSmithKline, Evotec, H. Lundbeck, Inflabloc, Jazz, Novartis, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire, Sunovion, Takeda, Theracos, and Wyeth; has received honoraria from Abbott, AstraZeneca, Avanir, Bristol-Myers Squibb, Brainsway, Cephalon, Dey, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc, Jazz, H. Lundbeck, Novartis, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics, Shire, Sunovion, Takeda, Theracos, Titan, and Wyeth; has received research support from AstraZeneca, Bristol-Myers Squibb, Forest, National Institute of Mental Health, Pamlab, Pfizer, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion, and Theracos, Inc; and has served (not currently) on the speakers bureau for Bristol-Myers Squibb and Pfizer. Dr Ionescu reports no potential conflict of interest. NR 33 TC 1 Z9 1 U1 2 U2 18 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP 1419 EP 1421 DI 10.4088/JCP.14ac09610 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500019 PM 25551237 ER PT J AU Zorick, T Mandelkern, MA Brody, AL AF Zorick, Todd Mandelkern, Mark A. Brody, Arthur L. TI A Naturalistic Study of the Association Between Antidepressant Treatment and Outcome of Smoking Cessation Treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ALCOHOL DEPENDENCE; MENTAL-ILLNESS; DOUBLE-BLIND; TOBACCO USE; SERTRALINE; METHAMPHETAMINE; PREDICTORS; DISORDERS; HEALTH AB Objective: Psychiatric, medical, and substance use comorbidities are highly prevalent among smokers, and many of these comorbidities have been found to be associated with reduced rate of success in clinical trials for smoking cessation. While much has been established about the best available treatments from these clinical trials, little is known about the effect of concomitant psychiatric medications on quit rates in smoking cessation programs. On the basis of results in populations with tobacco dependence and other substance use disorders, we hypothesized that smokers taking antidepressants would have a lower rate of quitting in an outpatient smoking cessation program. Method: We performed a naturalistic chart review of veterans (N = 144) enrolled in the Veterans Affairs Greater Los Angeles Mental Health Clinic Smoking Cessation Program from March 2011 through July 2013, who met DSM-IV-TR criteria for nicotine dependence. The primary outcome was smoking cessation with treatment, as evidenced by a patient report of at least 1 week of abstinence and an exhaled carbon monoxide level of = 6 ppm (if available) at the end of acute treatment, with comparators including concomitant psychotropic medication treatment, psychiatric and medical comorbidities, and the presence of a substance use disorder history. We utilized stepwise binary logistic regression as the main statistical technique. Results: We found that current antidepressant treatment (P =.003) and history of substance use disorder (P = .01) (particularly cocaine [P = .02]) were associated with a lower rate of quitting smoking. Furthermore, the association between antidepressant treatment and reduced rate of smoking cessation was primarily seen in patients with a history of substance use disorder (P =.003). Conclusions: While preliminary, these results suggest an important clinical interaction meriting future study. If these findings are confirmed, clinicians may want to consider the risk of reduced ability to quit smoking in patients with a history of substance use disorder who are taking antidepressants. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Zorick, Todd] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. [Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Imaging, Los Angeles, CA 90073 USA. [Zorick, Todd; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Zorick, T (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd,B210-2nd Floor, Los Angeles, CA 90073 USA. EM tzorick@mednet.ucla.edu FU VA Career Development Award [I01 BX007080]; National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [23XT-0002]; VA Merit Review Award [I01 CX000412] FX Dr Zorick is supported by a VA Career Development Award (I01 BX007080). Dr Brody receives grant funding from the National Institute on Drug Abuse (R01 DA20872), the Tobacco-Related Disease Research Program (23XT-0002), and a VA Merit Review Award (I01 CX000412). NR 25 TC 1 Z9 1 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP E1433 EP E1438 DI 10.4088/JCP.14m09012 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500003 PM 25551240 ER PT J AU Esterman, M Reagan, A Liu, GY Turner, C DeGutis, J AF Esterman, Michael Reagan, Andrew Liu, Guanyu Turner, Caroline DeGutis, Joseph TI Reward Reveals Dissociable Aspects of Sustained Attention SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article DE sustained attention; vigilance; reward; motivation ID VIGILANCE DECREMENT; DEFICIT/HYPERACTIVITY DISORDER; EGO DEPLETION; MEMORY LOAD; TASK; PERFORMANCE; RESOURCE; MINDLESSNESS; VARIABILITY; INHIBITION AB Although reward is known to have a powerful influence on performance, its effects on the ability to continuously sustain performance over time are poorly understood. The current study examines multiple measures of sustained attention (accuracy and variability) and their decrements over time, while introducing reward in the form of a monetary incentive or the promise of early completion. Compared with unrewarded participants, rewarded participants demonstrated greater overall accuracy and lower reaction time variability. However, rewarded and unrewarded participants displayed nearly identical decrements in performance over time, suggesting that these aspects of sustained attention are far less malleable by enhanced effort. This study helps to resolve conflicting models of sustained attention as it reveals that some aspects of performance are due to motivational lapses whereas others are due to the depletion of cognitive resources that cannot be easily overcome. C1 [Esterman, Michael; Reagan, Andrew; Liu, Guanyu; Turner, Caroline; DeGutis, Joseph] VA Boston Healthcare Syst, Boston Attent & Learning Lab,VA, Boston, MA 02130 USA. [Esterman, Michael] Boston Univ, Boston, MA 02215 USA. [DeGutis, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Esterman, M (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM esterman@bu.edu OI Esterman, Michael/0000-0002-9000-3920 FU CSRD VA [IK2 CX000706] NR 51 TC 10 Z9 10 U1 5 U2 21 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-3445 EI 1939-2222 J9 J EXP PSYCHOL GEN JI J. Exp. Psychol.-Gen. PD DEC PY 2014 VL 143 IS 6 BP 2287 EP 2295 DI 10.1037/xge0000019 PG 9 WC Psychology, Experimental SC Psychology GA AX4FD UT WOS:000346888200018 PM 25313950 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Prostaglandin pathways in duodenal chemosensing SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 15th Taishotoyama International Symposium on Gastroenterology CY SEP 26-28, 2013 CL Tokyo, JAPAN DE acid sensing; ATP-P2Y signal; bacterial sensing; dual oxidase ID COLONIC EPITHELIAL-CELLS; ARACHIDONIC-ACID RELEASE; HYDROGEN-PEROXIDE; BICARBONATE SECRETION; RAT DUODENUM; BACTERIAL OVERGROWTH; DUAL OXIDASE; CHLORIDE SECRETION; EXTRACELLULAR ATP; SENSING PATHWAYS AB Acid-sensing pathways, which trigger mucosal defense mechanisms in response to luminal acid, involve the rapid afferent-mediated capsaicin pathway and the sustained prostaglandin (PG) pathway. Luminal acid quickly increases protective PG synthesis and release from epithelia, although the mechanism by which luminal acid induces PG synthesis is still mostly unknown. Acid exposure augments purinergic ATP-P2Y signaling by inhibition of intestinal alkaline phosphatase activity. Since P2Y activation increases intracellular Ca2+, we further hypothesized that ATP-P2Y signals increase the generation of H2O2 derived from dual oxidase, a member of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family activated by Ca2+. Our recent studies suggest that acid exposure increases H2O2 output, followed by phospholipase A(2) and cyclooxygenase activation, increasing PG synthesis. Released prostaglandin E2 augments protective HCO3- and mucus secretion via EP4 receptor activation. Thus, the PG pathway as a component of duodenal acid sensing consists of acid-related intestinal alkaline phosphatase inhibition, ATP-P2Y signals, dual oxidase 2-derived H2O2 production, phospholipase A(2) activation, prostaglandin E2 synthesis, and EP4 receptor activation. The PG pathway is also involved in luminal bacterial sensing in the duodenum via activation of pattern recognition receptors, including Toll-like receptors and nucleotide-binding oligomerization domain 2. The presence of acute mucosal responses to luminal bacteria suggests that the duodenum is important for host defenses and may reduce bacterial loading to the hindgut using H2O2, complementing gastric acidity and anti-bacterial bile acids. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Akiba, Y (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angles Healthcare Syst, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU BLRD VA [I01 BX001245]; NIDDK NIH HHS [P30 DK041301, R01 DK054221, R01 DK54221] NR 67 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD DEC PY 2014 VL 29 SU 4 SI SI BP 93 EP 98 DI 10.1111/jgh.12731 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9MA UT WOS:000346580200018 PM 25521740 ER PT J AU Koyuncuoglu, CZ Metin, S Saylan, I Calisir, K Tuncer, O Kantarci, A AF Koyuncuoglu, Cenker Zeki Metin, Suleyman Saylan, Isil Calisir, Kerem Tuncer, Ozen Kantarci, Alpdogan TI Full-Mouth Rehabilitation of a Patient With Ectodermal Dysplasia With Dental Implants SO JOURNAL OF ORAL IMPLANTOLOGY LA English DT Article DE ectodermal dysplasia; implant; full-mouth rehabilitation; AlloDerm ID ENDOSSEOUS IMPLANTS; MANAGEMENT; CHILDREN; CLASSIFICATION; BONE AB Oral findings in patients with ectodermal dysplasia (ED) include complete or partial hypodontia, anodontia, loss of vertical dimension of occlusion, protuberant lips, malformed and widely spaced conical-shaped teeth, and underdeveloped alveolar ridges. These patients present a substantial challenge in dental treatment. This case report presents oral rehabilitation of a 22-year-old male patient diagnosed with ED using an implant tooth-supported telescopic partial denture at the mandible and a tooth-supported telescopic partial denture at the maxilla. Implants in the mandible were placed at the sites of the right and left lateral incisor teeth. Following implant placement, the remaining buccal bone dehiscence was filled with deproteinized bovine bone graft and covered with resorbable membrane. To manage the vestibular insufficiency and to increase the keratinized mucosa in maxilla, bilateral acellular dermal matrix allograft was used on the right and left buccal aspects. The treatment described here improved the patient's functional and esthetic status while significantly restoring his oral health and self-esteem. C1 [Koyuncuoglu, Cenker Zeki; Metin, Suleyman; Saylan, Isil; Tuncer, Ozen] Istanbul Aydin Univ, Fac Dent, Dept Periodontol, Istanbul, Turkey. [Calisir, Kerem] Istanbul Univ, Fac Dent, Dept Prosthodont, Istanbul, Turkey. [Kantarci, Alpdogan] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA. RP Koyuncuoglu, CZ (reprint author), Istanbul Aydin Univ, Fac Dent, Dept Periodontol, Istanbul, Turkey. EM cenker.k@gmail.com NR 29 TC 2 Z9 2 U1 4 U2 14 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0160-6972 EI 1548-1336 J9 J ORAL IMPLANTOL JI J. Oral Implant. PD DEC PY 2014 VL 40 IS 6 BP 715 EP 721 DI 10.1563/AAID-JOI-D-12-00072 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AX1NR UT WOS:000346714100011 PM 25506662 ER PT J AU Kostek, JA Beck, KD Gilbertson, MW Orr, SP Pang, KCH Servatius, RJ Myers, CE AF Kostek, John A. Beck, Kevin D. Gilbertson, Mark W. Orr, Scott P. Pang, Kevin C. H. Servatius, Richard J. Myers, Catherine E. TI Acquired Equivalence in US Veterans With Symptoms of Posttraumatic Stress: Reexperiencing Symptoms Are Associated With Greater Generalization SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID DISORDER AB The severity and number of reexperiencing symptoms (e.g., flashbacks) show considerable variability across individuals with posttraumatic stress disorder (PTSD). One interpretation of reexperiencing symptoms invokes generalization: Specifically, the traumatic memory may be stored in such a way that neutral stimuli that only vaguely resemble some feature of the traumatic event are sufficient to trigger the memory. If this is the case, then individuals with higher levels of reexperiencing symptoms might show greater generalization, even in contexts unrelated to trauma. In the current study, an acquired equivalence test was used to assess associative learning and generalization in 114 U.S. veterans who were also given a test of declarative memory. PTSD symptoms were rated by the veteran. After adjusting for demographic variables, psychoactive medication use, and initial learning, regression analyses showed that the number of PTSD reexperiencing symptoms significantly improved the model for generalization ( = -.23, R-2 = .34) but not associative learning or declarative memory. The results support the idea that generalization is linked to reexperiencing symptoms, is not limited to learning about traumatic events, and can emerge even in a relatively innocuous computer-based learning task. Resumen Equivalencia Adquirida en Veteranos La severidad y numero de sintomas de re-experimentacion (ej. flasbacks) muestra una variabilidad considerable entre los individuos con trastorno por estres post-traumatico (TEPT). Una interpretacion de los sintomas de re-experimentacion es que invoca generalizacion: especificamente, la memoria traumatica puede ser almacenada de tal manera que estimulos neutrales que solo vagamente se asemejan en algunos aspectos al evento traumatico son suficientes para desencadenar el recuerdo traumatico. Si este es el caso, entonces los individuos con niveles mas altos de sintomas de re-experimentacion pueden mostrar mayor generalizacion, incluso en contextos no relacionados al trauma. En este estudio, se uso un test de equivalencia adquirida (EA) para evaluar el aprendizaje asociativo y la generalizacion en 114 veteranos norteamericanos, a quienes tambien se les aplico un test de memoria declarativa. Los sintomas de TEPT fueron ranqueados por cada veterano. Despues de ajustar las variables demograficas, uso de medicamentos psicoactivos y aprendizaje inicial, el analisis de regresion mostro que el numero de sintomas de re-experimentacion de TEPT mejoro significativamente el modelo por generalizacion (B = -.23, R2 = .34) pero no el aprendizaje asociativo o la memoria declarativa. Estos resultados apoyan la idea que la generalizacion esta ligada a los sintomas de re-experimentacion, no esta limitada al aprendizaje sobre eventos traumaticos e incluso puede emerger en una tarea inocua de aprendizaje basado en un computador. Traditional and Simplified Chinese Abstracts by AsianSTSS ??: ?????????????????????????????????? ??: ??????(PTSD)??????????(???),?????????????????????????????????? ?????????,??????????????????????????????????????,?????????????????????,?????????????????????????,??114?????????????????,?????????????????????PTSD?????????????????????????????????, ??PTSD???????????????????( = -.23, R2 = .34),???????????????????????,??????????,?????????,??????????????????????? ??: ?????????????????????????????????? ??: ??????(PTSD)??????????(???),?????????????????????????????????? ?????????,?????????????????????????????????????,?????????????????????,?????????????????????????,??114?????????????????,?????????????????????PTSD?????????????????????????????????, ??PTSD???????????????????( = -.23, R2 = .34),???????????????????????,??????????,????????,???????????????????????? C1 [Kostek, John A.; Beck, Kevin D.; Pang, Kevin C. H.; Servatius, Richard J.; Myers, Catherine E.] VA New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ 07018 USA. [Kostek, John A.; Beck, Kevin D.; Pang, Kevin C. H.; Servatius, Richard J.; Myers, Catherine E.] Rutgers State Univ, New Jersey Med Sch, Stress & Motivated Behav Inst, Newark, NJ 07102 USA. [Gilbertson, Mark W.] Dept Vet Affairs, Manchester, NH USA. [Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Myers, CE (reprint author), VA New Jersey Hlth Care Syst, Neurobehav Res Lab, 385 Tremont Ave,Mail Stop 15, E Orange, NJ 07018 USA. EM Cather-ine.Myers2@va.gov OI Myers, Catherine/0000-0002-2776-4823 FU CSRD VA [I01 CX000771]; NIAAA NIH HHS [R01 AA018737] NR 10 TC 7 Z9 7 U1 6 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2014 VL 27 IS 6 BP 717 EP 720 DI 10.1002/jts.21974 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9SY UT WOS:000346598700012 PM 25470729 ER PT J AU Bovin, MJ Dodson, TS Smith, BN Gregor, K Marx, BP Pineles, SL AF Bovin, Michelle J. Dodson, Thomas S. Smith, Brian N. Gregor, Kristin Marx, Brian P. Pineles, Suzanne L. TI Does Guilt Mediate the Association Between Tonic Immobility and Posttraumatic Stress Disorder Symptoms in Female Trauma Survivors? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SEXUAL ASSAULT SURVIVORS; ADMINISTERED PTSD SCALE; EVENTS AB Tonic immobility (TI) is an involuntary freezing response that can occur during a traumatic event. TI has been identified as a risk factor for posttraumatic stress disorder (PTSD), although the mechanism for this relationship remains unclear. This study evaluated a particular possible mechanism for the relationship between TI and PTSD symptoms: posttraumatic guilt. To examine this possibility, we assessed 63 female trauma survivors for TI, posttraumatic guilt, and PTSD symptom severity. As expected, the role of guilt in the association between TI and PTSD symptom severity was consistent with mediation (B = 0.35; p < .05). Thus, guilt may be an important mechanism by which trauma survivors who experience TI later develop PTSD symptoms. We discuss the clinical implications, including the importance of educating those who experienced TI during their trauma about the involuntary nature of this experience. Resumen La inmovilidad tonica (IT) es una respuesta involuntaria de congelamiento que puede ocurrir durante un evento traumatico. La IT ha sido identificada como un factor de riesgo para el estres post-traumatico (TEPT), aunque el mecanismo de esta relacion permanece poco claro. Este estudio evaluo un posible mecanismo para la relacion entre IT y sintomas del TEPT: la culpa post-traumatica. Para examinar esta posibilidad, evaluamos a 63 mujeres sobrevivientes de trauma en cuanto a IT, culpa post-traumatica, y severidad de sintomas de TEPT. Como se esperaba, el rol de la culpa en la asociacion entre IT y la severidad de sintomas del TEPT fue consistente con la medicion (B = 0.35; p <.05). Es asi, como la culpa puede ser un mecanismo importante por el cual los sobrevivientes al trauma que experimentan IT, mas tarde desarrollan sintomas de TEPT. Son discutidas las implicancias clinicas, incluyendo la importancia de educar a quienes experimentaron IT durante sus traumas sobre la naturaleza involuntaria de esta experiencia. Traditional and Simplified Chinese Abstracts by AsianSTSS ??: ????????????????????????????????? ??: ????(TI)????????????????????TI ???????????(PTSD)?????,??????????????????????TI?PTSD??????????????????????????,?????63?????????TI???????PTSD????????????,?????????TI?PTSD??????????????(B = 0.35; p < .05)???,?????????????,????TI???????????PTSD?? ???????????,?????????TI??,?????????????????? ??: ???????????????????????????????? ??: ????(TI)???????????????????TI ???????????(PTSD)?????,??????????????????????TI?PTSD??????????????????????????,?????63?????????TI???????PTSD????????????,?????????TI?PTSD?????????????(B = 0.35; p < .05)???,?????????????,???TI???????????PTSD?? ????????????,????????TI??,????????????????? C1 [Bovin, Michelle J.; Dodson, Thomas S.; Smith, Brian N.; Gregor, Kristin; Marx, Brian P.; Pineles, Suzanne L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Bovin, Michelle J.; Smith, Brian N.; Gregor, Kristin; Marx, Brian P.; Pineles, Suzanne L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Bovin, MJ (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM Michelle.Bovin@va.gov NR 16 TC 5 Z9 5 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2014 VL 27 IS 6 BP 721 EP 724 DI 10.1002/jts.21963 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9SY UT WOS:000346598700013 PM 25385521 ER PT J AU Zhong, WY Driscoll, SJ Wu, MF Wang, SB Liu, Z Cha, TD Wood, KB Li, GA AF Zhong, Weiye Driscoll, Sean J. Wu, Minfei Wang, Shaobai Liu, Zhan Cha, Thomas D. Wood, Kirkham B. Li, Guoan TI In Vivo Morphological Features of Human Lumbar Discs SO MEDICINE LA English DT Article ID NUCLEUS PULPOSUS; INTERVERTEBRAL DISC; DEGENERATIVE SPONDYLOLISTHESIS; EXTENSION; FLEXION; SPINE; INDIVIDUALS; POPULATION; PREVALENCE; DEFORMATION AB Recent biomechanics studies have revealed distinct kinematic behavior of different lumbar segments. The mechanisms behind these segment-specific biomechanical features are unknown. This study investigated the in vivo geometric characteristics of human lumbar intervertebral discs. Magnetic resonance images of the lumbar spine of 41 young Chinese individuals were acquired. Disc geometry in the sagittal plane was measured for each subject, including the dimensions of the discs, nucleus pulposus (NP), and annulus fibrosus (AF). Segmental lordosis was also measured using the Cobb method. In general, the disc length increased from upper to lower lumbar levels, except that the L4/5 and L5/S1 discs had similar lengths. The L4/5 NP had a height of 8.6 +/- 1.3 mm, which was significantly higher than all other levels (P < 0.05). The L5/S1 NP had a length of 21.6 +/- 3.1 mm, which was significantly longer than all other levels (P < 0.05). At L4/5, the NP occupied 64.0% of the disc length, which was significantly less than the NP of the L5/S1 segment (72.4%) (P < 0.05). The anterior AF occupied 20.5% of the L4/5 disc length, which was significantly greater than that of the posterior AF (15.6%) (P < 0.05). At the L5/S1 segment, the anterior and posterior AFs were similar in length (14.1% and 13.6% of the disc, respectively). The height to length (H/L) ratio of the L4/5 NP was 0.45 +/- 0.06, which was significantly greater than all other segments (P < 0.05). There was no correlation between the NP H/L ratio and lordosis. Although the lengths of the lower lumbar discs were similar, the geometry of the AF and NP showed segment-dependent properties. These data may provide insight into the understanding of segment-specific biomechanics in the lower lumbar spine. The data could also provide baseline knowledge for the development of segment-specific surgical treatments of lumbar diseases. C1 [Zhong, Weiye; Driscoll, Sean J.; Wu, Minfei; Wang, Shaobai; Liu, Zhan; Cha, Thomas D.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg,Bioengn Lab, Boston, MA 02114 USA. [Zhong, Weiye] Second Xiangya Hosp, Dept Spinal Surg, Changsha, Hunan, Peoples R China. Cent S Univ, Changsha, Hunan, Peoples R China. [Wu, Minfei] Jilin Univ, China Japan Union Hosp, Dept Orthoped, Changchun, Jilin, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Bioengn Lab, 55 Fruit St GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R21AR057989]; Synthes, Inc; Department of Orthopedic Surgery of Massachusetts General Hospital; China Scholarship Council [201306370122] FX The authors would like to gratefully acknowledge the financial support from the National Institute of Health (R21AR057989), Synthes, Inc, Department of Orthopedic Surgery of Massachusetts General Hospital, and China Scholarship Council (201306370122). NR 36 TC 4 Z9 4 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD DEC PY 2014 VL 93 IS 28 DI 10.1097/MD.0000000000000333 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AX2GS UT WOS:000346762200065 PM 25526494 ER PT J AU Tenhula, WN Nezu, AM Nezu, CM Stewart, MO Miller, SA Steele, J Karlin, BE AF Tenhula, Wendy N. Nezu, Arthur M. Nezu, Christine Maguth Stewart, Michael O. Miller, Sarah A. Steele, Jennifer Karlin, Bradley E. TI Moving Forward: A Problem-Solving Training Program to Foster Veteran Resilience SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE veterans; problem solving; resilience; social problem solving; readjustment ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PATIENT-LEVEL OUTCOMES; NATIONAL DISSEMINATION; DEPRESSION; HEALTH; METAANALYSIS; CARE; PHQ-9 AB It is vital for mental health professionals serving veterans to be able to address the full range of needs presented by returning veterans, including those that affect a veterans' daily life (e.g., relationships, employment, and community functioning) but may not rise to the level of requiring specialty mental health care. This article describes the development and evaluation of an innovative Veterans Affairs program, Moving Forward, which focuses on building resilience and reducing emotional distress. Moving Forward is based on the principles of problem-solving therapy that have been adapted for use in a four-session, classroom-based training program for veterans. The program evaluation results indicate that Moving Forward is feasible, well-received by veterans, and yields improvements in social problem solving, resilience, and overall distress levels. Although there is a strong evidence base for problem-solving therapy in a range of clinical settings and with a variety of patient populations (Nezu et al., 2013), this represents the first effort to apply these principles in a program focusing on the readjustment and resilience of our nation's veterans. We include several recommendations for building on these results, including the use of Internet-based training, inclusion of family members in training, and recommendations for research in this important area. C1 [Tenhula, Wendy N.] US Dept Vet Affairs, Vet Affairs Dept Def Integrated Mental Hlth, Vet Hlth Adm, Washington, DC 20240 USA. [Nezu, Arthur M.; Nezu, Christine Maguth] Drexel Univ, Philadelphia, PA USA. [Stewart, Michael O.] US Dept Vet Affairs, Vet Hlth Adm, Washington, DC 20240 USA. [Miller, Sarah A.] US Dept Vet Affairs, Cent Off, Washington, DC 20240 USA. [Steele, Jennifer; Karlin, Bradley E.] US Dept Vet Affairs, Washington, DC 20240 USA. RP Tenhula, WN (reprint author), US Dept Vet Affairs, VA Dept Def Integrated Mental Hlth, Mental Hlth Serv 10P4M, Cent Off, 810 Vermont Ave NW, Washington, DC 20240 USA. EM wendy.tenhula@va.gov NR 31 TC 3 Z9 3 U1 1 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2014 VL 45 IS 6 SI SI BP 416 EP 424 DI 10.1037/a0037150 PG 9 WC Psychology, Multidisciplinary SC Psychology GA AX0HS UT WOS:000346634200005 ER PT J AU Sherman, MD Kauth, MR Ridener, L Shipherd, JC Bratkovich, K Beaulieu, G AF Sherman, Michelle D. Kauth, Michael R. Ridener, Lauren Shipherd, Jillian C. Bratkovich, Kristi Beaulieu, Gregory TI An Empirical Investigation of Challenges and Recommendations for Welcoming Sexual and Gender Minority Veterans Into VA Care SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE LGBT; veterans; mixed methods research; VA providers ID HEALTH-CARE; TRANSGENDER VETERANS; DISORDER; IDENTITY; SUICIDE; GAY AB Approximately 1 million gay and lesbian Americans are veterans. With the repeal of the "Don't Ask, Don't Tell," the Veterans Affairs (VA) health care system is focusing on the unique needs of lesbian, gay, bisexual, and transgender (LGBT) veterans. As a result of research in the private sector documenting stigmatizing attitudes and discrimination toward LGBT individuals in health care settings, the Institute of Medicine and The Joint Commission published recommendations for responding to the needs of LGBT individuals. However, minimal research has examined the unique needs of LGBT veterans and their experiences in VA. This 2-site (Oklahoma City, OK; Houston, TX), mixed-methods study included 202 VA providers and 58 LGBT veterans. Experiences at VA, comfort in providing/receiving care, barriers LGBT veterans face in coming to VA, and recommendations for making VA more welcoming were assessed. Six focus groups and 6 individual interviews were conducted with veterans, and providers completed anonymous surveys. Less than one third of LGBT veterans and providers viewed VA as welcoming to LGBT veterans. Half of providers indicated they do not assess sexual orientation with any of their patients. Furthermore, half of providers reported that they do not alter their treatment plans even if they know the veteran is lesbian, gay, or bisexual. Many constructive suggestions regarding how VA can be more welcoming arose in the veteran inquiry and the provider survey. Based on our findings and the broader literature, recommendations for providers and administrators are described. C1 [Sherman, Michelle D.] Oklahoma City VAMC, Family Mental Hlth Program, Oklahoma City, OK 73104 USA. [Sherman, Michelle D.; Ridener, Lauren] Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Norman, OK 73019 USA. [Kauth, Michael R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kauth, Michael R.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Sherman, Michelle D.; Ridener, Lauren] Oklahoma City VAMC, Oklahoma City, OK 73104 USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Bratkovich, Kristi] Oklahoma City VAMC, Ambulatory Mental Hlth Clin, Oklahoma City, OK 73104 USA. [Bratkovich, Kristi] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Beaulieu, Gregory] Michael E DeBakey VA Med Ctr, Community Integrat Program, Houston, TX USA. [Beaulieu, Gregory] Baylor Coll Med, Houston, TX 77030 USA. RP Sherman, MD (reprint author), Oklahoma City VAMC, 921 NE 13th St 183R, Oklahoma City, OK 73104 USA. EM michelle.sherman@va.gov NR 22 TC 11 Z9 11 U1 1 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2014 VL 45 IS 6 SI SI BP 433 EP 442 DI 10.1037/a0034826 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AX0HS UT WOS:000346634200007 ER PT J AU Maguen, S Madden, E Neylan, TC Cohen, BE Bertenthal, D Seal, KH AF Maguen, Shira Madden, Erin Neylan, Thomas C. Cohen, Beth E. Bertenthal, Daniel Seal, Karen H. TI Timing of Mental Health Treatment and PTSD Symptom Improvement Among Iraq and Afghanistan Veterans SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; GENDER-DIFFERENCES; MILITARY SERVICE; US VETERANS; COMBAT; TRAJECTORIES; SCREEN; CHECKLIST; DIAGNOSES AB Objective: This study examined demographic, military, temporal, and logistic variables associated with improvement of posttraumatic stress disorder (PTSD) among Iraq and Afghanistan veterans who received mental health outpatient treatment from the U.S. Department of Veterans Affairs (VA) health care system. The authors sought to determine whether time between last deployment and initiating mental health treatment was associated with a lack of improvement in PTSD symptoms. Methods: The authors conducted a retrospective analysis of existing medical records of Iraq and Afghanistan veterans who enrolled in VA health care, received a postdeployment PTSD diagnosis, and initiated treatment for one or more mental health problems between October 1, 2007, and December 31, 2011, and whose records contained results of PTSD screening at the start of treatment and approximately one year later (N=39,690). Results: At the start of treatment, 75% of veterans diagnosed as having PTSD had a positive PTSD screen. At follow-up, 27% of those with a positive screen at baseline had improved, and 43% of those with a negative screen at baseline remained negative. A negative PTSD screen at follow-up was associated with female gender, older age, white race, having never married, officer rank, non-Army service, closer proximity to the nearest VA facility, and earlier initiation of treatment after the end of the last deployment. Conclusions: Interventions to reduce delays in initiating mental health treatment may improve veterans' treatment response. Further studies are needed to test interventions for particular veteran subgroups who were less likely than others to improve with treatment. C1 [Maguen, Shira; Madden, Erin; Neylan, Thomas C.; Cohen, Beth E.; Bertenthal, Daniel; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Madden, Erin; Neylan, Thomas C.] Mental Illness Res Educ & Clin Ctr, Dept Mental Hlth, San Francisco, CA USA. [Cohen, Beth E.; Seal, Karen H.] Mental Illness Res Educ & Clin Ctr, Dept Med, San Francisco, CA USA. [Maguen, Shira; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth E.; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM shira.maguen@va.gov FU VA Health Services Research and Development Service (HSR& D) Career Development Award [RCD 06-042]; HSR& D Service Directed Research Award [SDR-08-408]; Department of Defense Mental Health Research Infrastructure Award [W81XWH-11-2-0189]; Department of Defense; VA FX This research was supported by VA Health Services Research and Development Service (HSR& D) Career Development Award (RCD 06-042) to Dr. Maguen, an HSR& D Service Directed Research Award (SDR-08-408) to Dr. Seal, and a Department of Defense Mental Health Research Infrastructure Award (W81XWH-11-2-0189) to Dr. Neylan. The authors thank Julie Dinh, B.A., for assistance.; Dr. Neylan has received study medication for a study funded by the Department of Defense and study medication for a study funded by the VA. The other authors report no competing interests. NR 31 TC 7 Z9 7 U1 1 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2014 VL 65 IS 12 BP 1414 EP 1419 DI 10.1176/appi.ps.201300453 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AW9TG UT WOS:000346599500017 PM 25082217 ER PT J AU Rosen, MI Ablondi, K Black, AC Mueller, L Serowik, KL Martino, S Mobo, B Rosenheck, RA AF Rosen, Marc I. Ablondi, Karen Black, Anne C. Mueller, Lisa Serowik, Kristin L. Martino, Steve Mobo, Ben Hur Rosenheck, Robert A. TI Work Outcomes After Benefits Counseling Among Veterans Applying for Service Connection for a Psychiatric Condition SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUPPORTED EMPLOYMENT; DISABILITY COMPENSATION; SOCIAL-SECURITY; MENTAL-ILLNESS; SUBSTANCE-ABUSE; PSYCHOMETRIC PROPERTIES; HOMELESS VETERANS; BENEFICIARIES; SEEKING AB Objective: This study's objective was to determine the efficacy of benefits counseling in a clinical trial. There has been concern that disability payments for psychiatric disorders reduce incentives for employment and rehabilitation. Benefits counseling, with education about opportunities to work and the financial implications of work on receipt of disability benefits, may counter these disincentives. Methods: This single-blind, six-month randomized clinical trial enrolled 84 veterans who had applied for service-connected compensation for a psychiatric condition. Veterans were randomly assigned to either four sessions of benefits counseling or of a control condition involving orientation to the U.S Department of Veterans Affairs health care system and services. Days of paid work and work-related activities were assessed at follow-up visits by using a time-line follow-back calendar. Results: Veterans assigned to benefits counseling worked for pay for significantly more days than did veterans in the control group (effect size=.69, p<.05), reflecting an average of three more days of paid employment during the 28 days preceding the six-month follow-up. Benefits counseling was associated with increased use of mental health services, but this correlation did not mediate the effect of benefits counseling on working. Conclusions: Barriers to employment associated with disability payments are remediable with basic counseling. More research is needed to understand the active ingredient of this counseling and to strengthen the intervention. C1 [Rosen, Marc I.; Ablondi, Karen; Black, Anne C.; Serowik, Kristin L.; Martino, Steve; Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Rosen, Marc I.; Ablondi, Karen; Black, Anne C.; Serowik, Kristin L.; Martino, Steve] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Dept Psychiat, West Haven, CT USA. [Rosenheck, Robert A.] VA New England Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Bedford, MA USA. [Mueller, Lisa] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Mobo, Ben Hur] Christiana Care Hlth Syst, Newark, DE USA. RP Rosen, MI (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM marc.rosen@yale.edu FU VA Rehabilitation Research and Development grant [D6432]; National Institute of Mental Health [R25 DA026636]; Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center FX The authors acknowledge the contributions of Rani Hoff, Ph.D., to the VA service use analyses in this study. This work was supported by VA Rehabilitation Research and Development grant D6432 to Dr. Rosen, National Institute of Mental Health grant R25 DA026636 to Dr. Martino, and the Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center. NR 47 TC 3 Z9 3 U1 3 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2014 VL 65 IS 12 BP 1426 EP 1432 DI 10.1176/appi.ps.201300478 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AW9TG UT WOS:000346599500019 PM 25082304 ER PT J AU Fricchione, GL AF Fricchione, Gregory L. TI The science of mind body medicine and the public health challenges of today SO SOUTH AFRICAN JOURNAL OF PSYCHOLOGY LA English DT Article DE Allostasis; allostatic loading; resiliency; stress ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RELAXATION RESPONSE; STRESS SYSTEM; TAI CHI; MYOCARDIAL-INFARCTION; DISEASE PREVENTION; ALLOSTATIC LOAD; MENTAL-HEALTH; DEPRESSION; INTERVENTIONS AB An expanding research base of mind body medicine is adding to our understanding of stress, allostasis, and resiliency. This article will summarize a rationale in support of efficiently and effectively using mind body approaches as agents of self-care enhancement in an effort to meet major public health challenges around the world. C1 [Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Fricchione, GL (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. EM Fricchione.Gregory@mgh.harvard.edu NR 79 TC 0 Z9 0 U1 2 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0081-2463 EI 2078-208X J9 S AFR J PSYCHOL JI South Afr. J. Psychol. PD DEC PY 2014 VL 44 IS 4 BP 404 EP 415 DI 10.1177/0081246314541025 PG 12 WC Psychology, Multidisciplinary SC Psychology GA AX0UE UT WOS:000346667100003 ER PT J AU Fang, C D'Souza, B Thompson, CF Clifton, MC Fairman, JW Fulroth, B Leed, A McCarren, P Wang, LL Wang, YK Feau, C Kaushik, VK Palmer, M Wei, G Golub, TR Hubbard, BK Serrano-Wu, MH AF Fang, Chao D'Souza, Brendan Thompson, Christopher F. Clifton, Matthew C. Fairman, James W. Fulroth, Ben Leed, Alison McCarren, Patrick Wang, Lili Wang, Yikai Feau, Clementine Kaushik, Virendar K. Palmer, Michelle Wei, Guo Golub, Todd R. Hubbard, Brian K. Serrano-Wu, Michael H. TI Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1) SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE MCL1; myeloid cell leukemia 1; sp(3)-rich; biophysical validation ID ISOTHERMAL TITRATION CALORIMETRY; DIFFERENTIAL SCANNING CALORIMETRY; BCL-2 PROTEIN FAMILY; DRUG DISCOVERY; INHIBITORS; SURVIVAL; ENERGETICS; STABILITY; STRATEGY; LIBRARY AB A direct binding screen of 100 000 sp(3)-rich molecules identified a single diastereomer of a macrolactam core that binds specifically to myeloid cell leukemia 1 (MCL1). A comprehensive toolbox of biophysical methods was applied to validate the original hit and subsequent analogues and also established a binding mode competitive with NOXA BH3 peptide. X-ray crystallography of ligand bound to MCL1 reveals a remarkable ligand/protein shape complementarity that diverges from previously disclosed MCL1 inhibitor costructures. C1 [Fang, Chao; D'Souza, Brendan; Thompson, Christopher F.; Fulroth, Ben; Leed, Alison; McCarren, Patrick; Wang, Lili; Wang, Yikai; Feau, Clementine; Kaushik, Virendar K.; Palmer, Michelle; Wei, Guo; Golub, Todd R.; Hubbard, Brian K.; Serrano-Wu, Michael H.] Broad Inst, Cambridge, MA 02142 USA. [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Golub, Todd R.] Howard Hughes Med Inst, Boston, MA 02215 USA. [Clifton, Matthew C.; Fairman, James W.] Beryllium, Bedford, MA 01730 USA. RP Fang, C (reprint author), Broad Inst, 415 Main St, Cambridge, MA 02142 USA. EM chaofang@broadinstitute.org; swu@broadinstitute.org FU Carlos Slim Health Institute in Mexico; Robertson Foundation FX This work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Health Institute in Mexico. Additional support was provided by the Robertson Foundation. NR 31 TC 10 Z9 11 U1 0 U2 2 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 DEC PY 2014 VL 5 IS 12 BP 1308 EP 1312 DI 10.1021/ml500388q PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AW5NU UT WOS:000346322500010 PM 25516789 ER PT J AU Genthon, A Frasure, S Kinnaman, K Huang, C Noble, V AF Genthon, Alissa Frasure, Sarah Kinnaman, Karen Huang, Calvin Noble, Vicki TI Bedside ultrasound diagnosis of a spontaneous splenic hemorrhage after tissue plasminogen activator administration SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RUPTURE; TRAUMA AB Emergency physicians (EPs) can use bedside ultrasound to diagnosis of intraabdominal free fluid in a variety of clinical scenarios. The purpose of this study is to review the sonographic appearance of intraabdominal free fluid and incidence of spontaneous splenic rupture. An EP used bedside ultrasound to diagnose spontaneous splenic rupture in a patient who had received tissue plasminogen activator for suspected acute ischemic stroke. Bedside ultrasound by a physician trained in basic ultrasound and the focused assessment with sonography for trauma can diagnose intraabdominal free fluid, facilitating appropriate and more rapid consultation, advanced imaging, and treatment. C1 [Genthon, Alissa; Kinnaman, Karen; Huang, Calvin; Noble, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frasure, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Genthon, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM agenthon@partners.org; kataju@hotmail.com; kkinnaman@partners.org; ckhuang@partners.org; vnoble@partners.org NR 5 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 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD DEC PY 2014 VL 32 IS 12 AR 1553.e1 DI 10.1016/j.ajem.2014.04.015 PG 2 WC Emergency Medicine SC Emergency Medicine GA AW6AX UT WOS:000346353000035 PM 25303848 ER PT J AU Sciscione, A Berghella, V Blackwell, S Boggess, K Helfgott, A Iriye, B Keller, J Menard, MK O'Keeffe, D Riley, L Stone, J AF Sciscione, Anthony Berghella, Vincenzo Blackwell, Sean Boggess, Kim Helfgott, Andrew Iriye, Brian Keller, James Menard, M. Kathryn O'Keeffe, Daniel Riley, Laura Stone, Joanne CA Soc Maternal-Fetal Med TI Society for Maternal-Fetal Medicine (SMFM) Special Report: the maternal-fetal medicine subspecialists' role within a health care system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE care of high-risk pregnancy; consultation; maternal-fetal medicine subspecialist; obstetric care providers; scope of maternal-fetal medicine; Society for Maternal-Fetal Medicine (SMFM) ID OUTCOMES AB A maternal-fetal medicine (MFM) subspecialist has advanced knowledge of the medical, surgical, obstetrical, fetal, and genetic complications of pregnancy and their effects on both the mother and fetus. MFM subspecialists are complementary to obstetric care providers in providing consultations, co-management, or transfer of care for complicated patients before, during, and after pregnancy. The MFM subspecialist provides peer and patient education and performs research concerning the most recent approaches and treatments for obstetrical problems, thus promoting risk-appropriate care for these complicated pregnancies. The relationship between the obstetric care provider and the MFM subspecialist depends on the acuity of the maternal and/or fetal condition and the local resources. To achieve the goal of promoting early access and sustained adequate prenatal care for all pregnant women, we encourage collaboration with obstetricians, family physicians, certified midwives, and others, and we also encourage providing preconception, prenatal, and postpartum care counseling and coordination. Effective communication between all obstetric care team members is imperative. This special report was written with the intent that it would be broad in scope and appeal to a diverse readership, including administrators, allowing it to be applied to various systems of care both horizontally and vertically. We understand that these relationships are often complex and there are more models of care than could be addressed in this document. However, we aimed to promote the development of a highly effective team approach to the care of the high-risk pregnancy that will be useful in the most common models for obstetric care in the United States. The MFM subspecialist functions most effectively within a fully integrated and collaborative health care environment. This document defines the various roles that the MFM subspecialist can fulfill within different heath care systems through consultation, co-management, and transfer of care, as well as education, research, and leadership. C1 [Sciscione, Anthony] Publicat Comm, Soc Maternal Fetal Med, Washington, DC 20436 USA. [Sciscione, Anthony] Christiana Care Hlth Syst, Delaware Ctr Maternal & Fetal Med, Newark, DE USA. [Berghella, Vincenzo] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, Philadelphia, PA 19107 USA. [Blackwell, Sean] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Obstet Gynecol & Reprod Sci, Houston, TX 77030 USA. [Boggess, Kim] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill Sch Med, Chapel Hill, NC 27599 USA. [Helfgott, Andrew] Univ S Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Columbia, SC 29208 USA. [Iriye, Brian] High Risk Pregnancy Ctr, Las Vegas, NV USA. [Keller, James] Advocate Med Grp, Downers Grove, IL USA. [Menard, M. Kathryn] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. [O'Keeffe, Daniel] Soc Maternal Fetal Med, Washington, DC USA. [Riley, Laura] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Stone, Joanne] Mt Sinai Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY 10029 USA. RP Sciscione, A (reprint author), Publicat Comm, Soc Maternal Fetal Med, Washington, DC 20436 USA. EM pubs@smfm.org OI Berghella, Vincenzo/0000-0003-2854-0239 NR 17 TC 2 Z9 2 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2014 VL 211 IS 6 BP 607 EP 616 DI 10.1016/j.ajog.2014.09.013 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW9NW UT WOS:000346585300008 ER PT J AU Creanga, AA Bateman, BT Mhyre, JM Kuklina, E Shilkrut, A Callaghan, WM AF Creanga, Andreea A. Bateman, Brian T. Mhyre, Jill M. Kuklina, Elena Shilkrut, Alexander Callaghan, William M. TI Performance of racial and ethnic minority-serving hospitals on delivery-related indicators SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE delivery; ethnicity; quality of care; race; United States ID LOW-BIRTH-WEIGHT; MATERNAL MORBIDITY; PRENATAL-CARE; UNITED-STATES; DISPARITIES; HOSPITALIZATIONS; MORTALITY AB OBJECTIVE: We sought to explore how racial/ethnic minority-serving hospitals perform on 15 delivery-related indicators, and examine whether indicators vary by race/ethnicity within the same type of hospitals. STUDY DESIGN: We used 2008 through 2011 linked State Inpatient Database and American Hospital Association data from 7 states, and designated hospitals with >50% of deliveries to non-Hispanic white, non-Hispanic black, and Hispanic women as white-, black-, and Hispanic-serving, respectively. We calculated indicator rates per 1000 deliveries by hospital type and, separately, for non-Hispanic white, non-Hispanic black, and Hispanic women within each hospital type. We fitted multivariate Poisson regression models to examine associations between delivery-related indicators and patient and hospital characteristics by hospital type. RESULTS: White-serving hospitals offer obstetric care to an older and wealthier population than black- or Hispanic-serving hospitals. Rates of the most prevalent indicators examined (complicated vaginal delivery, complicated cesarean delivery, obstetric trauma) were lowest in Hispanic-serving hospitals. Generally, indicator rates were similar in Hispanic- and white-serving hospitals. Black-serving hospitals performed worse than other hospitals on 12 of 15 indicators. Indicator rates varied greatly by race/ethnicity in white- and Hispanic-serving hospitals, with non-Hispanic blacks having 1.19-3.27 and 1.15-2.68 times higher rates than non-Hispanic whites, respectively, for 11 of 15 indicators. Conversely, there were few indicator rate differences by race/ethnicity in black-serving hospitals, suggesting an overall lower performance of these hospitals compared to white- and Hispanic-serving hospitals. CONCLUSION: We found considerable differences in delivery-related indicators by hospital type and patients' race/ethnicity. Obstetric care quality measures are needed to track racial/ethnic disparities at the facility and population levels. C1 [Creanga, Andreea A.; Callaghan, William M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA 30333 USA. [Kuklina, Elena] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Heart Dis & Stroke Prevent, Atlanta, GA USA. [Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. [Shilkrut, Alexander] New York Med Coll, Dept Obstet & Gynecol, Valhalla, NY 10595 USA. RP Creanga, AA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA 30333 USA. EM acreanga@cdc.gov OI Shilkrut, Alexander/0000-0001-7596-9770 NR 27 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2014 VL 211 IS 6 AR 647.e1 DI 10.1016/j.ajog.2014.06.006 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW9NW UT WOS:000346585300020 PM 24909341 ER PT J AU Yang, IV Pedersen, BS Rabinovich, E Hennessy, CE Davidson, EJ Murphy, E Guardela, BJ Tedrow, JR Zhang, YZ Singh, MK Correll, M Schwarz, MI Geraci, M Sciurba, FC Quackenbush, J Spira, A Kaminski, N Schwartz, DA AF Yang, Ivana V. Pedersen, Brent S. Rabinovich, Einat Hennessy, Corinne E. Davidson, Elizabeth J. Murphy, Elissa Guardela, Brenda Juan Tedrow, John R. Zhang, Yingze Singh, Mandal K. Correll, Mick Schwarz, Marvin I. Geraci, Mark Sciurba, Frank C. Quackenbush, John Spira, Avrum Kaminski, Naftali Schwartz, David A. TI Relationship of DNA Methylation and Gene Expression in Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE DNA methylation; gene expression; pulmonary fibrosis; quantitative trait; mapping ID GENOME-WIDE ASSOCIATION; CIGARETTE-SMOKING; MYOFIBROBLAST DIFFERENTIATION; EPIGENETIC REGULATION; LUNG-CANCER; TGF-BETA; SUSCEPTIBILITY; CASZ1; HYPERMETHYLATION; FIBROBLASTS AB Rationale: Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome. Objectives: To identify methylation marks that modify gene expression in IPF lung. Methods: We assessed DNA methylation (comprehensive highthroughput arrays for relative methylation arrays [CHARM]) and gene expression (Agilent gene expression arrays) in 94 patients with IPF and 67 control subjects, and performed integrative genomic analyses to define methylation-gene expression relationships in IPF lung. We validated methylation changes by a targeted analysis (Epityper), and performed functional validation of one of the genes identified by our analysis. Measurements and Main Results: We identified 2,130 differentially methylated regions (DMRs; <5% false discovery rate), of which 738 are associated with significant changes in gene expression and enriched for expected inverse relationship between methylation and expression (P < 2.2 X 10(-16)). We validated 13/15 DMRs by targeted analysis of methylation. Methylation-expression quantitative trait loci (methyl-eQTL) identified methylation marks that control cis and trans gene expression, with an enrichment for cis relationships (P < 2.2 X 10(-16)). We found five trans methyl-eQTLs where a methylation change at a single DMR is associated with transcriptional changes in a substantial number of genes; four of these DMRs are near transcription factors (castor zinc finger 1 [CASZ1], FOXC1, MXD4, and ZDHHC4). We studied the in vitro effects of change in CASZ1 expression and validated its role in regulation of target genes in the methyl-eQTL. Conclusions: These results suggest that DNA methylation may be involved in the pathogenesis of IPF. C1 [Yang, Ivana V.; Pedersen, Brent S.; Hennessy, Corinne E.; Davidson, Elizabeth J.; Murphy, Elissa; Schwarz, Marvin I.; Geraci, Mark; Schwartz, David A.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA. [Rabinovich, Einat; Tedrow, John R.; Zhang, Yingze; Singh, Mandal K.; Sciurba, Frank C.] Univ Pittsburgh, Med Ctr, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA USA. [Rabinovich, Einat; Tedrow, John R.; Zhang, Yingze; Singh, Mandal K.; Sciurba, Frank C.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Guardela, Brenda Juan; Kaminski, Naftali] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Correll, Mick; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Spira, Avrum] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Yang, IV (reprint author), Univ Colorado Denver, 12700 East 19th Ave,8611, Aurora, CO 80045 USA. EM ivana.yang@ucdenver.edu OI Kaminski, Naftali/0000-0001-5917-4601 FU National Institutes of Health/National Heart, Lung, and Blood Institute [R01-HL095393]; Lung Genomics Research Consortium [RC2-HL101715] FX Supported by National Institutes of Health/National Heart, Lung, and Blood Institute grant R01-HL095393 and Lung Genomics Research Consortium grant RC2-HL101715. NR 61 TC 27 Z9 27 U1 0 U2 12 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 DEC 1 PY 2014 VL 190 IS 11 BP 1263 EP 1272 DI 10.1164/rccm.201408-1452OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AW5RF UT WOS:000346331000010 PM 25333685 ER PT J AU Galassi, A Burg, A Schneider, J Williams, M Al-Ruzzieh, M Bigirimana, JB Buswell, L Challinor, J Cummings, G Day, S de Calvo, LEA Houlihan, K Nevidjon, B Teahon, M So, WN Were, P AF Galassi, Annette Burg, Allison Schneider, Julie Williams, Makeda Al-Ruzzieh, Majeda Bigirimana, Jean Bosco Buswell, Lori Challinor, Julia Cummings, Greta Day, Sara Esperanza Ayala de Calvo, Luz Houlihan, Kathy Nevidjon, Brenda Teahon, Marina So, Winnie Were, Pamela TI BUILDING CAPACITY FOR ONCOLOGY NURSING EDUCATION AND TRAINING IN LOW- AND MIDDLE-INCOME COUNTRIES: A CALL TO ACTION SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Galassi, Annette; Schneider, Julie; Williams, Makeda] NCI, Rockville, MD USA. [Burg, Allison] Amer Soc Clin Oncol, Alexandria, VA USA. [Al-Ruzzieh, Majeda] King Hussein Canc Ctr, Amman, Jordan. [Bigirimana, Jean Bosco] Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Buswell, Lori; Houlihan, Kathy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Challinor, Julia] Int Network Canc Treatment & Res, Brussels, Belgium. [Cummings, Greta; Nevidjon, Brenda] Int Soc Nurses Canc Care, Vancouver, BC, Canada. [Day, Sara] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Teahon, Marina] Union Int Canc Control, Geneva, Switzerland. [So, Winnie] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Were, Pamela] Epidemiol Burkitt Lymphoma East African Children, Eldoret, Kenya. 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 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 330 BP 9 EP 9 PG 1 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700026 ER PT J AU Payakachat, N Tilford, JM Kuhlthau, KA van Exel, NJ Kovacs, E Bellando, J Pyne, JM Brouwer, WBF AF Payakachat, Nalin Tilford, J. Mick Kuhlthau, Karen A. van Exel, N. Job Kovacs, Erica Bellando, Jayne Pyne, Jeffrey M. Brouwer, Werner B. F. TI Predicting Health Utilities for Children With Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE mapping; predictive algorithms; equating measure; autism; health utilities; clinical measure; behavioral measure; quality of life measure ID QUALITY-OF-LIFE; GENERIC CORE SCALES; ECONOMIC-EVALUATION; COST-EFFECTIVENESS; INTELLECTUAL DISABILITY; INTERVENTIONS; SCORES; INDEX; EQ-5D; PEDSQL(TM)-4.0 AB Comparative effectiveness of interventions for children with autism spectrum disorders (ASDs) that incorporates costs is lacking due to the scarcity of information on health utility scores or preference-weighted outcomes typically used for calculating quality-adjusted life years (QALYs). This study created algorithms for mapping clinical and behavioral measures for children with ASDs to health utility scores. The algorithms could be useful for estimating the value of different interventions and treatments used in the care of children with ASDs. Participants were recruited from two Autism Treatment Network sites. Health utility data based on the Health Utilities Index Mark 3 (HUI3) for the child were obtained from the primary caregiver (proxy-reported) through a survey (N=224). During the initial clinic visit, proxy-reported measures of the Child Behavior Checklist, Vineland II Adaptive Behavior Scales, and the Pediatric Quality of Life Inventory 4.0 (start measures) were obtained and then merged with the survey data. Nine mapping algorithms were developed using the HUI3 scores as dependent variables in ordinary least squares regressions along with the start measures, the Autism Diagnostic Observation Schedule, to measure severity, child age, and cognitive ability as independent predictors. In-sample cross-validation was conducted to evaluate predictive accuracy. Multiple imputation techniques were used for missing data. The average age for children with ASDs in this study was 8.4 (standard deviation=3.5) years. Almost half of the children (47%) had cognitive impairment (IQ70). Total scores for all of the outcome measures were significantly associated with the HUI3 score. The algorithms can be applied to clinical studies containing start measures of children with ASDs to predict QALYs gained from interventions. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Payakachat, Nalin; Tilford, J. Mick] Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, Little Rock, AR 72223 USA. [Tilford, J. Mick] Univ Arkansas Med Sci, Dept Hlth Policy & Management, Little Rock, AR 72223 USA. [Tilford, J. Mick; Bellando, Jayne] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72223 USA. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Adolescent Hlth Policy, Boston, MA 02114 USA. [van Exel, N. Job; Brouwer, Werner B. F.] Erasmus Univ, Dept Hlth Policy & Management, Rotterdam, Netherlands. [Kovacs, Erica] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Pyne, Jeffrey M.] Univ Arkansas Med Sci, Inst Psychiat Res, Little Rock, AR 72223 USA. RP Payakachat, N (reprint author), Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, 4301 W Markham St,522, Little Rock, AR 72223 USA. EM npayakachat@uams.edu FU National Institute of Mental Health [R01MH089466, R03MH102495]; Translational Research Institute through the NIH National Center for Research Resources [UL1TR000039]; National Center for Advancing Translational Sciences; U.S. Department of Health and Human Services [UA3MC11054]; Health Resources and Services Administration; Maternal and Child Health Research Program FX The project was supported by Grant No. R01MH089466 from the National Institute of Mental Health with JMT and KAK serving as principal investigators, and Grant No. R03MH102495 with NP as the principal investigator. JMT also was supported by the Translational Research Institute, Grant No. UL1TR000039 through the NIH National Center for Research Resources and National Center for Advancing Translational Sciences. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors acknowledge the members of the Autism Treatment Network for use of the data. The data for the study were collected as part of the Autism Treatment Network, a program of Autism Speaks. Further support came from a cooperative agreement (UA3MC11054) from the U.S. Department of Health and Human Services, Health Resources and Services Administration, and Maternal and Child Health Research Program, to the Massachusetts General Hospital. The work described in this article represents the independent efforts of the authors with no restrictions from the funding source or the Autism Treatment Network. None of the authors of this study reported a conflict of interest associated with the preparation of the manuscript. Maria Melguizo, Nupur Chowdhury, Rebecca Rieger, and Latunja Sockwell provided excellent research assistance. NR 81 TC 11 Z9 11 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 EI 1939-3806 J9 AUTISM RES JI Autism Res. PD DEC PY 2014 VL 7 IS 6 BP 649 EP 663 DI 10.1002/aur.1409 PG 15 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AW7TR UT WOS:000346467700002 PM 25255789 ER PT J AU Huber, RJ Lumsden, A Gusella, JF Myre, MA AF Huber, R. J. Lumsden, A. Gusella, J. F. Myre, M. A. TI Huntingtin: required for contractile vacuole biogenesis in Dictyostelium discoideum SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Meeting Abstract C1 [Huber, R. J.; Lumsden, A.; Gusella, J. F.; Myre, M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0829-8211 EI 1208-6002 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD DEC PY 2014 VL 92 IS 6 BP 594 EP 594 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AW6FX UT WOS:000346366200090 ER PT J AU Huber, RJ Cotman, SL Myre, MA AF Huber, R. J. Cotman, S. L. Myre, M. A. TI The Batten disease protein CLN3 negatively regulates proliferation and development in Dictyostelium discoideum SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Meeting Abstract C1 [Huber, R. J.; Cotman, S. L.; Myre, M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0829-8211 EI 1208-6002 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD DEC PY 2014 VL 92 IS 6 BP 594 EP 594 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AW6FX UT WOS:000346366200089 ER PT J AU Naritoku, WY Black-Schaffer, WS AF Naritoku, Wesley Y. Black-Schaffer, W. Stephen TI Cytopathology Fellowship Milestones SO CANCER CYTOPATHOLOGY LA English DT Review DE cytopathology; fellowship; milestone; accreditation; competency; Accreditation Council for Graduate Medical Education (ACGME); pathology; subspecialty; requirement AB The American Society of Cytopathology has provided guidelines for goals and objectives for cytopathology fellows. There are 90 Accreditation Council for Graduate Medical Education-accredited cytopathology fellowship training programs in the United States, each with its own unique curriculum designed to achieve these goals and objectives. The Accreditation Council for Graduate Medical Education cytopathology fellowship milestones were developed to ensure some uniformity in the outcomes of the various skill sets and competencies expected of a graduating cytopathology fellow. The rationale, development, and details of the cytopathology fellowship milestones are described herein. Cancer (Cancer Cytopathol) 2014;122:859-865. (c) 2014 American Cancer Society. There are 90 Accreditation Council for Graduate Medical Education (ACGME)-accredited cytopathology fellowship training programs in the United States, each with its own unique curriculum designed to achieve its goals and objectives. The ACGME cytopathology fellowship milestones were developed to ensure some uniformity in the outcomes of the various skill sets and competencies expected of a graduating cytopathology fellow. C1 [Naritoku, Wesley Y.] Los Angeles Cty Univ Southern Calif Med Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Keck Sch Med, Dept Pathol, Los Angeles, CA USA. [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Black-Schaffer, WS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 210,55 Fruit St, Boston, MA 02114 USA. EM sblackschaffer@partners.org NR 12 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC PY 2014 VL 122 IS 12 BP 859 EP 865 DI 10.1002/cncy.21483 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA AW5YY UT WOS:000346348000003 PM 25236620 ER PT J AU Sebastian, C Mostoslavsky, R AF Sebastian, Carlos Mostoslavsky, Raul TI Untangling the Fiber Yarn: Butyrate Feeds Warburg to Suppress Colorectal Cancer SO CANCER DISCOVERY LA English DT Editorial Material ID COLON AB Dietary composition has an important role in shaping the gut microbiota. In turn, changes in the diet directly impinge on bacterial metabolites present in the intestinal lumen. Whether such metabolites play a role in intestinal cancer has been a topic of hot debate. In this issue of Cancer Discovery, Donohoe and colleagues show that dietary fiber protects against colorectal carcinoma in a microbiota-dependent manner. Furthermore, fiber-derived butyrate acts as a histone deacetylase inhibitor, inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells experiencing the Warburg effect. (C) 2014 AACR. C1 [Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St,Simches Bldg CPZN 4208, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU NCI NIH HHS [R01 CA175727, CA175727-01A1]; NIDDK NIH HHS [DK088190-01A1]; NIGMS NIH HHS [GM093072-01, R01 GM093072] NR 9 TC 5 Z9 5 U1 0 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2014 VL 4 IS 12 BP 1368 EP 1370 DI 10.1158/2159-8290.CD-14-1231 PG 3 WC Oncology SC Oncology GA AW8HJ UT WOS:000346501900019 PM 25477104 ER PT J AU Wargo, JA Cooper, ZA Flaherty, KT AF Wargo, Jennifer A. Cooper, Zachary A. Flaherty, Keith T. TI Universes Collide: Combining Immunotherapy with Targeted Therapy for Cancer SO CANCER DISCOVERY LA English DT Review ID RECOMBINANT INTERLEUKIN-2 THERAPY; GASTROINTESTINAL STROMAL TUMORS; RAF INHIBITOR RESISTANCE; METASTATIC MELANOMA; BRAF INHIBITION; T-CELLS; ANTIGEN-EXPRESSION; ANTITUMOR-ACTIVITY; SIGNALING PATHWAY; VEMURAFENIB AB There have been significant advances in the past several years with regard to targeted therapy and immunotherapy for cancer. This is highlighted in melanoma, where treatment with targeted therapy (against the BRAF oncoprotein) results in responses in the majority of patients, although the duration of response is limited. In contrast, treatment with immunotherapy results in a lower response rate, but one that tends to be more durable. Insights about mechanisms of response and potential synergy between these treatment strategies for melanoma are a focus of this review, with opportunities to extend these insights to the treatment of other cancers. Significance: Two major advances in melanoma have occurred concurrently and involve treatment with targeted therapy and immune checkpoint blockade. However, each of these approaches has limitations with regard to overall response rates or duration of response. To address this, investigators have proposed combining these strategies, and this concept is being tested empirically in clinical trials. There is a scientific rationale supporting the combination of targeted therapy and immunotherapy, and these concepts are discussed herein. (C) 2014 AACR. C1 [Wargo, Jennifer A.; Cooper, Zachary A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Wargo, Jennifer A.; Cooper, Zachary A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Flaherty, Keith T.] Harvard Univ, Boston, MA 02115 USA. RP Wargo, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jwargo@mdanderson.org OI Cooper, Zachary/0000-0003-1059-0940 FU NIH [1K08CA160692-01A1, U54CA163125-01] FX J.A. Wargo acknowledges NIH grant 1K08CA160692-01A1 and the generous philanthropic support of several families whose lives have been affected by melanoma. J.A. Wargo and K.T. Flaherty acknowledge NIH grant U54CA163125-01. NR 69 TC 32 Z9 32 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2014 VL 4 IS 12 BP 1377 EP 1386 DI 10.1158/2159-8290.CD-14-0477 PG 10 WC Oncology SC Oncology GA AW8HJ UT WOS:000346501900022 PM 25395294 ER PT J AU Hu, YD Petit, SA Ficarro, SB Toomire, KJ Xie, AY Lim, E Cao, SLA Park, E Eck, MJ Scully, R Brown, M Marto, JA Livingston, DM AF Hu, Yiduo Petit, Sarah A. Ficarro, Scott B. Toomire, Kimberly J. Xie, Anyong Lim, Elgene Cao, Shiliang A. Park, Eunyoung Eck, Michael J. Scully, Ralph Brown, Myles Marto, Jarrod A. Livingston, David M. TI PARP1-Driven Poly-ADP-Ribosylation Regulates BRCA1 Function in Homologous Recombination-Mediated DNA Repair SO CANCER DISCOVERY LA English DT Article ID SISTER-CHROMATID RECOMBINATION; SUSCEPTIBILITY PROTEIN BRCA1; NEGATIVE BREAST-CANCER; DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; DAMAGE RESPONSE; GENOMIC STABILITY; MAMMALIAN-CELLS; OVARIAN-CANCER; TARGETS BRCA1 AB BRCA1 promotes homologous recombination-mediated DNA repair (HRR). However, HRR must be tightly regulated to prevent illegitimate recombination. We previously found that BRCA1 HRR function is regulated by the RAP80 complex, but the mechanism was unclear. We have now observed that PARP1 interacts with and poly-ADP-ribosylates (aka PARsylates) BRCA1. PARsylation is directed at the BRCA1 DNA binding domain and downmodulates its function. Moreover, RAP80 contains a poly-ADP-ribose-interacting domain that binds PARsylated BRCA1 and helps to maintain the stability of PARP1-BRCA1-RAP80 complexes. BRCA1 PARsylation is a key step in BRCA1 HRR control. When BRCA1 PARsylation is defective, it gives rise to excessive HRR and manifestations of genome instability. BRCA1 PARsylation and/or RAP80 expression is defective in a subset of sporadic breast cancer cell lines and patient-derived tumor xenograft models. These observations are consistent with the possibility that such defects, when chronic, contribute to tumor development in BRCA1(+/+) individuals. SIGNIFICANCE: We propose a model that describes how BRCA1 functions to both support and restrict HRR. BRCA1 PARsylation is a key event in this process, failure of which triggers hyper-recombination and chromosome instability. Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions. (C) 2014 AACR. C1 [Hu, Yiduo; Petit, Sarah A.; Ficarro, Scott B.; Toomire, Kimberly J.; Park, Eunyoung; Eck, Michael J.; Marto, Jarrod A.; Livingston, David M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Hu, Yiduo; Petit, Sarah A.; Toomire, Kimberly J.; Livingston, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Livingston, David M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ficarro, Scott B.; Park, Eunyoung; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Xie, Anyong] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Lim, Elgene; Cao, Shiliang A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM david_livingston@dfci.harvard.edu RI Scully, Ralph/F-5008-2013; OI Brown, Myles/0000-0002-8213-1658 FU NCI; Breast Cancer Research Foundation; Susan G. Komen Foundation; NCI SPORE grant in breast cancer research; U.S. Department of Defense postdoctoral fellowship award [W81XWH-09-1-0632] FX This work was supported by grants from the NCI, the Breast Cancer Research Foundation, and the Susan G. Komen Foundation for the Cure (to D.M. Livingston), and by an NCI SPORE grant in breast cancer research to Dana-Farber/Harvard Cancer Center. Y. Hu was supported by a U.S. Department of Defense postdoctoral fellowship award (W81XWH-09-1-0632). NR 85 TC 19 Z9 19 U1 0 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2014 VL 4 IS 12 BP 1430 EP 1447 DI 10.1158/2159-8290.CD-13-0891 PG 18 WC Oncology SC Oncology GA AW8HJ UT WOS:000346501900027 PM 25252691 ER PT J AU Gopal, YNV Rizos, H Chen, G Deng, WL Frederick, DT Cooper, ZA Scolyer, RA Pupo, G Komurov, K Sehgal, V Zhang, JX Patel, L Pereira, CG Broom, BM Mills, GB Ram, P Smith, PD Wargo, JA Long, GV Davies, MA AF Gopal, Y. N. Vashisht Rizos, Helen Chen, Guo Deng, Wanleng Frederick, Dennie T. Cooper, Zachary A. Scolyer, Richard A. Pupo, Gulietta Komurov, Kakajan Sehgal, Vasudha Zhang, Jiexin Patel, Lalit Pereira, Cristiano G. Broom, Bradley M. Mills, Gordon B. Ram, Prahlad Smith, Paul D. Wargo, Jennifer A. Long, Georgina V. Davies, Michael A. TI Inhibition of mTORC1/2 Overcomes Resistance to MAPK Pathway Inhibitors Mediated by PGC1 alpha and Oxidative Phosphorylation in Melanoma SO CANCER RESEARCH LA English DT Article ID METASTATIC MELANOMA; IMPROVED SURVIVAL; BRAF; MUTATION; TUMORS; VEMURAFENIB; DABRAFENIB; AZD8055; POTENT; CELLS AB Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1 alpha. Notably, all selumetinib-resistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inhibitor AZD8055, whereas this combination was ineffective in resistant cell lines with low OxPhos. In both BRAF- and NRAS-mutant melanoma cells, MEK inhibition increased MITF expression, which in turn elevated levels of PGC1 alpha. In contrast, mTORC1/2 inhibition triggered cytoplasmic localization of MITF, decreasing PGC1 alpha expression and inhibiting OxPhos. Analysis of tumor biopsies from patients with BRAF-mutant melanoma progressing on BRAF inhibitor +/- MEK inhibitor revealed that PGC1 alpha levels were elevated in approximately half of the resistant tumors. Overall, our findings highlight the significance of OxPhos in melanoma and suggest that combined targeting of the MAPK and mTORC pathways may offer an effective therapeutic strategy to treat melanomas with this metabolic phenotype. (C) 2014 AACR. C1 [Gopal, Y. N. Vashisht; Chen, Guo; Deng, Wanleng; Pereira, Cristiano G.; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Rizos, Helen; Scolyer, Richard A.; Pupo, Gulietta; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Rizos, Helen; Scolyer, Richard A.; Pupo, Gulietta; Long, Georgina V.] Westmead Hosp, Sydney, NSW, Australia. [Frederick, Dennie T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Komurov, Kakajan] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA. [Sehgal, Vasudha; Mills, Gordon B.; Ram, Prahlad; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Zhang, Jiexin; Broom, Bradley M.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat, Houston, TX 77030 USA. [Patel, Lalit] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Smith, Paul D.] Astra Zeneca, Macclesfield, Cheshire, England. RP Gopal, YNV (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1515 Holcombe Blvd,Unit 904, Houston, TX 77030 USA. EM vynanda@mdanderson.org RI Pereira, Cristiano/M-9963-2014; OI Patel, Lalit/0000-0002-9064-5560 FU CPRIT [RP110532]; RPPA Core by NCI [CA16672]; MDACC SPORE in Melanoma [P50 CA093459]; Cancer Institute New South Wales Research Fellowships; NHMRC Fellowship; MDACC-AstraZeneca Collaborative Research Alliance; Adelson Medical Research Foundation FX The siRNA synthetic lethality screen was supported by CPRIT (RP110532) and RPPA Core by NCI (CA16672). T200 sequence analysis was supported by Sheikh Khalifa Foundation to the Sheikh Khalifa Bin Zayed Al Nahyan IPCT. Y.N.V. Gopal is supported by a grant from the MDACC SPORE in Melanoma (P50 CA093459). G.V. Long and H. Rizos are supported by a Cancer Institute New South Wales Research Fellowships and NHMRC Fellowship to HR. This study was also supported by grants from MDACC-AstraZeneca Collaborative Research Alliance and Adelson Medical Research Foundation. NR 23 TC 24 Z9 24 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 7037 EP 7047 DI 10.1158/0008-5472.CAN-14-1392 PG 11 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400028 PM 25297634 ER PT J AU Schubbert, S Cardenas, A Chen, H Garcia, C Guo, W Bradner, J Wu, H AF Schubbert, Suzanne Cardenas, Anjelica Chen, Harrison Garcia, Consuelo Guo, Wei Bradner, James Wu, Hong TI Targeting the MYC and PI3K Pathways Eliminates Leukemia-Initiating Cells in T-cell Acute Lymphoblastic Leukemia SO CANCER RESEARCH LA English DT Article ID CANCER STEM-CELLS; GAMMA-SECRETASE INHIBITORS; BET BROMODOMAIN INHIBITION; ACUTE MYELOID-LEUKEMIA; AURORA KINASES; C-MYC; PTEN; NOTCH1; MUTATIONS; GROWTH AB Disease relapse remains the major clinical challenge in treating T-cell acute lymphoblastic leukemia (T-ALL), particularly those with PTEN loss. We hypothesized that leukemia-initiating cells (LIC) are responsible for T-ALL development and treatment relapse. In this study, we used a genetically engineered mouse model of Pten(-/-) T-ALL with defined blast and LIC-enriched cell populations to demonstrate that LICs are responsible for therapeutic resistance. Unlike acute and chronic myelogenous leukemia, LICs in T-ALL were actively cycling, were distinct biologically, and responded differently to targeted therapies in comparison with their differentiated blast cell progeny. Notably, we found that T-ALL LICs could be eliminated by cotargeting the deregulated pathways driven by PI3K and Myc, which are altered commonly in human T-ALL and are associated with LIC formation. Our findings define critical events that may be targeted to eliminate LICs in T-ALL as a new strategy to treat the most aggressive relapsed forms of this disease. (C) 2014 AACR. C1 [Schubbert, Suzanne; Cardenas, Anjelica; Chen, Harrison; Garcia, Consuelo; Guo, Wei; Wu, Hong] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Cardenas, Anjelica] Calif State Univ Northridge, Dept Biol, Northridge, CA 91330 USA. [Bradner, James] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Hong] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. [Wu, Hong] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. RP Wu, H (reprint author), Peking Univ, 5 Yheyuan Rd, Beijing 100871, Peoples R China. EM hongwu@pku.edu.cn FU William Lawrence & Blanche Hughes Foundation; Leukemia and Lymphoma Society; National Cancer Institute training award [T32-CA009120-36]; CSUN-UCLA Bridges to Stem Cell Research Program [TB1-01183] FX This work was supported by a grant from the William Lawrence & Blanche Hughes Foundation (H. Wu). S. Schubbert was supported by a fellowship from the Leukemia and Lymphoma Society and National Cancer Institute training award T32-CA009120-36. A. Cardenas was supported by the CSUN-UCLA Bridges to Stem Cell Research Program TB1-01183. NR 44 TC 7 Z9 7 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 7048 EP 7059 DI 10.1158/0008-5472.CAN-14-1470 PG 12 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400029 PM 25287161 ER PT J AU Goetz, EM Ghandi, M Treacy, DJ Wagle, N Garraway, LA AF Goetz, Eva M. Ghandi, Mahmoud Treacy, Daniel J. Wagle, Nikhil Garraway, Levi A. TI ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors SO CANCER RESEARCH LA English DT Article ID METASTATIC MELANOMA; RAF INHIBITION; ACQUIRED-RESISTANCE; RANDOM MUTAGENESIS; IMPROVED SURVIVAL; MEK INHIBITION; HUMAN CANCER; BRAF; VEMURAFENIB; IDENTIFICATION AB The use of targeted therapeutics directed against BRAF(V600)-mutant metastatic melanoma improves progression-free survival in many patients; however, acquired drug resistance remains a major medical challenge. By far, the most common clinical resistance mechanism involves reactivation of the MAPK (RAF/MEK/ERK) pathway by a variety of mechanisms. Thus, targeting ERK itself has emerged as an attractive therapeutic concept, and several ERK inhibitors have entered clinical trials. We sought to preemptively determine mutations in ERK1/2 that confer resistance to either ERK inhibitors or combined RAF/MEK inhibition in BRAF(V600)-mutant melanoma. Using a random mutagenesis screen, we identified multiple point mutations in ERK1 (MAPK3) and ERK2 (MAPK1) that could confer resistance to ERK or RAF/MEK inhibitors. ERK inhibitor-resistant alleles were sensitive to RAF/MEK inhibitors and vice versa, suggesting that the future development of alternating RAF/MEK and ERK inhibitor regimens might help circumvent resistance to these agents. (C)2014 AACR. C1 [Goetz, Eva M.; Treacy, Daniel J.; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Goetz, Eva M.; Ghandi, Mahmoud; Wagle, Nikhil; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Levi_Garraway@dfci.harvard.edu OI Ghandi, Mahmoud/0000-0003-1897-2265 FU Novartis Institutes for BioMedical Research; Melanoma Research Alliance; Starr Cancer Consortium; Dr. Miriam and Sheldon Adelson Medical Research Foundation; NCI FX E.M. Goetz was supported by the Novartis Institutes for BioMedical Research. L.A. Garraway was supported by the Novartis Institutes for BioMedical Research, Melanoma Research Alliance, Starr Cancer Consortium, Dr. Miriam and Sheldon Adelson Medical Research Foundation, and NCI. NR 39 TC 20 Z9 20 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 7079 EP 7089 DI 10.1158/0008-5472.CAN-14-2073 PG 11 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400032 PM 25320010 ER PT J AU Chung, MK Holcomb, RG Mittal, S Steinberg, JS Gleva, MJ Mela, T Uslan, DZ Mitchell, K Poole, JE AF Chung, Mina K. Holcomb, Richard G. Mittal, Suneet Steinberg, Jonathan S. Gleva, Marye J. Mela, Theofanie Uslan, Daniel Z. Mitchell, Kevin Poole, Jeanne E. CA REPLACE Investigators TI REPLACE DARE (Death After Replacement Evaluation) Score Determinants of All-Cause Mortality After Implantable Device Replacement or Upgrade From the REPLACE Registry SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE defibrillators, implantable; mortality; pacemakers ID CARDIOVERTER-DEFIBRILLATOR; ATRIAL-FIBRILLATION; HEART-FAILURE; RISK; COMPLICATIONS; THERAPY AB Background-Identifying factors predictive of mortality may be important to decrease risk associated with cardiac implantable electrical device (CIED) replacement procedures. This study aimed to determine whether clinical factors and complications independently associate with death and to develop a mortality risk prediction tool after CIED replacement. Methods and Results-The prospective REPLACE Registry determined 6-month complication and mortality rates after CIED replacement with or without planned lead addition or revision. Vital status was collected. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were performed to identify patient, procedural, or complication variables predictive of death. The REPLACE DARE (Death After Replacement Evaluation) Score was constructed using hazard ratios, reflecting relative risk contributions of each variable, combined into an additive mortality risk score equation. At 6 months, 70 of 1744 (4.0%) patients had died. Cox regression analysis found no significant association between major complications and death. However, recent heart failure admission, New York Heart Association class III/IV, antiarrhythmic drug use, cerebrovascular disease, and chronic kidney disease stage were independently associated with 6-month mortality. The REPLACE DARE Score was 2.0 +/- 1.4 in survivors versus 3.5 +/- 1.8 in nonsurvivors (P<0.001), with predictive receiver operating characteristic value=0.758 (P<0.001). Risk of death was 1.0% for DARE=0 and 55.6% for DARE=7. The hazard ratio was 1.8 for each change of 1 DARE unit. Conclusions-Comorbidities, but not complications, were significantly associated with mortality after CIED replacement. The REPLACE DARE Score is a novel tool that can identify patients with substantial mortality risk. Such patients should have the relative risk and benefit of their procedure considered carefully. C1 [Chung, Mina K.] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH 44195 USA. [Holcomb, Richard G.] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Minnetonka, MN USA. [Mittal, Suneet; Steinberg, Jonathan S.] Valley Hlth Syst, Arrhythmia Inst, New York, NY USA. [Gleva, Marye J.] Washington Univ, Dept Med, Div Cardiol, St Louis, MO USA. [Mela, Theofanie] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Mela, Theofanie] Harvard Univ, Sch Med, Boston, MA USA. [Uslan, Daniel Z.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Mitchell, Kevin] BIOTRONIK, Lake Oswego, OR USA. [Poole, Jeanne E.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. RP Chung, MK (reprint author), Cleveland Clin, Dept Cardiovasc Med, 9500 Euclid Ave,J2-2, Cleveland, OH 44195 USA. EM chungm@ccf.org FU BIOTRONIK FX The REPLACE Registry was sponsored by BIOTRONIK. NR 20 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD DEC PY 2014 VL 7 IS 6 BP 1048 EP U128 DI 10.1161/CIRCEP.114.001671 PG 28 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW6DR UT WOS:000346360100011 PM 25221331 ER PT J AU Luneburg, N Lieb, W Zeller, T Chen, MH Maas, R Carter, AM Xanthakis, V Glazer, NL Schwedhelm, E Seshadri, S Ikram, MA Longstreth, WT Fornage, M Konig, IR Loley, C Ojeda, FM Schillert, A Wang, TJ Sticht, H Kittel, A Konig, J Benjamin, EJ Sullivan, LM Bernges, I Anderssohn, M Ziegler, A Gieger, C Illig, T Meisinger, C Wichmann, HE Wild, PS Schunkert, H Psaty, BM Wiggins, KL Heckbert, SR Smith, N Lackner, K Lunetta, KL Blankenberg, S Erdmann, J Munzel, T Grant, PJ Vasan, RS Boger, RH AF Lueneburg, Nicole Lieb, Wolfgang Zeller, Tanja Chen, Ming-Huei Maas, Renke Carter, Angela M. Xanthakis, Vanessa Glazer, Nicole L. Schwedhelm, Edzard Seshadri, Sudha Ikram, Mohammad Arfan Longstreth, William T., Jr. Fornage, Myriam Koenig, Inke R. Loley, Christina Ojeda, Francisco M. Schillert, Arne Wang, Thomas J. Sticht, Heinrich Kittel, Anja Koenig, Joerg Benjamin, Emelia J. Sullivan, Lisa M. Bernges, Isabel Anderssohn, Maike Ziegler, Andreas Gieger, Christian Illig, Thomas Meisinger, Christa Wichmann, H. -Erich Wild, Philipp S. Schunkert, Heribert Psaty, Bruce M. Wiggins, Kerri L. Heckbert, Susan R. Smith, Nicholas Lackner, Karl Lunetta, Kathryn L. Blankenberg, Stefan Erdmann, Jeanette Munzel, Thomas Grant, Peter J. Vasan, Ramachandran S. Boeger, Rainer H. TI Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE biological markers; genome wide association study; nitric oxide ID ANTIHYPERTENSIVE DRUG THERAPIES; PRIMARY HYPEROXALURIA TYPE-1; INTIMA-MEDIA THICKNESS; NITRIC-OXIDE SYNTHASE; ASYMMETRIC DIMETHYLARGININE; MYOCARDIAL-INFARCTION; ISCHEMIC-STROKE; RENAL-FUNCTION; N-G; RISK AB Background-Dimethylarginines (DMA) interfere with nitric oxide formation by inhibiting nitric oxide synthase (asymmetrical DMA [ADMA]) and l-arginine uptake into the cell (ADMA and symmetrical DMA [SDMA]). In prospective clinical studies, ADMA has been characterized as a cardiovascular risk marker, whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterize the environmental and genetic contributions to interindividual variability of these biomarkers. Methods and Results-This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (Framingham Heart Study [FHS; n=2992], Gutenberg Health Study [GHS; n=4354], and Multinational Monitoring of Trends and Determinants in Cardiovascular Disease Study [MONICA]/Cooperative Health Research in the Augsburg Area, Augsburg, Bavaria, Germany [KORA] F3 [n=581]) and identified replicated loci (DDAH1, MED23, Arg1, and AGXT2) associated with the interindividual variability in ADMA, l-arginine, and SDMA. Experimental in silico and in vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants, and various cardiometabolic risk factors. AGXT2 variants were not associated with poststroke survival in the Leeds study or were they associated with incident stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Conclusions-These genome-wide association study support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and l-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. C1 [Lueneburg, Nicole; Seshadri, Sudha; Bernges, Isabel; Anderssohn, Maike; Boeger, Rainer H.] Univ Med Ctr Hamburg Eppendorf, Dept Clin Pharmacol & Toxicol, D-20246 Hamburg, Germany. [Zeller, Tanja; Ojeda, Francisco M.; Blankenberg, Stefan] Univ Med Ctr Hamburg Eppendorf, Univ Heart Ctr, D-20246 Hamburg, Germany. [Chen, Ming-Huei; Xanthakis, Vanessa; Glazer, Nicole L.; Seshadri, Sudha; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Koenig, Inke R.; Loley, Christina; Schillert, Arne; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Maas, Renke; Kittel, Anja; Koenig, Joerg] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol, D-91054 Erlangen, Germany. [Schunkert, Heribert] Univ Erlangen Nurnberg, Inst Biochem, D-91054 Erlangen, Germany. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds, W Yorkshire, England. [Chen, Ming-Huei; Xanthakis, Vanessa; Wang, Thomas J.; Benjamin, Emelia J.; Sullivan, Lisa M.; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Chen, Ming-Huei; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Ikram, Mohammad Arfan] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, Mohammad Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Longstreth, William T., Jr.; Psaty, Bruce M.; Wiggins, Kerri L.; Smith, Nicholas] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. [Longstreth, William T., Jr.; Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Longstreth, William T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Boston, MA USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Boston, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gieger, Christian; Illig, Thomas; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Oberschleissheim, Germany. [Meisinger, Christa; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Oberschleissheim, Germany. [Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany. [Wild, Philipp S.; Munzel, Thomas] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany. [Lackner, Karl] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany. [Wild, Philipp S.] Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis, Mainz, Germany. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas] VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Sticht, Heinrich] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Sticht, Heinrich] Munich Heart Alliance, German Ctr Cardiovasc Res, Munich, Germany. [Ziegler, Andreas; Erdmann, Jeanette] German Ctr Cardiovasc Res, Lubeck, Germany. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Ziegler, Andreas] Med Univ Lubeck, Ctr Clin Trial, D-23538 Lubeck, Germany. RP Luneburg, N (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Clin Pharmacol & Toxicol, Martinistr 52, D-20246 Hamburg, Germany. EM n.lueneburg@uke.de RI Meisinger, Christine/B-5358-2014; Konig, Inke/A-4544-2009; Lieb, Wolfgang/C-1990-2012; Erdmann, Jeanette/P-7513-2014; OI Ikram, Mohammad Arfan/0000-0003-0372-8585; Seshadri, Sudha/0000-0001-6135-2622; Ramachandran, Vasan/0000-0001-7357-5970; Erdmann, Jeanette/0000-0002-4486-6231; Benjamin, Emelia/0000-0003-4076-2336; Gieger, Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397; Meisinger, Christa/0000-0002-9026-6544; Sticht, Heinrich/0000-0001-5644-045X FU NHGRI NIH HHS [U01 HG004729] NR 51 TC 9 Z9 10 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD DEC PY 2014 VL 7 IS 6 BP 864 EP U318 DI 10.1161/CIRCGENETICS.113.000264 PG 30 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AW6DE UT WOS:000346358800017 PM 25245031 ER PT J AU Bianchi, G Ghobrial, IM AF Bianchi, Giada Ghobrial, Irene M. TI Team Work Matters: Dual Inhibition Puts Non-Hodgkin Lymphoma Under Siege SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CELL LYMPHOMA; PI3K AB Inhibitors of PI3K/mTOR and histone deacetylases (HDAC) are effective in non-Hodgkin lymphoma (NHL). However, clinical resistance eventually ensues and combinatory therapies are sought to prevent it. Preclinical evaluation of dual PI3K/mTOR and HDAC inhibition is synergistic against NHL, paving the way for bench-to-bedside translation. (C) 2014 AACR. C1 [Bianchi, Giada; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Harvard Inst Med, 450 Brookline Ave, Boston, MA 02215 USA. EM Irene_Ghobrial@dfci.harvard.edu FU NCI NIH HHS [R01CA154648, R01 CA125690, R01CA181683] NR 12 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2014 VL 20 IS 23 BP 5863 EP 5865 DI 10.1158/1078-0432.CCR-14-2055 PG 3 WC Oncology SC Oncology GA AW7AS UT WOS:000346417400001 PM 25294900 ER PT J AU Bodell, L Forney, KJ Keel, P Gutierrez, P Joiner, TE AF Bodell, Lindsay Forney, Katherine Jean Keel, Pamela Gutierrez, Peter Joiner, Thomas E. TI Consequences of Making Weight: A Review of Eating Disorder Symptoms and Diagnoses in the United States Military SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE eating disorder symptoms; eating disorders; military; purging; risk factors; veterans ID CONTRIBUTING FACTORS; PSYCHIATRIC COMORBIDITY; BODY DISSATISFACTION; HEALTH BEHAVIORS; BULIMIA-NERVOSA; AIR-FORCE; FOLLOW-UP; PREVALENCE; VETERANS; FEMALE AB Eating disorders are serious psychiatric illnesses associated with health problems. Such problems may compromise military performance, highlighting the need to establish the level of eating pathology that exists in military samples. This article qualitatively reviews prevalence estimates of eating disorder symptoms and diagnoses in military samples, providing nonmilitary estimates for context. Findings suggest that eating disorder symptoms are prevalent in cadets and active duty service members, especially when using self-report measures. The increased salience of weight in the military and increased exposure to trauma may influence risk for eating disorders. Alternatively, individuals at risk for eating disorders may self-select into the military. Overall, this review suggests that eating disorder symptoms are common in military samples and that further research is warranted. C1 [Bodell, Lindsay; Forney, Katherine Jean; Keel, Pamela; Joiner, Thomas E.] Florida State Univ, Tallahassee, FL 32306 USA. [Gutierrez, Peter] Denver VA Med Ctr, Denver, CO USA. RP Joiner, TE (reprint author), Florida State Univ, Dept Psychol, 1107 West Call St, Tallahassee, FL 32306 USA. EM joiner@psy.fsu.edu FU NIMH NIH HHS [T32 MH093311] NR 46 TC 7 Z9 7 U1 5 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0969-5893 EI 1468-2850 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD DEC PY 2014 VL 21 IS 4 BP 398 EP 409 DI 10.1111/cpsp.12082 PG 12 WC Psychology, Clinical SC Psychology GA AW5UC UT WOS:000346338200006 PM 25642105 ER PT J AU Rychert, J Danziger-Isakov, L Yen-Lieberman, B Storch, G Buller, R Sweet, SC Mehta, AK Cheeseman, JA Heeger, P Rosenberg, ES Fishman, JA AF Rychert, Jenna Danziger-Isakov, Lara Yen-Lieberman, Belinda Storch, Gregory Buller, Richard Sweet, Stewart C. Mehta, Aneesh K. Cheeseman, Jennifer A. Heeger, Peter Rosenberg, Eric S. Fishman, Jay A. TI Multicenter comparison of laboratory performance in cytomegalovirus and Epstein-Barr virus viral load testing using international standards SO CLINICAL TRANSPLANTATION LA English DT Article DE clinical trial; cytomegalovirus; Epstein-Barr virus; quantitative nucleic acid testing; viral load; WHO standards ID SOLID-ORGAN TRANSPLANTATION; TIME PCR ASSAYS; RECIPIENTS; MANAGEMENT; INFECTION; DNA; QUANTITATION; DISEASE AB BackgroundInfections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation and the Clinical Trials in Organ Transplantation in Children (CTOT and CTOTC). MethodsViral load testing was performed on well-defined viral preparations according to standard operating procedures at each site. ResultsAmong centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. Epstein-Barr virus viral load data were more variable and less accurate despite the use of international standards. ConclusionsThese data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials. C1 [Rychert, Jenna; Rosenberg, Eric S.] Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. [Danziger-Isakov, Lara] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Yen-Lieberman, Belinda] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Storch, Gregory; Buller, Richard; Sweet, Stewart C.] Washington Univ, Sch Med, St Louis, MO USA. [Mehta, Aneesh K.; Cheeseman, Jennifer A.] Emory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Mehta, Aneesh K.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. [Heeger, Peter] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Rosenberg, Eric S.; Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rosenberg, Eric S.; Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fishman, Jay A.] MGH Transplant Ctr, Boston, MA 02114 USA. RP Fishman, JA (reprint author), MGH Transplant Ctr, 55 Fruit St,WH510A, Boston, MA 02114 USA. EM jfishman@partners.org RI Mehta, Aneesh/B-8054-2012 OI Mehta, Aneesh/0000-0002-6552-9162 FU American Recovery and Reinvestment (ARRA) from the National Institute of Allergy and Infectious Diseases [U0163594]; NIH/NIAID [U01-AI077816-01, U01AI063623-04, 1U01AI77810-01, U01 AI084150-01] FX This research was performed as part of an American Recovery and Reinvestment (ARRA) funded project under Award Number U0163594 (Peter Heeger, PI) from the National Institute of Allergy and Infectious Diseases. The work was carried out by members of the Clinical Trials in Organ Transplantation (CTOT) and Clinical Trials in Organ Transplantation in Children (CTOT-C) consortia. These studies were also supported by awards from the NIH/NIAID: U01-AI077816-01 and U01AI063623-04 (JAF), 1U01AI77810-01 (GS, LDI), and U01 AI084150-01 (AM, CL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. NR 19 TC 5 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD DEC PY 2014 VL 28 IS 12 BP 1416 EP 1423 DI 10.1111/ctr.12473 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA AW3JE UT WOS:000346181800014 PM 25303316 ER PT J AU Qi, J AF Qi, Jun TI \ Bromodomain and Extraterminal Domain Inhibitors (BETi) for Cancer Therapy: Chemical Modulation of Chromatin Structure SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID C-MYC; LEUKEMIA; TARGET AB In cancer, epigenetic proteins are intensely studied targets for therapeutic drug discovery, showing great promise. These proteins include the chromatin-modifying enzymes that "write" and "erase" histone posttranslational modifications (PTM), and those that "read" these marks through binding modules. In an effort to find a compound that could disrupt the protein-protein interactions between a PTM and reader, JQ1 has proven to be a first-in-class, drug-like inhibitor of the "bromodomain and extraterminal domain" epigenetic readers (BETs), which recognize histone lysine acetylation marks. JQ1 has facilitated the mechanistic study and therapeutic application in cancer of this kind of epigenetic inhibition. By using this chemical probe, we have discovered that the bromodomain inhibitors (BETi) have compelling activity in preclinical models of multiple myeloma and acute myeloid leukemia. In particular, BETi down-regulates the MYC, IL-7R, and E2F transcriptional programs. We are continuously integrating the transcriptional consequences of BETi with changes in the epigenomic landscapes of cancer cells to elucidate the mechanisms underlying response to BETi using chemical and genetic perturbations. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Qi, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jun_qi@dfci.harvard.edu NR 5 TC 10 Z9 10 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD DEC PY 2014 VL 6 IS 12 AR a018663 DI 10.1101/cshperspect.a018663 PG 3 WC Cell Biology SC Cell Biology GA AW7MX UT WOS:000346449100012 PM 25452384 ER PT J AU Wang, R Wiggs, JL AF Wang, Ryan Wiggs, Janey L. TI Common and Rare Genetic Risk Factors for Glaucoma SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID OPEN-ANGLE GLAUCOMA; PRIMARY CONGENITAL GLAUCOMA; CENTRAL CORNEAL THICKNESS; GENOME-WIDE ASSOCIATION; TRABECULAR MESHWORK CELLS; NAIL-PATELLA SYNDROME; CYTOCHROME P4501B1 CYP1B1; NITRIC-OXIDE SYNTHASE; BINDING-PROTEIN 2; OPTIC-NERVE HEAD AB The characterization of genes responsible for glaucoma is the critical first step toward the development of gene-based diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. Early-onset forms of glaucoma affecting children and young adults are typically inherited as Mendelian autosomal dominant or recessive traits whereas glaucoma affecting older adults has complex inheritance. In this report, we present a comprehensive overview of the genes and genomic regions contributing to inherited glaucoma. C1 [Wang, Ryan; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 109 TC 10 Z9 10 U1 0 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD DEC PY 2014 VL 4 IS 12 AR a017244 DI 10.1101/cshperspect.a017244 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW8PB UT WOS:000346523200005 PM 25237143 ER PT J AU Blackney, K Quraishi, S Viktorsdottir, O Lee, J AF Blackney, Kevin Quraishi, Sadeq Viktorsdottir, Olof Lee, Jarone TI DELAYED PRESENTATION OF AN IATROGENIC BURN IN THE ICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Blackney, Kevin; Quraishi, Sadeq; Viktorsdottir, Olof; Lee, Jarone] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 1197 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211801418 ER PT J AU Cai, XM Herrington, T Nguyen, R Seifter, J Varian, K Warren, L Feske, S AF Cai, Xuemei Herrington, Todd Nguyen, Rita Seifter, Julian Varian, Kenneth Warren, Lauren Feske, Steven TI REVERSAL OF OSMOTIC MYELINOLYSIS SYNDROME BY RELOWERING SERUM SODIUM SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cai, Xuemei; Herrington, Todd] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Rita; Seifter, Julian; Varian, Kenneth; Warren, Lauren; Feske, Steven] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 1211 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211801432 ER PT J AU de la Cruz, JS Sally, M Patel, M Crutchfield, M Malinoski, D AF de la Cruz, J. Salvador Sally, Mitchell Patel, Madhukar Crutchfield, Megan Malinoski, Darren TI THE IMPACT OF DONOR HOSPITAL MANAGEMENT ON ORGAN DONATION OUTCOMES SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [de la Cruz, J. Salvador; Sally, Mitchell] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [de la Cruz, J. Salvador; Crutchfield, Megan; Malinoski, Darren] Portland VA Med Ctr, Portland, OR USA. [Patel, Madhukar] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 552 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800517 ER PT J AU George, E Voscopoulos, C MacNabb, C Freeman, J AF George, Ed Voscopoulos, Christopher MacNabb, Colin Freeman, Jenny TI RESPIRATORY VOLUME MONITORING: EARLY WARNING OF RESPIRATORY DEPRESSION & IDENTIFYING FALSE ALARMS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [George, Ed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Voscopoulos, Christopher] Duke Univ, Durham, NC USA. [MacNabb, Colin; Freeman, Jenny] Resp Mot Inc, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 677 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800642 ER PT J AU Han, S Snavely, C Jerome, J Mallampalli, R AF Han, SeungHye Snavely, Courtney Jerome, Jake Mallampalli, Rama TI LIPOPOLYSACCHARIDE PRIMES THE INFLAMMASOME BY INCREASING LEVELS OF IMMUNOREACTIVE NALP3 SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Han, SeungHye] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Snavely, Courtney; Jerome, Jake; Mallampalli, Rama] Univ Pittsburgh, Pittsburgh, PA USA. [Mallampalli, Rama] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 47 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800048 ER PT J AU Kirschen, M Elkind, J Lim, M Putnam, B Cohen, A AF Kirschen, Matthew Elkind, Jaclynn Lim, Miranda Putnam, Brendan Cohen, Akiva TI THE ROLE OF BRANCHED CHAIN AMINO ACIDS IN THE FUNCTIONAL RECOVERY FROM TRAUMATIC BRAIN INJURY SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kirschen, Matthew; Elkind, Jaclynn; Putnam, Brendan; Cohen, Akiva] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Lim, Miranda] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 108 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800073 ER PT J AU Lin, H Piriyapatsom, A Schmidt, U Bittner, E Pirrone, M De Pascale, G de Moya, M Berra, L AF Lin, Hsin Piriyapatsom, Annop Schmidt, Ulrich Bittner, Edward Pirrone, Massimiliano De Pascale, Gennaro de Moya, Marc Berra, Lorenzo TI INFECTION RELATED VENTILATOR ASSOCIATED CONDITIONS CAPTURE THE MINORITY OF VAP IN TRAUMA PATIENTS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lin, Hsin; Piriyapatsom, Annop; Schmidt, Ulrich; Bittner, Edward; Pirrone, Massimiliano; De Pascale, Gennaro; de Moya, Marc; Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 1044 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211801295 ER PT J AU Lin, H Bukovskaya, Y de Moya, M Schmidt, U AF Lin, Hsin Bukovskaya, Yana de Moya, Marc Schmidt, Ulrich TI VANCOMYCIN CONTINUOUS VERSUS INTERMITTENT INFUSION DURING CONTINUOUS VENOVENOUS HEMOFILTRATION SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lin, Hsin; Bukovskaya, Yana; de Moya, Marc; Schmidt, Ulrich] Massachussets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 503 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800468 ER PT J AU Meier, A Scully, E Bui, J Altfeld, M AF Meier, Angela Scully, Eileen Bui, Jack Altfeld, Marcus TI PROPOFOL AND DEXMEDETOMIDINE DIFFERENTIALLY IMPACT TLR RESPONSES OF HUMAN DCS AND MONOCYTES SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Meier, Angela] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meier, Angela; Scully, Eileen; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Bui, Jack] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 651 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800616 ER PT J AU Pirrone, M Pinciroli, R Mietto, C Imber, D Chenelle, C Kacmarek, R Berra, L AF Pirrone, Massimiliano Pinciroli, Riccardo Mietto, Cristina Imber, David Chenelle, Christopher Kacmarek, Robert Berra, Lorenzo TI EFFICACY STUDY OF A NOVEL DEVICE TO CLEAN THE ENDOTRACHEAL TUBE SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pirrone, Massimiliano; Pinciroli, Riccardo; Mietto, Cristina; Imber, David; Chenelle, Christopher; Kacmarek, Robert; Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 718 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800683 ER PT J AU Pirrone, M Mietto, C Chipman, D Fisher, D Corona, J Chenelle, C Kacmarek, R Berra, L AF Pirrone, Massimiliano Mietto, Cristina Chipman, Daniel Fisher, Daniel Corona, Javier Chenelle, Christopher Kacmarek, Robert Berra, Lorenzo TI TAILORED VENTILATION IN MORBID OBESE PATIENTS. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pirrone, Massimiliano; Mietto, Cristina; Chipman, Daniel; Fisher, Daniel; Corona, Javier; Chenelle, Christopher; Kacmarek, Robert; Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 679 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800644 ER PT J AU Quraishi, S DePascale, G Needleman, J Camargo, C Bajwa, E Bhan, I AF Quraishi, Sadeq DePascale, Gennaro Needleman, Joseph Camargo, Carlos, Jr. Bajwa, Ednan Bhan, Ishir TI EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON VITAMIN D STATUS AND CATHELICIDIN IN SEPSIS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Quraishi, Sadeq; DePascale, Gennaro; Needleman, Joseph; Camargo, Carlos, Jr.; Bajwa, Ednan; Bhan, Ishir] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 59 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800060 ER PT J AU Seethala, R Hou, P Wilcox, S Kaafarani, H Yeh, D Aisiku, I Cobb, JP Lee, J AF Seethala, Raghu Hou, Peter Wilcox, Susan Kaafarani, Haytham Yeh, Daniel Aisiku, Imo Cobb, J. Perren Lee, Jarone TI THE ASSOCIATION OF AGE WITH SHORT-TERM AND LONG-TERM MORTALITY IN ADULTS ADMITTED TO THE ICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Seethala, Raghu; Hou, Peter; Aisiku, Imo] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wilcox, Susan; Kaafarani, Haytham; Yeh, Daniel; Cobb, J. Perren; Lee, Jarone] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 376 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800341 ER PT J AU Tainter, C Levine, A Stahl, D Butterly, A Quraishi, S Lee, J AF Tainter, Christopher Levine, Alexander Stahl, David Butterly, Arielle Quraishi, Sadeq Lee, Jarone TI EFFECT OF AN OVERNIGHT "QUIET TIME" PROGRAM ON AMBIENT SOUND LEVELS IN THE SURGICAL ICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tainter, Christopher; Levine, Alexander; Stahl, David; Butterly, Arielle; Quraishi, Sadeq; Lee, Jarone] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 856 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211801106 ER PT J AU Tainter, C Cudemus, G Bittner, E AF Tainter, Christopher Cudemus, Gaston Bittner, Edward TI USING A "FLIPPED CLASSROOM" MODEL TO TEACH BEDSIDE ECHOCARDIOGRAPHY IN A SURGICAL ICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tainter, Christopher; Cudemus, Gaston; Bittner, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI 向飞, 郭/A-1604-2016 NR 0 TC 0 Z9 0 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 305 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800270 ER PT J AU Wilcox, S Saia, M Waden, H Gates, J McGahn, S Cocchi, M Genthon, A Richards, J AF Wilcox, Susan Saia, Mark Waden, Heather Gates, Jonathan McGahn, Susan Cocchi, Michael Genthon, Alissa Richards, Jeremy TI IMPROVED OXYGENATION AFTER CRITICAL CARE TRANSPORT IN PATIENTS WITH HYPOXEMIC RESPIRATORY FAILURE SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wilcox, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gates, Jonathan] Brigham & Womens Hosp, Brookline, MA USA. [McGahn, Susan] Boston MedFlight, Bedford, MA USA. [Cocchi, Michael; Richards, Jeremy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Genthon, Alissa] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 716 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800681 ER PT J AU Yeh, D Cropano, C Quraishi, S Fuentes, E Kaafarani, H Lee, J Chang, YC Velmahos, G AF Yeh, Daniel Cropano, Catrina Quraishi, Sadeq Fuentes, Eva Kaafarani, Haytham Lee, Jarone Chang, Yuchiao Velmahos, George TI IMPLEMENTATION OF AN AGGRESSIVE ENTERAL NUTRITION PROTOCOL AND THE EFFECT ON CLINICAL OUTCOMES SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yeh, Daniel; Cropano, Catrina; Quraishi, Sadeq; Fuentes, Eva; Kaafarani, Haytham; Lee, Jarone; Chang, Yuchiao; Velmahos, George] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 327 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800292 ER PT J AU Zhao, K Ladha, K Quraishi, S Tainter, C Seethala, R Kaafarani, H Eikermann, M Lee, J AF Zhao, Kevin Ladha, Karim Quraishi, Sadeq Tainter, Christopher Seethala, Raghu Kaafarani, Haytham Eikermann, Matthias Lee, Jarone TI ELIXHAUSER COMORBIDITY INDEX BETTER PREDICTS ICU MORTALITY THAN CHARLSON COMORBIDITY INDEX SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhao, Kevin; Ladha, Karim; Tainter, Christopher; Kaafarani, Haytham; Lee, Jarone] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seethala, Raghu] Brigham & Womens Hosp, Boston, MA 02115 USA. [Eikermann, Matthias] Departmnt Anesthesia Crit Care & Pain Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 384 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800349 ER PT J AU Soble, JR Eichstaedt, KE Waseem, H Mattingly, ML Benbadis, SR Bozorg, AM Vale, FL Schoenberg, MR AF Soble, Jason R. Eichstaedt, Katie E. Waseem, Hena Mattingly, Michelle L. Benbadis, Selim R. Bozorg, Ali M. Vale, Fernando L. Schoenberg, Mike R. TI Clinical utility of the Wechsler Memory Scale-Fourth Edition (WMS-IV) in predicting laterality of temporal lobe epilepsy among surgical candidates SO EPILEPSY & BEHAVIOR LA English DT Article DE Temporal lobe epilepsy; Neuropsychological assessment; Presurgical evaluation; Wechsler Memory Scale-Fourth Edition (WMS-IV); Rey Auditory Verbal Learning Test (RAVLT) ID BOSTON NAMING TEST; NEUROPSYCHOLOGICAL ASSESSMENT; ULTIMATE SIDE; SURGERY; PERFORMANCE; VALIDATION; LOBECTOMY; OUTCOMES; ABILITY; EEG AB This study evaluated the accuracy of the Wechsler Memory Scale-Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal-visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal-visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT. (C) 2014 Elsevier Inc. All rights reserved. C1 [Soble, Jason R.] South Texas Vet Hlth Care Syst, Psychol Serv 116B, San Antonio, TX 78229 USA. [Eichstaedt, Katie E.; Mattingly, Michelle L.; Schoenberg, Mike R.] Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Sci, Tampa, FL 33613 USA. [Waseem, Hena; Vale, Fernando L.; Schoenberg, Mike R.] Univ S Florida, USF Hlth, Morsani Coll Med, Dept Neurosurg & Brain Repair, Tampa, FL 33606 USA. [Benbadis, Selim R.; Bozorg, Ali M.; Schoenberg, Mike R.] Univ S Florida, USF Hlth, Morsani Coll Med, Dept Neurol, Tampa, FL 33606 USA. RP Schoenberg, MR (reprint author), Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Sci, 3515 East Fletcher Ave, Tampa, FL 33613 USA. EM Jason.Soble@va.gov; keichsta@health.usf.edu; hwaseem@health.usf.edu; mmatting@health.usf.edu; sbenbadi@health.usf.edu; abozorg@health.usf.edu; fvale@health.usf.edu; mschoenb@health.usf.edu RI Schoenberg, Mike/J-9018-2012; OI Schoenberg, Mike/0000-0003-1355-3651 NR 38 TC 4 Z9 4 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2014 VL 41 BP 232 EP 237 DI 10.1016/j.yebeh.2014.10.014 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AW3LH UT WOS:000346187700045 PM 25461222 ER PT J AU Zemke, AC Shiva, S Burns, JL Moskowitz, SM Pilewski, JM Gladwin, MT Bomberger, JM AF Zemke, Anna C. Shiva, Sruti Burns, Jane L. Moskowitz, Samuel M. Pilewski, Joseph M. Gladwin, Mark T. Bomberger, Jennifer M. TI Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Pseudomonas aeruginosa; Biofilm; Sodium nitrite; Colistimethate; Colistin; Polymyxin ID CYSTIC-FIBROSIS PATIENTS; PSEUDOMONAS-AERUGINOSA BIOFILMS; ESCHERICHIA-COLI; ANAEROBIC RESPIRATION; HELICOBACTER-PYLORI; ACIDIFIED NITRITE; INHALED COLISTIN; OXIDE; INHIBITION; RESISTANCE AB Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic-resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics. We grew P. aeruginosa on the apical surface of primary human airway epithelial cells to test the efficacy of sodium nitrite against biotic biofilms. Nitrite alone prevented 99% of biofilm growth. We then identified significant cooperative interactions between nitrite and polymyxins. For P. aeruginosa growing on primary CF airway cells, combining nitrite and colistimethate resulted in an additional log of bacterial inhibition compared to treating with either agent alone. Nitrite and colistimethate additively inhibited oxygen consumption by P. aeruginosa. Surprisingly, whereas the antimicrobial effects of nitrite in planktonic, aerated cultures are nitric oxide (NO) dependent, antimicrobial effects under other growth conditions are not. The inhibitory effect of nitrite on bacterial oxygen consumption and biofilm growth did not require NO as an intermediate as chemically scavenging NO did not block growth inhibition. These data suggest an NO-radical independent nitrosative or oxidative inhibition of respiration. The combination of nebulized sodium nitrite and colistimethate may provide a novel therapy for chronic P. aeruginosa airway infections, because sodium nitrite, unlike other antibiotic respiratory chain "poisons," can be safely nebulized at high concentration in humans. (C) 2014 Elsevier Inc. All rights reserved. C1 [Zemke, Anna C.; Pilewski, Joseph M.; Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15219 USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15219 USA. [Burns, Jane L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gladwin, Mark T.] Pittsburgh Heart Lung Blood & Vasc Med Inst, Pittsburgh, PA 15219 USA. [Bomberger, Jennifer M.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. RP Bomberger, JM (reprint author), Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. EM jbomb@pitt.edu FU Cystic Fibrosis Foundation; Breathe Pennsylvania Research Grant [J.L.B5P30DK089507-04, P30DK072506, R00HL098342-01]; Cystic Fibrosis Foundation [R01HL098032, RO1HL096973, P01HL103455, T32 HL110849, MOSKOW13P0]; Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania [R01AI067653]; [2T32HL007563-26] FX The authors thank Lauren Lashua, Stefanie Brown, and Catherine Corey for technical assistance. Strains were kindly provided by Dr. John LiPuma (B. cepacia Research Laboratory and Repository; supported by the Cystic Fibrosis Foundation). We acknowledge the following sources of funding: 2T32HL007563-26 (A.C.Z.); J.L.B5P30DK089507-04, J.M.P. P30DK072506; R00HL098342-01, Breathe Pennsylvania Research Grant (J.M.B.); Cystic Fibrosis Foundation (J.M.P.) R01HL098032, RO1HL096973, and P01HL103455, T32 HL110849, the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania (M.T.G.), and R01AI067653 and Cystic Fibrosis Foundation MOSKOW13P0 (S.M.M.). NR 55 TC 13 Z9 13 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2014 VL 77 BP 307 EP 316 DI 10.1016/j.freeradbiomed.2014.08.011 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AW6QA UT WOS:000346392500030 PM 25229185 ER PT J AU Albergotti, WG Byrd, JK De Almeida, JR Kim, S Duvvuri, U AF Albergotti, W. Greer Byrd, J. Kenneth De Almeida, John R. Kim, Seungwon Duvvuri, Umamaheswar TI Robot-assisted level II-IV neck dissection through a modified facelift incision: initial North American experience SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE head and neck surgery; robotic neck dissection; cancer ID THYROIDECTOMY; CARCINOMA; SURGERY AB BackgroundCosmesis is of increasing importance to the otolaryngology patient population. This is the first report of clinical outcomes of robot-assisted neck dissection by North American groups. MethodsThis is a retrospective case-control study. Cases included three patients who underwent isolated, ipsilateral robot-assisted neck dissection. Operative time, estimated blood loss, lymph node retrieval, total drainage, hospital stay and complications from this group were compared against the outcomes of six consecutive patients who underwent conventional neck dissection. ResultsOperative times were longer in robot-assisted neck dissection (mean 234min) compared with the conventional neck dissection (mean 110min). There were no significant differences between the two groups in other outcomes. ConclusionsRobot-assisted selective neck dissection of levels II-IV is feasible through a modified facelift incision. Our initial data suggest that this procedure is surgically sound. It should be applied by experienced surgeons who wish to avoid a cervical incision. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Albergotti, W. Greer; Byrd, J. Kenneth; Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [De Almeida, John R.] Univ Toronto, Dept Otolaryngology Head & Neck Surg, Toronto, ON, Canada. RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Otolaryngol, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM duvuriu@upmc.edu FU Department of Veterans Affairs; PNC Foundation; Intuitive Surgical Inc. FX This study was supported in part by funds from the Department of Veterans Affairs, the PNC Foundation, and a research grant from Intuitive Surgical Inc. The funding organizations had no role in the design or conduct of the study, collection, management, analysis or interpretation of the data. They had no role in the preparation, review or approval of this manuscript and the decision to submit this manuscript was solely the decision of the authors. NR 17 TC 6 Z9 7 U1 0 U2 3 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 DEC PY 2014 VL 10 IS 4 BP 391 EP 396 DI 10.1002/rcs.1585 PG 6 WC Surgery SC Surgery GA AW4TG UT WOS:000346272700002 ER PT J AU Byrd, JK Leonardis, RL Bonawitz, SC Losee, JE Duvvuri, U AF Byrd, James K. Leonardis, Rachel L. Bonawitz, Steven C. Losee, Joseph E. Duvvuri, Umamaheswar TI Transoral robotic surgery for pharyngeal stenosis SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE robotics; pharyngoplasty; local flaps ID ACQUIRED NASOPHARYNGEAL STENOSIS; BALLOON DILATION AB BackgroundPharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. MethodsA retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. ResultsFive patients were identified, ages 8-75years. Length of follow-up ranged from 1-12months. There was one failure, a 74year old male with a history of chemoradiation to the area who has required additional procedures. ConclusionTORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Byrd, James K.; Leonardis, Rachel L.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA. [Byrd, James K.; Leonardis, Rachel L.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Bonawitz, Steven C.] Johns Hopkins Univ, Dept Plast & Reconstruct, Baltimore, MD USA. [Losee, Joseph E.] Childrens Hosp Pittsburgh, Div Pediat Plast Surg, Pittsburgh, PA 15213 USA. RP Byrd, JK (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM byrdjk@upmc.edu NR 7 TC 2 Z9 2 U1 0 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 DEC PY 2014 VL 10 IS 4 BP 418 EP 422 DI 10.1002/rcs.1591 PG 5 WC Surgery SC Surgery GA AW4TG UT WOS:000346272700006 PM 24737499 ER PT J AU Cheney, MD Chen, YL Lim, R Winrich, BK Grosu, AL Trofimov, AV Depauw, N Shih, HA Schwab, JH Hornicek, FJ DeLaney, TF AF Cheney, Matthew D. Chen, Yen-Lin Lim, Ruth Winrich, Barbara K. Grosu, Anca L. Trofimov, Alexei V. Depauw, Nicolas Shih, Helen A. Schwab, Joseph H. Hornicek, Francis J. DeLaney, Thomas F. TI [18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID SACRAL CHORDOMA; NECK-CANCER; SURGICAL-MANAGEMENT; PROGNOSTIC-FACTORS; RADIOTHERAPY; FLUOROMISONIDAZOLE; HEAD; SACRECTOMY; EXPERIENCE; THERAPY AB Purpose: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. Methods and Materials: A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values >= 1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. Results: The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (>= 5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Conclusions: Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted. (C) 2014 Elsevier Inc. C1 [Cheney, Matthew D.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Yen-Lin; Winrich, Barbara K.; Grosu, Anca L.; Trofimov, Alexei V.; Depauw, Nicolas; Shih, Helen A.; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lim, Ruth] Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. [Schwab, Joseph H.; Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthoped Oncol, Boston, MA 02114 USA. [Depauw, Nicolas] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia. RP Cheney, MD (reprint author), Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Lunder Bldg LL2,55 Fruit St, Boston, MA 02114 USA. EM mcheney@lroc.harvard.edu OI Cheney, Matthew/0000-0001-8367-3427 FU NCI NIH HHS [C06 CA059267] NR 37 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2014 VL 90 IS 5 BP 1030 EP 1036 DI 10.1016/j.ijrobp.2014.08.016 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AW6ZP UT WOS:000346414500012 PM 25539367 ER PT J AU Kamran, SC Collier, JM Lane, AM Kim, I Niemierko, A Chen, YLE MacDonald, SM Munzenrider, JE Gragoudas, E Shih, HA AF Kamran, Sophia C. Collier, John M. Lane, Anne Marie Kim, Ivana Niemierko, Andrzej Chen, Yen-Lin E. MacDonald, Shannon M. Munzenrider, John E. Gragoudas, Evangelos Shih, Helen A. TI Outcomes of Proton Therapy for the Treatment of Uveal Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; CHOROIDAL METASTASES; MANAGEMENT; CARCINOMA; MELANOMA; CANCER; TUMORS; EYE AB Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. Themedian survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-termsurvivors, the risk of retinal injury with vision loss increases significantly over the first year. (C) 2014 Elsevier Inc. C1 [Kamran, Sophia C.] Harvard Univ, Sch Med, Boston, MA USA. [Collier, John M.; Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lane, Anne Marie; Kim, Ivana; Gragoudas, Evangelos] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hshih@partners.org OI Kamran, Sophia/0000-0001-9283-6515 NR 21 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2014 VL 90 IS 5 BP 1044 EP 1050 DI 10.1016/j.ijrobp.2014.08.003 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AW6ZP UT WOS:000346414500014 PM 25442038 ER PT J AU Shah, RV Murthy, VL Abbasi, SA Blankstein, R Kwong, RY Goldfine, AB Jerosch-Herold, M Lima, JAC Ding, JZ Allison, MA AF Shah, Ravi V. Murthy, Venkatesh L. Abbasi, Siddique A. Blankstein, Ron Kwong, Raymond Y. Goldfine, Allison B. Jerosch-Herold, Michael Lima, Joao A. C. Ding, Jingzhong Allison, Matthew A. CA MESA Study TI Visceral Adiposity and the Risk of Metabolic Syndrome Across Body Mass Index The MESA Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiometabolic risk; metabolic syndrome; obesity ID CARDIOVASCULAR-DISEASE; LONGITUDINAL CHANGES; JAPANESE-AMERICANS; INSULIN-RESISTANCE; FAT DISTRIBUTION; HITACHI HEALTH; ABDOMINAL FAT; WEIGHT-LOSS; OBESE MEN; ATHEROSCLEROSIS AB OBJECTIVES This study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) categories. BACKGROUND The regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals. METHODS We studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS. RESULTS Higher VF was associated with cardiometaboLic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm(2)/m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval [Cl]: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm(2)/m, 95% CI: 1.08 to 1.44 per 100 cm(2)/m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area. CONCLUSIONS VF is modestly associated with BMI. However, across BMI, a single measure of and Longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease. (C) 2014 by the American College of Cardiology Foundation. C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Cardiothorac Imaging Div, Ann Arbor, MI 48109 USA. [Abbasi, Siddique A.; Blankstein, Ron; Kwong, Raymond Y.; Jerosch-Herold, Michael] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Lima, Joao A. C.] Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA. [Ding, Jingzhong] Wake Forest Baptist Med Ctr, Dept Med, Winston Salem, NC USA. [Allison, Matthew A.] Univ Calif San Diego, Dept Family & Preventat Med, San Diego, CA 92103 USA. RP Murthy, VL (reprint author), Univ Michigan, Dept Internal Med Cardiovasc Med, 1338 Cardiovasc Ctr 1500 East Med Ctr Dr,SPC 5873, Ann Arbor, MI 48109 USA. EM vlmurthy@med.umich.edu RI Murthy, Venkatesh/B-3448-2013 OI Murthy, Venkatesh/0000-0002-7901-1321 FU National Heart, Lung, and Blood Institute [R01-HL088451] FX Dr. Allison was supported by funding for the MESA Abdominal Body Composition Ancillary study from the National Heart, Lung, and Blood Institute (R01-HL088451). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Shah and Murthy have contributed equally to this work. NR 29 TC 3 Z9 3 U1 1 U2 5 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 DEC PY 2014 VL 7 IS 12 BP 1222 EP 1235 PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AX0DQ UT WOS:000346624000007 ER PT J AU Pascoe, VL Kimball, AB AF Pascoe, Vanessa L. Kimball, Alexandra B. TI Hidradenitis Suppurativa Current Progress and Future Questions SO JAMA DERMATOLOGY LA English DT Editorial Material ID DISEASE; PREVALENCE C1 [Pascoe, Vanessa L.; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Pascoe, Vanessa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kimball, Alexandra B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Ste 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 14 TC 3 Z9 3 U1 0 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 DEC PY 2014 VL 150 IS 12 BP 1263 EP 1264 DI 10.1001/jamadermatol.2014.1871 PG 2 WC Dermatology SC Dermatology GA AW4ER UT WOS:000346234500002 PM 25229429 ER PT J AU Everett, JN Raymond, VM Dandapani, M Marvin, M Kohlmann, W Chittenden, A Koeppe, E Gustafson, SL Else, T Fullen, DR Johnson, TM Syngal, S Gruber, SB Stoffel, EM AF Everett, Jessica N. Raymond, Victoria M. Dandapani, Monica Marvin, Monica Kohlmann, Wendy Chittenden, Anu Koeppe, Erika Gustafson, Shanna L. Else, Tobias Fullen, Douglas R. Johnson, Timothy M. Syngal, Sapna Gruber, Stephen B. Stoffel, Elena M. TI Screening for Germline Mismatch Repair Mutations Following Diagnosis of Sebaceous Neoplasm SO JAMA DERMATOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MUIR-TORRE-SYNDROME; LYNCH-SYNDROME; MSH2; RECOMMENDATIONS; INDIVIDUALS; DEFICIENCY; EXPRESSION; PROTEINS; FAMILIES AB IMPORTANCE Sebaceous neoplasms (SNs) define the Muir-Torre syndrome variant of Lynch syndrome (LS), which is associated with increased risk for colon and other cancers necessitating earlier and more frequent screening to reduce morbidity and mortality. Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in SNs can be used to screen for LS, but data on subsequent germline genetic testing to confirm LS diagnosis are limited. OBJECTIVE To characterize the utility of IHC screening of SNs in identification of germline MMR mutations confirming LS. DESIGN, SETTING, AND PARTICIPANTS Retrospective study at 2 academic cancer centers of 86 adult patients referred for clinical genetics evaluation after diagnosis of SN. MAIN OUTCOMES AND MEASURES Results of tumor IHC testing and germline genetic testing were reviewed to determine positive predictive value and sensitivity of IHC testing in diagnosis of LS. Clinical variables, including age at diagnosis of SN, clinical diagnostic criteria for LS and Muir-Torre syndrome, and family history characteristics were compared between mutation carriers and noncarriers. RESULTS Of 86 patients with SNs, 25 (29%) had germline MMR mutations confirming LS. Among 77 patients with IHC testing on SNs, 38 (49%) had loss of staining of 1 or more MMR proteins and 14 had germline MMR mutations. Immunohistochemical analysis correctly identified 13 of 16 MMR mutation carriers, corresponding to 81% sensitivity. Ten of 12 patients (83%) with more than 1 SN had MMR mutations. Fifty-two percent of MMR mutation carriers did not meet clinical diagnostic criteria for LS, and 11 of 25 (44%) did not meet the clinical definition of Muir-Torre syndrome. CONCLUSIONS AND RELEVANCE Immunohistochemical screening of SNs is effective in identifying patients with germline MMR mutations and can be used as a first-line test when LS is suspected. Abnormal IHC results, including absence of MSH2, are not diagnostic of LS and should be interpreted cautiously in conjunction with family history and germline genetic testing. Use of family history to select patients for IHC screening has substantial limitations, suggesting that universal IHC screening of SNs merits further study. Clinical genetics evaluation is warranted for patients with abnormal IHC test results, normal IHC test results with personal or family history of other LS-associated neoplasms, and/or multiple SNs. C1 [Everett, Jessica N.; Raymond, Victoria M.; Marvin, Monica; Koeppe, Erika] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Marvin, Monica] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Fullen, Douglas R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Johnson, Timothy M.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Dandapani, Monica; Chittenden, Anu; Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kohlmann, Wendy] Huntsman Canc Inst, Salt Lake City, UT USA. [Gruber, Stephen B.] USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. RP Everett, JN (reprint author), Univ Michigan, Dept Internal Med, 300 N Ingalls Ave,NI3 A17, Ann Arbor, MI 48109 USA. EM jever@umich.edu FU National Institutes of Health [P30CA042014, T32-DK007425, SR01CA132829-04, K24-K24CA113433-08, P30 CA014089, P30 CA046592, K07CA120448-5] FX This study was supported in part by National Institutes of Health grants P30 CA042014 (Dr Kohlmann), T32-DK007425 (Dr Else), SR01CA132829-04 (Dr Syngal), K24-K24CA113433-08 (Dr Syngal), P30 CA014089 (Dr Gruber), P30 CA046592 (Dr Gruber), and K07CA120448-5 (Dr Stoffel). NR 24 TC 8 Z9 8 U1 0 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 DEC PY 2014 VL 150 IS 12 BP 1315 EP 1321 DI 10.1001/jamadermatol.2014.1217 PG 7 WC Dermatology SC Dermatology GA AW4ER UT WOS:000346234500010 PM 25006859 ER PT J AU Lian, CG Sholl, LM Zakka, LR Teresa, MO Liu, C Xu, SY Stanek, E Garcia, E Jia, YH MacConaill, LE Murphy, GF Waner, M Mihm, MC AF Lian, Christine Guo Sholl, Lynette M. Zakka, Labib R. Teresa, M. O. Liu, Cynthia Xu, Shuyun Stanek, Ewelina Garcia, Elizabeth Jia, Yonghui MacConaill, Laura E. Murphy, George F. Waner, Milton Mihm, Martin C., Jr. TI Novel Genetic Mutations in a Sporadic Port-Wine Stain SO JAMA DERMATOLOGY LA English DT Article ID ACTIVATING MUTATIONS; GROWTH-FACTOR; EXPRESSION AB IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking. OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant (c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-beta, and PIK3CA. CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations in GNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets. C1 [Lian, Christine Guo; Sholl, Lynette M.; Liu, Cynthia; Xu, Shuyun; Stanek, Ewelina; Garcia, Elizabeth; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lian, Christine Guo; Sholl, Lynette M.; Liu, Cynthia; Xu, Shuyun; Stanek, Ewelina; Garcia, Elizabeth; Murphy, George F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sholl, Lynette M.; Jia, Yonghui; MacConaill, Laura E.] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Sch Med, Boston, MA 02115 USA. [Zakka, Labib R.; Mihm, Martin C., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Waner, Milton] Lenox Hill Hosp, Vasc Birthmark Inst New York, North Shore LIJ Sch Med, Dept Otorhinolaryngol Head & Neck Surg, New York, NY 10021 USA. RP Mihm, MC (reprint author), Brigham & Womens Hosp, Dept Dermatol, Melanoma Program, 41 Ave Louis Pasteur, Boston, MA 02115 USA. EM mmihm@partners.org NR 15 TC 13 Z9 13 U1 0 U2 0 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 DEC PY 2014 VL 150 IS 12 BP 1336 EP 1340 DI 10.1001/jamadermatol.2014.1244 PG 5 WC Dermatology SC Dermatology GA AW4ER UT WOS:000346234500016 PM 25188413 ER PT J AU Zhang, JM Sheerin, C Mandel, H Banducci, AN Myrick, H Acierno, R Amstadter, AB Wang, ZW AF Zhang, Jingmei Sheerin, Christina Mandel, Howard Banducci, Anne N. Myrick, Hugh Acierno, Ronald Amstadter, Ananda B. Wang, Zhewu TI Variation in SLC1A1 is related to combat-related posttraumatic stress disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; SLC1A1; Combat stress disorders; Genes; Veterans ID OBSESSIVE-COMPULSIVE DISORDER; GENOME-WIDE ASSOCIATION; ENVIRONMENTAL CONTRIBUTIONS; TRAUMA EXPOSURE; 2 GENERATIONS; PTSD; SYMPTOMS; TWIN; GLUTAMATE; SAMPLE AB Candidate gene studies have yet to investigate the glutamate system, the primary excitatory neurotransmitter of the HPA-axis related to PTSD risk. We investigated 13 SNPs in the glutamate transporter gene (SLC1A1) in relation to PTSD among combat-exposed veterans. Participants (n = 418) completed a diagnostic interview and provided a blood sample for DNA isolation and genotyping. A subset of participants (n = 391) had severity and combat exposure data available. In the primary logistic regression gender and rsl 0739062 were significant predictors of PTSD diagnosis (OR = 0.50; OR = 1.43). In the linear regression analysis, combat exposure was the only significant predictor (beta = 0.16) of severity. A computed genetic risk sum score was significant in relation to PTSD diagnosis (OR = 1.15) and severity scores (beta = 0.14) above and beyond the effects of combat exposure. This study provides preliminary support for the relationship of glutamate transporter polymorphisms to PTSD risk and the need for further genetic studies within this system. Published by Elsevier Ltd: C1 [Zhang, Jingmei; Myrick, Hugh; Acierno, Ronald; Wang, Zhewu] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Mandel, Howard; Myrick, Hugh; Acierno, Ronald; Wang, Zhewu] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Sheerin, Christina] McGuire VA Med Ctr, Richmond, VA USA. [Banducci, Anne N.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA. RP Wang, ZW (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA. EM wanzh@musc.edu OI Banducci, Anne N/0000-0003-1213-7998 NR 38 TC 1 Z9 1 U1 3 U2 5 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 DEC PY 2014 VL 28 IS 8 BP 902 EP 907 DI 10.1016/j.janxdis.2014.09.013 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW8WM UT WOS:000346540200021 PM 25445080 ER PT J AU Araujo, AB Yang, M Suarez, EA Dagincourt, N Abraham, JR Chiu, G Holick, MF Bouxsein, ML Zmuda, JM AF Araujo, Andre B. Yang, May Suarez, Elizabeth A. Dagincourt, Nicholas Abraham, Jonathan R. Chiu, Gretchen Holick, Michael F. Bouxsein, Mary L. Zmuda, Joseph M. TI Racial/Ethnic and Socioeconomic Differences in Bone Loss Among Men SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE AGING; DXA; GENETIC STUDIES; OSTEOPOROSIS; GENERAL POPULATION STUDIES ID MINERAL DENSITY; HIP FRACTURE; OLDER MEN; RACIAL-DIFFERENCES; AFRICAN ANCESTRY; UNITED-STATES; ELDERLY-MEN; WOMEN; ASSOCIATION; POPULATION AB As men age, they lose bone and are susceptible to fracture. Despite having lower fracture rates than women, men have worse fractures than women do. Racial/ethnic and socioeconomic status (SES) disparities in fracture rates exist, yet data on rates of bone loss by race/ethnicity and SES among men are limited. We examined annualized percentage change in bone mineral density (%BMD) at the hip (N=681), spine (N=663), and forearm (N=636) during 7 years of follow-up among men aged 30-79 years at baseline. Multivariable models tested whether race/ethnicity, income, or genetic ancestry predicted annualized %BMD after controlling for an extensive set of covariates. Annualized %BMD ranged from -0.65(0.04)% (femoral neck) to +0.26(0.03)% (1/3 distal radius), and changes were consistent across age groups with the exception of the ultradistal radius, where annualized declines increased with age. Neither self-identified race/ethnicity nor genetic ancestry were associated with annualized %BMD. In contrast, income was strongly associated (dose-response) with annualized %BMD at total hip (independent of confounders, self-identified race/ethnicity, and genetic ancestry). Fully adjusted least-square mean change in annualized %BMD at the total hip were -0.24(0.12)% and -0.16(0.06)% steeper among men with low and moderate incomes, respectively, than among men with higher incomes (overall p=0.0293). Results show a linear decline in bone that begins relatively early in life among men, that rates of bone loss do not vary with race/ethnicity (self-identified or objectively measured), and that income plays an important role in relation to bone loss at the hip. These data suggest that fracture risk in men may be driven in part by income-related differences in bone loss, but also, that the known higher fracture risk among white men is not the result of racial/ethnic differences in bone loss, but rather, early life exposures that lead to attainment of higher peak bone mass among minorities. (c) 2014 American Society for Bone and Mineral Research. C1 [Araujo, Andre B.; Yang, May; Suarez, Elizabeth A.; Dagincourt, Nicholas; Abraham, Jonathan R.] New England Res Inst Inc, Dept Epidemiol, Watertown, MA 02472 USA. [Araujo, Andre B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Chiu, Gretchen] Trinity Partners LLC, Waltham, MA USA. [Holick, Michael F.] Boston Univ, Med Ctr, Dept Med, Sect Endocrinol Nutr & Diabet, Boston, MA USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bouxsein, Mary L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Araujo, AB (reprint author), New England Res Inst Inc, Dept Epidemiol, 9 Galen St, Watertown, MA 02472 USA. EM araujo.andre.b@gmail.com FU NIH [NIA R01AG020727, NIDDK U01DK056842]; [UL-1-RR-25711] FX This study was supported by NIH awards NIA R01AG020727 and NIDDK U01DK056842. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIA, NIDDK, or NIH. This study was conducted at the BU GCRU, which is funded under UL-1-RR-25711. Dr. Araujo, Ms. Yang, and Ms. Chiu had full access to all of the data in the study and take responsibility for the integrity/accuracy of the data and analysis. The authors gratefully acknowledge the contributions of Julia Akeroyd (project management), Rebecca Piccolo (project management), Carrie Wager (devise and implement imputation strategy), Heather Litman (execute imputation models), Adrian Turner (bone assessment), Robert Chang (data cleaning), Teresa Curto (statistical support), and Angela Fang Ren (statistical quality control). NR 52 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2014 VL 29 IS 12 BP 2552 EP 2560 DI 10.1002/jbmr.2305 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AW4UB UT WOS:000346274700006 PM 24984683 ER PT J AU Alston, TA AF Alston, Theodore A. TI Why does methylene blue reduce methemoglobin in benzocaine poisoning but beneficially oxidize hemoglobin in cyanide poisoning? SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter ID SUPEROXIDE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM talston@partners.org NR 11 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD DEC PY 2014 VL 26 IS 8 BP 702 EP 703 DI 10.1016/j.jclinane.2014.09.001 PG 2 WC Anesthesiology SC Anesthesiology GA AX3CW UT WOS:000346819100023 PM 25441551 ER PT J AU Walcott, BP Khanna, A Kwon, CS Phillips, HW Nahed, BV Coumans, JV AF Walcott, Brian P. Khanna, Arjun Kwon, Churl-Su Phillips, H. Westley Nahed, Brian V. Coumans, Jean-Valery TI Time interval to surgery and outcomes following the surgical treatment of acute traumatic subdural hematoma SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aspirin; Craniectomy; Gastrostomy; Subdural; Surgery; Tracheostomy; Trauma ID BRAIN-INJURY; HEAD-INJURY; INTRACRANIAL HEMORRHAGE; PROGNOSTIC-FACTORS; COMATOSE PATIENTS; CLINICAL ARTICLE; MORTALITY; THERAPY; RISK; MORBIDITY AB Although the pre-surgical management of patients with acute traumatic subdural hematoma prioritizes rapid transport to the operating room, there is conflicting evidence regarding the importance of time interval from injury to surgery with regards to outcomes. We sought to determine the association of surgical timing with outcomes for subdural hematoma. A retrospective review was performed of 522 consecutive patients admitted to a single center from 2006-2012 who underwent emergent craniectomy for acute subdural hematoma. After excluding patients with unknown time of injury, penetrating trauma, concurrent cerebrovascular injury, epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there remained 45 patients identified for analysis. Using a multiple regression model, we examined the effect of surgical timing, in addition to other variables on in-hospital mortality (primary outcome), as well as the need for tracheostomy or gastrostomy (secondary outcome). We found that increasing injury severity score (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035-1.270; p = 0.009) and age (OR1.066; 95%CI 1.006-1.129; p = 0.031) were associated with in-hospital mortality in multivariate analysis. In this model, increasing time to surgery was not associated with mortality, and in fact had a significant effect in decreasing mortality (OR 0.984; 95%CI 0.971-0.997; p = 0.018). Premorbid aspirin use was associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001-0.392; p = 0.010). In this patient sample, shorter time interval from injury to surgery was not associated with better outcomes. While there are potential confounding factors, these findings support the evaluation of rigorous preoperative resuscitation as a priority in future study. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 29 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2014 VL 21 IS 12 BP 2107 EP 2111 DI 10.1016/j.jocn.2014.05.016 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX0DF UT WOS:000346622900010 PM 25065950 ER PT J AU Walcott, BP Patel, AP Stapleton, CJ Trivedi, RA Young, AMH Ogilvy, CS AF Walcott, Brian P. Patel, Anoop P. Stapleton, Christopher J. Trivedi, Rikin A. Young, Adam M. H. Ogilvy, Christopher S. TI Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: Characterization of differential expression patterns in cerebral vasospasm SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aneurysm; Biomarker; Subarachnoid hemorrhage; Vasospasm ID RECEPTOR TYROSINE KINASE; SMOOTH-MUSCLE-CELLS; VITRONECTIN RECEPTOR; SYMPTOMATIC VASOSPASM; BINDING-PROTEIN; FISHER SCALE; CANCER; TETRANECTIN; PROLIFERATION; POLYMORPHISMS AB Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (Discovery-MAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00] =16.33, p = 0.005), angiogenin (F [1.00,7.00] = 7.65, p = 0.028), apolipoprotein A-IV (F [1.00,7.00] =6.308, p = 0.040), granulocyte colony-stimulating factor (F [1.00,7.00] = 9.08, p = 0.020), macrophage-stimulating protein (F [1.00,7.00] = 24.21, p = 0.002), tetranectin (F [1.00,7.00] = 5.46, p < 0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00] = 6.94, p = 0.034), and significantly increased for vitronectin (F [1.00,7.00] = 5.79, p = 0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Patel, Anoop P.; Stapleton, Christopher J.; Young, Adam M. H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Patel, Anoop P.; Stapleton, Christopher J.; Young, Adam M. H.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Trivedi, Rikin A.; Young, Adam M. H.] Addenbrookes Hosp, Dept Neurosurg, Cambridge, England. [Trivedi, Rikin A.; Young, Adam M. H.] Univ Cambridge, Cambridge, England. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Brain Aneurysm Foundation FX This study received funding from The Brain Aneurysm Foundation. NR 42 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2014 VL 21 IS 12 BP 2135 EP 2139 DI 10.1016/j.jocn.2014.06.004 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX0DF UT WOS:000346622900015 PM 25082408 ER PT J AU First, MB Bhat, V Adler, D Dixon, L Goldman, B Koh, S Levine, B Oslin, D Siris, S AF First, Michael B. Bhat, Venkat Adler, David Dixon, Lisa Goldman, Beth Koh, Steve Levine, Bruce Oslin, David Siris, Sam TI How Do Clinicians Actually Use the Diagnostic and Statistical Manual of Mental Disorders in Clinical Practice and Why We Need to Know More SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE DSM-IV; clinical use; DSM-5; use of DSM in clinical practice ID DSM-III-R; PSYCHIATRIC-DIAGNOSIS; UNITED-STATES; GLOBAL SURVEY; RELIABILITY; CRITERIA; CLASSIFICATION; CARE; INTERVIEWS; ATTITUDES AB The clinical use of the Diagnostic and Statistical Manual of Mental Disorders (DSM) is explicitly stated as a goal for both the DSM Fourth Edition and DSM Fifth Edition (DSM-5) revisions. Many uses assume a relatively faithful application of the DSM diagnostic definitions. However, studies demonstrate significant discrepancies between clinical psychiatric diagnoses with those made using structured interviews suggesting that clinicians do not systematically apply the diagnostic criteria. The limited information regarding how clinicians actually use the DSM raises important questions: a) How can the clinical use be improved without first having a baseline assessment? b) How can potentially significant shifts in practice patterns based on wording changes be assessed without knowing the extent to which the criteria are used as written? Given the American Psychiatric Association's plans for interim revisions to the DSM-5, the value of a detailed exploration of its actual use in clinical practice remains a significant ongoing concern and deserves further study including a number of survey and in vivo studies. C1 [First, Michael B.; Dixon, Lisa] Columbia Univ, Med Ctr, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Bhat, Venkat] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Adler, David] Tufts Univ, Sch Med, Dept Psychiat, Tufts Med Ctr, Boston, MA 02111 USA. [Goldman, Beth] Blue Cross Blue Shield Michigan, Behav Hlth, Detroit, MI USA. [Koh, Steve] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Levine, Bruce] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Oslin, David] Univ Penn, Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Siris, Sam] Zucker Hillside Hosp, Glen Oaks, NY USA. RP First, MB (reprint author), Columbia Univ, Med Ctr, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr,Unit 60, New York, NY 10032 USA. EM mbf2@columbia.edu NR 34 TC 4 Z9 4 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2014 VL 202 IS 12 BP 841 EP 844 DI 10.1097/NMD.0000000000000210 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW4QJ UT WOS:000346265400001 PM 25390931 ER PT J AU Jeon, HJ Lee, C Fava, M Mischoulon, D Shim, EJ Heo, JY Choi, H Park, JH AF Jeon, Hong Jin Lee, Christina Fava, Maurizio Mischoulon, David Shim, Eun-Jung Heo, Jung-Yoon Choi, Hong Park, Jae-Hyun TI Childhood Trauma, Parental Death, and Their Co-occurrence in Relation to Current Suicidality Risk in Adults A Nationwide Community Sample of Korea SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Suicidality; childhood trauma; parental death; emotional abuse ID INVENTORY-SELF REPORT; PSYCHOMETRIC PROPERTIES; MENTAL-DISORDERS; SEXUAL-ABUSE; ADVERSITIES; ASSOCIATION; ONSET; PSYCHOPATHOLOGY; ANTECEDENTS; ADOLESCENTS AB Although previous studies have suggested that childhood trauma and parental death are strongly associated with suicidality in adulthood, it is still unclear how these factors interact within the same population. A total of 1396 adults were recruited through nationwide multistage probability sampling in South Korea. Subjects were evaluated through face-to-face interviews using the Suicidality Module of the Mini-International Neuropsychiatric Interview and the Early Trauma Inventory Self Report-Short Form. Among the 1396 adults, the group that experienced both childhood trauma and parental death had the highest current suicidality risks (F = 12.16, p < 0.0001) and lifetime suicide attempt ((2) = 35.81, p < 0.0001) compared with the other groups, which were only childhood trauma, only parental death, and neither. Multivariate logistic regression analyses revealed that middle-to-high current suicidality risk and lifetime suicide attempt were significantly associated with concurrent childhood trauma and parental death (odds ratio, 3.64; 95% confidence interval, 1.99-6.65) as well as with only childhood trauma (odds ratio, 1.95; 95% confidence interval, 1.33-2.87), after adjusting for age, sex, education, marital status, household monthly income, and living area. Emotional abuse was the only type of childhood trauma significantly associated with higher current suicidality scores in those who experienced childhood parental death than in those who did not (F = 3.26, p = 0.041). Current suicidality risk and lifetime suicide attempt are associated with experiencing both parental death and trauma, especially emotional abuse, in childhood, whereas experiencing only childhood parental death is associated with neither. C1 [Jeon, Hong Jin; Heo, Jung-Yoon; Choi, Hong; Park, Jae-Hyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin] SAIHST, Seoul, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Lee, Christina] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. [Shim, Eun-Jung] Pusan Natl Univ, Dept Psychol, Pusan, South Korea. [Park, Jae-Hyun] Sungkyunkwan Univ, Sch Med, Dept Social & Prevent Med, Samsung Biomed Res Inst, Suwon 440746, Gyeonggi Do, South Korea. RP Park, JH (reprint author), Sungkyunkwan Univ, Sch Med, Dept Social & Prevent Med, Samsung Biomed Res Inst, 300 Cheoncheon Dong, Suwon 440746, Gyeonggi Do, South Korea. EM pjaehyun@skku.edu FU Samsung Social Mental Health Institute [SMHI 2010-04]; National Research Foundation of Korea [2011-0013064] FX Funding for this study was provided by the Samsung Social Mental Health Institute (SMHI 2010-04) and the National Research Foundation of Korea (no. 2011-0013064); both had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 31 TC 4 Z9 4 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2014 VL 202 IS 12 BP 870 EP 876 DI 10.1097/NMD.0000000000000217 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW4QJ UT WOS:000346265400006 PM 25370752 ER PT J AU Hartmann, AS Thomas, JJ Greenberg, JL Matheny, NL Wilhelm, S AF Hartmann, Andrea S. Thomas, Jennifer J. Greenberg, Jennifer L. Matheny, Natalie L. Wilhelm, Sabine TI A Comparison of Self-Esteem and Perfectionism in Anorexia Nervosa and Body Dysmorphic Disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Anorexia nervosa; body dysmorphic disorder; perfectionism; self-esteem ID OBSESSIVE-COMPULSIVE DISORDER; EATING-DISORDERS; BULIMIA-NERVOSA; IMAGE; DEPRESSION; DELUSIONALITY; RELIABILITY; VALIDITY; BELIEFS; SCALE AB Previous studies have identified phenotypic similarities between anorexia nervosa (AN) and body dysmorphic disorder (BDD), which share the common feature of negative body image. Studies comparing endophenotypes that may cut across both disordersas suggested by the National Institute of Mental Health's Research Domain Criteriaare limited. Sixty-nine individuals (AN, n = 24; BDD, n = 23; mentally healthy controls [MHCs], n = 22) completed diagnostic interviews and self-reports assessing self-esteem and perfectionism. Clinical groups showed greater perfectionism in almost all subdimensions as well as poorer self-esteem compared with MHCs, with no clinical group differences when controlling for level of depression. Depression was a mediator of the relationship between symptom severity and self-esteem in both clinical groups. Comparable low self-esteem and greater perfectionism in AN and BDD corroborated existing etiological models and previous studies. Depression was a significant contributor to negative self-esteem in both disorders. C1 [Hartmann, Andrea S.] Univ Osnabruck, Inst Psychol, D-49069 Osnabruck, Germany. [Hartmann, Andrea S.; Thomas, Jennifer J.; Greenberg, Jennifer L.; Matheny, Natalie L.; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hartmann, Andrea S.; Thomas, Jennifer J.; Greenberg, Jennifer L.; Matheny, Natalie L.; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. RP Hartmann, AS (reprint author), Univ Osnabruck, Inst Psychol, Dept Human Sci, Knollstr 15, D-49069 Osnabruck, Germany. EM andrea.hartmann@uni-osnabrueck.de FU Swiss National Science Foundation [PBSKP1_134330/1, PBSKP1_140040] FX The present study was supported by a postdoctoral fellowship awarded to the first authors by the Swiss National Science Foundation (PBSKP1_134330/1 and PBSKP1_140040). NR 51 TC 6 Z9 6 U1 4 U2 42 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2014 VL 202 IS 12 BP 883 EP 888 DI 10.1097/NMD.0000000000000215 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW4QJ UT WOS:000346265400008 PM 25390930 ER PT J AU Eberlin, KR Gfrerer, L Liao, EC AF Eberlin, Kyle R. Gfrerer, Lisa Liao, Eric C. TI Trans-axillary approach for breast implant exchange in high risk cases of irradiated or attenuated skin SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Article DE Breast cancer; Implant reconstruction; Trans-axillary; Irradiated; Post-mastectomy radiation; Tissue expander ID ACELLULAR DERMAL MATRIX; RADIATION-THERAPY; PATIENT SATISFACTION; SPARING MASTECTOMY; CANCER PATIENTS; PARADIGM SHIFT; RECONSTRUCTION; IMMEDIATE; COMPLICATIONS; OUTCOMES AB Background: Breast reconstruction with implants after tissue expansion is one of the most common methods of reconstruction. Although this approach is generally reliable, exchange of breast tissue expander for implant through the standard anterior incision presents a challenge in cases with attenuated soft tissue envelope due to radiation, thin anatomy, prior surgery, or combination of the above. We propose that a trans-axillary approach is a safe and alternate approach for implant exchange in the high-risk patients. Technique and case examples: A case series of 16 patients with multiple risk factors for compromised soft tissue that underwent a trans-axillary approach for implant exchange is reported. The trans-axillary implant exchange technique involves use of a standard 4 cm axillary incision, removal of the expander, judicious capsulotomy, placement of permanent implant, and closure in three separate tissue layers. Results: All trans-axillary cases were successful and all incisions were well healed without dehiscence, infection, or seroma. The average patient age was 49.4 years, and 50% of patients had received or were scheduled to receive radiation therapy. Nine patients underwent unilateral trans-axillary expander exchange while 7 patients were bilateral. Median implant size was 360 cc (mean 369 cc, range 150-600 cc), and mean follow-up for all patients was over 24 months. There were no cases of implant extrusion, capsular contracture requiring re-operation, or lymphedema. Six patients underwent concurrent or subsequent nipple reconstruction. Conclusions: This approach illustrates application of a technique commonly used in breast aesthetic augmentation to address a common reconstructive dilemma, which we believe to be a useful tool in prosthesis-based breast reconstruction, especially in patients with compromised soft tissue envelopes. (C) 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Eberlin, Kyle R.; Gfrerer, Lisa; Liao, Eric C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Liao, EC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, WACC 435,15 Parkman St, Boston, MA 02114 USA. EM cliao@partners.org NR 33 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 EI 1878-0539 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD DEC PY 2014 VL 67 IS 12 BP 1624 EP 1629 DI 10.1016/j.bjps.2014.07.019 PG 6 WC Surgery SC Surgery GA AW8ZB UT WOS:000346546600002 PM 25127109 ER PT J AU Ward, RE Boudreau, RM Caserotti, P Harris, TB Zivkovic, S Goodpaster, BH Satterfield, S Kritchevsky, SB Schwartz, AV Vinik, AI Cauley, JA Simonsick, EM Newman, AB Strotmeyer, ES AF Ward, Rachel E. Boudreau, Robert M. Caserotti, Paolo Harris, Tamara B. Zivkovic, Sasa Goodpaster, Bret H. Satterfield, Suzanne Kritchevsky, Stephen B. Schwartz, Ann V. Vinik, Aaron I. Cauley, Jane A. Simonsick, Eleanor M. Newman, Anne B. Strotmeyer, Elsa S. CA Hlth Aging Body Composition Study TI Sensory and Motor Peripheral Nerve Function and Incident Mobility Disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE peripheral nerve function; disability; older adults; longitudinal analysis; muscle strength ID MUSCLE STRENGTH; OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL PERFORMANCE; DIABETIC-NEUROPATHY; WOMENS HEALTH; AGE; CONDUCTION; BLACK; DEGENERATION AB ObjectivesTo assess the relationship between sensorimotor nerve function and incident mobility disability over 10years. DesignProspective cohort study with longitudinal analysis. SettingTwo U.S. clinical sites. ParticipantsPopulation-based sample of community-dwelling older adults with no mobility disability at 2000/01 examination (N=1,680; mean age SD 76.52.9, body mass index 27.14.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). MeasurementsMotor nerve conduction amplitude (poor <1 mV) and velocity (poor <40m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10- and 1.4-g monofilaments and vibration detection threshold at the toe. Lower extremity symptoms included numbness or tingling and aching or burning pain. Incident mobility disability assessed semiannually over 8.5years (interquartile range 4.5-9.6years) was defined as two consecutive self-reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. ResultsNerve impairments were detected in 55% of participants, and 30% developed mobility disability. Worse motor amplitude (HR=1.29 per SD, 95% CI=1.16-1.44), vibration detection threshold (HR=1.13 per SD, 95% CI=1.04-1.23), symptoms (HR=1.65, 95% CI=1.26-2.17), two motor impairments (HR=2.10, 95% CI=1.43-3.09), two sensory impairments (HR=1.91, 95% CI=1.37-2.68), and three or more nerve impairments (HR=2.33, 95% CI=1.54-3.53) predicted incident mobility disability after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. ConclusionPoor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions such as strength training for preventing disability and improving function in older adults with poor nerve function. C1 [Ward, Rachel E.] Spaulding Rehabil Hosp, Cambridge, England. [Ward, Rachel E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Boudreau, Robert M.; Cauley, Jane A.; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Harris, Tamara B.] NIA, Lab Epidemiol Biometry & Demog, NIH, Bethesda, MD USA. [Zivkovic, Sasa] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Kritchevsky, Stephen B.] Wake Forest, Div Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Neurobiol, Norfolk, VA 23501 USA. [Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,Rm 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Cauley, Jane/N-4836-2015; Newman, Anne B./C-6408-2013; OI Cauley, Jane/0000-0003-0752-4408; Newman, Anne B./0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; National Institute of Nursing Research Grant [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG024827]; American Diabetes Association [1-04-JF-46] FX This research was supported by National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and Grant 1-R01-AG 028050 (to ESS) and National Institute of Nursing Research Grant R01-NR012459 and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, the University of Pittsburgh Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to ESS), and the American Diabetes Association (1-04-JF-46 to ESS). NR 33 TC 10 Z9 10 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2014 VL 62 IS 12 BP 2273 EP 2279 DI 10.1111/jgs.13152 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600005 PM 25482096 ER PT J AU Pa, J Goodson, W Bloch, A King, AC Yaffe, K Barnes, DE AF Pa, Judy Goodson, William Bloch, Andrew King, Abby C. Yaffe, Kristine Barnes, Deborah E. TI Effect of Exercise and Cognitive Activity on Self-Reported Sleep Quality in Community-Dwelling Older Adults with Cognitive Complaints: A Randomized Controlled Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE physical activity; cognition; sleep; aging; intervention ID MODERATE-INTENSITY EXERCISE; NONPHARMACOLOGIC TREATMENT; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL TREATMENT; PRACTICE PARAMETERS; CHRONIC INSOMNIA; ELDERLY PERSONS; RATED QUALITY; TAI-CHI; IMPAIRMENT AB ObjectivesTo compare the effects of different types of physical and mental activity on self-reported sleep quality over 12weeks in older adults with cognitive and sleep complaints. DesignRandomized controlled trial. SettingGeneral community. ParticipantsSeventy-two inactive community-dwelling older adults with self-reported sleep and cognitive problems (mean age 73.36.1; 60% women). InterventionRandom allocation to four arms using a two-by-two factorial design: aerobic+cognitive training, aerobic+educational DVD, stretching+cognitive training, and stretching+educational DVD arms (60min/d, 3d/wk for physical and mental activity for 12weeks). MeasurementsChange in sleep quality using seven questions from the Sleep Disorders Questionnaire on the 2005 to 2006 National Health and Nutrition Examination Survey (range 0-28, with higher scores reflecting worse sleep quality). Analyses used intention-to-treat methods. ResultsSleep quality scores did not differ at baseline, but there was a significant difference between the study arms in change in sleep quality over time (P<.005). Mean sleep quality scores improved significantly more in the stretching+educational DVD arm (5.1 points) than in the stretching+cognitive training (1.2 points), aerobic+educational DVD (1.1 points), or aerobic+cognitive training (0.25 points) arms (all P<.05, corrected for multiple comparisons). Differences between arms were strongest for waking at night (P=.02) and taking sleep medications (P=.004). ConclusionSelf-reported sleep quality improved significantly more with low-intensity physical and mental activities than with moderate- or high-intensity activities in older adults with self-reported cognitive and sleep difficulties. Future longer-term studies with objective sleep measures are needed to corroborate these results. C1 [Pa, Judy; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Pa, Judy] Univ So Calif, Inst Neuroimaging & Informat, Dept Neurol, Los Angeles, CA USA. [Goodson, William] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bloch, Andrew] James Quillen Vet Affairs Med Ctr, Mountain Home, TN USA. [King, Abby C.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [King, Abby C.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), San Francisco VA Med Ctr, 4150 Clement St 151R, San Francisco, CA 94121 USA. EM Deborah.Barnes@ucsf.edu FU Alzheimer's Association [IIRG-06-27306, NIRP-12-259277]; National Institutes of Health (NIH) [K01-AG024069, K01-AG034175, R01-AG026720]; NIH/National Center for Research Resources/University of California, San Francisco-Clinical and Translational Science Institute [KL2 RR024130] FX This work was supported by the Alzheimer's Association (IIRG-06-27306, NIRP-12-259277) and the National Institutes of Health (NIH; K01-AG024069, K01-AG034175, R01-AG026720). This work also was supported by NIH/National Center for Research Resources/University of California, San Francisco-Clinical and Translational Science Institute (KL2 RR024130). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Exercise space and equipment donated by the YMCA of San Francisco, California. Computer equipment donated by Posit Science Corp., San Francisco, California. NR 42 TC 5 Z9 7 U1 4 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2014 VL 62 IS 12 BP 2319 EP 2326 DI 10.1111/jgs.13158 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600011 PM 25516028 ER PT J AU Kinosian, B AF Kinosian, Bruce TI Twenty-First Century Home-Centered Medicine: It's About the Touch, Not the Tech... SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID PRIMARY-CARE; TECHNOLOGY; TRIAL C1 [Kinosian, Bruce] Univ Penn, Leonard Davis Inst Hlth Econ, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Geriatr & Extended Care Data Anal Ctr, Philadelphia, PA USA. RP Kinosian, B (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. NR 13 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2014 VL 62 IS 12 BP 2433 EP 2435 DI 10.1111/jgs.13176 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600030 PM 25516039 ER PT J AU Brem, EA Davids, MS AF Brem, Elizabeth A. Davids, Matthew S. TI Is Bcl-2 a valid target in the treatment of indolent non-Hodgkin lymphoma? SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID MANTLE CELL LYMPHOMA; OBATOCLAX; BORTEZOMIB; INHIBITOR; RITUXIMAB C1 [Brem, Elizabeth A.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Davids, Matthew S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Davids, MS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM matthew_davids@dfci.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2014 VL 55 IS 12 BP 2675 EP 2677 DI 10.3109/10428194.2014.918971 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA AW9IQ UT WOS:000346571100001 PM 24794805 ER PT J AU Liao, W Jordaan, G Coriaty, N Sharma, S AF Liao, Wei Jordaan, Gwen Coriaty, Natalie Sharma, Sanjai TI Amplification of B cell receptor-Erk signaling by Rasgrf-1 overexpression in chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE CLL; B cell receptor; guanine exchange factor; Rasgrf-1; Erk pathway ID EXCHANGE FACTOR; TYROSINE KINASE; RAS PROTEINS; DEPENDENT ACTIVATION; THERAPEUTIC TARGET; GDP/GTP EXCHANGE; DOWN-REGULATION; UP-REGULATION; IN-VITRO; EXPRESSION AB Rasgrf-1 is a guanine exchange factor (GEF) that catalyzes the exchange of GDP for GTP. In a RNA microarray analysis of chronic lymphocytic leukemia (CLL) specimens (n = 5), this gene was found to be overexpressed in CLL as compared to normal peripheral blood mononuclear cell (PBMC) CD19 + B cells (n = 3). CLL specimens (n = 29) expressed Rasgrf-1 RNA at levels 5-300-fold higher as compared to normal B cells. CLL specimens expressed a 75 kDa isoform that was smaller than the expected full-length protein (140 kDa) and the truncated variant had higher GEF activity. Knockdown of Rasgrf-1 in CLL specimens inhibited active GTP-bound Ras and the Ras/Erk/mitogen-activated protein kinase (MAPK) pathway. Rasgrf-1 was phosphorylated and activated by B cell receptor (BCR) signaling that increased its GEF function, and this phosphorylation was blocked by Src and Bruton's tyrosine kinase (BTK) inhibitors. Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens. C1 [Liao, Wei; Jordaan, Gwen; Coriaty, Natalie; Sharma, Sanjai] Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Healthcare Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 304,Rm E1-115, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU Flight Attendant Medical Research Institute Fund (FAMRI); Veterans Administration Merit Review Grant FX We thank Dr. Alan Lichtenstein for useful discussions regarding this project. This work was supported by a grant from the Flight Attendant Medical Research Institute Fund (FAMRI) and a Veterans Administration Merit Review Grant to S.S. NR 58 TC 1 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2014 VL 55 IS 12 BP 2907 EP 2916 DI 10.3109/10428194.2014.898759 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA AW9IQ UT WOS:000346571100036 PM 24597981 ER PT J AU Bryant, JH Rottmann, J Lewis, JH Mishra, P Keall, PJ Berbeco, RI AF Bryant, Jonathan H. Rottmann, Joerg Lewis, John H. Mishra, Pankaj Keall, Paul J. Berbeco, Ross I. TI Registration of clinical volumes to beams-eye-view images for real-time tracking SO MEDICAL PHYSICS LA English DT Article DE radiotherapy; EPID; MV imaging; tracking ID LUNG-TUMOR TRACKING; PORTAL IMAGES; COLLIMATOR TRACKING; FIDUCIAL MARKERS; TARGET TRACKING; VERIFICATION; RADIOTHERAPY; CT; ACCURACY; POSITION AB Purpose: The authors combine the registration of 2D beam's eye view (BEV) images and 3D planning computed tomography (CT) images, with relative, markerless tumor tracking to provide automatic absolute tracking of physician defined volumes such as the gross tumor volume (GTV). Methods: During treatment of lung SBRT cases, BEV images were continuously acquired with an electronic portal imaging device (EPID) operating in cine mode. For absolute registration of physician-defined volumes, an intensity based 2D/3D registration to the planning CT was performed using the end-of-exhale (EoE) phase of the four dimensional computed tomography (4DCT). The volume was converted from Hounsfield units into electron density by a calibration curve and digitally reconstructed radiographs (DRRs) were generated for each beam geometry. Using normalized cross correlation between the DRR and an EoE BEV image, the best in-plane rigid transformation was found. The transformation was applied to physician-defined contours in the planning CT, mapping them into the EPID image domain. A robust multiregion method of relative markerless lung tumor tracking quantified deviations from the EoE position. Results: The success of 2D/3D registration was demonstrated at the EoE breathing phase. By registering at this phase and then employing a separate technique for relative tracking, the authors are able to successfully track target volumes in the BEV images throughout the entire treatment delivery. Conclusions: Through the combination of EPID/4DCT registration and relative tracking, a necessary step toward the clinical implementation of BEV tracking has been completed. The knowledge of tumor volumes relative to the treatment field is important for future applications like real-time motion management, adaptive radiotherapy, and delivered dose calculations. (C) 2014 American Association of Physicists in Medicine. C1 [Bryant, Jonathan H.; Rottmann, Joerg; Lewis, John H.; Mishra, Pankaj; Berbeco, Ross I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Bryant, Jonathan H.; Rottmann, Joerg; Lewis, John H.; Mishra, Pankaj; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Keall, Paul J.] Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu FU National Cancer Institute of the National Institutes of Health [R21CA156068]; Kaye Scholar Award FX This project was supported, in part, by the National Cancer Institute of the National Institutes of Health under award number R21CA156068 as well as a Kaye Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 28 TC 6 Z9 6 U1 1 U2 13 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2014 VL 41 IS 12 AR 121703 DI 10.1118/1.4900603 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW3HE UT WOS:000346176300006 PM 25471950 ER PT J AU Rottmann, J Berbeco, R AF Rottmann, Joerg Berbeco, Ross TI Using an external surrogate for predictor model training in real-time motion management of lung tumors SO MEDICAL PHYSICS LA English DT Article DE prediction; respiratory motion; lung; external surrogate; real-time ID IMAGE-GUIDED RADIOTHERAPY; RESPIRATORY MOTION; TRACKING SYSTEM; ACCURACY AB Purpose: Precise prediction of respiratory motion is a prerequisite for real-time motion compensation techniques such as beam, dynamic couch, or dynamic multileaf collimator tracking. Collection of tumor motion data to train the prediction model is required for most algorithms. To avoid exposure of patients to additional dose from imaging during this procedure, the feasibility of training a linear respiratory motion prediction model with an external surrogate signal is investigated and its performance benchmarked against training the model with tumor positions directly. Methods: The authors implement a lung tumor motion prediction algorithm based on linear ridge regression that is suitable to overcome system latencies up to about 300 ms. Its performance is investigated on a data set of 91 patient breathing trajectories recorded from fiducial marker tracking during radiotherapy delivery to the lung of ten patients. The expected 3D geometric error is quantified as a function of predictor lookahead time, signal sampling frequency and history vector length. Additionally, adaptive model retraining is evaluated, i.e., repeatedly updating the prediction model after initial training. Training length for this is gradually increased with incoming (internal) data availability. To assess practical feasibility model calculation times as well as various minimum data lengths for retraining are evaluated. Relative performance of model training with external surrogate motion data versus tumor motion data is evaluated. However, an internal-external motion correlation model is not utilized, i.e., prediction is solely driven by internal motion in both cases. Results: Similar prediction performance was achieved for training the model with external surrogate data versus internal (tumor motion) data. Adaptive model retraining can substantially boost performance in the case of external surrogate training while it has little impact for training with internal motion data. A minimum adaptive retraining data length of 8 s and history vector length of 3 s achieve maximal performance. Sampling frequency appears to have little impact on performance confirming previously published work. By using the linear predictor, a relative geometric 3D error reduction of about 50% was achieved (using adaptive retraining, a history vector length of 3 s and with results averaged over all investigated lookahead times and signal sampling frequencies). The absolute mean error could be reduced from (2.0 +/- 1.6) mm when using no prediction at all to (0.9 +/- 0.8) mm and (1.0 +/- 0.9) mm when using the predictor trained with internal tumor motion training data and external surrogate motion training data, respectively (for a typical lookahead time of 250 ms and sampling frequency of 15 Hz). Conclusions: A linear prediction model can reduce latency induced tracking errors by an average of about 50% in real-time image guided radiotherapy systems with system latencies of up to 300 ms. Training a linear model for lung tumor motion prediction with an external surrogate signal alone is feasible and results in similar performance as training with (internal) tumor motion. Particularly for scenarios where motion data are extracted from fluoroscopic imaging with ionizing radiation, this may alleviate the need for additional imaging dose during the collection of model training data. (C) 2014 American Association of Physicists in Medicine. C1 [Rottmann, Joerg; Berbeco, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rottmann, Joerg; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rottmann, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM jrottmann@lroc.harvard.edu FU National Cancer Institute [R21CA156068] FX The project described was supported, in part, by Award No. R21CA156068 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors would like to thank Dr. Hiroki Shirato and Dr. Seiko Nishioka for the opportunity to acquire the data set used in this study. NR 13 TC 0 Z9 0 U1 1 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2014 VL 41 IS 12 AR 121706 DI 10.1118/1.4901252 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW3HE UT WOS:000346176300009 PM 25471953 ER PT J AU Moskwa, P Zinn, PO Choi, YE Shukla, SA Fendler, W Chen, CC Lu, J Golub, TR Hjelmeland, A Chowdhury, D AF Moskwa, Patryk Zinn, Pascal O. Choi, Young Eun Shukla, Sachet A. Fendler, Wojciech Chen, Clark C. Lu, Jun Golub, Todd R. Hjelmeland, Anita Chowdhury, Dipanjan TI A Functional Screen Identifies miRs That Induce Radioresistance in Glioblastomas SO MOLECULAR CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; CANCER CELL-LINES; PROSTATE-CANCER; SMALL RNAS; MICRORNAS; THERAPY; CHK1; ATR; RADIOTHERAPY; CHECKPOINT AB The efficacy of radiotherapy in many tumor types is limited by normal tissue toxicity and by intrinsic or acquired radioresistance. Therefore, it is essential to understand the molecular network responsible for regulating radiosensitivity/resistance. Here, an unbiased functional screen identified four microRNAs (miR1, miR125a, miR150, and miR425) that induce radioresistance. Considering the clinical importance of radiotherapy for patients with glioblastoma, the impact of these miRNAs on glioblastoma radioresistance was investigated. Overexpression of miR1, miR125a, miR150, and/or miR425 in glioblastoma promotes radioresistance through upregulation of the cell-cycle checkpoint response. Conversely, antagonizing with antagomiRs sensitizes glioblastoma cells to irradiation, suggesting their potential as targets for inhibiting therapeutic resistance. Analysis of glioblastoma datasets from The Cancer Genome Atlas (TCGA) revealed that these miRNAs are expressed in glioblastoma patient specimens and correlate with TGF beta signaling. Finally, it is demonstrated that expression of miR1 and miR125a can be induced by TGF beta and antagonized by a TGF beta receptor inhibitor. Together, these results identify and characterize a new role for miR425, miR1, miR125, and miR150 in promoting radioresistance in glioblastomas and provide insight into the therapeutic application of TGFb inhibitors in radiotherapy. (C)2014 AACR. C1 [Moskwa, Patryk; Choi, Young Eun; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. [Moskwa, Patryk] Med Univ Greifswald, Dept Internal Med A, Greifswald, Germany. [Zinn, Pascal O.] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. [Zinn, Pascal O.] M Anderson Canc Ctr, Houston, TX USA. [Shukla, Sachet A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shukla, Sachet A.; Golub, Todd R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Fendler, Wojciech] Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, Lodz, Poland. [Chen, Clark C.] Univ Calif San Diego, Moores Canc Ctr, Ctr Theoret & Appl Neurooncol, Div Neurosurg, San Diego, CA 92103 USA. [Lu, Jun] Yale Univ, Yale Stem Cell Ctr, New Haven, CT USA. [Lu, Jun] Yale Univ, Dept Genet, New Haven, CT USA. [Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Hjelmeland, Anita] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. EM dipanjan_chowdhury@dfci.harvard.edu RI Fendler, Wojciech/S-9592-2016 OI Fendler, Wojciech/0000-0002-5083-9168 FU NCI [R01CA142698]; NIAID [R01 AI101897-01]; Basic Scholar Grant (American Cancer Society); Leukemia and Lymphoma Scholar Award; Ann-Fuller Foundation; Mary Kay Foundation; National Science Center (Poland) [2012/05/E/NZ5/02130]; [R01CA151522] FX D. Chowdhury is supported by R01CA142698 (NCI), R01 AI101897-01 (NIAID), Basic Scholar Grant (American Cancer Society), Leukemia and Lymphoma Scholar Award, Ann-Fuller Foundation, and Mary Kay Foundation. A. Hjelmeland is supported by R01CA151522. W. Fendler is supported by grant number 2012/05/E/NZ5/02130 of the National Science Center (Poland). NR 39 TC 5 Z9 5 U1 0 U2 2 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 DEC PY 2014 VL 12 IS 12 BP 1767 EP 1778 DI 10.1158/1541-7786.MCR-14-0268 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW9EN UT WOS:000346560400007 PM 25256711 ER PT J AU Mahal, BA Inverso, G Aizer, AA Donoff, RB Chuang, SK AF Mahal, Brandon A. Inverso, Gino Aizer, Ayal A. Donoff, R. Bruce Chuang, Sung-Kiang TI Impact of African-American race on presentation, treatment, and survival of head and neck cancer SO ORAL ONCOLOGY LA English DT Article DE Head and neck cancer; Healthcare disparities; African Americans; Minority health; Head and neck cancer specific survival ID SQUAMOUS-CELL CARCINOMA; DENTAL-CARE USE; RACIAL-DIFFERENCES; UNITED-STATES; OROPHARYNGEAL CANCER; PHARYNGEAL CANCER; ORAL-CAVITY; DISPARITIES; DETERMINANTS; ALCOHOL AB Objectives: To determine the associations between African American race and stage at diagnosis, receipt of definitive therapy, and cancer-specific mortality among patients with head and neck cancer. Materials and methods: The Surveillance, Epidemiology and End Results (SEER) database was used to conduct a retrospective study on 34,437 patients diagnosed with head and neck cancer from 2007 to 2010. Multivariable logistic regression analyses were applied to determine the impact of race on cancer stage at presentation (metastatic vs. non-metastatic) and receipt of definitive treatment. Fine and Gray competing-risks regression modeled the association between race and head and neck cancer-specific mortality. Results: African Americans were more likely to present with metastatic cancer compared to non-African Americans (Adjusted Odds Ratio [AOR] 1.76; CI 1.50-2.07; P < 0.001). Among patients with non-metastatic disease, African Americans were less likely to receive definitive treatment (AOR 0.63; CI 0.55-0.72; P < 0.001). After a median follow-up of 19 months, African Americans with non-metastatic disease were found to have a higher risk of head and neck cancer specific mortality (AHR 1.19; 95% CI 1.09-1.29; P < 0.001). Conclusion: African Americans with head and neck cancer are more likely to present with metastatic disease, less likely to be treated definitively, and are more likely to die from head and neck cancer. The unacceptably high rates of disparity found in this study should serve as immediate targets for urgent healthcare policy intervention. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mahal, Brandon A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Inverso, Gino; Donoff, R. Bruce; Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Aizer, Ayal A.] Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Donoff, R. Bruce; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Chuang, SK (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM sung-kiang_chuang@hms.harvard.edu NR 36 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD DEC PY 2014 VL 50 IS 12 BP 1177 EP 1181 DI 10.1016/j.oraloncology.2014.09.004 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA AW3TP UT WOS:000346209300012 PM 25261298 ER PT J AU Silvera, VM Danehy, AR Newton, AW Stamoulis, C Carducci, C Grant, PE Wilson, CR Kleinman, PK AF Silvera, V. Michelle Danehy, Amy R. Newton, Alice W. Stamoulis, Catherine Carducci, Chiara Grant, P. Ellen Wilson, Celeste R. Kleinman, Paul K. TI Retroclival collections associated with abusive head trauma in children SO PEDIATRIC RADIOLOGY LA English DT Article DE Child abuse; Brain; Trauma; Magnetic resonance imaging; Pediatric; Clivus; Computed tomography; Child; Abusive head trauma ID CLIVUS EPIDURAL HEMATOMA; OF-THE-LITERATURE; EXTRADURAL HEMATOMA; SUBDURAL-HEMATOMA; ATLANTOOCCIPITAL DISLOCATION; COMPUTED-TOMOGRAPHY; DIAGNOSIS; INJURY; MEMBRANE; FRACTURE AB Retroclival collections are rare lesions reported almost exclusively in children and strongly associated with trauma. We examine the incidence and imaging characteristics of retroclival collections in young children with abusive head trauma. We conducted a database search to identify children with abusive head trauma a parts per thousand currency sign3 years of age with brain imaging performed between 2007 and 2013. Clinical data and brain images of 65 children were analyzed. Retroclival collections were identified in 21 of 65 (32%) children. Ten (48%) were subdural, 3 (14%) epidural, 2 (10%) both, and 6 (28%) indeterminate. Only 8 of 21 retroclival collections were identifiable on CT and most were low or intermediate in attenuation. Eighteen of 21 retroclival collections were identifiable on MRI: 3 followed cerebral spinal fluid in signal intensity and 15 were bloody/proteinaceous. Additionally, 2 retroclival collections demonstrated a fluid-fluid level and 2 enhanced in the 5 children who received contrast material. Sagittal T1-weighted images, sagittal fluid-sensitive sequences, and axial FLAIR (fluid-attenuated inversion recovery) images showed the retroclival collections best. Retroclival collections were significantly correlated with supratentorial and posterior fossa subdural hematomas and were not statistically correlated with skull fracture or parenchymal brain injury. Retroclival collections, previously considered rare lesions strongly associated with accidental injury, were commonly identified in this cohort of children with abusive head trauma, suggesting that retroclival collections are an important component of the imaging spectrum in abusive head trauma. Retroclival collections were better demonstrated on MRI than CT, were commonly identified in conjunction with intracranial subdural hematomas, and were not significantly correlated with the severity of brain injury or with skull fractures. C1 [Silvera, V. Michelle; Danehy, Amy R.; Stamoulis, Catherine; Carducci, Chiara; Grant, P. Ellen; Kleinman, Paul K.] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA. [Newton, Alice W.] Harvard Univ, Sch Med, Child Protect Program, Dept Pediat,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stamoulis, Catherine] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA. [Wilson, Celeste R.] Harvard Univ, Sch Med, Div Gen Pediat, Dept Med,Boston Childrens Hosp, Boston, MA 02115 USA. RP Silvera, VM (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM michelle.silvera@tch.harvard.edu NR 40 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 2014 VL 44 SU 4 SI SI BP 621 EP 631 DI 10.1007/s00247-014-3170-2 PG 11 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AW4KG UT WOS:000346249400012 PM 25501734 ER PT J AU Kruse, GR Rigotti, NA AF Kruse, Gina Rae Rigotti, Nancy A. TI Routine screening of hospital patients for secondhand tobacco smoke exposure: A feasibility study SO PREVENTIVE MEDICINE LA English DT Article DE Secondhand tobacco smoke exposure; Electronic health records; Smoke-free homes ID PEDIATRIC NURSES; NATIONAL-SURVEY; UNITED-STATES; CESSATION; PARENTS; INTERVENTION; CHILDREN AB Objective. Secondhand tobacco smoke (SHS) exposure causes over 40,000 deaths per year, but healthcare systems rarely address this risk factor. In September 2012, Massachusetts General Hospital initiated routine inpatient screening for SHS exposure by adding a question to the nurses' computerized admission assessment form ("Is smoking allowed in your home or car?"). We measured the implementation of this screening question over 1 year. Methods. Multivariable analysis of hospital records of adult and pediatric admissions (N = 35,701) from September 1, 2012 to August 31, 2013, to assess screening question completion and identify characteristics of nonsmokers who may be exposed to SHS. Results. Nurses entered "Yes" or "No" to the screening question for 91% of 34,295 adult admissions and 86% of 1406 pediatric admissions. Among nonsmokers, smoking in the home or car was allowed for 3% of adult admissions and 4% of pediatric admissions. Adults admitted for psychiatric diagnoses, children admitted for asthma, and patients with Medicaid insurance had higher odds of exposure to SHS in their home or car. Conclusion. Routine screening of SHS among hospitalized patients by nurses is feasible. Doing so offers hospitals an opportunity to intervene and to promote smoke-free policies in patients' homes and cars. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kruse, Gina Rae; Rigotti, Nancy A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA USA. [Kruse, Gina Rae; Rigotti, Nancy A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA USA. [Kruse, Gina Rae] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Kruse, GR (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM gkruse@mgh.harvard.edu FU Flight Attendant Medical Research Institute [2008A057502]; National Cancer Institute [5 R25 CA 0571120]; Harvard School of Public Health; Dept. of Social and Behavioral Sciences FX This project was funded by the Flight Attendant Medical Research Institute Grant # 2008A057502. Dr. Kruse's efforts are supported by the National Cancer Institute Grant # 5 R25 CA 0571120 for Postdoctoral fellowship, Harvard School of Public Health, and Dept. of Social and Behavioral Sciences. NR 16 TC 2 Z9 2 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 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD DEC PY 2014 VL 69 BP 141 EP 145 DI 10.1016/j.ypmed.2014.09.017 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AW3ZN UT WOS:000346221600025 PM 25284258 ER PT J AU Vela, RM AF Vela, Ricardo M. TI The Effect of Severe Stress on Early Brain Development, Attachment, and Emotions A Psychoanatomical Formulation SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Child abuse; Child neglect; Limbic system development; Emotions; Attachment; Amygdala; Psychoanatomical formulation ID NEONATAL AMYGDALA LESIONS; SOCIAL-BEHAVIOR; RHESUS-MONKEYS; LIMBIC SYSTEM; DISORDERS; FRAMEWORK; NEGLECT; ABUSE AB Child abuse is the most extreme form of stress in childhood and adolescence, and has severe effects on the child's development. Limbic nuclei and circuitry development are especially vulnerable to child abuse and neglect during the first year of life. Development at the neuronal level can be severely disturbed by trauma during early infancy, resulting in maladaptive synaptic formation, impeding experience-expectant brain development. Development of basic emotions may favor the development of negative instead of positive emotions. The new concept of psychoanatomical formulation is introduced. A case vignette is presented and analyzed, based on the disturbed neuroanatomy underlying symptom expression. C1 [Vela, Ricardo M.] Massachusetts Gen Hosp, North Suffolk Mental Hlth Assoc, Child Serv, Chelsea, MA 02150 USA. [Vela, Ricardo M.] Massachusetts Gen Hosp, North Suffolk Mental Hlth Assoc, Family Serv, Chelsea, MA 02150 USA. RP Vela, RM (reprint author), Massachusetts Gen Hosp, North Suffolk Mental Hlth Assoc, Child Serv, 301 Broadway, Chelsea, MA 02150 USA. EM rvela@mgh.harvard.edu NR 52 TC 2 Z9 2 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2014 VL 37 IS 4 BP 519 EP + DI 10.1016/j.psc.2014.08.005 PG 17 WC Psychiatry SC Psychiatry GA AX0CB UT WOS:000346620000004 PM 25455063 ER PT J AU Pressman, SD Gallagher, MW Lopez, SJ Campos, B AF Pressman, Sarah D. Gallagher, Matthew W. Lopez, Shane J. Campos, Belinda TI Incorporating Culture Into the Study of Affect and Health SO PSYCHOLOGICAL SCIENCE LA English DT Editorial Material ID IDEAL AFFECT; AMERICAN; EMOTIONS; COUPLES; EAST C1 [Pressman, Sarah D.] Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA 92617 USA. [Gallagher, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Jamaica Plain, MA USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Lopez, Shane J.] Gallup Clifton Strengths Inst, Omaha, NE USA. [Campos, Belinda] Univ Calif Irvine, Dept Chicano Latino Studies, Irvine, CA 92617 USA. RP Pressman, SD (reprint author), Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA 92617 USA. EM pressman@uci.edu NR 20 TC 5 Z9 5 U1 0 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD DEC PY 2014 VL 25 IS 12 BP 2281 EP 2283 DI 10.1177/0956797614551573 PG 3 WC Psychology, Multidisciplinary SC Psychology GA AW4MD UT WOS:000346254200019 PM 25287666 ER PT J AU Binks, AP Evans, KC Reed, JD Moosavi, SH Banzett, RB AF Binks, Andrew P. Evans, Karleyton C. Reed, Jeffrey D. Moosavi, Shakeeb H. Banzett, Robert B. TI The time-course of cortico-limbic neural responses to air hunger SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE Air hunger; Dyspnea; fMRI; Limbic; Insula; Time-course ID CENTRAL HYPOVENTILATION SYNDROME; OBSTRUCTIVE PULMONARY-DISEASE; NOXIOUS INHIBITORY CONTROLS; VENTILATED QUADRIPLEGICS; TERMINAL DYSPNEA; INSULAR CORTEX; FMRI SIGNAL; PAIN; HUMANS; HYPERCAPNIA AB Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (similar to 45 mmHg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V-T) was alternated every 90 s between high V-T (0.96 +/- 0.23 L) that provided respiratory comfort (12 +/- 6% full scale) and low V-T (0.48 +/- 0.08 L) which evoked air hunger (56 +/- 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30 s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. (C) 2014 Elsevier B.V. All rights reserved. C1 [Binks, Andrew P.] Univ S Carolina, Sch Med, Dept Biomed Sci, Greenville, SC USA. [Evans, Karleyton C.; Reed, Jeffrey D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Evans, Karleyton C.; Banzett, Robert B.] Harvard Univ, Sch Med, Boston, MA USA. [Moosavi, Shakeeb H.] Oxford Brookes Univ, Dept Biol & Med Sci, Oxford OX3 0BP, England. [Banzett, Robert B.] Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. RP Evans, KC (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, Lab Neuroimaging Anxiety & Resp Psychophysiol, 13th St,Bldg 149,Suite 2625, Charlestown, MA 02129 USA. EM kcevans@partners.org FU Pfizer Ltd.; [NIH-HL46690]; [NIH-K23MH086619] FX We wish to acknowledge Leslie Moser Howes, Jared Zimmerman and Tina Chou for technical assistance, as well as Drs. Lewis Adams, Richard Gracely, Rick Hoge, Robert Lansing and Andrea Vovk, for their thoughtful discussion and comments. This work was supported primarily by NIH-HL46690 (R.B.B.) and secondarily by NIH-K23MH086619 (K.C.E.). Dr. Evans discloses grant support from Pfizer Ltd., unrelated to the present study. NR 56 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 EI 1878-1519 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD DEC 1 PY 2014 VL 204 SI SI BP 78 EP 85 DI 10.1016/j.resp.2014.09.005 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA AW7PT UT WOS:000346457900012 PM 25263029 ER PT J AU Rudolph, JW Raemer, DB Simon, R AF Rudolph, Jenny W. Raemer, Daniel B. Simon, Robert TI Establishing a Safe Container for Learning in Simulation The Role of the Presimulation Briefing SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Debriefing; Prebrief; Psychological safety; Realism; Education AB Statement In the absence of theoretical or empirical agreement on how to establish and maintain engagement in instructor-led health care simulation debriefings, we organize a set of promising practices we have identified in closely related fields and our own work. We argue that certain practices create a psychologically safe context for learning, a so-called safe container. Establishing a safe container, in turn, allows learners to engage actively in simulation plus debriefings despite possible disruptions to that engagement such as unrealistic aspects of the simulation, potential threats to their professional identity, or frank discussion of mistakes. Establishing a psychologically safe context includes the practices of (1) clarifying expectations, (2) establishing a fiction contract with participants, (3) attending to logistic details, and (4) declaring and enacting a commitment to respecting learners and concern for their psychological safety. As instructors collaborate with learners to perform these practices, consistency between what instructors say and do may also impact learners' engagement. C1 [Rudolph, Jenny W.; Raemer, Daniel B.; Simon, Robert] Ctr Med Simulat, Boston, MA USA. [Rudolph, Jenny W.; Raemer, Daniel B.; Simon, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rudolph, Jenny W.; Raemer, Daniel B.; Simon, Robert] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JW (reprint author), 100 1st Ave,Suite 400, Boston, MA 02129 USA. EM JWRudolph@mgh.harvard.edu NR 0 TC 29 Z9 29 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD DEC PY 2014 VL 9 IS 6 BP 339 EP 349 DI 10.1097/SIH.0000000000000047 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TK UT WOS:000346336500002 PM 25188485 ER PT J AU Cheng, A Raemer, DB AF Cheng, Adam Raemer, Daniel B. TI Is Clinical Trial Registration for Simulation-Based Research Necessary? SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Simulation; Research; Clinical trial; Registration AB Statement The International Committee of Medical Journal Editors requires that all clinical trials be prospectively registered before being considered for publication in their member journals. Clinical trial registries are Web-based databases of clinical trials, providing researchers, journal editors, and reviewers detailed study information to help inform trial results. What is unclear is whether clinical trial registration is required for simulation-based studies, where typically health care providers are the subjects and where the outcomes may be provider based or patient based. In this article, we describe the background and reasoning behind clinical trial registration and discuss whether simulation-based studies should be registered as a prerequisite to publication. C1 [Cheng, Adam] Univ Calgary, Alberta Childrens Hosp, Dept Pediat, KidSIM ASPIRE Simulat Res Program, Calgary, AB T3B 6A8, Canada. [Raemer, Daniel B.] Massachusetts Gen Hosp, Ctr Med Simulat, Boston, MA 02114 USA. [Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Raemer, Daniel B.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Cheng, A (reprint author), Univ Calgary, Alberta Childrens Hosp, Dept Pediat, KidSIM ASPIRE Simulat Res Program, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM chenger@me.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD DEC PY 2014 VL 9 IS 6 BP 350 EP 352 DI 10.1097/SIH.0000000000000064 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TK UT WOS:000346336500003 PM 25503529 ER PT J AU Abbott, CH Zakriski, AL AF Abbott, Caroline H. Zakriski, Audrey L. TI Grief and Attitudes Toward Suicide in Peers Affected by a Cluster of Suicides as Adolescents SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID SOCIAL SUPPORT; BEREAVEMENT; INVENTORY; BEHAVIOR; SCALE AB Eighty-five young adults exposed to a cluster of peer suicides as adolescents completed measures of attitudes toward suicide, grief, and social support. Closeness to the peers lost to suicide was positively correlated with grief and the belief that suicide is not preventable, with grief further elevated in close individuals with high social support from friends. Overall, social support was related to healthy attitudes about suicide including preventability, yet it was also related to some stigmatizing beliefs. Compared with 67 young adults who had not been exposed to a suicide cluster, the exposed sample was more likely to think that suicide is normal but more likely to think of it as incomprehensible. C1 [Abbott, Caroline H.; Zakriski, Audrey L.] Connecticut Coll, New London, CT 06320 USA. RP Abbott, CH (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, 450 Brookline Ave, Boston, MA 02215 USA. EM CarolineH_Abbott@dfci.harvard.edu NR 22 TC 2 Z9 2 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD DEC PY 2014 VL 44 IS 6 BP 668 EP 681 DI 10.1111/sltb.12100 PG 14 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AW7XC UT WOS:000346473800007 PM 24806293 ER PT J AU Falit, BP Halperin, EC Loeffler, JS AF Falit, Benjamin P. Halperin, Edward C. Loeffler, Jay S. TI Green Eggs and Ham: Strategies to Address the Growing Phenomenon of Selling a Medical School's Name SO ACADEMIC MEDICINE LA English DT Article AB In 2008, the authors published a review that highlighted an emerging trend for medical schools to change their names to those of wealthy donors. Since 2008, the names of ten benefactors have been added to the medical schools receiving their gifts. Twenty-three of the 141 U.S. medical schools accredited by the Liaison Committee on Medical Education are currently named after donors. Large donations have the potential to positively affect all stakeholders by improving the resources that are available for research, teaching, and clinical care, but the rapid increase in the naming of medical schools after wealthy benefactors raises important concerns for those same stakeholders. In this perspective, the authors explore such concerns and identify mitigating strategies that institutions facing these issues in the future can use to ensure that the benefit associated with a gift outweighs any adverse impact. The authors argue for a strong presumption of impropriety when a donor possesses a conflict of interest with the potential to affect clinicians' judgment. They go on to assess how donors' control of funds may have an impact on institutional mission and research agenda, and analyze the right of an organization to remove a benefactor's name for alleged wrongdoing. The perspective considers how renaming may negatively affect brand recognition and the associated impact on students, residents, faculty, and alumni. Finally, it concludes with an analysis of taxpayer-funded organizations and the concern that educational renaming will lead to a slippery slope in which other public goods are effectively purchased by wealthy donors. C1 [Falit, Benjamin P.] Harvard Radiat Oncol Program, Boston, MA USA. [Halperin, Edward C.] New York Med Coll, Valhalla, NY 10595 USA. [Halperin, Edward C.] Touro Coll & Univ Syst, New York, NY USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Boston, MA USA. RP Falit, BP (reprint author), Massachusetts Gen Hosp, Harvard Radiat Oncol Program, 100 Blossom St, Boston, MA 02114 USA. EM bfalit@partners.org NR 4 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD DEC PY 2014 VL 89 IS 12 BP 1614 EP 1616 DI 10.1097/ACM.0000000000000397 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AU9ND UT WOS:000345919500018 PM 24988422 ER PT J AU Bascom, PB Bordley, JL Lawton, AJ AF Bascom, Paul B. Bordley, Jessica L. Lawton, Andrew J. TI High-Dose Neuroleptics and Neuroleptic Rotation for Agitated Delirium Near the End of Life SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE agitated delirium; terminal delirium; palliative sedation; chlorpromazine; olanzapine; end-of-life care ID PALLIATIVE SEDATION; ADVANCED CANCER; OLANZAPINE; CHLORPROMAZINE; HALOPERIDOL; TRIAL AB Reason for the study: Agitated delirium presents unique challenges for hospice and palliative care clinicians. Haloperidol, the recommended neuroleptic, may be ineffective at low dose, or poorly tolerated at higher doses. Main Findings: This article reports on two patients with refractory agitated delirium. Both developed extrapyramidal symptoms from haloperidol and required rotation to an alternate neuroleptic. Patient #1 received 2000 mg/day oral chlorpromazine. Patient #2 received greater than 200 mg/day sublingual olanzapine. Control of agitation was achieved, though the doses were substantially higher than has previously reported in the literature. Each patient experienced considerable sedation, though this was an acceptable side effect for the family. Each patient was transferred from the acute care hospital to a location of family preference. There they died within a week of transfer. Conclusions: Agitated delirium is a palliative care emergency. High doses of neuroleptic medications, with rotation to an alternate neuroleptic when side effects occur with standard haloperidol, may effectively palliate agitated delirium. This remedy can provide the patient with a peaceful dying in a place of their choosing. C1 [Bascom, Paul B.] Palliat Care Phys, Portland, OR USA. [Bordley, Jessica L.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97232 USA. [Lawton, Andrew J.] Oregon Hlth & Sci Univ, Portland, OR 97232 USA. RP Bascom, PB (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97232 USA. EM paulbbascom@gmail.com NR 21 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD DEC PY 2014 VL 31 IS 8 BP 808 EP 811 DI 10.1177/1049909113507124 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW2AR UT WOS:000346091100004 PM 24081790 ER PT J AU Svenson, J Cunningham, M Dasgupta, S Gilkeson, GS AF Svenson, John Cunningham, Melissa Dasgupta, Subhajit Gilkeson, Gary S. TI Estrogen Receptor Alpha Modulates Mesangial Cell Responses to Toll-Like Receptor Ligands SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Mesangial cells; Estrogen receptors; Toll-like receptors; Innate immunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASE; EXPRESSION; ACID; MOUSE; 17-BETA-ESTRADIOL; PHOSPHORYLATION; DIFFERENTIATION; RECOGNITION; DEFICIENCY AB The female predominance in lupus is incompletely understood. The mechanisms for this difference are multifactorial involving the sex chromosomes, the hormones, and their receptors. We, and others, demonstrated that estrogen receptor alpha (ER)-deficient female mice developed significantly less lupus-like renal disease. This protective effect of ER deficiency occurred despite no impact on glomerular immune complex deposition. We hypothesized that decreased renal disease in ER-deficient mice was due to a dampened renal response to inflammatory stimuli. Given the role of Toll-like receptors (TLRs) in lupus, we assessed whether there was an interaction between TLR responses and ER. Herein, we show that TLR3, 4, and 7 ligands all enhanced mesangial cell (MC) ER expression, whereas neither estrogen, nor ER, impacted TLR3, 4, or 7 expression in MCs. The lack of ER markedly decreased MC production of interleukin 6 and monocyte chemoattractant protein 1 (MCP-1) following addition of TLR3, 4, and 7 ligands. In MCs, TLR ligands induced ER phosphorylation and nuclear localization. TLR3-induced nuclear factor B nuclear translocation in MCs was not significantly affected by estrogen or ER. Finally, we demonstrate that female MCs express more TLR3 and respond to TLR ligands with a significantly increased production of interleukin-6 compared with male MCs. These results identify a significant impact/interaction of ER in TLR-mediated inflammatory responses in MCs. C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), 96 Jonathan Lucas St,Suite 816,MSC 637, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI Cunningham, Melissa/0000-0002-9207-1986 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Biomedical Laboratory Research and Development [I01BX000470] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Biomedical Laboratory Research and Development, I01BX000470. NR 35 TC 4 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 2014 VL 348 IS 6 BP 492 EP 500 DI 10.1097/MAJ.0000000000000339 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AW0XK UT WOS:000346014300008 PM 25343264 ER PT J AU Gerrard, P Luce, J Bean, JF Jette, AM Zafonte, R AF Gerrard, Paul. Luce, John Bean, Jonathan F. Jette, Alan M. Zafonte, Ross TI Benchmarking Functional Status in Older Adults SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Factor analysis, statistical; Geriatric assessment; Geriatrics; Rehabilitation ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; SUBSEQUENT DISABILITY; INDEPENDENCE MEASURE; ELDERLY PEOPLE; BARTHEL INDEX; FIT INDEXES; LAST YEAR; VALIDITY; HEALTH AB Objective: To characterize the manner of functional status difficulties with age across multiple functional domains: lower extremity function, upper extremity function, and cognitive/social function. Construct validity of a functional status measure composed of these domains was assessed as part of this goal. Design: Cross-sectional survey of the community-dwelling civilian population in the United States. Setting: Community. Participants: Community-dwelling adults aged 60 years and older (N=7968). Interventions: Not applicable. Main Outcome Measures: Model fit of a 20-item functional status measure to a confirmatory factor analysis model was assessed with the root mean square error of approximation and the root mean square residual. Functional status benchmarks for age were developed with curves plotting activity difficulty percentiles versus age for the general U.S. population. Results: The 20-item activity difficulty index modeled as a 3-factor construct had a root mean square error of approximation of .045 and a root mean squared residual of .052, indicating good fit. Benchmarks based on percentiles show that the median activity difficulty score is quite low for the full range studied but that there is a steady increase with increasing age. The domain regarding cognition and social function appeared to be less sensitive than the upper and lower extremity skills domains to increasing age. Conclusions: A broad measure of difficulty with functional activities can be meaningfully treated as a 3-domain construct. The scores represented by the index measuring this construct can be used to compare patients to a national sample of age-matched individuals to assess functional status using normative values. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Gerrard, Paul.; Luce, John; Bean, Jonathan F.; Zafonte, Ross] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Gerrard, Paul.; Luce, John; Bean, Jonathan F.; Zafonte, Ross] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Gerrard, Paul.] Newton Wellesley Hosp, Dept Med, Div Phys Med & Rehabil, Newton, MA USA. [Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02215 USA. RP Gerrard, P (reprint author), 110 Marginal Way 706, Portland, ME 04101 USA. EM pbgerrard@gmail.com RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU NICHD NIH HHS [K24 HD070966] NR 55 TC 1 Z9 1 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2014 VL 95 IS 12 BP 2264 EP 2271 DI 10.1016/j.apmr.2014.06.012 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AW0AY UT WOS:000345954000005 PM 24996065 ER PT J AU Jain, S Khera, R Corrales-Medina, VF Townsend, RR Chirinos, JA AF Jain, Snigdha Khera, Rohan Corrales-Medina, Vicente F. Townsend, Raymond R. Chirinos, Julio A. TI "Inflammation and arterial stiffness in humans" SO ATHEROSCLEROSIS LA English DT Review DE Arterial stiffness; Inflammation; Pulse wave velocity; Cardiovascular risk ID PULSE-WAVE VELOCITY; NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; FACTOR-ALPHA THERAPY; SMOOTH-MUSCLE-CELLS; RHEUMATOID-ARTHRITIS; AORTIC STIFFNESS AB Arterial stiffness is an established marker of cardiovascular morbidity and mortality and a potential therapeutic target. While hypertension and aging are established factors contributing to arterial stiffness, the role of inflammation in stiffening of the arteries is less well understood. We summarize existing literature regarding inflammation and arterial stiffness, including a discussion of the potential mechanisms by which inflammation may lead to arterial stiffening and studies assessing: (1) The association between subclinical inflammation and arterial stiffness in the general population; (2) The presence of increased arterial stiffness in primary inflammatory diseases; (3) The effect of anti-inflammatory therapy on arterial stiffness in primary inflammatory disease including the effect of statins; (4) Experimental evidence of immunization-induced arterial stiffening in normal adults. We discuss potential opportunities to assess the impact of anti-inflammatory interventions on arterial stiffness in subjects without primary inflammatory conditions. We also review the effect of inflammation on wave reflections. Published by Elsevier Ireland Ltd. C1 [Jain, Snigdha; Khera, Rohan] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Corrales-Medina, Vicente F.] Univ Ottawa, Ottawa, ON, Canada. [Corrales-Medina, Vicente F.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Townsend, Raymond R.; Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19060 USA. [Townsend, Raymond R.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Chirinos, JA (reprint author), Univ Penn, Philadelphia, PA 19060 USA. EM julio.chirinos@uphs.upenn.edu RI Khera, Rohan/H-9029-2012; OI Khera, Rohan/0000-0001-9467-6199; Corrales-Medina, Vicente/0000-0002-9691-491X FU NIH [1R21AG043802] FX This work was supported by NIH grant 1R21AG043802 (JAC). NR 94 TC 34 Z9 35 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP 381 EP 390 DI 10.1016/j.atherosclerosis.2014.09.011 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600031 PM 25463062 ER PT J AU Hajsadeghi, F Nabavi, V Bhandari, A Choi, A Vincent, H Flores, F Budoff, M Ahmadi, N AF Hajsadeghi, Fereshteh Nabavi, Vahid Bhandari, Ajay Choi, Andrew Vincent, Hunter Flores, Ferdinand Budoff, Matthew Ahmadi, Naser TI Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events SO ATHEROSCLEROSIS LA English DT Article DE Epicardial adipose tissue (EAT); Computed tomography angiography (CTA); Major adverse cardiac event (MACE); Coronary artery disease (CAD) ID PERICARDIAL FAT; RISK-FACTORS; ADIPOCYTES AB Background: Increased-epicardial-adipose tissue (EAT) is associated with the presence and severity of subclinical-atherosclerosis. This study investigates the long-term clinical-outcome of subjects with and without increased-EAT. Methods: Two hundred and forty-five subjects, aged 61 +/- 9 years and 34% women underwent clinically-indicated computed-tomography-angiography (CTA), and body-surfacearea adjusted EAT was measured and were followed prospectively. CTA-diagnosed coronary-arterydisease (CAD) was defined as obstructive (luminal-stenosis >= 50%), non-obstructive (luminal-stenosis: 1 -49%) and zero-obstruction. Major-adverse-cardiac-event (MACE) was defined as myocardial-infarction or cardiovascular-death. Results: EAT increased significantly from subjects with zero-obstructioncoronaries (93 +/- 37 cm(3)/m(2)) to non-obstructive-CAD (132 +/- 25 cm(3)/m(2)) to obstructive-CAD (145 +/- 35 cm(3)/m(2)) (P = 0.01). During the 48-month follow-up, the event-rate was 8.6% (21). The event free survival-rate decreased significantly from 99% in the lowest-quartile to 86.6% in the highestquartile of EAT. After adjustment for risk-factors, the hazard ratio of MACE was 1.4, 3.1 and 5.7 in lower mid-, upper mid-and highest-quartiles of EAT as compared to lowest-quartile of EAT (P < 0.05). Conclusion: Increased EAT is directly associated with CAD and predicts MACE independent of the age, gender and conventional-risk-factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Hajsadeghi, Fereshteh; Nabavi, Vahid; Bhandari, Ajay; Choi, Andrew; Vincent, Hunter; Flores, Ferdinand; Budoff, Matthew; Ahmadi, Naser] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Hajsadeghi, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM drfsadeghi@gmail.com NR 10 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP 486 EP 489 DI 10.1016/j.atherosclerosis.2014.09.037 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600047 PM 25463078 ER PT J AU Menzaghi, C Fontana, A Copetti, M Rizza, S Spoto, B Buranasupkajorn, P Tripepi, G Marucci, A Bailetti, D Hastings, T Testa, A Mendonca, C Mallamaci, F De Cosmo, S Bacci, S Federici, M Doria, A Zoccali, C Trischitta, V AF Menzaghi, Claudia Fontana, Andrea Copetti, Massimiliano Rizza, Stefano Spoto, Belinda Buranasupkajorn, Patinut Tripepi, Giovanni Marucci, Antonella Bailetti, Diego Hastings, Timothy Testa, Alessandra Mendonca, Christine Mallamaci, Francesca De Cosmo, Salvatore Bacci, Simonetta Federici, Massimo Doria, Alessandro Zoccali, Carmine Trischitta, Vincenzo TI Joint effect of insulin signaling genes on all-cause mortality SO ATHEROSCLEROSIS LA English DT Article DE ENPP1; IRS1; TRIB3; Prospective study ID AMINO-ACID POLYMORPHISM; HUMAN ENDOTHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; CARDIOVASCULAR RISK; GLYCEMIC TRAITS; RESISTANCE; DISEASE; GLUCOSE; VARIANT; SECRETION AB Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q rs1044498; 1RS1 G972R, rs1801278; TRIM Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events. We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry. Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py). Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426 py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325 py. Results: In the first sample, individuals carrying 1 or >= 2 risk alleles had 33%(p = 0.06) and 51%(p = 0.02) increased risk of mortality, as compared with individuals with no risk alleles. A similar, though not significant, trend was obtained in the two replication samples only for subject carrying >= 2 risk alleles. In a pooled analysis, individuals carrying >= 2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR = 1.34, 95%Cl = 1.08-1.67; p = 0.008), and as compared to those carrying only one risk allele (HR = 1.41, 95% CI = 1.13-1.75; p = 0.002). This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status. Conclusion: Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality risk. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Menzaghi, Claudia; Marucci, Antonella; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, I-71013 San Giovanni Rotondo, Italy. [Fontana, Andrea; Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Biostat Unit, I-71013 San Giovanni Rotondo, Italy. [Rizza, Stefano; Federici, Massimo] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. [Spoto, Belinda; Tripepi, Giovanni; Testa, Alessandra; Mallamaci, Francesca; Zoccali, Carmine] CNR IBIM, Res Unit Clin Epidemiol & Physiopathol Renal Dis, Reggio Di Calabria, Italy. [Buranasupkajorn, Patinut; Hastings, Timothy; Mendonca, Christine; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Buranasupkajorn, Patinut; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bailetti, Diego] IRCSS Casa Sollievo Sofferenza, Mendel Lab, Rome, Italy. [Bailetti, Diego; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [De Cosmo, Salvatore; Bacci, Simonetta] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, I-71013 San Giovanni Rotondo, Italy. RP Menzaghi, C (reprint author), IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, Viale Padre Pio, I-71013 San Giovanni Rotondo, Italy. EM c.menzaghi@operapadrepio.it; vincenzo.trischitta@uniroma1.it RI Fontana, Andrea/J-8584-2016; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; Copetti, Massimiliano/K-3186-2016; Federici, Massimo/G-9940-2012; marucci, antonella/B-8722-2017; OI Fontana, Andrea/0000-0002-6660-5315; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; Copetti, Massimiliano/0000-0002-7960-5947; Federici, Massimo/0000-0003-4989-5194; marucci, antonella/0000-0001-8131-8317; Menzaghi, Claudia/0000-0002-7438-8955; TESTA, ALESSANDRA/0000-0002-0529-6571 FU Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST; PO Puglia FESR; Italian Ministry of Health [RC2011, RC2012, RC2013, RC2014]; NIH [R01 DK073168, DK110400] FX This study was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006 and PO Puglia FESR 2007-2013, Italian Ministry of Health grants RC2011, RC2012, RC2013, RC2014 (CM), and NIH grants R01 DK073168 and DK110400 (AD). NR 31 TC 6 Z9 6 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP 639 EP 644 DI 10.1016/j.atherosclerosis.2014.10.005 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600068 PM 25463099 ER PT J AU Oklu, R Barallobre-Barreiro, J Fava, M Yin, X Albadawi, H Langley, SR Jahangiri, M Watkins, MT Misra, S Mayr, M AF Oklu, R. Barallobre-Barreiro, J. Fava, M. Yin, X. Albadawi, H. Langley, S. R. Jahangiri, M. Watkins, M. T. Misra, S. Mayr, M. TI PROTEOMIC PROFILING OF THE HUMAN VENOUS EXTRACELLULAR MATRIX REVEALS A ROLE FOR MAST CELL PROTEASES IN THE PATHOGENESIS OF VARICOSE VEINS SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT Autumn Meeting of the British-Atherosclerosis-Society (BAS) CY SEP 25-26, 2014 CL Queens Coll, Cambridge, ENGLAND SP British Atherosclerosis Soc HO Queens Coll C1 [Oklu, R.; Barallobre-Barreiro, J.; Fava, M.; Yin, X.; Albadawi, H.; Langley, S. R.; Jahangiri, M.; Watkins, M. T.; Misra, S.; Mayr, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Oklu, R.; Barallobre-Barreiro, J.; Fava, M.; Yin, X.; Albadawi, H.; Langley, S. R.; Jahangiri, M.; Watkins, M. T.; Misra, S.; Mayr, M.] Kings Coll London, Kings British Heart Fdn Ctr, London, England. [Oklu, R.; Barallobre-Barreiro, J.; Fava, M.; Yin, X.; Albadawi, H.; Langley, S. R.; Jahangiri, M.; Watkins, M. T.; Misra, S.; Mayr, M.] NHS Trust, St Georges Hosp, London, England. [Oklu, R.; Barallobre-Barreiro, J.; Fava, M.; Yin, X.; Albadawi, H.; Langley, S. R.; Jahangiri, M.; Watkins, M. T.; Misra, S.; Mayr, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Oklu, R.; Barallobre-Barreiro, J.; Fava, M.; Yin, X.; Albadawi, H.; Langley, S. R.; Jahangiri, M.; Watkins, M. T.; Misra, S.; Mayr, M.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP E7 EP E8 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600022 ER PT J AU Tripathi, A Drake, CG Harshman, LC AF Tripathi, Abhishek Drake, Charles G. Harshman, Lauren C. TI Harnessing the PD-1 Pathway in Renal Cell Carcinoma: Current Evidence and Future Directions SO BIODRUGS LA English DT Review ID HIGH-DOSE INTERLEUKIN-2; HUMAN OVARIAN-CANCER; PHASE-III TRIAL; T-CELLS; ANTI-PD-1 ANTIBODY; INTERFERON-ALPHA; DENDRITIC CELLS; IMMUNE SURVEILLANCE; PROGRAMMED DEATH-1; PROGNOSTIC-FACTORS AB Programmed cell death-1 (PD-1) is a recognized immune checkpoint. It is frequently upregulated on the T cells that infiltrate tumors, providing an inhibitory signal, which may facilitate immune escape. Blocking antibodies have been developed to interrupt the interaction of PD-1 with its ligands PD-L1/PD-L2, with the goal of increasing the host antitumor immune response. Initial results have been encouraging, with durable responses in both treatment-naive and pretreated patients, along with an acceptable toxicity profile. This tolerability makes PD-1 blockade an excellent potential partner for combination strategies with the approved targeted agents, such as tyrosine kinase inhibitors (TKIs) and anti-vascular endothelial growth factor (anti-VEGF) antibodies, as well as other investigational immune checkpoint inhibitors or agonist antibodies that may costimulate an immune response. PD-L1 expression on tumor cells and tumor-infiltrating immune cells is also being evaluated as a predictive biomarker of response to treatment. This review summarizes the biological basis, preclinical studies, ongoing trials, and future challenges associated with targeting the PD-1 pathway in renal cell carcinoma. C1 [Tripathi, Abhishek] Univ Massachusetts, Sch Med, Dept Internal Med, Worcester, MA USA. [Drake, Charles G.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Drake, Charles G.] Johns Hopkins Univ, Brady Urol Inst, Baltimore, MD USA. [Harshman, Lauren C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Harshman, LC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM laurenc_harshman@dfci.harvard.edu FU Bristol-Myers Squibb (BMS); Advro Biotech; Janssen Pharmaceuticals; Astellas/Medivation FX Charles G. Drake has received research funding from Bristol-Myers Squibb (BMS), Advro Biotech, and Janssen Pharmaceuticals; participated in advisory boards for BMS, Compugen, Dendreon, ImmunExcite, Roche/Genentech, and Pfizer; received manuscript preparation support from BMS (not for this work); received stock options from Comugen; and received royalties from Amplimmune.; Lauren C. Harshman has received past research funding from BMS; receives current research funding from Pfizer and Astellas/Medivation; and has participated in advisory boards for BMS, Pfizer, NCCN, Dendreon, and Aveo. NR 112 TC 2 Z9 2 U1 1 U2 20 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1173-8804 EI 1179-190X J9 BIODRUGS JI Biodrugs PD DEC PY 2014 VL 28 IS 6 BP 513 EP 526 DI 10.1007/s40259-014-0111-4 PG 14 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA AW0OX UT WOS:000345993600004 PM 25445176 ER PT J AU Driver, JA AF Driver, Jane A. TI Inverse association between cancer and neurodegenerative disease: review of the epidemiologic and biological evidence SO BIOGERONTOLOGY LA English DT Review DE Cancer; Neurodegeneration; Alzheimer's disease; Parkinson's disease; Epidemiology ID MILD AD DEMENTIA; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; INTRANASAL INSULIN; DIFFERENTIAL EXPRESSION; CORTICAL SIGNATURE; MALIGNANT-MELANOMA; OXIDATIVE DAMAGE; IN-VITRO; RISK AB Growing evidence suggests an unusual epidemiologic association between cancer and certain neurological conditions, particularly age-related neurodegenerative diseases. Cancer survivors have a 20-50 % lower risk of developing Parkinson's and Alzheimer's disease, and patients with these neurodegenerative conditions have a substantially lower incidence of cancer. We review the epidemiologic evidence for this inverse co-morbidity and show that it is not simply an artifact of survival bias or under-diagnosis. We then review the potential biological explanations for this association, which is intimately linked to the very different nature of dividing cells and neurons. The known genetic and metabolic connections between cancer and neurodegeneration generally fall within two categories. The first includes shared genes and pathways such as Pin1 and the ubiquitin proteasome system that are dysregulated in different directions to cause one disease or the other. The second includes common pathophysiological mechanisms such as mitochondrial dysfunction, oxidative stress and DNA damage that drive both conditions, but with different cellular fates. We discuss examples of these biological links and their implications for developing new approaches to prevention and treatment of both diseases. C1 [Driver, Jane A.] Brigham & Womens Hosp, VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA 02120 USA. [Driver, Jane A.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02120 USA. [Driver, Jane A.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Driver, Jane A.] Harvard Univ, Sch Med, Boston, MA USA. RP Driver, JA (reprint author), Brigham & Womens Hosp, Div Aging, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jdriver@partners.org FU Merit Review Award from the Veteran's Administration FX Dr. Driver is supported by a Merit Review Award from the Veteran's Administration. NR 78 TC 23 Z9 26 U1 2 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 EI 1573-6768 J9 BIOGERONTOLOGY JI Biogerontology PD DEC PY 2014 VL 15 IS 6 SI SI BP 547 EP 557 DI 10.1007/s10522-014-9523-2 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AW3EH UT WOS:000346168100002 PM 25113739 ER PT J AU Hartinger, AE Nam, AS Chico-Calero, I Vakoc, BJ AF Hartinger, Alzbeta E. Nam, Ahhyun S. Chico-Calero, Isabel Vakoc, Benjamin J. TI Monte Carlo modeling of angiographic optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID SPECTRAL RANGE; SIMULATIONS; TISSUES; IMAGES; BLOOD AB Optical coherence tomography (OCT) provides both structural and angiographic imaging modes. Because of its unique capabilities, OCT-based angiography has been increasingly adopted into small animal and human subject imaging. To support the development of the signal and image processing algorithms on which OCT-based angiography depends, we describe here a Monte Carlo-based model of the imaging approach. The model supports arbitrary three-dimensional vascular network geometries and incorporates methods to simulate OCT signal temporal decorrelation. With this model, it will be easier to compare the performance of existing and new angiographic signal processing algorithms, and to quantify the accuracy of vascular segmentation algorithms. The quantitative analysis of key algorithms within OCT-based angiography may, in turn, simplify the selection of algorithms in instrument design and accelerate the pace of new algorithm development. (C) 2014 Optical Society of America C1 [Hartinger, Alzbeta E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hartinger, AE (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM ahartinger@mgh.harvard.edu FU Center for Biomedical OCT Research and Translation [P41EB015903]; National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health; NIH [R01CA163528]; Natural Sciences and Engineering Research Council of Canada FX This project was supported by the Center for Biomedical OCT Research and Translation through Grant Number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. This work was also supported by NIH grant R01CA163528 and by the Natural Sciences and Engineering Research Council of Canada. NR 13 TC 4 Z9 4 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2014 VL 5 IS 12 BP 4338 EP 4349 DI 10.1364/BOE.5.004338 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AW1TD UT WOS:000346071900021 PM 25574442 ER PT J AU Kim, M Kang, D Wu, T Tabatabaei, N Carruth, RW Martinez, RV Whitesides, GM Nakajima, Y Tearney, GJ AF Kim, Minkyu Kang, DongKyun Wu, Tao Tabatabaei, Nima Carruth, Robert W. Martinez, Ramses V. Whitesides, George M. Nakajima, Yoshikazu Tearney, Guillermo J. TI Miniature objective lens with variable focus for confocal endomicroscopy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; ELECTRICALLY TUNABLE LENS; MICROSCOPY; CAPSULE; TRACT AB Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that can rapidly image large areas of luminal organs at microscopic resolution. One of the main challenges for large-area SECM imaging in vivo is maintaining the same imaging depth within the tissue when patient motion and tissue surface irregularity are present. In this paper, we report the development of a miniature vari-focal objective lens that can be used in an SECM endoscopic probe to conduct adaptive focusing and to maintain the same imaging depth during in vivo imaging. The vari-focal objective lens is composed of an aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic membrane. The water volume within the chamber was changed to control curvature of the elastic membrane, which subsequently altered the position of the SECM focus. The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A vari-focal range of 240 mu m was achieved while maintaining lateral resolution better than 2.6 mu m and axial resolution better than 26 mu m. Volumetric SECM images of swine esophageal tissues were obtained over the vari-focal range of 260 mu m. SECM images clearly visualized cellular features of the swine esophagus at all focal depths, including basal cell nuclei, papillae, and lamina propria. (C) 2014 Optical Society of America C1 [Kim, Minkyu; Kang, DongKyun; Wu, Tao; Tabatabaei, Nima; Carruth, Robert W.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Minkyu; Kang, DongKyun; Wu, Tao; Tabatabaei, Nima; Carruth, Robert W.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Minkyu; Nakajima, Yoshikazu] Univ Tokyo, Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan. [Martinez, Ramses V.; Whitesides, George M.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Whitesides, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Martinez, Ramses V.] Madrid Inst Adv Studies, IMDEA Nanosci, Madrid 28049, Spain. [Tearney, Guillermo J.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kim, M (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gtearny@partners.org RI Martinez, Ramses/C-5219-2009 OI Martinez, Ramses/0000-0002-0234-7732 FU FP7 People program under the project Marie Curie [IOF-275148]; NinePoint Medical, Cambridge, MA FX Authors thank Drs. Kengyeh K. Chu, Tim N Ford, Kanwarpal Singh and Manabu Kashiwagi for their assistance in OCT measurement of the lens profile. R. V. M acknowledges funding by the FP7 People program under the project Marie Curie IOF-275148. This research was supported in part through a sponsored research agreement with NinePoint Medical, Cambridge, MA. Dr. Tearney consults for NinePoint Medical. Massachusetts General Hospital has a licensing arrangement with NinePoint Medical. Dr. Tearney has the rights to receive royalty payments as part of this licensing arrangement. NR 25 TC 3 Z9 3 U1 4 U2 24 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2014 VL 5 IS 12 BP 4350 EP 4361 DI 10.1364/BOE.5.004350 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AW1TD UT WOS:000346071900022 PM 25574443 ER PT J AU Menon, U Talaat, A Rosenthal, AN Macdonald, ND Jeyerajah, AR Skates, SJ Sibley, K Oram, DH Jacobs, IJ AF Menon, Usha Talaat, Ahmed Rosenthal, Adam N. Macdonald, Nicola D. Jeyerajah, Arjun R. Skates, Steven J. Sibley, Karen Oram, David H. Jacobs, Ian J. TI Performance of ultrasound as a second line test to serum CA 125 in ovarian cancer screening SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; ASYMPTOMATIC WOMEN; ULTRASONOGRAPHY; COLOR AB Objective To assess the performance of ultrasonography in a multimodal ovarian cancer screening strategy. Design Prospective ovarian cancer screening trial between December 1986 and June 1993. Setting General practice, occupational health departments and an ovarian cancer screening clinic at a London teaching hospital. Population Postmenopausal women, >= 45 years with a raised CAl25. Methods Volunteers with a CAl25 >= 30 U/mL underwent a pelvic ultrasound. Scans were classified as normal, abnormal (ovarian volume >= 8.8 mL) or equivocal (normal volume with abnormal morphology). Abnormal ovarian morphology was subclassified as simple cyst (single, thin walled cyst with no septa or papillary projections) or complex (all other abnormalities). Volunteers with abnormal scans were referred for a gynaecological opinion. Follow up was via the cancer registry and postal questionnaires. Main outcome measures Sensitivity, specificity and positive predictive value of different ultrasound criteria for detection of index cancer (e.g. primary invasive epithelial carcinoma of the ovary and fallopian tube). Results Seven hundred and forty-one women underwent 1219 scans and 20 index cancers occurred during a median follow up of 6.8 years. The sensitivity for detection of ovarian cancer of different ultrasound criteria was 100% for abnormal morphology, 89.5% for abnormal volume and 84% for complex morphology. The highest specificity (97%) and positive predictive value (37.2%) was achieved using complex morphology. Conclusion A variety of ultrasound criteria can achieve high sensitivity, specificity and positive predictive value for index cancers in postmenopausal women with an elevated CA 125. Use of ovarian morphology to interpret ultrasound may increase sensitivity and use of complex ovarian morphology may increase the positive predictive value. C1 [Menon, Usha; Talaat, Ahmed; Rosenthal, Adam N.; Macdonald, Nicola D.; Jeyerajah, Arjun R.; Sibley, Karen; Oram, David H.; Jacobs, Ian J.] Royal Hosp NHS Trust, St Bartholomews Hosp, Gynaecol Canc Res Unit, London EC1A 7BE, England. [Skates, Steven J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobs, IJ (reprint author), Royal Hosp NHS Trust, St Bartholomews Hosp, Gynaecol Canc Res Unit, London EC1A 7BE, England. OI Rosenthal, Adam/0000-0001-6924-0721 FU Clinical Training Fellowship Grant from St Bartholomew's Hospital Joint Research Board; Gynaecology Cancer Research Fund; Research into Ovarian Cancer; British Medical Association; WellBeing FX We are grateful for the co-operation of British United Provident Association (BUPA) and the occupational health departments of Marks and Spencer and the National Westminster Bank. We thank Dr R. Woolas, Dr A. P. Davies, Dr J. Bridges, Dr I. Stabile, Dr T. Fay, Mrs M. Butcher and Dr P. Weidman for their contribution to the study, as well as all the general practitioners whose collaboration was essential to the study. U.M. was funded by a Clinical Training Fellowship Grant from the St Bartholomew's Hospital Joint Research Board. The trial was supported by grants from the Gynaecology Cancer Research Fund, Research into Ovarian Cancer, the British Medical Association (TP Gunton Award) and WellBeing. NR 14 TC 2 Z9 2 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2014 VL 121 SU 7 SI SI BP 35 EP 39 DI 10.1111/1471-0528.13211 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW1NG UT WOS:000346055500008 PM 25488086 ER PT J AU Arnold, KB Hermos, JA Anderson, KB Minasian, L Tangen, CM Probstfield, JF Cook, ED AF Arnold, Kathryn B. Hermos, John A. Anderson, Karen B. Minasian, Lori Tangen, Catherine M. Probstfield, Jeffrey F. Cook, Elise D. TI Retention of Black and White Participants in the Selenium and Vitamin E Cancer Prevention Trial (SWOG-Coordinated Intergroup Study S0000) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN MEN; FOLLOW-UP; CLINICAL-TRIALS; PROSTATE-CANCER; MINORITY RECRUITMENT; SCREENING TRIAL; COLORECTAL-CANCER; RISK; HEALTH; SELECT AB Background: Disproportionally low retention of minority populations can adversely affect the generalizability of clinical research trials. We determine the overall retention rates for White and Black participants from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and explore participant and site characteristics associated with retention failure (study disengagement) for these groups. Methods: A secondary analysis of 28,118 White (age >= 55), and 4,322 Black (age >= 50) SELECT participants used multivariate Cox regression to estimate overall retention rates and to calculate HRs and 95% confidence intervals (CI). Results: Blacks had higher age-adjusted risk of disengagement than Whites (HR, 1.92; 95% CI, 1.77-2.08). Among Black participants, those ages 50 to 54 were at three times the risk of disengagement than those >= 65 years of age (HR, 3.61; 95% CI, 2.41-5.41). Blacks age >= 65 had 1.6 times the risk of disengagement than Whites age >= 65 (HR, 1.60; 95% CI, 1.38-1.87). By 6 years after randomization, 84% of Whites and 69% of Blacks remained engaged in the study. Current smoking status was an independent risk factor for study disengagement for both White and Black participants. For both groups, sites whose staffs missed SELECT training sessions or who received SELECT Retention and Adherence grants were associated with increased and decreased disengagement risks, respectively. Conclusions: SELECT retention was disproportionately lower for Blacks than for Whites. Impact: The observed difference in retention rates for Blacks and Whites and factors identified by race for study disengagement in SELECT may inform retention efforts for future long-term, cancer prevention trials. (C) 2014 AACR. C1 [Arnold, Kathryn B.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98109 USA. [Hermos, John A.] VA Boston Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, Boston, MA USA. [Anderson, Karen B.] SWOG Data Management Canc Res & Biostat, Seattle, WA USA. [Minasian, Lori] NCI, Div Canc Prevent, Rockville, MD USA. [Probstfield, Jeffrey F.] Univ Washington, Dept Med, Clin Trials Serv Unit, Seattle, WA USA. [Cook, Elise D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Arnold, KB (reprint author), Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave North,M3-C102,POB 19024, Seattle, WA 98109 USA. EM karnold@fhcrc.org FU Public Health Service Cooperative Agreement, National Cancer Institute, NIH, Department of Health and Human Services [CA37429]; National Center for Complementary and Alternative Medicine (NIH) FX This research was supported in part by Public Health Service Cooperative Agreement grant CA37429 (to K.B. Arnold, K.B. Anderson, C.M. Tangen; and PI, C. Blanke) awarded by the National Cancer Institute, NIH, Department of Health and Human Services, and in part by the National Center for Complementary and Alternative Medicine (NIH). Study agents and packaging were provided by Perrigo Company (Allegan, MI), Sabinsa Corporation (Piscataway, NJ), Tishcon Corporation (Westbury, NY), and DSM Nutritional Products Inc. NR 46 TC 2 Z9 2 U1 0 U2 2 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 DEC PY 2014 VL 23 IS 12 BP 2895 EP 2905 DI 10.1158/1055-9965.EPI-14-0724 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300031 PM 25242051 ER PT J AU Du, MM Zhang, XH Hoffmeister, M Schoen, RE Baron, JA Berndt, SI Brenner, H Carlson, CS Casey, G Chan, AT Curtis, KR Duggan, D Gauderman, WJ Giovannucci, EL Gong, J Harrison, TA Hayes, RB Henderson, BE Hopper, JL Hsu, L Hudson, TJ Hutter, CM Jenkins, MA Jiao, S Kocarnik, JM Kolonel, LN Le Marchand, L Lin, Y Newcomb, PA Rudolph, A Seminara, D Thornquist, MD Ulrich, CM White, E Wu, K Zanke, BW Campbell, PT Slattery, ML Peters, U Chang-Claude, J Potter, JD AF Du, Mengmeng Zhang, Xuehong Hoffmeister, Michael Schoen, Robert E. Baron, John A. Berndt, Sonja I. Brenner, Hermann Carlson, Christopher S. Casey, Graham Chan, Andrew T. Curtis, Keith R. Duggan, David Gauderman, W. James Giovannucci, Edward L. Gong, Jian Harrison, Tabitha A. Hayes, Richard B. Henderson, Brian E. Hopper, John L. Hsu, Li Hudson, Thomas J. Hutter, Carolyn M. Jenkins, Mark A. Jiao, Shuo Kocarnik, Jonathan M. Kolonel, Laurence N. Le Marchand, Loic Lin, Yi Newcomb, Polly A. Rudolph, Anja Seminara, Daniela Thornquist, Mark D. Ulrich, Cornelia M. White, Emily Wu, Kana Zanke, Brent W. Campbell, Peter T. Slattery, Martha L. Peters, Ulrike Chang-Claude, Jenny Potter, John D. CA Colon Canc Family Registry Geneti TI No Evidence of Gene-Calcium Interactions from Genome-Wide Analysis of Colorectal Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ENVIRONMENT INTERACTIONS; SUSCEPTIBILITY LOCI; METAANALYSIS AB Background: Calcium intake may reduce risk of colorectal cancer, but the mechanisms remain unclear. Studies of interaction between calcium intake and SNPs in calcium-related pathways have yielded inconsistent results. Methods: To identify gene-calcium interactions, we tested interactions between approximately 2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 colorectal cancer cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide alpha = 5E-08. Results: After accounting for multiple comparisons, there were no statistically significant SNP interactions with total, dietary, or supplemental calcium intake. Conclusions: We found no evidence of SNP interactions with calcium intake for colorectal cancer risk in a large population of 18,509 individuals. Impact: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and colorectal cancer in European populations. (C) 2014 AACR. C1 [Du, Mengmeng; Carlson, Christopher S.; Curtis, Keith R.; Gong, Jian; Harrison, Tabitha A.; Hsu, Li; Hutter, Carolyn M.; Jiao, Shuo; Kocarnik, Jonathan M.; Lin, Yi; Newcomb, Polly A.; Thornquist, Mark D.; Ulrich, Cornelia M.; White, Emily; Peters, Ulrike; Potter, John D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Du, Mengmeng; Kocarnik, Jonathan M.; Newcomb, Polly A.; Ulrich, Cornelia M.; White, Emily; Peters, Ulrike; Potter, John D.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Du, Mengmeng; Zhang, Xuehong; Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Du, Mengmeng; Zhang, Xuehong; Chan, Andrew T.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Casey, Graham] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Duggan, David] Genet Basis Human Dis Translat Genom Res Inst TGe, Phoenix, AZ USA. [Gauderman, W. James] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Giovannucci, Edward L.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hayes, Richard B.; Jenkins, Mark A.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Hutter, Carolyn M.; Seminara, Daniela; Chang-Claude, Jenny] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Zanke, Brent W.] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Du, MM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave North,M4-B402, Seattle, WA 98109 USA. EM mdu@fhcrc.org RI Hoffmeister, Michael/B-5745-2012; Brenner, Hermann/B-4627-2017; Jenkins, Mark/P-7803-2015; OI Hoffmeister, Michael/0000-0002-8307-3197; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Jenkins, Mark/0000-0002-8964-6160; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute, NIH, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; NIH [R01 CA60987, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, P50 CA127003, R01 CA137178, P01 CA 087969, P50 CA 127003, R01 CA42182, R37 CA54281, P01 CA033619, R01 CA63464, U01 CA074783, U01 HG004446, R01 CA076366]; NIH (RFA) [CA-95011]; National Cancer Institute, NIH [U01 CA122839, R25 CA94880]; NIH: Australasian Colorectal Cancer Family Registry [U01 CA097735]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 17046-1, BR 17046-3, BR 17046-4, CH1171-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI) [Z01 CP 010200]; NIH GEI [U01 HG 004438]; NIH from the National Cancer Institute [K05 CA154337]; NIH from the Office of Dietary Supplements; ACS; GECCO [R01 CA059045]; National Institutes of Environmental Health Sciences [ES020801]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; [U19 CA148107] FX C.S. Carlson, K.R. Curtis, M. Du, J. Gong, T. A. Harrison, L. Hsu, C.M. Hutter, J.M. Kocarnik, S. Jiao, Y. Lin, U. Peters, M.D. Thornquist, and C.M. Ulrich are affiliated with GECCO, which is supported by the following grants from the National Cancer Institute, NIH, U.S. Department of Health and Human Services: U01 CA137088 and R01 CA059045.; L. Le Marchand is affiliated with COLO2& 3, which is supported by the NIH (R01 CA60987).; J.A. Baron, G. Casey, J.L. Hopper, M.A. Jenkins, and P.A. Newcomb are affiliated with CCFR, which is supported by the NIH (RFA # CA-95011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, NIH by U01 CA122839. The following Colon CFR centers contributed data to this article and were supported by NIH: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and Seattle Colorectal Cancer Family Registry (U01 CA074794).; H. Brenner, J. Chang-Claude, M. Hoffmeister, and A. Rudolph are affiliated with DACHS, which was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 17046-1, BR 17046-3, BR 17046-4 and CH1171-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; J.D. Potter and M.L. Slattery are affiliated with DALS, which was supported by the NIH (R01 CA48998 to M.L. Slattery). A.T. Chan, E.L. Giovannucci, K. Wu, and X. Zhang are affiliated with HPFS, NHS, and PHS. HPFS was supported by the NIH (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA127003), NHS by the NIH (R01 CA137178, P01 CA 087969, and P50 CA 127003), and PHS by the NIH (R01 CA42182).; B.E. Henderson, L.N. Kolonel, and L. Le Marchand are affiliated with MEC, which is supported by the following grants from the NIH: R37 CA54281, P01 CA033619, and R01 CA63464.; T.J. Hudson and B.W. Zanke are affiliated with OFCCR, which is supported by the NIH, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; S.I. Berndt, R.B. Hayes, and R.E. Schoen are affiliated with PLCO, which was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. In addition, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M and colleagues Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May; 39(5): 645-9), Colon CGEMS pancreatic cancer scan (PanScan; Amundadottir, L and colleagues Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986-90, and Petersen, GM and colleagues A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224-8), and the Lung Cancer and Smoking study (Landi MT, and colleagues A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;85(5):679-91). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment, and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping.; P.A. Newcomb is affiliated with PMH, which is supported by the NIH (R01 CA076366 to P.A. Newcomb). E. White is affiliated with VITAL, which is supported in part by the NIH (K05 CA154337) from the National Cancer Institute and Office of Dietary Supplements.; P.T. Campbell is at the American Cancer Society (ACS) and funded through ACS.; M. Du is supported by the National Cancer Institute, NIH (R25 CA94880).; D. Duggan is affiliated with TGEN and funded through a subaward with GECCO (R01 CA059045).; W.J. Gauderman is affiliated with Colorectal Transdisciplinary Study (CORECT), which is funded through U19 CA148107, and by the National Institutes of Environmental Health Sciences (ES020801).; D. Seminara is a Senior Scientist and Consortia Coordinator at the Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, NIH.; The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 8 TC 1 Z9 1 U1 0 U2 3 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 DEC PY 2014 VL 23 IS 12 BP 2971 EP 2976 DI 10.1158/1055-9965.EPI-14-0893 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300040 PM 25192705 ER PT J AU Olsen, LR Campos, B Barnkob, MS Winther, O Brusic, V Andersen, MH AF Olsen, Lars Ronn Campos, Benito Barnkob, Mike Stein Winther, Ole Brusic, Vladimir Andersen, Mads Hald TI Bioinformatics for cancer immunotherapy target discovery SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE Cancer vaccines; Tumor antigens; T cell epitopes; Biological databases; Computational biology ID HLA CLASS-I; PEPTIDE BINDING PREDICTION; HUMAN TUMOR-ANTIGENS; EPITOPE-BASED DIAGNOSTICS; REGULATORY T-CELLS; MHC CLASS-II; EXPRESSION PROFILES; PROSTATE-CANCER; GENE-EXPRESSION; HIGH-THROUGHPUT AB The mechanisms of immune response to cancer have been studied extensively and great effort has been invested into harnessing the therapeutic potential of the immune system. Immunotherapies have seen significant advances in the past 20 years, but the full potential of protective and therapeutic cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes and co-targets for single-epitope and multi-epitope strategies. We provide examples of application to the well-known tumor antigen HER2 and suggest bioinformatics methods to ameliorate therapy resistance and ensure efficient and lasting control of tumors. C1 [Olsen, Lars Ronn; Winther, Ole] Univ Copenhagen, Bioinformat Ctr, Dept Biol, DK-2200 Copenhagen, Denmark. [Olsen, Lars Ronn] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark. [Olsen, Lars Ronn; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Campos, Benito] Univ Heidelberg Hosp, Div Expt Neurosurg, Dept Neurosurg, D-69120 Heidelberg, Germany. [Barnkob, Mike Stein] Univ Southern Denmark, Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense C, Denmark. [Winther, Ole] Tech Univ Denmark, DTU Comp, DK-2800 Lyngby, Denmark. [Brusic, Vladimir] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan. [Andersen, Mads Hald] Herlev Hosp, Dept Hematol, Ctr Canc Immune Therapy, DK-2730 Herlev, Denmark. RP Olsen, LR (reprint author), Univ Copenhagen, Bioinformat Ctr, Dept Biol, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. EM lro@binf.ku.dk OI Barnkob, Mike Bogetofte/0000-0002-5892-1174; Olsen, Lars Ronn/0000-0002-6725-7850 FU Novo Nordisk Foundation; Danish Cancer Society; Herlev Hospital FX We wish to thank the reviewers for their critical appraisal of this manuscript. We apologize in advance to all investigators whose research, methods, or software could not be appropriately cited due to space limitations. Lars Ronn Olsen and Ole Winther wish to acknowledge funding from the Novo Nordisk Foundation, and Mads Hald Andersen was funded by the Danish Cancer Society and Herlev Hospital. NR 147 TC 4 Z9 4 U1 2 U2 24 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 DEC PY 2014 VL 63 IS 12 BP 1235 EP 1249 DI 10.1007/s00262-014-1627-7 PG 15 WC Oncology; Immunology SC Oncology; Immunology GA AW0EK UT WOS:000345963000001 PM 25344903 ER PT J AU Chow, MT Luster, AD AF Chow, Melvyn T. Luster, Andrew D. TI Chemokines in Cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID REGULATORY T-CELLS; ENHANCES TUMOR PROGRESSION; HUMAN BREAST-CANCER; IFN-GAMMA; ANTITUMOR-ACTIVITY; ADAPTIVE IMMUNITY; OVARIAN-CANCER; MYELOID CELLS; LYMPH-NODE; METASTASIS AB Chemokines are chemotactic cytokines that control the migration of cells between tissues and the positioning and interactions of cells within tissue. The chemokine superfamily consists of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane spanning signaling receptors. Chemokines mediate the host response to cancer by directing the trafficking of leukocytes into the tumor microenvironment. This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and protumor activities. Although chemokines were initially appreciated as important mediators of immune cell migration, we now know that they also play important roles in the biology of nonimmune cells important for tumor growth and progression. Chemokines can directly modulate the growth of tumors by inducing the proliferation of cancer cells and preventing their apoptosis. They also direct tumor cell movement required for metastasis. Chemokines can also indirectly modulate tumor growth through their effects on tumor stromal cells and by inducing the release of growth and angiogenic factors from cells in the tumor microenvironment. In this Masters of Immunology primer, we focus on recent advances in understanding the complex nature of the chemokine system in tumor biology with a focus on how the chemokine system could be used to augment cancer immunotherapeutic strategies to elicit a more robust and long-lasting host antitumor immune response. (C) 2014 AACR. C1 [Chow, Melvyn T.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Sch Med,Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Fruit St, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu FU NIH [R01CA069212, P01AI112521, R37AI040618, U19AI095261, P30DK043351] FX M.T. Chow and A.D. Luster were supported by grants from the NIH (R01CA069212, P01AI112521, R37AI040618, U19AI095261, and P30DK043351). NR 77 TC 26 Z9 28 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD DEC PY 2014 VL 2 IS 12 BP 1125 EP 1131 DI 10.1158/2326-6066.CIR-14-0160 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA AW2RE UT WOS:000346135500001 PM 25480554 ER PT J AU Harshman, LC Drake, CG Choueiri, TK AF Harshman, Lauren C. Drake, Charles G. Choueiri, Toni K. TI PD-1 Blockade in Renal Cell Carcinoma: To Equilibrium and Beyond SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; DENDRITIC CELLS; PROGRAMMED DEATH-1; TARGETED THERAPY; PATIENT SURVIVAL; CANCER; TUMOR; EXPRESSION; B7-H1; INFILTRATION AB The past several years have witnessed a resurgence of interest in cancer immunotherapy. The development of blocking antibodies against the inhibitory programmed death-1 (PD-1) pathway represents a clinical breakthrough in the treatment of solid tumors such as melanoma, and these agents show great promise in renal cell carcinoma (RCC). The early data have been surprising in that they demonstrate that blockade of a single immune checkpoint can elicit objective responses in patients with RCC, despite the recognized complexity of the immunosuppressive tumor microenvironment. Reinvigorating the patient's own immune cells to reactivate and to target the tumor has the potential advantages of more selective killing and thus decreased toxicity. In addition, checkpoint blockade immunotherapy has the advantage of inducing a memory response that is unattainable with our current cytotoxic and targeted therapies. This Crossroads overview will highlight the emerging investigation of PD-1 blockade in RCC and how this T cell-targeted strategy may thwart the tumor's escape mechanisms and shift the immune system/tumor balance back to a state of equilibrium and even to tumor elimination. (C) 2014 AACR. C1 [Harshman, Lauren C.; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Drake, Charles G.] Johns Hopkins Univ, Dept Oncol, Boston, MA USA. [Drake, Charles G.] Johns Hopkins Univ, Brady Urol Inst, Boston, MA USA. RP Harshman, LC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM LaurenC_Harshman@dfci.harvard.edu FU Bristol-Myers Squib; Janssen; Compugen; NexImmune FX L.C. Harshman is a consultant/advisory board member for Bristol-Myers Squib, Pfizer, Dendreon, and Aveo. C.G. Drake reports receiving a commercial research grant from Bristol-Myers Squib and Janssen; has ownership interest (including patents) in Compugen and NexImmune; and is a consultant/advisory board member for Bristol-Myers Squibb, Compugen, Dendreon, Roche/Genenetch, Novartis, and Merck. T.K. Choueiri is a consultant/advisory board member for Merck, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Novartis, and Bayer. NR 59 TC 13 Z9 13 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD DEC PY 2014 VL 2 IS 12 BP 1132 EP 1141 DI 10.1158/2326-6066.CIR-14-0193 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA AW2RE UT WOS:000346135500002 PM 25480555 ER PT J AU Farough, S Karaa, A Walker, MA Slate, N Dasu, T Verbsky, J Fusunyan, R Canapari, C Kinane, TB Van Cleave, J Sweetser, DA Sims, KB Walter, JE AF Farough, S. Karaa, A. Walker, M. A. Slate, N. Dasu, T. Verbsky, J. Fusunyan, R. Canapari, C. Kinane, T. B. Van Cleave, J. Sweetser, D. A. Sims, K. B. Walter, J. E. TI Coenzyme Q10 and immunity: A case report and new implications for treatment of recurrent infections in metabolic diseases SO CLINICAL IMMUNOLOGY LA English DT Article DE Coenzyme Q(10); Mitochondria; Recurrent infections; Immune deficiency ID Q(10) DEFICIENCY; LYMPHOCYTES AB Coenzyme Q(10) (CoQ(10)) deficiency can manifest diversely, from isolated myopathy to multisystem involvement. Immune dysregulation has not been reported as a feature of the disease. We report a four-year old girl with failure to thrive, recurrent infections, developmental delay with hypotonia, and CoQ(10) deficiency with impaired immune function, which improved after CoQ(10) and immunoglobulin replacement therapy. Immune dysfunction in Cog deficiency should be considered and treated appropriately. (C) 2014 Elsevier Inc. All rights reserved. C1 [Farough, S.; Slate, N.; Fusunyan, R.; Canapari, C.; Kinane, T. B.; Van Cleave, J.; Sweetser, D. A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Karaa, A.] Brigham & Womens Hosp, Childrens Hosp, Dept Genet, Boston, MA 02115 USA. [Walker, M. A.; Sims, K. B.] Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. [Dasu, T.; Verbsky, J.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Walter, J. E.] Massachusetts Gen Hosp Children, Pediat Immunodeficiency Program, Boston, MA USA. RP Farough, S (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM sfarough@bwh.harvard.edu; jewalter@mgh.harvard.edu NR 13 TC 0 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2014 VL 155 IS 2 BP 209 EP 212 DI 10.1016/j.clim.2014.09.010 PG 4 WC Immunology SC Immunology GA AW2JQ UT WOS:000346114300006 PM 25264263 ER PT J AU Kleinnijenhuis, J Quintin, J Preijers, F Joosten, LAB Jacobs, C Xavier, RJ van der Meer, JWM van Crevel, R Netea, MG AF Kleinnijenhuis, Johanneke Quintin, Jessica Preijers, Frank Joosten, Leo A. B. Jacobs, Cor Xavier, Rannnik J. van der Meer, Jos W. M. van Crevel, Reinout Netea, Mihai G. TI BCG-induced trained immunity in NK cells: Role for non-specific protection to infection SO CLINICAL IMMUNOLOGY LA English DT Article DE Trained immunity; BCG; Innate immunity; Vaccination ID NATURAL-KILLER-CELLS; MEMORY; REINFECTION; MECHANISMS; MONOCYTES; VACCINES AB Adaptive features of innate immunity, also termed 'trained immunity', have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination. BCG vaccination of healthy volunteers increased proinflammatory cytokine production following ex vivo stimulation of NK cells with mycobacteria and other unrelated pathogens up until at least three months after vaccination. In addition, in a murine model of disseminated candidiasis, BCG vaccination led to an increased survival in SOD mice, which was partially dependent on NK cells. These findings suggest that NK cells may contribute to the non-specific (heterologous) beneficial effects of BCG vaccination. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kleinnijenhuis, Johanneke; Quintin, Jessica; Joosten, Leo A. B.; Jacobs, Cor; van der Meer, Jos W. M.; van Crevel, Reinout; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands. [Preijers, Frank] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Hematol Lab, NL-6525 GA Nijmegen, Netherlands. [Xavier, Rannnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Rannnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Rannnik J.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Xavier, Rannnik J.] Harvard Univ, Cambridge, MA 02142 USA. RP Kleinnijenhuis, J (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med 463, Geert Grooteplein Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM johanneke.kleinnijenhuis@radboudumc.nl RI van Crevel, reinout/A-6636-2010; Joosten, Leo/H-3138-2015; Netea, Mihai/N-5155-2014; Kleinnijenhuis, Johanneke/P-6309-2015; Preijers, F.W.M.B./L-4586-2015; kleinnijenhuis, johanneke/G-7978-2016; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 FU Vici Grant of the Netherlands Organization for Scientific Research; Vidi Grant of the Netherlands Organization for Scientific Research; US National Institutes of Health; Helmsley Trust [AI 062773, DK 043351, DK 83756] FX This work was supported by a Vici Grant of the Netherlands Organization for Scientific Research [to M.G.N.], a Vidi Grant of the Netherlands Organization for Scientific Research [to R.v.C] and by grants from the US National Institutes of Health; and the Helmsley Trust [AI 062773, DK 043351 and DK 83756 to R.J.X.]. NR 18 TC 30 Z9 31 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2014 VL 155 IS 2 BP 213 EP 219 DI 10.1016/j.clim.2014.10.005 PG 7 WC Immunology SC Immunology GA AW2JQ UT WOS:000346114300007 PM 25451159 ER PT J AU Broder-Fingert, S Ferrone, CF Giauque, A Connors, SL AF Broder-Fingert, Sarabeth Ferrone, Christine F. Giauque, Ann Connors, Susan L. TI Residents' Knowledge and Comfort With Caring for Children With Autism Spectrum Disorder SO CLINICAL PEDIATRICS LA English DT Article ID PHYSICIAN SURVEY C1 [Broder-Fingert, Sarabeth] MassGen Hosp Children, Boston, MA 02114 USA. [Ferrone, Christine F.; Giauque, Ann; Connors, Susan L.] MassGen Hosp Lurie Ctr Autism, Lexington, MA USA. RP Broder-Fingert, S (reprint author), MassGen Hosp Children, 175 Cambridge St,Cpz 501c, Boston, MA 02114 USA. EM sbroder-finger@partners.org OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 FU Agency for Healthcare Research and Quality, National Research Service Award [T32 HS000063]; Lurie Center for Autism at the Massachusetts General Hospital/MassGeneral Hospital for Children FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Sarabeth Broder-Fingert, MD, is funded through the Agency for Healthcare Research and Quality, National Research Service Award T32 HS000063. The authors also wish to acknowledge the Lurie Center for Autism at the Massachusetts General Hospital/MassGeneral Hospital for Children for their support of this work. NR 6 TC 1 Z9 1 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 EI 1938-2707 J9 CLIN PEDIATR JI Clin. Pediatr. PD DEC PY 2014 VL 53 IS 14 BP 1390 EP 1392 DI 10.1177/0009922814526982 PG 3 WC Pediatrics SC Pediatrics GA AW1YN UT WOS:000346084900011 PM 24647693 ER PT J AU Friedlander, AH AF Friedlander, A. H. TI The need to develop a strategy for managing incidental findings on maxillofacial imaging studies: a call for action SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Letter ID TOMOGRAPHY; CT C1 [Friedlander, A. H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, A. H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Friedlander, AH (reprint author), Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. EM arthur.friedlander@med.va.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X EI 1476-542X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD DEC PY 2014 VL 43 IS 8 AR 20140284 DI 10.1259/dmfr.20140284 PG 2 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA AW4DL UT WOS:000346231400009 PM 25299932 ER PT J AU Trief, PM Weinstock, RS Cibula, D Delahanty, LM AF Trief, Paula M. Weinstock, Ruth S. Cibula, Donald Delahanty, Linda M. TI Sustained weight loss one year after group telephone intervention: 3-Year results from the SHINE study SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Obesity; Obesity; Diabetes Prevention Program; Metabolic syndrome; Telephone intervention; Weight loss ID DIABETES PREVENTION PROGRAM; LIFE-STYLE INTERVENTION; METABOLIC SYNDROME; METFORMIN; ADULTS; REGAIN AB A telephone delivered translation of the DPP weight loss program, delivered by trained primary care staff over 2 years, resulted in significant weight loss for patients with metabolic syndrome. Participants in groups (conference calls) continued to lose weight a full year after the program ended, while those called individually regained. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Trief, Paula M.; Weinstock, Ruth S.; Cibula, Donald] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. RP Trief, PM (reprint author), SUNY Upstate Med Univ, 750 E Adams St, Syracuse, NY 13210 USA. EM triefp@upstate.edu FU National Institutes of Health (NIDDK) [R18-DK078553] FX Contributors: We thank our participants, their primary care providers, the health care professionals who served as educators, and our dietician coaches. We also thank Philip Morin, MS for project management, Julie J. Stone, RN for performing the participant assessments, and Jane D. Bulger, MS, CCRC and Michael J. Wade, MS for facilitating data collection and entry. Funders: This study was supported by grant R18-DK078553 from the National Institutes of Health (NIDDK; Trief and Weinstock PIs). Prior presentations: Some of these findings were published in abstract form and presented in oral and poster sessions at the annual meetings of the American Diabetes Association in June, 2012, June, 2013 and June 2014. NR 16 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2014 VL 106 IS 3 BP E74 EP E78 DI 10.1016/j.diabres.2014.09.032 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AW1PF UT WOS:000346060800007 PM 25451907 ER PT J AU Yoon, WJ Daglilar, ES Mino-Kenudson, M Morales-Oyarvide, V Pitman, MB Brugge, WR AF Yoon, Won Jae Daglilar, Ebubekir S. Mino-Kenudson, Mari Morales-Oyarvide, Vicente Pitman, Martha B. Brugge, William R. TI Characterization of epithelial subtypes of intraductal papillary mucinous neoplasm of the pancreas with endoscopic ultrasound and cyst fluid analysis SO ENDOSCOPY LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; CARCINOEMBRYONIC ANTIGEN; COLORECTAL-CANCER; MANAGEMENT; DIAGNOSIS; IPMN; CLASSIFICATION; CEA; MALIGNANCY; ATYPIA AB Background and study aims: Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. There are limited data on the endoscopic ultrasound (EUS) findings and/or cyst fluid analysis of the epithelial subtypes. The objective of this study was to determine whether there are differences in EUS and cyst fluid characteristics (carcinoembryonic antigen [CEA] concentration and cytology) among the subtypes. Patients and methods: The study cohort consisted of 85 patients (median age 68 years, 40 men) with resected and histologically confirmed branch-duct or mixed-type IPMNs who underwent preoperative EUS-guided fine-needle aspiration between 1999 and 2010 for the evaluation of pancreatic cysts. EUS and cyst fluid characteristics were analyzed retrospectively and correlated with the subtypes. Results: The numbers of evaluated cystic lesions were 1 in 79 patients, 2 in 5 patients, and 3 in 1 patient. Of 92 IPMNs analyzed, gastric-type IPMNs were the most common (n=68, 73.9%), followed by intestinal (n=17, 18.5%), oncocytic (n=5, 5.4%), and pancreatobiliary subtypes (n=2, 2.2%). Gastric-type IPMNs were significantly smaller (cutoff 30mm; P=0.002), and less likely than other subtypes to have a mass lesion or mural nodule (P=0.046) on EUS. Cyst fluid CEA concentration varied among the subtypes (median concentrations for gastric, intestinal, oncocytic, and pancreatobiliary types 619.8, 83.0, 5.1, and 270.0 ng/mL, respectively; P=0.012). The presence of neoplastic epithelial cells (P=0.624) and extracellular mucin (P=0.208) on cytology had no association with subtypes. Conclusions: Gastric-type IPMNs, the most common subtype, are characterized by high concentrations of cyst fluid CEA, small cyst diameter, and low risk EUS imaging features. C1 [Yoon, Won Jae; Daglilar, Ebubekir S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Yoon, Won Jae] Inje Univ, Coll Med, Seoul Paik Hosp, Dept Internal Med, Seoul, South Korea. [Mino-Kenudson, Mari; Morales-Oyarvide, Vicente; Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org 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) [8UL1TR000170-05]; Harvard Catalyst, The Harvard Clinical and Translational Science Center - Harvard University FX This work was conducted with support from Harvard Catalyst, 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 8UL1TR000170-05 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 9 Z9 9 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD DEC PY 2014 VL 46 IS 12 BP 1071 EP 1077 DI 10.1055/s-0034-1377629 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AU9JN UT WOS:000345908600006 PM 25208034 ER PT J AU Choi, JW Kim, JK Choi, M Kim, YR Yun, SH AF Choi, Jin Woo Kim, Jun Ki Choi, Myunghwan Kim, Yi Rang Yun, Seok Hyun TI In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis SO ENDOSCOPY LA English DT Article ID STEM-CELLS; CANCER; BOWEL AB Background and study aims: A diagnostic molecular marker for pre-neoplastic lesions, particularly before polyposis, is still lacking. Lgr5 has been broadly accepted as a marker for intestinal cancer stem cells. The aim of this study was to investigate the monitoring of Lgr5(+) cells as a useful tool for the early diagnosis of premalignant lesions before polyp formation. Methods: In vivo molecular imaging was performed to examine colon tumorigenesis in Lgr5-EGFP mice treated with azoxymethane and dextran sodium sulfate. eGFP(+) Lgr5(+) regions in the descending colon were longitudinally monitored using side-view confocal endomicroscopy. Based on the eGFP signal intensity on the luminal surface, polyps were classified into two groups - Lgr5-high and Lgr5-low. White light colonoscopy was used to monitor polyp formation. Results: Approximately 75% of the polyps originated from foci containing Lgr5-eGFP(+) cells, whereas 25% of the polyps emerged from Lgr5(-) foci. Among eGFP(+) foci, Lgr5-high foci grew faster than Lgr5-low foci. Conclusions: Polyps developed at Lgr5(+) regions. Luminal Lgr5 expression was correlated with the growth rate of early-stage adenomas. Lgr5 is a promising molecular marker for the early diagnosis of colon tumors. C1 [Choi, Jin Woo; Choi, Myunghwan; Kim, Yi Rang; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Dept Pharmacol, Iksan, Chonbuk, South Korea. [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Inst Dent Res, Iksan, Chonbuk, South Korea. [Kim, Jun Ki] Asan Med Ctr, Asan Inst Life Sci, Biomed Engn R&D Ctr, Seoul, South Korea. [Kim, Jun Ki] Univ Ulsan, Coll Med, Seoul, South Korea. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Wellman Ctr, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu OI Choi, Myunghwan/0000-0002-4235-7003 FU National Institutes of Health [U54CA143837, P41EB015903]; National Research Foundation of Korea [WCU R31-2008-000-10071-0, NRF-2011-357-C00141, 2008-0062484] FX This work was supported through grants from the National Institutes of Health (U54CA143837, P41EB015903) and the National Research Foundation of Korea (WCU R31-2008-000-10071-0, NRF-2011-357-C00141, and 2008-0062484). NR 13 TC 6 Z9 6 U1 3 U2 7 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD DEC PY 2014 VL 46 IS 12 BP 1110 EP 1115 DI 10.1055/s-0034-1377631 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AU9JN UT WOS:000345908600012 PM 25216325 ER PT J AU Waltz, TJ Campbell, DG Kirchner, JE Lombardero, A Bolkan, C Zivin, K Lanto, AB Chaney, EF Rubenstein, LV AF Waltz, Thomas J. Campbell, Duncan G. Kirchner, JoAnn E. Lombardero, Anayansi Bolkan, Cory Zivin, Kara Lanto, Andrew B. Chaney, Edmund F. Rubenstein, Lisa V. TI Veterans With Depression in Primary Care: Provider Preferences, Matching, and Care Satisfaction SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE care satisfaction; patient centered care; primary care mental health; treatment matching; treatment preference ID MENTAL-HEALTH; PATIENT PREFERENCE; COLLABORATIVE CARE; AUDIT-C; DSM-IV; DISORDERS; AFFAIRS; INTERVENTIONS; COMORBIDITY; AFGHANISTAN AB Primary care is often the first point of care for individuals with depression. Depressed patients often have comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Understanding variations in treatment preferences and care satisfaction in this population can improve care planning and outcomes. The design involved a cross-sectional comparison of veterans screening positive for depression. Veterans receiving primary care during the previous year were contacted (n = 10, 929) and were screened for depression using the PHQ-2/PHQ-9. Those with probable depression (n = 761) underwent a comprehensive assessment including screens for AUD and PTSD, treatment provider preferences, treatments received, and satisfaction with care. Treatment provider preferences differed based on specific mental health comorbidities, and satisfaction with care was associated with receipt of preferred care. Depressed veterans with comorbid PTSD were more likely to prefer care from more than one provider type (e.g., a psychiatrist and a primary care provider) and were more likely to receive treatment that matched their preferences than veterans without comorbid PTSD. Veterans receiving full or partial treatment matches affirmed satisfaction with care at higher rates, and veterans with comorbid PTSD were least satisfied when care did not match their preferences. Patient satisfaction with care is an increasingly important focus for health care systems. This study found significant variations in depressed patients' satisfaction with care in terms of treatment matching, particularly among those with comorbid PTSD. Delivery of care that matches patient treatment preferences is likely to improve depressed patient's satisfaction with the care provided. C1 [Waltz, Thomas J.] Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. [Waltz, Thomas J.; Kirchner, JoAnn E.] Arkansas Dept Vet Affairs, Mental Hlth QUERI, HSR&D, North Little Rock, AR USA. [Campbell, Duncan G.; Lombardero, Anayansi] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Kirchner, JoAnn E.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Bolkan, Cory] Washington State Univ Vancouver, Dept Human Dev, Vancouver, BC 98686, Canada. [Zivin, Kara] Vet Affairs Ann Arbor, CCMR, HSR&D, Ann Arbor, MI USA. [Zivin, Kara] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Zivin, Kara] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Zivin, Kara] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. [Lanto, Andrew B.] Vet Affairs Greater Los Angeles, HSR&D, Los Angeles, CA USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles, HSR&D Ctr Implementat Practice & Res Support, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Waltz, TJ (reprint author), Eastern Michigan Univ, Dept Psychol, 341 Sci Complex, Ypsilanti, MI 48197 USA. EM twaltz1@emich.edu OI Waltz, Thomas/0000-0001-7976-430X FU Department of Veterans Affairs (VA) Health Services Research and Development (HSRD) Service; VA Quality Enhancement Research Initiative (QUERI) [MHI 99-375, MNT 01-027, MHQ 10-06]; Department of Veterans Affairs [CD2 07-206-1, IIR 10-176-3]; VA Office of Academic Affiliations (OAA) Associated Health Postdoctoral Fellowship Program at the HSR&D Center for Mental Healthcare Outcomes Research (CeMHOR) FX The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. This project was funded by the Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service and the VA Quality Enhancement Research Initiative (QUERI) (Project nos. MHI 99-375, MNT 01-027, MHQ 10-06) and Department of Veterans Affairs CD2 07-206-1 and IIR 10-176-3. Dr. Waltz was funded by a VA Office of Academic Affiliations (OAA) Associated Health Postdoctoral Fellowship Program at the HSR&D Center for Mental Healthcare Outcomes Research (CeMHOR). We thank Valorie Shue for editorial comments on a draft of this article. NR 37 TC 2 Z9 2 U1 1 U2 13 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 DEC PY 2014 VL 32 IS 4 BP 367 EP 377 DI 10.1037/fsh0000071 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 AW1US UT WOS:000346076900002 PM 25090611 ER PT J AU Crawford, JM Bry, L Pfeifer, J Caughron, SK Black-Schaffer, S Kant, JA Kaufman, JH AF Crawford, James M. Bry, Lynn Pfeifer, John Caughron, Samuel K. Black-Schaffer, Stephen Kant, Jeffrey A. Kaufman, Jill H. TI The business of genomic testing: a survey of early adopters SO GENETICS IN MEDICINE LA English DT Article DE business; genomics; informatics; next-generation sequencing; personalized medicine ID HEALTH-CARE; MEDICINE AB Purpose: The practice of "genomic" (or "personalized") medicine requires the availability of appropriate diagnostic testing. Our study objective was to identify the reasons for health systems to bring next-generation Sequencing into their clinical laboratories and to understand the process by which such decisions were made. Such information may be of value to other health systems seeking to provide next-generation sequencing-testing to their patient populations. Methods: A standardized open-ended interview was conducted With the laboratory medical directors and/or department of pathology chairs of 13 different academic institutions in 10 different states. Results: Genomic testing for cancer dominated the institutional decision making, with three primary reasons: more effective delivery of cancer care, the perceived need for institutional leadership in the field of genomics, and the premise that genomics will eventually be cost-effective. Barriers to implementation included implementation cost; the time and effort needed to maintain this newer testing; challenges in interpreting genetic variants; establishing the bioinformatics infrastructure; and curating data from medical, ethical, and legal standpoints. Ultimate success depended on alignment with institutional strengths and priorities and working closely with institutional clinical programs. Conclusion: These early adopters uniformly viewed genomic analysis as an imperative for developing their expertise in the implementation and practice of genomic medicine. C1 [Crawford, James M.] Hofstra North Shore LIJ Sch Med, Uniondale, NY USA. [Bry, Lynn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Pfeifer, John] Washington Univ, Sch Med, St Louis, MO USA. [Caughron, Samuel K.] Mawd Pathol Grp, North Kansas City, MO USA. [Black-Schaffer, Stephen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kant, Jeffrey A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kaufman, Jill H.] Coll Amer Pathologists, Northfield, IL USA. RP Crawford, JM (reprint author), Hofstra North Shore LIJ Sch Med, Uniondale, NY USA. EM jcrawford1@nshs.edu FU College of American Pathologists FX We thank the College of American Pathologists for its support of the staff effort to conduct this study and support of the author participation through face-to-face meetings and telecommunications. We thank the survey participants for their participation and frank discussion of issues and challenges that their institutions and departments faced, and were facing, in implementing NGS testing for clinical programming. An educational webinar based on the initial study findings, sponsored by the College of American Pathologists, was presented on 11 December 2012. The recorded webinar is available at http://www.cap.org. We note the untimely passing of J.A.K. in September 2012; the loss of his contribution to the future of genomic medicine will be keenly felt. NR 24 TC 3 Z9 3 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2014 VL 16 IS 12 BP 954 EP 961 DI 10.1038/gim.2014.60 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AW1HN UT WOS:000346040900014 PM 25010053 ER PT J AU Young, RH AF Young, Robert H. TI The Yolk Sac Tumor: Reflections on a Remarkable Neoplasm and Two of the Many Intrigued By It-Gunnar Teilum and Aleksander Talerman-and the Bond It Formed Between Them SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE yolk sac tumor; ovary; testis; germ cell tumor ID ENDODERMAL SINUS TUMOR; GERM-CELL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; TESTICULAR TERATOMAS; ALPHA-FETOPROTEIN; OVARY; TESTIS; DIFFERENTIATION; ADULTS; CARCINOMA AB One of the most remarkable of human neoplasms, the yolk sac tumor, is reviewed, emphasizing its histologic diversity and differential diagnosis, occurrence at many sites, and the shared passion for this unique neoplasm of Dr Gunnar Teilum (who deserves almost all credit for delineation of the nature of the tumor and its features) and Dr Aleksander Talerman (who made his own contribution to our knowledge of it) and the friendship it helped forge between these 2 distinguished pathologists. In a unique series of articles, beginning in the early 1940s, Teilum delineated the distinctive features of the neoplasm and recognized that it was 1 of 2 initially included as mesonephroma ovarii by Dr Walter Schiller in 1939 (the second we now know as clear cell carcinoma). Teilum named the tumor endodermal sinus tumor because it came to his attention that papillary formations common in the yolk sac tumor resembled the endodermal sinuses of the rat placenta. He focused on the histogenesis of the tumor and its morphologic features culminating in a classic paper in Cancer in 1959. Although Teilum and others recognized that yolk sac tumor could be a component of mixed germ cell tumors, Talerman was one of the first to emphasize that, particularly in the testis, it was common to see yolk sac tumor as a component of a mixed germ cell tumor. Teilum, working in Copenhagen, and Talerman, when the former was alive, working in Rotterdam, developed a warm friendship in part due to their great interest in the yolk sac tumor, although it also extended to other areas of gonadal neoplasia and indeed beyond the boundaries of medicine when they shared time together. The typical histologic features of the yolk sac tumor are the reticular-microcystic patterns Teilum described, but various other patterns, including solid and even rarer ones such as glandular and hepatoid, are now well known. There are some interesting variations in the age distribution of this tumor at various sites: for example, vaginal examples are almost restricted to children under 2 years of age; those of the testis that are pure also occur mostly in young boys (average age about 20 months) but are occasionally seen in later years; ovarian examples peak at about 19 years of age; mediastinal forms are mostly restricted to young adult males. Brief consideration is also given to the occurrence of this tumor at well-known extragonadal sites such as retroperitoneum, mediastinum, and pineal as well as more exotic locations. Note is made of the recently emphasized occurrence of the yolk sac tumor on the background of a somatic neoplasm, most often endometrioid carcinoma of the ovary. Given the wide ranging and fascinating clinical and pathologic aspects of the neoplasm, it is no surprise that it continues to be a source of great interest to any pathologist who sees one or more examples, and we are indebted to Dr Teilum for his monumental studies and to Dr Talerman for his own contributions. C1 [Young, Robert H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Young, RH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Homer Wright Pathol Labs,Massachusetts Gen Hosp, Warren 215,55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 54 TC 7 Z9 7 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD DEC PY 2014 VL 22 IS 8 BP 677 EP 687 DI 10.1177/1066896914558265 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA AW1YJ UT WOS:000346084400001 PM 25395492 ER PT J AU Lawton, TJ Acs, G Argani, P Farshid, G Gilcrease, M Goldstein, N Koerner, F Rowe, JJ Sanders, M Shah, SS Reynolds, C AF Lawton, Thomas J. Acs, Geza Argani, Pedram Farshid, Gelareh Gilcrease, Michael Goldstein, Neal Koerner, Frederick Rowe, J. Jordi Sanders, Melinda Shah, Sejal S. Reynolds, Carol TI Interobserver Variability by Pathologists in the Distinction Between Cellular Fibroadenomas and Phyllodes Tumors SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE fibroepithelial lesion; phyllodes tumor; cellular fibroadenoma ID CYSTOSARCOMA-PHYLLODES; SURGICAL MARGINS; BREAST; RECURRENCE; FEATURES; LESIONS; GRADE AB Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors. C1 [Lawton, Thomas J.] Univ N Carolina, Chapel Hill, NC USA. [Acs, Geza] Ruffolo Hooper & Associates, Tampa, FL USA. [Argani, Pedram] Johns Hopkins Univ, Med Ctr, Baltimore, MD USA. [Farshid, Gelareh] SA Pathol, Adelaide, SA, Australia. [Farshid, Gelareh] Univ Adelaide, Adelaide, SA, Australia. [Gilcrease, Michael] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Goldstein, Neal] Clarient Inc, Aliso Viejo, CA USA. [Koerner, Frederick] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rowe, J. Jordi] Cleveland Clin, Cleveland, OH 44106 USA. [Sanders, Melinda] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. [Shah, Sejal S.; Reynolds, Carol] Mayo Clin, Rochester, MN USA. RP Lawton, TJ (reprint author), Univ N Carolina, Womens & Childrens Hosp, Dept Pathol, Third Floor,Room 30149,101 Manning Dr, Chapel Hill, NC 27514 USA. EM thomaslawton@mac.com FU NCI NIH HHS [P30 CA006973] NR 20 TC 13 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD DEC PY 2014 VL 22 IS 8 BP 695 EP 698 DI 10.1177/1066896914548763 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA AW1YJ UT WOS:000346084400003 PM 25161205 ER PT J AU Liu, Q Waltz, S Woodruff, G Ouyang, J Israel, MA Herrera, C Sarsoza, F Tanzi, RE Koo, EH Ringman, JM Goldstein, LSB Wagner, SL Yuan, SH AF Liu, Qing Waltz, Shannon Woodruff, Grace Ouyang, Joe Israel, Mason A. Herrera, Cheryl Sarsoza, Floyd Tanzi, Rudolph E. Koo, Edward H. Ringman, John M. Goldstein, Lawrence S. B. Wagner, Steven L. Yuan, Shauna H. TI Effect of Potent gamma-Secretase Modulator in Human Neurons Derived From Multiple Presenilin 1-Induced Pluripotent Stem Cell Mutant Carriers SO JAMA NEUROLOGY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; DOPAMINERGIC-NEURONS; DEFINED FACTORS; IPS CELLS; INDUCTION; A-BETA-42; MECHANISM; ES AB IMPORTANCE Although considerable effort has been expended developing drug candidates for Alzheimer disease, none have yet succeeded owing to the lack of efficacy or to safety concerns. One potential shortcoming of current approaches to Alzheimer disease drug discovery and development is that they rely primarily on transformed cell lines and animal models that substantially overexpress wild-type or mutant proteins. It is possible that drug development failures thus far are caused in part by the limits of these approaches, which do not accurately reveal how drug candidates will behave in naive human neuronal cells. OBJECTIVE To analyze purified neurons derived from human induced pluripotent stem cells from patients carrying 3 different presenilin 1 (PS1) mutations and nondemented control individuals in the absence of any overexpression. We tested the efficacy of gamma-secretase inhibitor and gamma-secretase modulator (GSM) in neurons derived from both normal control and 3 PS1 mutations (A246E, H163R, and M146L). DESIGN, SETTING, AND PARTICIPANTS Adult human skin biopsieswere obtained from volunteers at the Alzheimer Disease Research Center, University of California, San Diego. Cell cultures were treated with.-secretase inhibitor or GSM. Comparisons of total beta-amyloid (A beta) and A beta peptides 38, 40, and 42 in the media were made between vehicle-vs drug-treated cultures. MAIN OUTCOMES AND MEASURES Soluble A beta levels in the media were measured by enzyme-linked immunosorbent assay. RESULTS As predicted, mutant PS1 neurons exhibited an elevated A beta 42: A beta 40 ratio (P < .05) at the basal state as compared with the nondemented control neurons. Treatment with a potent non-nonsteroidal anti-inflammatory druglike GSM revealed a new biomarker signature that differs from all previous cell types and animals tested. This new signature was the same in both the mutant and control neurons and consisted of a reduction in A beta 42, A beta 40, and A beta 38 and in the A beta 42: A beta 40 ratio, with no change in the total Ab levels. CONCLUSIONS AND RELEVANCE This biomarker discrepancy is likely due to overexpression of amyloid precursor protein in the transformed cellular models. Our results suggest that biomarker signatures obtained with such models are misleading and that human neurons derived from human induced pluripotent stem cells provide a unique signature that will more accurately reflect drug response in human patients and in cerebrospinal fluid biomarker changes observed during GSM treatment. C1 [Liu, Qing; Waltz, Shannon; Sarsoza, Floyd; Koo, Edward H.; Wagner, Steven L.; Yuan, Shauna H.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Woodruff, Grace; Ouyang, Joe; Israel, Mason A.; Herrera, Cheryl; Goldstein, Lawrence S. B.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Ouyang, Joe] Capitalbio, San Diego, CA USA. [Israel, Mason A.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA USA. [Ringman, John M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, Los Angeles, CA USA. RP Yuan, SH (reprint author), Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr,MTF Room 151, La Jolla, CA 92093 USA. EM shyuan@ucsd.edu FU National Institutes of Health [U01-AG10483, U01-NS074501, P50 AG005131-26, P50-AG016750]; California Institute of Regenerative Medicine Comprehensive [RC1-00116]; Cure Alzheimer's Fund; California Institute of Regenerative Medicine clinical training fellowship FX This work was funded by National Institutes of Health grants U01-AG10483, U01-NS074501 (DrWagner), P50 AG005131-26 (Alzheimer's Disease Research Centers pilot grant to Dr Yuan), and P50-AG016750 (Dr Rungman); California Institute of Regenerative Medicine Comprehensive grant RC1-00116 (Dr Goldstein); Cure Alzheimer's Fund (Drs Tanzi and Wagner); and California Institute of Regenerative Medicine clinical training fellowship (Dr Yuan) and predoctoral fellowship (Dr Israel). NR 31 TC 14 Z9 15 U1 3 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2014 VL 71 IS 12 BP 1481 EP 1489 DI 10.1001/jamaneurol.2014.2482 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YA UT WOS:000346083500005 PM 25285942 ER PT J AU Gardner, RC Burke, JF Nettiksimmons, J Kaup, A Barnes, DE Yaffe, K AF Gardner, Raquel C. Burke, James F. Nettiksimmons, Jasmine Kaup, Allison Barnes, Deborah E. Yaffe, Kristine TI Dementia Risk After Traumatic Brain Injury vs Nonbrain Trauma The Role of Age and Severity SO JAMA NEUROLOGY LA English DT Article ID YOUNG ONSET DEMENTIA; ALZHEIMERS-DISEASE; HEAD-INJURY; ADMINISTRATIVE DATA; PARKINSONS-DISEASE; OLDER-ADULTS; POPULATION; COHORT; MORTALITY; ACCURACY AB IMPORTANCE Epidemiologic evidence regarding the importance of traumatic brain injury (TBI) as a risk factor for dementia is conflicting. Few previous studies have used patients with non-TBI trauma (NTT) as controls to investigate the influence of age and TBI severity. OBJECTIVE To quantify the risk of dementia among adults with recent TBI compared with adults with NTT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was performed from January 1, 2005, through December 31, 2011 (follow-up, 5-7 years). All patients 55 years or older diagnosed as having TBI or NTT in 2005 and 2006 and who did not have baseline dementia or die during hospitalization (n = 164 661) were identified in a California statewide administrative health database of emergency department (ED) and inpatient visits. EXPOSURES Mild vs moderate to severe TBI diagnosed by Centers for Disease Control and Prevention criteria using International Classification of Diseases, Ninth Revision (ICD-9) codes, and NTT, defined as fractures excluding fractures of the head and neck, diagnosed using ICD-9 codes. MAIN OUTCOMES AND MEASURES Incident ED or inpatient diagnosis of dementia (using ICD-9 codes) 1 year or more after initial TBI or NTT. The association between TBI and risk of dementia was estimated using Cox proportional hazards models before and after adjusting for common dementia predictors and potential confounders. We also stratified by TBI severity and age category (55-64, 65-74, 75-84, and >85 years). RESULTS A total of 51 799 patients with trauma (31.5%) had TBI. Of these, 4361 (8.4%) developed dementia compared with 6610 patients with NTT (5.9%) (P < .001). We found that TBI was associated with increased dementia risk (hazard ratio [HR], 1.46; 95% CI, 1.41-1.52; P < .001). Adjustment for covariates had little effect except adjustment for age category (fully adjusted model HR, 1.26; 95% CI, 1.21-1.32; P < .001). In stratified adjusted analyses, moderate to severe TBI was associated with increased risk of dementia across all ages (age 55-64: HR, 1.72; 95% CI, 1.40-2.10; P < .001; vs age 65-74: HR, 1.46; 95% CI, 1.30-1.64; P < .001), whereas mild TBI may be a more important risk factor with increasing age (age 55-64: HR, 1.11; 95% CI, 0.80-1.53; P = .55; vs age 65-74: HR, 1.25; 95% CI, 1.04-1.51; P = .02; age interaction P < .001). CONCLUSIONS AND RELEVANCE Among patients evaluated in the ED or inpatient settings, those with moderate to severe TBI at 55 years or older or mild TBI at 65 years or older had an increased risk of developing dementia. Younger adults may be more resilient to the effects of recent mild TBI than older adults. C1 [Gardner, Raquel C.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Gardner, Raquel C.; Nettiksimmons, Jasmine; Kaup, Allison; Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA 94121 USA. [Burke, James F.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Burke, James F.] Ann Arbor Vet Affairs Healthcare Syst, Vet Affairs Ctr Clin Management & Res, Dept Vet Affairs, Ann Arbor, MI USA. [Nettiksimmons, Jasmine; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kaup, Allison; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gardner, RC (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs, 4150 Clement St,Campus Mailbox 127, San Francisco, CA 94121 USA. EM raquel.gardner@ucsf.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center; National Institutes of Health [K24 AG031155, K08 NS082597]; Department of Defense, the Department of Veterans Affairs [W81XWH-12-1-0581]; California Department of Public Health; Bright Focus Foundation; Alzheimer's Association FX Drs Gardner and Kaup reported having received support from the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center. Dr Yaffe reported having received research support from grant K24 AG031155 from the National Institutes of Health, grant W81XWH-12-1-0581 from the Department of Defense, the Department of Veterans Affairs, the California Department of Public Health, the Bright Focus Foundation, and the Alzheimer's Association. Dr Burke reported having received research support from grant K08 NS082597 from the National Institutes of Health. No other disclosures were reported. NR 42 TC 50 Z9 52 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2014 VL 71 IS 12 BP 1490 EP 1497 DI 10.1001/jamaneurol.2014.2668 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YA UT WOS:000346083500006 PM 25347255 ER PT J AU Pasquale, LR Jiwani, AZ Zehavi-Dorin, T Majd, A Rhee, DJ Chen, T Turalba, A Shen, L Brauner, S Grosskreutz, C Gardiner, M Chen, S Borboli-Gerogiannis, S Greenstein, SH Chang, K Ritch, R Loomis, S Kang, JH Wiggs, JL Levkovitch-Verbin, H AF Pasquale, Louis R. Jiwani, Aliya Z. Zehavi-Dorin, Tzukit Majd, Arow Rhee, Douglas J. Chen, Teresa Turalba, Angela Shen, Lucy Brauner, Stacey Grosskreutz, Cynthia Gardiner, Matthew Chen, Sherleen Borboli-Gerogiannis, Sheila Greenstein, Scott H. Chang, Kenneth Ritch, Robert Loomis, Stephanie Kang, Jae H. Wiggs, Janey L. Levkovitch-Verbin, Hani TI Solar Exposure and Residential Geographic History in Relation to Exfoliation Syndrome in the United States and Israel SO JAMA OPHTHALMOLOGY LA English DT Article ID 5-YEAR FOLLOW-UP; PSEUDOEXFOLIATION SYNDROME; ULTRAVIOLET-RADIATION; CATARACT-SURGERY; LENS OPACITIES; REYKJAVIK EYE; RISK-FACTORS; LOXL1 GENE; PREVALENCE; ASSOCIATION AB IMPORTANCE Residential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome (XFS) but, to our knowledge, detailed lifetime solar exposure has not been previously evaluated in XFS. OBJECTIVE To assess the relation between residential history, solar exposure, and XFS. DESIGN, SETTING, AND PARTICIPANTS This clinic-based case-control study was conducted in the United States and Israel. It involved XFS cases and control individuals (all >= 60-year-old white individuals) enrolled from 2010 to 2012 (United States: 118 cases and 106 control participants; Israel: 67 cases and 72 control participants). MAIN OUTCOMES AND MEASURES Weighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires. RESULTS In multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with 11% increased odds of XFS (pooled odds ratio [OR], 1.11; 95% CI, 1.05-1.17; P<.001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with 4% increased odds of XFS (pooled OR, 1.04; 95% CI, 1.00-1.07; P=.03). For every 1% of average lifetime summer time between 10 AM and 4 PM that sunglasses were worn, the odds of XFS decreased by 2%(OR, 0.98; 95% CI, 0.97-0.99; P<.001) in the United States but not in Israel (OR, 1.00; 95% CI, 0.99-1.01; P=.92; P for heterogeneity =.005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of XFS (OR, 3.86; 95% CI, 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and XFS (P>.57). CONCLUSIONS AND RELEVANCE Lifetime outdoor activities may contribute to XFS. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in XFS etiology. Copyright 2014 American Medical Association. All rights reserved. C1 [Pasquale, Louis R.; Loomis, Stephanie; Kang, Jae H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02114 USA. [Pasquale, Louis R.; Jiwani, Aliya Z.; Rhee, Douglas J.; Chen, Teresa; Turalba, Angela; Shen, Lucy; Brauner, Stacey; Grosskreutz, Cynthia; Gardiner, Matthew; Chen, Sherleen; Borboli-Gerogiannis, Sheila; Greenstein, Scott H.; Chang, Kenneth; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Zehavi-Dorin, Tzukit; Majd, Arow; Levkovitch-Verbin, Hani] Tel Aviv Univ, Chaim Sheba Med Ctr, Goldschleger Eye Inst, Tel Hashomer, Israel. [Rhee, Douglas J.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA. [Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Einhorn Clin Res Ctr, New York, NY USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM louis_pasquale@meei.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 FU Arthur Ashley Foundation - National Institutes of Health [EY020928]; Research to Prevent Blindness; Harvard Medical School; Doris Duke Charitable Foundation FX This work was supported by the Arthur Ashley Foundation, grant EY020928 from the National Institutes of Health (Dr Wiggs), a Physician Scientist Award from Research to Prevent Blindness (Dr Pasquale), a Harvard Medical School Ophthalmology Scholar Award (Dr Pasquale), and a Doris Duke Charitable Foundation grant (Dr Jiwani). Dr Wiggs has received an honorarium for travel expenses from Research to Prevent Blindness. NR 51 TC 6 Z9 6 U1 0 U2 3 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 DEC PY 2014 VL 132 IS 12 BP 1439 EP 1445 DI 10.1001/jamaophthalmol.2014.3326 PG 7 WC Ophthalmology SC Ophthalmology GA AW3HF UT WOS:000346176400011 PM 25188364 ER PT J AU Williams, BA Ahalt, C Stijacic-Cenzer, I Smith, AK Goldenson, J Ritchie, CS AF Williams, Brie A. Ahalt, Cyrus Stijacic-Cenzer, Irena Smith, Alexander K. Goldenson, Joe Ritchie, Christine S. TI Pain Behind Bars: The Epidemiology of Pain in Older Jail Inmates in a County Jail SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-CARE; PALLIATIVE CARE; NONMALIGNANT PAIN; SCREENING-TEST; MANAGEMENT; ADULTS; PRISON; POPULATIONS; GUIDELINES; DISTRESS AB Background: The number of older jail inmates in poor health is increasing rapidly. Among older adults, pain is common and leads to greater acute care use. In jail, pain management is complicated by concerns about misuse and diversion. A lack of data about the prevalence and management of pain in older jail inmates limits our ability to develop optimal palliative care strategies for this population. Objective: To describe the prevalence of and factors associated with pain and analgesic use in a population of older jail inmates. Design: Cross-sectional study. chi(2) tests assessed association between characteristics, pain, and analgesic use. Setting/Subjects: Two hundred ten jail inmates age 55 or older. Measurements: "Severe frequent pain" defined as "severe or very severe" pain experienced "frequently or constantly" using the validated Memorial Symptom Assessment Scale. Medical conditions, substance use, and analgesic treatment determined through self-report and jail medical records. Results: Participants' mean age was 59 years; 69% had multimorbidity; 75% reported any pain; 39% reported severe frequent pain. Report of severe frequent pain was associated with multimorbidity, functional impairment, and pre-jail acute care use (p<0.05), but not with substance use (57% versus 56%, p=0.89). Within a week of their interview, most participants with severe frequent pain had received an analgesic (87%) and many received an opioid (70%). Conclusion: High rates of pain in a rapidly growing population of older jail inmates with multimorbidity and functional impairment suggest that jails are an important site for assessing symptom burden and developing appropriate palliative care interventions. C1 [Williams, Brie A.; Ahalt, Cyrus; Stijacic-Cenzer, Irena; Smith, Alexander K.; Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. [Williams, Brie A.; Smith, Alexander K.; Ritchie, Christine S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Goldenson, Joe] San Francisco Dept Publ Hlth, Jail Hlth Serv, San Francisco, CA USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM brie.williams@ucsf.edu FU National Institute of Aging [K23AG033102]; Jacob & Valeria Langeloth Foundation; UCSF Program for the Aging Century; National Palliative Care Research Center (NPCRC) FX B.A.W received support from the National Institute of Aging (K23AG033102), The Jacob & Valeria Langeloth Foundation, and The UCSF Program for the Aging Century. This project was also supported in part by a Pilot and Exploratory Project Support Grant from the National Palliative Care Research Center (NPCRC). Sponsors played no role in the design, methods, subject recruitment, data collection, analysis, or preparation of this manuscript. NR 58 TC 4 Z9 4 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1336 EP 1343 DI 10.1089/jpm.2014.0160 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200010 PM 25265035 ER PT J AU Smith, GM Schaefer, KG AF Smith, Grant M. Schaefer, Kristen G. TI Missed Opportunities To Train Medical Students in Generalist Palliative Care during Core Clerkships SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; EDUCATION; CURRICULUM; DEATH; PATIENT; SCHOOL; EXPERIENCES; KNOWLEDGE; DOCTORS AB Background: To improve the quality of care for dying patients, experts have called for all clinicians to be able to provide a generalist level of palliative care. Core clinical clerkships provide an opportunity to incorporate palliative care training to address the lack of required palliative care rotations at most U.S. medical schools. Objective: The objective of this study was to identify and quantify missed opportunities to train third-year medical students in generalist palliative care during required core clerkships. Design: This study was a cross-sectional survey of third-year students at a leading U.S. medical school without a required palliative care rotation. Measurements: Students completed a survey during the last 4 months of the 2012-2013 academic year quantifying and evaluating their experiences caring for dying patients. Attitudes were assessed using a scale from a national survey of students, residents, and faculty. Results: Eighty-eight students responded (response rate [RR]=56%). More than one-quarter (26%) never participated in caring for a patient who died. More than one-half (55%) never delivered significant bad news and 38% never worked with a specialist in palliative medicine. Eighty-four percent of students who cared for a patient who died and 60% of students who delivered significant bad news had one or more of those experiences that were not debriefed. Conclusions: At an institution without a required palliative care rotation, third-year medical students rarely or never care for patients who die during core clerkships, and when they do, their teams do not debrief or reflect on these experiences. Clinical faculty, including palliative care consultants, can address missed opportunities for palliative care training during core clerkships by augmenting and routinely debriefing students' experiences giving bad news and caring for dying patients. C1 [Smith, Grant M.] Harvard Univ, Sch Med, Boston, MA USA. [Schaefer, Kristen G.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Schaefer, KG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Kristen_Schaefer@dfci.harvard.edu NR 25 TC 0 Z9 0 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1344 EP 1347 DI 10.1089/jpm.2014.0107 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200011 PM 24971609 ER PT J AU DiMartino, LD Weiner, BJ Mayer, DK Jackson, GL Biddle, AK AF DiMartino, Lisa D. Weiner, Bryan J. Mayer, Deborah K. Jackson, George L. Biddle, Andrea K. TI Do Palliative Care Interventions Reduce Emergency Department Visits among Patients with Cancer at the End of Life? A Systematic Review SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID LUNG-CANCER; QUALITY; IMPROVEMENT; POPULATION; INDICATORS; FRAMEWORK; SERVICES; OUTCOMES; TRIAL; DEATH AB Background: Frequent emergency department (ED) visits are an indicator of poor quality of cancer care. Coordination of care through the use of palliative care teams may limit aggressive care and improve outcomes for patients with cancer at the end of life. Objectives: To systematically review the literature to determine whether palliative care interventions implemented in the hospital, home, or outpatient clinic are more effective than usual care in reducing ED visits among patients with cancer at the end of life. Eligibility Criteria: PubMed, EMBASE, and CINAHL databases were searched from database inception to May 7, 2014. Only randomized/non-randomized controlled trials (RCTs) and observational studies examining the effect of palliative care interventions on ED visits among adult patients with cancer with advanced disease were considered. Data Extraction and Data Synthesis: Data were abstracted from the articles that met all the inclusion criteria. A second reviewer independently abstracted data from 2 articles and discrepancies were resolved. From 464 abstracts, 2 RCTs, 10 observational studies, and 1 non-RCT/quasi-experimental study were included. Overall there is limited evidence to support the use of palliative care interventions to reduce ED visits, although studies examining effect of hospice care and those conducted outside of the United States reported a statistically significant reduction in ED visits. Conclusions: Evidence regarding whether palliative care interventions implemented in the hospital, home or outpatient clinic are more effective than usual care at reducing ED visits is not strongly substantiated based on the literature reviewed. Improvements in the quality of reporting for studies examining the effect of palliative care interventions on ED use are needed. C1 [DiMartino, Lisa D.; Weiner, Bryan J.; Biddle, Andrea K.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Mayer, Deborah K.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. [Jackson, George L.] US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Jackson, George L.] Duke Univ, Div Gen Internal Med, Durham, NC USA. RP DiMartino, LD (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Campus Box 7411, Chapel Hill, NC 27599 USA. EM lisa.dimartino@unc.edu OI Biddle, Andrea/0000-0003-0273-7439 NR 32 TC 3 Z9 3 U1 2 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1384 EP 1399 DI 10.1089/jpm.2014.0092 PG 16 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200017 PM 25115197 ER PT J AU Daubman, BR AF Daubman, Bethany-Rose TI Bracketing SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. RP Daubman, BR (reprint author), Massachusetts Gen Hosp, Div Palliat Care, 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM bethanyrose.daubman@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1403 EP 1403 DI 10.1089/jpm.2014.0058 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200019 PM 25407365 ER PT J AU Shera, CA AF Shera, Christopher A. TI On the method of lumens SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID CAT TYMPANIC MEMBRANE; WAVE MODEL AB Parent and Allen [(2007). J. Acoust. Soc. Am. 122, 918-931] introduced the "method of lumens" to compute the plane-wave reflectance in a duct terminated with a nonuniform impedance. The method involves splitting the duct into multiple, fictitious subducts (lumens), solving for the reflectance in each subduct, and then combining the results. The method of lumens has considerable intuitive appeal and is easily implemented in the time domain. Previously applied only in a complex acoustical setting where proper evaluation is difficult (i.e., in a model of the ear canal and tympanic membrane), the method is tested here by using it to compute the reflectance from an area constriction in an infinite lossless duct considered in the long-wavelength limit. Neither the original formulation of the method-shown here to violate energy conservation except when the termination impedance is uniform-nor a reformulation consistent with basic physical constraints yields the correct solution to this textbook problem in acoustics. The results are generalized and the nature of the errors illuminated. (C) 2014 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM christopher.shera@gmail.com FU NIH [R01 DC003687] FX Supported by NIH grant R01 DC003687. The author thanks Jont Allen and Roger Serwy for useful discussions and Heidi Nakajima and Elizabeth Olson for helpful comments on the manuscript. NR 9 TC 0 Z9 0 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2014 VL 136 IS 6 BP 3126 EP 3131 DI 10.1121/1.4900919 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AW0IX UT WOS:000345976500028 PM 25480060 ER PT J AU Ravicz, ME Cheng, JT Rosowski, JJ AF Ravicz, Michael E. Cheng, Jeffrey Tao Rosowski, John J. TI Sound pressure distribution within natural and artificial human ear canals: Forward stimulation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ACOUSTIC ENERGY REFLECTANCE; TYMPANIC-MEMBRANE; SPATIAL-DISTRIBUTION; ELEMENT METHOD; CADAVER EARS; EARDRUM; MOTION; SURFACE; SPECIFICATION; HOLOGRAPHY AB This work is part of a study of the interaction of sound pressure in the ear canal (EC) with tympanic membrane (TM) surface displacement. Sound pressures were measured with 0.5-2 mm spacing at three locations within the shortened natural EC or an artificial EC in human temporal bones: near the TM surface, within the tympanic ring plane, and in a plane transverse to the long axis of the EC. Sound pressure was also measured at 2-mm intervals along the long EC axis. The sound field is described well by the size and direction of planar sound pressure gradients, the location and orientation of standing-wave nodal lines, and the location of longitudinal standing waves along the EC axis. Standing-wave nodal lines perpendicular to the long EC axis are present on the TM surface >11-16 kHz in the natural or artificial EC. The range of sound pressures was larger in the tympanic ring plane than at the TM surface or in the transverse EC plane. Longitudinal standing-wave patterns were stretched. The tympanic-ring sound field is a useful approximation of the TM sound field, and the artificial EC approximates the natural EC. (C) 2014 Acoustical Society of America. C1 [Ravicz, Michael E.; Cheng, Jeffrey Tao; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Ravicz, Michael E.; Cheng, Jeffrey Tao; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Mike_Ravicz@meei.harvard.edu FU National Institute on Deafness and other Communication Disorders FX The authors thank Diane Jones and the Otopathology Laboratory at the Massachusetts Eye & Ear Infirmary for their help in procuring temporal bone specimens, Ellery Harrington, Cosme Furlong, and Ivo Dobrev at the Worcester Polytechnic Institute, and Jeremie Guignard for helpful comments on earlier drafts of this manuscript, Melissa McKinnon and Haobing Wang for assistance with figures, and the staff of the Eaton-Peabody Laboratory for technical assistance and general support. This work was supported by National Institute on Deafness and other Communication Disorders. NR 39 TC 6 Z9 6 U1 0 U2 5 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2014 VL 136 IS 6 BP 3132 EP 3146 DI 10.1121/1.4898420 PG 15 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AW0IX UT WOS:000345976500029 PM 25480061 ER PT J AU Zanartu, M Galindo, GE Erath, BD Peterson, SD Wodicka, GR Hillman, RE AF Zanartu, Matias Galindo, Gabriel E. Erath, Byron D. Peterson, Sean D. Wodicka, George R. Hillman, Robert E. TI Modeling the effects of a posterior glottal opening on vocal fold dynamics with implications for vocal hyperfunction SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AIR-FLOW; 2-MASS MODEL; VOICE PRODUCTION; FEMALE SPEAKERS; PHONATION; QUALITY; TRACT; SIMULATIONS; PERCEPTION; WOMEN AB Despite the frequent observation of a persistent opening in the posterior cartilaginous glottis in normal and pathological phonation, its influence on the self-sustained oscillations of the vocal folds is not well understood. The effects of a posterior gap on the vocal fold tissue dynamics and resulting acoustics were numerically investigated using a specially designed flow solver and a reduced-order model of human phonation. The inclusion of posterior gap areas of 0.03-0.1 cm(2) reduced the energy transfer from the fluid to the vocal folds by more than 42%-80% and the radiated sound pressure level by 6-14 dB, respectively. The model was used to simulate vocal hyperfucntion, i.e., patterns of vocal misuse/abuse associated with many of the most common voice disorders. In this first approximation, vocal hyperfunction was modeled by introducing a compensatory increase in lung air pressure to regain the vocal loudness level that was produced prior to introducing a large glottal gap. This resulted in a significant increase in maximum flow declination rate and amplitude of unsteady flow, thereby mimicking clinical studies. The amplitude of unsteady flow was found to be linearly correlated with collision forces, thus being an indicative measure of vocal hyperfunction. (C) 2014 Acoustical Society of America. C1 [Zanartu, Matias; Galindo, Gabriel E.] Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile. [Erath, Byron D.] Clarkson Univ, Dept Mech & Aeronaut Engn, Potsdam, NY 13699 USA. [Peterson, Sean D.] Univ Waterloo, Dept Mech & Mechatron Engn, Waterloo, ON N2L 3G1, Canada. [Wodicka, George R.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Wodicka, George R.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hillman, Robert E.] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Zanartu, M (reprint author), Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile. EM matias.zanartu@usm.cl RI Zanartu, Matias/I-3133-2012; researchers, ac3e/N-2008-2016 OI Zanartu, Matias/0000-0001-5581-4392; FU CONICYT [FONDECYT 11110147, STIC-AMSUD 13STIC-08, BASAL FB00008]; NIH [R21/R33-DC011588] FX The authors acknowledge the support from CONICYT grants FONDECYT 11110147, STIC-AMSUD 13STIC-08, and BASAL FB00008, as well as the NIH grant R21/R33-DC011588. NR 45 TC 6 Z9 6 U1 1 U2 5 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2014 VL 136 IS 6 BP 3262 EP 3271 DI 10.1121/1.4901714 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AW0IX UT WOS:000345976500040 PM 25480072 ER PT J AU Beckson, M Tucker, D AF Beckson, Mace Tucker, Douglas TI Commentary: Craving Diagnostic Validity in DSM-5 Substance Use Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material ID DEPENDENCE SYNDROME; ALCOHOL DEPENDENCE; CRITERIA; CLASSIFICATION; ADOLESCENTS; CANNABIS; COCAINE; ABUSE AB Drs. Norko and Fitch examine questions raised by DSM-5 in the forensic context of criminal defendant diversion to treatment, where eligibility has commonly relied on the view that addiction to alcohol or drugs is distinct from alcohol or drug use, misuse, and abuse. The creation in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), of the new unidimensional spectrum diagnosis of Substance Use Disorder (SUD), which includes three Abuse criteria from DSM-IV, has resulted in a need to re-examine policies that evolved with the DSM-III-R/DSM-IV biaxial abuse-dependence conceptual paradigm. DSM-5 acknowledges the common usage of the term addiction to describe severe problems, and that some clinicians choose to use the word to describe more extreme presentations. Limiting the concept of addiction to the severe form of DSM-5 SUD would maximize validity and support for an expert opinion that an individual has an addiction, as well as facilitate research inquiry into the underlying psychobiological nature of addiction. However, in some contexts, such as criminal diversion, achieving such specificity at the expense of sensitivity may be undesirably restrictive if it excludes appropriate candidates. Future research and experience in both clinical and forensic settings are needed for a fuller understanding of the DSM-5 SUD diagnoses and associated real-world implications. C1 [Beckson, Mace] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Beckson, Mace] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90024 USA. [Tucker, Douglas] Univ Calif San Francisco, Sch Med, Program Psychiat & Law, San Francisco, CA USA. RP Tucker, D (reprint author), 2930 Domingo Ave 306, Berkeley, CA 94705 USA. EM dtuckermd@gmail.com NR 26 TC 1 Z9 1 U1 0 U2 9 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD DEC 1 PY 2014 VL 42 IS 4 BP 453 EP 458 PG 6 WC Law; Psychiatry SC Government & Law; Psychiatry GA AW2XD UT WOS:000346149100008 PM 25492071 ER PT J AU Hammond, SP Swaminathan, S Bensinger, WI Baden, LR AF Hammond, Sarah P. Swaminathan, Sankar Bensinger, William I. Baden, Lindsey R. TI Hepatitis B Virus Screening and Potential Reactivation in Patients Undergoing Treatment for Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID RECEIVING CYTOTOXIC CHEMOTHERAPY; PREVENTION; LAMIVUDINE; INFECTION; THERAPY; ANTIGEN C1 [Hammond, Sarah P.; Baden, Lindsey R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hammond, Sarah P.] Brigham & Womens Hosp, Clin Fac, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.; Baden, Lindsey R.] Dana Farber Canc Inst, Boston, MA USA. [Swaminathan, Sankar] Univ Utah, Salt Lake City, UT 84112 USA. [Bensinger, William I.] Fred Hutchinson Canc Res Ctr, Autologous Stem Cell Transplant Program, Seattle, WA USA. RP Hammond, SP (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 21 TC 2 Z9 2 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 DEC PY 2014 VL 12 IS 12 BP 1655 EP 1657 PG 3 WC Oncology SC Oncology GA AW3MM UT WOS:000346190900002 PM 25505205 ER PT J AU Tuttle, RM Haddad, RI Ball, DW Byrd, D Dickson, P Duh, QY Ehya, H Haymart, M Hoh, C Hunt, JP Iagaru, A Kandeel, F Kopp, P Lamonica, DM Lydiatt, WM McCaffrey, J Moley, JF Parks, L Raeburn, CD Ridge, JA Ringel, MD Scheri, RP Shah, JP Sherman, SI Sturgeon, C Waguespack, SG Wang, TN Wirth, LJ Hoffmann, KG Hughes, M AF Tuttle, R. Michael Haddad, Robert I. Ball, Douglas W. Byrd, David Dickson, Paxton Duh, Quan-Yang Ehya, Hormoz Haymart, Megan Hoh, Carl Hunt, Jason P. Iagaru, Andrei Kandeel, Fouad Kopp, Peter Lamonica, Dominick M. Lydiatt, William M. McCaffrey, Judith Moley, Jeffrey F. Parks, Lee Raeburn, Christopher D. Ridge, John A. Ringel, Matthew D. Scheri, Randall P. Shah, Jatin P. Sherman, Steven I. Sturgeon, Cord Waguespack, Steven G. Wang, Thomas N. Wirth, Lori J. Hoffmann, Karin G. Hughes, Miranda TI Thyroid Carcinoma, Version 2.2014 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID TYROSINE-KINASE INHIBITORS; PHASE-II TRIAL; EXTERNAL-BEAM RADIOTHERAPY; QUALITY-OF-LIFE; RADIOACTIVE IODINE; TARGETED THERAPIES; DOUBLE-BLIND; ALTERNATING COMBINATION; RADIOIODINE UPTAKE; CLINICAL-TRIALS AB These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/ or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on " Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents. C1 [Tuttle, R. Michael; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Ball, Douglas W.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Byrd, David] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Dickson, Paxton] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Duh, Quan-Yang] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Ehya, Hormoz; Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Haymart, Megan] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Hoh, Carl] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Hunt, Jason P.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Iagaru, Andrei] Stanford Canc Inst, Stanford, CA USA. [Kandeel, Fouad] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kopp, Peter; Sturgeon, Cord] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lamonica, Dominick M.] Roswell Pk Canc Inst, Buffalo, NY USA. [Lydiatt, William M.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [McCaffrey, Judith] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Moley, Jeffrey F.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Moley, Jeffrey F.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Parks, Lee] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Raeburn, Christopher D.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Ringel, Matthew D.] Ohio State Univ, James Canc Hosp, Comprehens Canc Ctr, Columbus, OH USA. [Ringel, Matthew D.] Ohio State Univ, Solove Res Inst, Columbus, OH USA. [Scheri, Randall P.] Duke Canc Inst, Durham, NC USA. [Sherman, Steven I.; Waguespack, Steven G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wang, Thomas N.] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hoffmann, Karin G.; Hughes, Miranda] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Tuttle, RM (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. OI Sherman, Steven/0000-0002-3079-5153; Shah, Jatin/0000-0002-6444-6592 NR 88 TC 40 Z9 46 U1 2 U2 8 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 DEC PY 2014 VL 12 IS 12 BP 1671 EP 1680 PG 10 WC Oncology SC Oncology GA AW3MM UT WOS:000346190900005 PM 25505208 ER PT J AU Ettinger, DS Wood, DE Akerley, W Bazhenova, LA Borghaei, H Camidge, DR Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Dilling, TJ Govindan, R Grannis, FW Horn, L Jahan, TM Komaki, R Kris, MG Krug, LM Lackner, RP Lanuti, M Lilenbaum, R Lin, J Loo, BW Martins, R Otterson, GA Patel, JD Pisters, KM Reckamp, K Riely, GJ Rohren, E Schild, S Shapiro, TA 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. Demmy, Todd L. Dilling, Thomas J. Govindan, Ramaswamy Grannis, Frederic W., Jr. Horn, Leora Jahan, Thierry M. Komaki, Ritsuko Kris, Mark G. Krug, Lee M. 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. Rohren, Eric Schild, Steven Shapiro, Theresa A. Swanson, Scott J. Tauer, Kurt Yang, Stephen C. Gregory, Kristina Hughes, Miranda TI Non-Small Cell Lung Cancer, Version 1.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID STEREOTACTIC BODY RADIOTHERAPY; PHASE-II-TRIAL; SOUTHWEST-ONCOLOGY-GROUP; CLINICAL-PRACTICE GUIDELINE; RANDOMIZED CONTROLLED-TRIAL; DIAGNOSED BRAIN METASTASES; RADIATION-DOSE-ESCALATION; RESECTED STAGE-II; INDIVIDUAL PATIENT DATA; LONG-TERM SURVIVAL AB This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for earlystage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/ palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice. C1 [Ettinger, David S.; Shapiro, Theresa A.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Wood, Douglas E.; Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 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.; Demmy, Todd L.] 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. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Grannis, Frederic W., Jr.; Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA 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.; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kris, Mark G.; Krug, Lee M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lackner, Rudy P.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE 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, Stanford, CA USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Otterson, Gregory A.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Schild, Steven] Mayo Clin, Ctr Canc, Rochester, MN USA. [Tauer, Kurt] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. NR 283 TC 43 Z9 57 U1 1 U2 23 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 DEC PY 2014 VL 12 IS 12 BP 1738 EP 1761 PG 24 WC Oncology SC Oncology GA AW3MM UT WOS:000346190900012 PM 25505215 ER PT J AU Bauman, JR Temel, JS AF Bauman, Jessica R. Temel, Jennifer S. TI The Integration of Early Palliative Care With Oncology Care: The Time Has Come for a New Tradition SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; OF-LIFE CARE; REFERRAL PRACTICES; PROSPECTIVE COHORT; PEOPLE DIE; END; CHEMOTHERAPY; OUTCOMES; SYMPTOMS AB The past decade has brought forth innovative research that questions the traditional oncology care model for patients with advanced cancer. Through integrating palliative care (PC) early into the disease course for patients with a poor-prognosis cancer, 3 seminal studies showed improvements in outcomes, ranging from quality of life, mood, patient satisfaction, prognostic understanding, health service use, and possibly survival. The results of these paradigm-changing studies generate questions about the mechanisms through which early PC improves patient outcomes and about how best to disseminate early PC models. This article reviews the 3 studies, examines challenges to conducting PC research, and considers future directions in the field. C1 [Bauman, Jessica R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Bauman, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB 2, Boston, MA 02114 USA. EM jrbauman@partners.org FU NCI NIH HHS [T32 CA071345] NR 49 TC 20 Z9 20 U1 5 U2 15 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 DEC PY 2014 VL 12 IS 12 BP 1763 EP 1771 PG 9 WC Oncology SC Oncology GA AW3MM UT WOS:000346190900013 PM 25505216 ER PT J AU Macleod, AC Klug, LR Patterson, J Griffith, DJ Beadling, C Town, A Heinrich, MC AF Macleod, Alison C. Klug, Lillian R. Patterson, Janice Griffith, Diana J. Beadling, Carol Town, Ajia Heinrich, Michael C. TI Combination Therapy for KIT-Mutant Mast Cells: Targeting Constitutive NFAT and KIT Activity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RECEPTOR TYROSINE KINASE; PROTOONCOGENE C-KIT; CYCLOSPORINE-A; TRANSCRIPTION FACTOR; ACTIVATING MUTATION; CATALYTIC DOMAIN; POINT MUTATION; LEUKEMIA-CELL; T-CELLS; MASTOCYTOSIS AB Resistant KIT mutations have hindered the development of KIT kinase inhibitors for treatment of patients with systemic mastocytosis. The goal of this research was to characterize the synergistic effects of a novel combination therapy involving inhibition of KIT and calcineurin phosphatase, a nuclear factor of activated T cells (NFAT) regulator, using a panel of KIT-mutant mast cell lines. The effects of monotherapy or combination therapy on the cellular viability/survival of KIT-mutant mast cells were evaluated. In addition, NFAT-dependent transcriptional activity was monitored in a representative cell line to evaluate the mechanisms responsible for the efficacy of combination therapy. Finally, shRNA was used to stably knockdown calcineurin expression to confirm the role of calcineurin in the observed synergy. The combination of a KIT inhibitor and a calcineurin phosphatase inhibitor (CNPI) synergized to reduce cell viability and induce apoptosis in six distinct KIT-mutant mast cell lines. Both KIT inhibitors and CNPIs were found to decrease NFAT-dependent transcriptional activity. NFAT-specific inhibitors induced similar synergistic apoptosis induction as CNPIs when combined with a KIT inhibitor. Notably, NFAT was constitutively active in each KIT-mutant cell line tested. Knockdown of calcineurin subunit PPP3R1 sensitized cells to KIT inhibition and increased NFAT phosphorylation and cytoplasmic localization. Constitutive activation of NFAT appears to represent a novel and targetable characteristic of KIT-mutant mast cell disease. Our studies suggest that combining KIT inhibition with NFAT inhibition might represent a new treatment strategy for mast cell disease. (C) 2014 AACR. C1 [Macleod, Alison C.; Klug, Lillian R.; Patterson, Janice; Griffith, Diana J.; Beadling, Carol; Town, Ajia; Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR 97239 USA. [Macleod, Alison C.; Klug, Lillian R.; Patterson, Janice; Griffith, Diana J.; Beadling, Carol; Town, Ajia; Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, R&D 19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933 FU VA Merit Review grant; Life Raft Group; GIST Cancer Research Fund FX This work was supported in part by funding from a VA Merit Review grant (to M.C. Heinrich), the Life Raft Group (to M.C. Heinrich), and the GIST Cancer Research Fund (to M.C. Heinrich) NR 49 TC 2 Z9 2 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2014 VL 13 IS 12 BP 2840 EP 2851 DI 10.1158/1535-7163.MCT-13-0830 PG 12 WC Oncology SC Oncology GA AW2QH UT WOS:000346132900007 PM 25253785 ER PT J AU Wang, T Yang, SH Mei, LA Parmar, CK Gillespie, JW Praveen, KP Petrenko, VA Torchilin, VP AF Wang, Tao Yang, Shenghong Mei, Leslie A. Parmar, Chirag K. Gillespie, James W. Praveen, Kulkarni P. Petrenko, Valery A. Torchilin, Vladimir P. TI Paclitaxel-Loaded PEG-PE-Based Micellar Nanopreparations Targeted with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and Efficiently Reduce Tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER CELLS; PHASE-I; POLYMERIC MICELLES; MITOTIC ARREST; COAT PROTEIN; DELIVERY; NANOCARRIERS; DOXORUBICIN; LIPOSOMES; BINDING AB In an effort to improve the therapeutic index of cancer chemotherapy, we developed an advanced nanopreparation based on the combination of landscape phage display to obtain new targeting ligands with micellar nanoparticles for tumor targeting of water-insoluble neoplastic agents. With paclitaxel as a drug, this self-assembled nanopreparation composed of MCF-7-specific phage protein and polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles showed selective toxicity to target cancer cells rather than nontarget, non cancer cells in vitro. In vivo, the targeted phage micelles triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was also verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathologic changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment. (C) 2014 AACR. C1 [Wang, Tao; Mei, Leslie A.; Parmar, Chirag K.; Torchilin, Vladimir P.] Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. [Yang, Shenghong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gillespie, James W.; Petrenko, Valery A.] Auburn Univ, Dept Pathobiol, Auburn, AL 36849 USA. [Praveen, Kulkarni P.] Northeastern Univ, Ctr Translat Imaging, Boston, MA 02115 USA. [Torchilin, Vladimir P.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. RP Torchilin, VP (reprint author), Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, 140 Fenway Bldg,360 Huntington Ave, Boston, MA 02115 USA. EM v.torchilin@neu.edu RI Gillespie, James/H-3496-2013 OI Gillespie, James/0000-0003-3779-1072 FU NIH [R01 CA125063-01, 1U54CA151881]; Animal Health and Disease Research grant [2006-9]; College of Veterinary Medicine, Auburn University FX This work was supported by NIH grant R01 CA125063-01 and the Animal Health and Disease Research grant 2006-9, College of Veterinary Medicine, Auburn University to V.A. Petrenko and by NIH grant 1U54CA151881 to V.P. Torchilin. NR 36 TC 4 Z9 4 U1 0 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2014 VL 13 IS 12 BP 2864 EP 2875 DI 10.1158/1535-7163.MCT-14-0052 PG 12 WC Oncology SC Oncology GA AW2QH UT WOS:000346132900009 PM 25239936 ER PT J AU Saito, N Sakakibara, K Sato, T Friedman, JM Kufe, DW VonHoff, DD Kawabe, T AF Saito, Naoya Sakakibara, Keiichi Sato, Takuji Friedman, Jonathan M. Kufe, Donald W. VonHoff, Daniel D. Kawabe, Takumi TI CBS9106-Induced CRM1 Degradation Is Mediated by Cullin Ring Ligase Activity and the Neddylation Pathway SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID UBIQUITIN-PROTEASOME SYSTEM; ORDER CHROMOSOME STRUCTURE; MLN4924 INDUCES AUTOPHAGY; NUCLEAR EXPORT; NEDD8-ACTIVATING ENZYME; COP9 SIGNALOSOME; LEPTOMYCIN-B; CANCER-THERAPY; FISSION YEAST; IN-VIVO AB Chromosome region maintenance 1 (CRM1) mediates the nuclear export of proteins and mRNAs, and is overexpressed in various cancers. Recent studies have also reported that CRM1 protein expression is a negative prognostic factor in patients with cancer. Therefore, CRM1 is considered a potential target for anticancer therapy. Our previous study demonstrated that CBS9106, a synthetic small-molecular inhibitor of CRM1, decreases CRM1 protein through proteasomal degradation without affecting CRM1 mRNA levels. However, the mechanism by which CRM1 is degraded is not well understood. Here, we demonstrate a novel signaling pathway that plays an important role in CBS9106-induced CRM1 degradation. We found that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), effectively inhibits cullin neddylation and attenuates CBS9106-induced CRM1 degradation in a time- and dose-dependent manner. MLN4924 also attenuated CBS9106-induced nuclear accumulation of Ran-binding protein 1 (RanBP1), cell growth inhibition, and apoptosis. Furthermore, RNAi-mediated knockdown of neddylation pathway proteins (NEDD8 and UBA3) or cullin ring ligase (CRL) component protein (Rbx1) attenuated CRM1 protein degradation and G1 phase cell-cycle arrest by CBS9106. Knockdown of CSN5 or CAND1 also partially inhibited CBS9106-induced CRM1 degradation. These findings demonstrate that CBS9106-induced CRM1 degradation is conferred by CRL activity involving the neddylation pathway, and that this response to CBS9106 leads to cell growth inhibition and apoptosis. (C) 2014 AACR. C1 [Saito, Naoya; Sakakibara, Keiichi; Sato, Takuji; Friedman, Jonathan M.; Kawabe, Takumi] CanBas Co Ltd, Numazu, Shizuoka 4100801, Japan. [Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [VonHoff, Daniel D.] Translat Genom Res Inst TGen, Phoenix, AZ USA. RP Kawabe, T (reprint author), CanBas Co Ltd, 2-2-1 Ote Machi, Numazu, Shizuoka 4100801, Japan. EM takumi@canbas.co.jp OI friedman, jonathan/0000-0001-6908-5928 NR 49 TC 4 Z9 6 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2014 VL 13 IS 12 BP 3013 EP 3023 DI 10.1158/1535-7163.MCT-14-0064 PG 11 WC Oncology SC Oncology GA AW2QH UT WOS:000346132900022 PM 25253782 ER PT J AU Panka, DJ Buchbinder, E Giobbie-Hurder, A Schalck, AP Montaser-Kouhsari, L Sepehr, A Lawrence, DP McDermott, DF Cohen, R Carlson, A Wargo, JA Merritt, R Seery, VJ Hodi, FS Gunturi, A Fredrick, D Atkins, MB Iafrate, AJ Flaherty, KT Mier, JW Sullivan, RJ AF Panka, David J. Buchbinder, Elizabeth Giobbie-Hurder, Anita Schalck, Aislyn P. Montaser-Kouhsari, Laleh Sepehr, Alireza Lawrence, Donald P. McDermott, David F. Cohen, Rachel Carlson, Alexander Wargo, Jennifer A. Merritt, Ryan Seery, Virginia J. Hodi, F. Stephen Gunturi, Anasuya Fredrick, Dennie Atkins, Michael B. Iafrate, A. John Flaherty, Keith T. Mier, James W. Sullivan, Ryan J. TI Clinical Utility of a Blood-Based BRAF(V600E) Mutation Assay in Melanoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BRAF V600E MUTATION; POLYMERASE-CHAIN-REACTION; RAF INHIBITOR RESISTANCE; PARAFFIN-EMBEDDED TISSUE; REAL-TIME PCR; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; IMPROVED SURVIVAL; PERIPHERAL-BLOOD AB BRAF inhibitors (BRAFi) have led to clinical benefit in patients with melanoma. The development of a blood-based assay to detect and quantify BRAF levels in these patients has diagnostic, prognostic, and predictive capabilities that could guide treatment decisions. Blood BRAF(V600E) detection and quantification were performed on samples from 128 patients with stage II (19), III (67), and IV (42) melanoma. Tissue BRAF analysis was performed in all patients with stage IV disease and in selected patients with stage II and III disease. Clinical outcomes were correlated to initial BRAF levels as well as BRAF level dynamics. Serial analysis was performed on 17 stage IV melanoma patients treated with BRAFi and compared with tumor measurements by RECIST. The assay was highly sensitive (96%) and specific (95%) in the stage IV setting, using a blood level of 4.8 pg as "positive." BRAF levels typically decreased following BRAFi. A subset of these patients (5) had an increase in BRAF(V600E) values 42 to 112 days before clinical or radiographic disease progression (PD). From 86 patients with resected, stage II or III melanoma, 39 had evidence of disease relapse (45.3%). Furthermore, BRAF mutation in the blood after surgical resection in these patients was not associated with a difference in relapse risk, although tissue BRAF status was only available for a subset of patients. In summary, we have developed a highly sensitive and specific, blood-based assay to detect BRAF(V600) mutation in patients with melanoma. (C) 2014 AACR. C1 [Panka, David J.; Buchbinder, Elizabeth; Montaser-Kouhsari, Laleh; Sepehr, Alireza; McDermott, David F.; Cohen, Rachel; Carlson, Alexander; Seery, Virginia J.; Gunturi, Anasuya; Mier, James W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Giobbie-Hurder, Anita; Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA USA. [Schalck, Aislyn P.; Lawrence, Donald P.; Merritt, Ryan; Fredrick, Dennie; Iafrate, A. John; Sullivan, Ryan J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Panka, DJ (reprint author), Harvard Univ, Sch Med, RW 571,330 Brookline Ave, Boston, MA 02215 USA. EM dpanka@bidmc.harvard.edu FU NCI SPORE in Skin Cancer [2P50CA93683]; Egan Memorial Research Laboratory for Melanoma Translational Research; Conquer Cancer Foundation Career Development Award [K12]; Clinical Investigator Training Program FX J.W. Mier was supported by the NCI SPORE in Skin Cancer 2P50CA93683; J.W. Mier and R.J. Sullivan were supported by the Egan Memorial Research Laboratory for Melanoma Translational Research; and R.J. Sullivan was supported by the Conquer Cancer Foundation Career Development Award, K12, and Clinical Investigator Training Program. NR 45 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2014 VL 13 IS 12 BP 3210 EP 3218 DI 10.1158/1535-7163.MCT-14-0349 PG 9 WC Oncology SC Oncology GA AW2QH UT WOS:000346132900038 PM 25319388 ER PT J AU van Steenoven, I Aarsland, D Hurtig, H Chen-Plotkin, A Duda, JE Rick, J Chahine, LM Dahodwala, N Trojanowski, JQ Roalf, DR Moberg, PJ Weintraub, D AF van Steenoven, Inger Aarsland, Dag Hurtig, Howard Chen-Plotkin, Alice Duda, John E. Rick, Jacqueline Chahine, Lama M. Dahodwala, Nabila Trojanowski, John Q. Roalf, David R. Moberg, Paul J. Weintraub, Daniel TI Conversion Between Mini-Mental State Examination, Montreal Cognitive Assessment, and Dementia Rating Scale-2 Scores in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; Mini-Mental State Examination; Montreal Cognitive Assessment; Dementia Rating Scale-2; cognitive screening scales ID SOCIETY TASK-FORCE; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; IMPAIRMENT; MOCA; MULTICENTER; VALIDITY; PROFILE AB Cognitive impairment is one of the earliest, most common, and most disabling non-motor symptoms in Parkinson's disease (PD). Thus, routine screening of global cognitive abilities is important for the optimal management of PD patients. Few global cognitive screening instruments have been developed for or validated in PD patients. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Dementia Rating Scale-2 (DRS-2) have been used extensively for cognitive screening in both clinical and research settings. Determining how to convert the scores between instruments would facilitate the longitudinal assessment of cognition in clinical settings and the comparison and synthesis of cognitive data in multicenter and longitudinal cohort studies. The primary aim of this study was to apply a simple and reliable algorithm for the conversion of MoCA to MMSE scores in PD patients. A secondary aim was to apply this algorithm for the conversion of DRS-2 to both MMSE and MoCA scores. The cognitive performance of a convenience sample of 360 patients with idiopathic PD was assessed by at least two of these cognitive screening instruments. We then developed conversion scores between the MMSE, MoCA, and DRS-2 using equipercentile equating and log-linear smoothing. The conversion score tables reported here enable direct and easy comparison of three routinely used cognitive screening assessments in PD patients. (C) 2014 International Parkinson and Movement Disorder Society C1 [van Steenoven, Inger; Aarsland, Dag] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Dis, Stavanger, Norway. [Aarsland, Dag] Akershus Univ Hosp, Dept Neurol, Oslo, Norway. [Hurtig, Howard; Chen-Plotkin, Alice; Rick, Jacqueline; Chahine, Lama M.; Dahodwala, Nabila; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Roalf, David R.; Moberg, Paul J.] Univ Penn, Perelman Sch Med, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. RP van Steenoven, I (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden. EM ingervansteenoven@gmail.com OI Aarsland, Dag/0000-0001-6314-216X FU NIA NIH HHS [K23 AG034236]; NIMH NIH HHS [K01 MH102609]; NINDS NIH HHS [P50 NS053488, U01 NS082134] NR 47 TC 13 Z9 14 U1 4 U2 13 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 DEC PY 2014 VL 29 IS 14 BP 1809 EP 1815 DI 10.1002/mds.26062 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AW1EY UT WOS:000346034400016 PM 25381961 ER PT J AU Li, WD Cavelti-Weder, C Zhang, YY Clement, K Donovan, S Gonzalez, G Zhu, J Stemann, M Xu, K Hashimoto, T Yamada, T Nakanishi, M Zhang, YM Zeng, S Gifford, D Meissner, A Weir, G Zhou, Q AF Li, Weida Cavelti-Weder, Claudia Zhang, Yinying Clement, Kendell Donovan, Scott Gonzalez, Gabriel Zhu, Jiang Stemann, Marianne Xu, Ke Hashimoto, Tatsu Yamada, Takatsugu Nakanishi, Mio Zhang, Yuemei Zeng, Samuel Gifford, David Meissner, Alexander Weir, Gordon Zhou, Qiao TI Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells SO NATURE BIOTECHNOLOGY LA English DT Article ID IN-VIVO; DEFINED FACTORS; FUNCTIONAL-NEURONS; INSULIN-SECRETION; EXOCRINE CELLS; ISLETS; FIBROBLASTS; GROWTH; CARDIOMYOCYTES; MICE AB Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for > 1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype. C1 [Li, Weida; Zhang, Yinying; Clement, Kendell; Donovan, Scott; Gonzalez, Gabriel; Xu, Ke; Nakanishi, Mio; Zhang, Yuemei; Zeng, Samuel; Meissner, Alexander; Zhou, Qiao] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Cavelti-Weder, Claudia; Stemann, Marianne; Yamada, Takatsugu; Weir, Gordon] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Zhang, Yinying; Clement, Kendell; Donovan, Scott; Zhu, Jiang; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA USA. [Clement, Kendell] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gonzalez, Gabriel] Harvard Univ, Sch Med, West Roxbury, MA USA. [Zhu, Jiang] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Zhu, Jiang] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Hashimoto, Tatsu; Gifford, David] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Zhou, Q (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM qiao_zhou@harvard.edu FU US National Institutes of Health; Juvenile Diabetes Research Foundation; Swiss Science Foundation; Swiss Foundation for Grants in Biology and Medicine FX We thank M. Shear, J. Brown, J. Hollister-Lock, and R. Zhao for technical assistance; H.-H. Chen for assistance with gene profiling; D. Yu and T. Fabbro for statistical analysis; Boston Children's Hospital core facility for an Illumina array; Joslin Specialized Assay Core for insulin measurement; members of the Zhou laboratory for advice and feedback; and D. Melton and D. Breault for discussion and reading of the manuscript. Q.Z. was supported by awards from the US National Institutes of Health. W.L. is supported by a postdoctoral fellowship from the Juvenile Diabetes Research Foundation. C.C.-W. is supported by postdoctoral fellowships from the Swiss Science Foundation and the Swiss Foundation for Grants in Biology and Medicine. NR 34 TC 26 Z9 27 U1 1 U2 18 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 DEC PY 2014 VL 32 IS 12 BP 1223 EP U79 DI 10.1038/nbt.3082 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AW3AD UT WOS:000346156800024 PM 25402613 ER PT J AU Wu, H Wu, XJ Shen, L Zhang, Y AF Wu, Hao Wu, Xiaoji Shen, Li Zhang, Yi TI Single-base resolution analysis of active DNA demethylation using methylase-assisted bisulfite sequencing SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; GENOME-WIDE ANALYSIS; TET PROTEINS; 5-METHYLCYTOSINE OXIDATION; MAMMALIAN DNA; SELF-RENEWAL; ES CELLS; 5-HYDROXYMETHYLCYTOSINE; 5-CARBOXYLCYTOSINE; 5-FORMYLCYTOSINE AB Active DNA demethylation in mammals involves TET-mediated iterative oxidation of 5-methylcytosine (5mC)/5-hydroxymethylcytosine (5hmC) and subsequent excision repair of highly oxidized cytosine bases 5-formylcytosine (5fC)/5-carboxylcytosine (5caC) by thymine DNA glycosylase (TDG). However, quantitative and high-resolution analysis of active DNA demethylation activity remains challenging. Here, we describe M. SssI methylase-assisted bisulfite sequencing (MAB-seq), a method that directly maps 5fC/5caC at single-base resolution. Genome-wide MAB-seq allows systematic identification of 5fC/5caC in Tdg-depleted embryonic stem cells, thereby generating a base-resolution map of active DNA demethylome. A comparison of 5fC/5caC and 5hmC distribution maps indicates that catalytic processivity of TET enzymes correlates with local chromatin accessibility. MAB-seq also reveals strong strand asymmetry of active demethylation within palindromic CpGs. Integrating MAB-seq with other base-resolution mapping methods enables quantitative measurement of cytosine modification states at key transitioning steps of the active DNA demethylation cascade and reveals a regulatory role of 5fC/5caC excision repair in this step-wise process. C1 [Wu, Hao; Wu, Xiaoji; Shen, Li; Zhang, Yi] Howard Hughes Med Inst, Boston, MA 02115 USA. [Wu, Hao; Wu, Xiaoji; Shen, Li; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wu, Hao; Wu, Xiaoji; Shen, Li; Zhang, Yi] Harvard Stem Cell Inst, Boston, MA USA. [Wu, Hao; Wu, Xiaoji; Shen, Li; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Zhang, Y (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM haowu7@gmail.com; yzhang@genetics.med.harvard.edu FU National Institutes of Health [U01DK089565]; Jane Coffin Childs Memorial Fund for Medical Research; National Human Genome Research Institute [K99HG007982]; China Scholarship Council FX We thank S. Yamaguchi and F. Lu for generating and characterizing Tet mutant mouse ESCs. We also thank L.M. Tuesta and S. Yamaguchi for critical reading of the manuscript. This project is supported by National Institutes of Health grant U01DK089565. H.W. was supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research and is currently supported by the National Human Genome Research Institute (K99HG007982). X.W. was supported by the China Scholarship Council. Y.Z. is an investigator of the Howard Hughes Medical Institute. NR 47 TC 31 Z9 33 U1 4 U2 38 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 DEC PY 2014 VL 32 IS 12 BP 1231 EP U92 DI 10.1038/nbt.3073 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AW3AD UT WOS:000346156800025 PM 25362244 ER PT J AU Doench, JG Hartenian, E Graham, DB Tothova, Z Hegde, M Smith, I Sullender, M Ebert, BL Xavier, RJ Root, DE AF Doench, John G. Hartenian, Ella Graham, Daniel B. Tothova, Zuzana Hegde, Mudra Smith, Ian Sullender, Meagan Ebert, Benjamin L. Xavier, Ramnik J. Root, David E. TI Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN-CELLS; CAS9; ENDONUCLEASE; SYSTEM; DNA; IDENTIFICATION; SPECIFICITY; NUCLEASES; IMMUNITY; CANCER AB Components of the prokaryotic clustered, regularly interspaced, short palindromic repeats (CRISPR) loci have recently been repurposed for use in mammalian cells(1-6). The CRISPR-associated (Cas) 9 can be programmed with a single guide RNA (sgRNA) to generate site-specific DNA breaks, but there are few known rules governing on-target efficacy of this system(7,8). We created a pool of sgRNAs, tiling across all possible target sites of a panel of six endogenous mouse and three endogenous human genes and quantitatively assessed their ability to produce null alleles of their target gene by antibody staining and flow cytometry. We discovered sequence features that improved activity, including a further optimization of the protospacer-adjacent motif (PAM) of Streptococcus pyogenes Cas9. The results from 1,841 sgRNAs were used to construct a predictive model of sgRNA activity to improve sgRNA design for gene editing and genetic screens. We provide an online tool for the design of highly active sgRNAs for any gene of interest. C1 [Doench, John G.; Hartenian, Ella; Graham, Daniel B.; Tothova, Zuzana; Hegde, Mudra; Smith, Ian; Sullender, Meagan; Ebert, Benjamin L.; Xavier, Ramnik J.; Root, David E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Tothova, Zuzana; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Doench, JG (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM jdoench@broadinstitute.org; droot@broadinstitute.org OI Sullender, Meagan/0000-0001-6666-8650; Doench, John/0000-0002-3707-9889 FU US National Institutes of Health [5T32CA009172-39] FX E.H., D B G., Z T. and J.G.D. designed experiments; E.H., M.S., D.B.G. and Z.T. ran experiments; E.H. and J.G.D. analyzed experimental results; M.H. and J.G.D. analyzed sequencing data and developed analysis tools; I. S. developed the sgRNA scoring model; E.H., D.E.R. and J.G.D. wrote the manuscript with help from other authors; B.L.E., R.J.X. and D.E.R. supervised the research. J.G.D. is a Merkin Institute Fellow. Z.T. is supported by US National Institutes of Health 5T32CA009172-39. NR 25 TC 198 Z9 208 U1 22 U2 136 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 DEC PY 2014 VL 32 IS 12 BP 1262 EP U130 DI 10.1038/nbt.3026 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AW3AD UT WOS:000346156800029 PM 25184501 ER PT J AU Videnovic, A Lazar, AS Barker, RA Overeem, S AF Videnovic, Aleksandar Lazar, Alpar S. Barker, Roger A. Overeem, Sebastiaan TI 'The clocks that time us'-circadian rhythms in neurodegenerative disorders SO NATURE REVIEWS NEUROLOGY LA English DT Review ID TRANSGENIC MOUSE MODEL; HEART-RATE-VARIABILITY; REST-ACTIVITY DISRUPTION; BRIGHT-LIGHT TREATMENT; CORE-BODY-TEMPERATURE; ALZHEIMER-DISEASE PATIENTS; BLOOD MONONUCLEAR-CELLS; PITUITARY-ADRENAL AXIS; SLEEP-WAKE CYCLE; PARKINSONS-DISEASE AB Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep-wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep-wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep-wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases. C1 [Videnovic, Aleksandar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USA. [Lazar, Alpar S.; Barker, Roger A.] Univ Cambridge, John Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 2PY, England. [Overeem, Sebastiaan] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. RP Videnovic, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, 165 Cambridge St Suite 650, Boston, MA 02114 USA. EM avidenovic@mgh.harvard.edu RI Overeem, Sebastiaan/D-2139-2010 FU NIH [K23 NS072283]; CHDI Foundation [RG50786]; Evelyn Trust [RG66030]; Butterfield Trust [RG68592]; NIHR Biomedical Research Centre and Biomedical Research Unit Award [RG68592]; Netherlands Organization for Scientific Research [016.116.371] FX A.V. has received research grant support from the NIH (K23 NS072283). A.S.L. has received research grant support from the CHDI Foundation (RG50786). R.A.B. has received research grant support from the CHDI Foundation (RG50786), Evelyn Trust (RG66030), Butterfield Trust (RG68592), and the NIHR Biomedical Research Centre and Biomedical Research Unit Award to Addenbrooke's Hospital/University of Cambridge (RG68592). S.O. has received research grant support from the Netherlands Organization for Scientific Research (grant no. 016.116.371). NR 171 TC 49 Z9 50 U1 6 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD DEC PY 2014 VL 10 IS 12 BP 683 EP 693 DI 10.1038/nrneurol.2014.206 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AW2JP UT WOS:000346114200006 PM 25385339 ER PT J AU Barbour, T DeCross, SN Holmes, AJ Boeke, EA Wolthusen, RPF Crowell, S Beam, E Coombs, G Nyer, M Tootell, RBH Fava, M Farabaugh, AH Holt, DJ AF Barbour, Tracy DeCross, Stephanie N. Holmes, A. J. Boeke, Emily A. Wolthusen, Rick P. F. Crowell, Susanna Beam, Ellie Coombs, Garth Nyer, Maren Tootell, Roger B. H. Fava, Maurizio Farabaugh, Amy H. Holt, Daphne J. TI Insecure Attachment in At-risk Youth is Associated with Hyper-responsivity of a Parietofrontal Cortical Network Involved in Social Behavior SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE Attachment; Imaging; Social Behavior; fMRI C1 [Barbour, Tracy; DeCross, Stephanie N.; Holmes, A. J.; Boeke, Emily A.; Wolthusen, Rick P. F.; Crowell, Susanna; Beam, Ellie; Coombs, Garth; Nyer, Maren; Tootell, Roger B. H.; Fava, Maurizio; Farabaugh, Amy H.; Holt, Daphne J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M229 BP S263 EP S265 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000437 ER PT J AU Besnard, A Langberg, T Levinson, S Scobie, K Leonardo, D Hen, R Sahay, A AF Besnard, Antoine Langberg, Tomer Levinson, Sally Scobie, Kimberly Leonardo, David Hen, Rene Sahay, Amar TI Klf9 Transcriptionally Promotes Resilience to Chronic Stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE resilience; stress; hippocampus; fear C1 [Besnard, Antoine; Langberg, Tomer; Levinson, Sally; Scobie, Kimberly; Leonardo, David; Hen, Rene; Sahay, Amar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M24 BP S126 EP S127 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000232 ER PT J AU Bui, E Orr, S Ojserkis, R Simon, N Hoge, E AF Bui, Eric Orr, Scott Ojserkis, Rebecca Simon, Naomi Hoge, Elizabeth TI Influence of Intranasal Oxytocin on Fear Consolidation in Healthy Humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE oxytocin; fear conditioning; memory C1 [Bui, Eric; Orr, Scott; Ojserkis, Rebecca; Simon, Naomi; Hoge, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 0 TC 0 Z9 0 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T257 BP S464 EP S465 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001255 ER PT J AU Camprodon, J Kaur, N Deckersbach, T Evans, K Kopell, B Halverson, J Kondziolka, D Howland, R Eskandar, E Dougherty, D AF Camprodon, Joan Kaur, Navneet Deckersbach, Thilo Evans, Karl Kopell, Brian Halverson, Jerry Kondziolka, Douglas Howland, Robert Eskandar, Emad Dougherty, Darin TI Epidural Cortical Stimulation of the Left DLPFC Leads to Dose-dependent Enhancement of Working Memory in Patients with MDD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE Brain Stimulation; Neuromodulation; Cognitive Enhancement; Major Depressive Disorder C1 [Camprodon, Joan; Kaur, Navneet; Deckersbach, Thilo; Evans, Karl; Kopell, Brian; Halverson, Jerry; Kondziolka, Douglas; Howland, Robert; Eskandar, Emad; Dougherty, Darin] Harvard Univ, Sch Med, Massachussets Gen Hosp, Boston, MA USA. RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W143 BP S565 EP S565 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002142 ER PT J AU Cohen, L Viguera, AC McInerney, KA Kwiatkowski, M Murphy, S Lemon, E Hernandez-Diaz, S AF Cohen, Lee Viguera, Adele C. McInerney, Kathryn A. Kwiatkowski, Molly Murphy, Shannon Lemon, Elizabeth Hernandez-Diaz, Sonia TI The National Pregnancy Registry for Atypical Antipsychotics: Effects of Fetal Exposure on Risk for Major Malformations and Extrapyramidal Symptoms SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE Atypical antipsychotics; Pregnancy; Registry; Bipolar disorder C1 [Cohen, Lee; Viguera, Adele C.; McInerney, Kathryn A.; Kwiatkowski, Molly; Murphy, Shannon; Lemon, Elizabeth; Hernandez-Diaz, Sonia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T250 BP S459 EP S460 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001248 ER PT J AU Deckersbach, T Dougherty, D Peters, A Strange, J Peckham, A Arulpragasam, A Sylvia, L Nierenberg, A AF Deckersbach, Thilo Dougherty, Darin Peters, Amy Strange, Jonathan Peckham, Andrew Arulpragasam, Amanda Sylvia, Louisa Nierenberg, Andrew TI Efficacy of Cognitive Behavior Therapy and Supportive Psychotherapy for Depression in Bipolar Disorder: Neurocognitive Predictors of Treatment Response SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE bipolar disorder; depression; cognitive behavior therapy; fMRI C1 [Deckersbach, Thilo; Dougherty, Darin; Peters, Amy; Strange, Jonathan; Peckham, Andrew; Arulpragasam, Amanda; Sylvia, Louisa; Nierenberg, Andrew] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 7 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W142 BP S564 EP S564 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002141 ER PT J AU Fava, M Durgam, S Mergel, V Earley, W Nemeth, G Laszlovszky, I AF Fava, Maurizio Durgam, Suresh Mergel, Victor Earley, Willie Nemeth, Gyoergy Laszlovszky, Istvan TI Efficacy and Safety of Cariprazine as Adjunctive Therapy in Major Depressive Disorder: A Double-blind, Placebo-controlled Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE cariprazine; depression; dopamine C1 [Fava, Maurizio; Durgam, Suresh; Mergel, Victor; Earley, Willie; Nemeth, Gyoergy; Laszlovszky, Istvan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T95 BP S352 EP S353 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001094 ER PT J AU Gatchel, J Jordan-Author, B Lewandowski, K Copersino, M Shassian, D Harper, D Forester, B AF Gatchel, Jennifer Jordan-Author, Brittany Lewandowski, Kathryn Copersino, Marc Shassian, Daniel Harper, David Forester, Brent TI Cognitive Dysfunction in Geriatric Bipolar Disorder and Major Depressive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE Bipolar Disorder; Depression; Geriatric; Cognition C1 [Gatchel, Jennifer; Jordan-Author, Brittany; Lewandowski, Kathryn; Copersino, Marc; Shassian, Daniel; Harper, David; Forester, Brent] McLean Hosp, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W52 BP S506 EP S507 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002052 ER PT J AU Holt, D DeCross, S Holmes, A Boeke, E Wolthusen, R Beam, E Coombs, G Nyer, M Buckner, R Fava, M Farabaugh, A AF Holt, Daphne DeCross, Stephanie Holmes, Avram Boeke, Emily Wolthusen, Rick Beam, Elizabeth Coombs, Garth Nyer, Maren Buckner, Randy Fava, Maurizio Farabaugh, Amy TI Abnormal Amygdala Functional Connectivity in Youth with Subclinical Delusions SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE psychosis; connectivity; amygdala; risk C1 [Holt, Daphne; DeCross, Stephanie; Holmes, Avram; Boeke, Emily; Wolthusen, Rick; Beam, Elizabeth; Coombs, Garth; Nyer, Maren; Buckner, Randy; Fava, Maurizio; Farabaugh, Amy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M236 BP S269 EP S270 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000444 ER PT J AU Jimenez, A Lee, J Wynn, J Horan, W Bender, A McGee, M Engel, S Glahn, D Nuechterlein, K Cohen, M Green, M AF Jimenez, Amy Lee, Junghee Wynn, Jonathan Horan, William Bender, Amanda McGee, Mark Engel, Stephen Glahn, David Nuechterlein, Keith Cohen, Mark Green, Michael TI Deficits at the Perception-Attention Interface in Schizophrenia: An fMRI Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE schizophrenia; fMRI; cognition C1 [Jimenez, Amy; Lee, Junghee; Wynn, Jonathan; Horan, William; Bender, Amanda; McGee, Mark; Engel, Stephen; Glahn, David; Nuechterlein, Keith; Cohen, Mark; Green, Michael] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W49 BP S504 EP S504 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002049 ER PT J AU Lynn, S Bui, E Palitz, S Keshaviah, A Fischer, L Barrett, L Simon, N AF Lynn, Spencer Bui, Eric Palitz, Sophie Keshaviah, Aparna Fischer, Laura Barrett, Lisa Simon, Naomi TI Working Memory Capacity Promotes Optimal Emotion Perception SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE Working Memory Capacity; Emotion Perception; Decision Making; Signal Detection Theory C1 [Lynn, Spencer; Bui, Eric; Palitz, Sophie; Keshaviah, Aparna; Fischer, Laura; Barrett, Lisa; Simon, Naomi] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W68 BP S516 EP S517 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002068 ER PT J AU Maeng, L Cover, K Landau, A Glynn, S Lebron-Milad, K Milad, M AF Maeng, Lisa Cover, Kara Landau, Aaron Glynn, Siobhan Lebron-Milad, Kelimer Milad, Mohammed TI Estradiol Shifts Neuronal Activity Within the Infralimbic and Prelimbic Cortices to Enhance Fear Extinction Memory Consolidation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE estradiol; fear extinction; anxiety; infralimbic cortex C1 [Maeng, Lisa; Cover, Kara; Landau, Aaron; Glynn, Siobhan; Lebron-Milad, Kelimer; Milad, Mohammed] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M262 BP S285 EP S285 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000470 ER PT J AU Manoach, D AF Manoach, Dara TI Sleep Spindle Deficits in Schizophrenia: A Treatable Mechanism of Impaired Cognition? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol C1 [Manoach, Dara] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA 47.1 BP S86 EP S86 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000165 ER PT J AU Marin, MF Song, HJ Staples-Bradley, LK VanElzakker, MB Lasko, NB Shin, LM Milad, MR AF Marin, Marie-France Song, Huijin Staples-Bradley, Lindsay K. VanElzakker, Michael B. Lasko, Natasha B. Shin, Lisa M. Milad, Mohammed R. TI Using Brain Glucose Metabolism to Predict the Neural Correlates of Extinction Memory Recall Among Trauma-unexposed and Trauma-exposed Individuals SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE PET Resting Metabolism; Extinction Memory Recall; fMRI; PTSD C1 [Marin, Marie-France; Song, Huijin; Staples-Bradley, Lindsay K.; VanElzakker, Michael B.; Lasko, Natasha B.; Shin, Lisa M.; Milad, Mohammed R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M242 BP S273 EP S273 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000450 ER PT J AU McFadden, K Tregellas, J AF McFadden, Kristina Tregellas, Jason TI Neuronal and Behavioral Effects of an Implicit Priming Intervention to Reduce High-calorie Food Appeal SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE implicit priming; obesity; food preferences; fMRI C1 [McFadden, Kristina; Tregellas, Jason] Univ Colorado, Denver VA Med Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W147 BP S567 EP S568 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002146 ER PT J AU Mitchell, J Weinstein, D Arcuni, P Woolley, J AF Mitchell, Jennifer Weinstein, Dawn Arcuni, Peter Woolley, Joshua TI Intranasal Oxytocin Selectively Modulates Social Perception, Approach Behavior, and Craving in Human Alcohol Abusers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE oxytocin; alcohol abuse; social perception; cue reactivity C1 [Mitchell, Jennifer; Weinstein, Dawn; Arcuni, Peter; Woolley, Joshua] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T261 BP S467 EP S467 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001259 ER PT J AU Ozburn, A Kern, J Parekh, P Logan, R Liu, Z Purohit, K Huang, YH McClung, C AF Ozburn, Angela Kern, Joseph Parekh, Puja Logan, Ryan Liu, Zheng Purohit, Kush Huang, Yanhua McClung, Colleen TI Mechanisms Mediating Circadian Gene Effects on Anxiety-like behavior: Focus on NPAS2 & GABAA SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE anxiety; circadian; GABAA; NPAS2 C1 [Ozburn, Angela; Kern, Joseph; Parekh, Puja; Logan, Ryan; Liu, Zheng; Purohit, Kush; Huang, Yanhua; McClung, Colleen] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T36 BP S313 EP S314 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001036 ER PT J AU Papakostas, G Swee, MB Baer, L Shelton, RC AF Papakostas, George Swee, Michaela B. Baer, Lee Shelton, Richard C. TI An 8-week, Randomized, Double-blind, Placebo-controlled Trial of Adjunctive Ziprasidone in Patients with Major Depressive Disorder Receiving Treatment with Escitalopram SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE ziprasidone; escitalopram; augmentation; adjunctive C1 [Papakostas, George; Swee, Michaela B.; Baer, Lee; Shelton, Richard C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T83 BP S344 EP S345 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001083 ER PT J AU Peskind, E Petrie, E Mayer, C Pagulayan, K Huber, B Meabon, J Raskind, M Cook, D Zhang, J Banks, W AF Peskind, Elaine Petrie, Eric Mayer, Cynthia Pagulayan, Kathleen Huber, Bertram Meabon, James Raskind, Murray Cook, David Zhang, Jin Banks, William TI Cerebrospinal Fluid Biomarkers in Iraq and Afghanistan Veterans: Effects of Deployment and Blast Concussion Mild Traumatic Brain Injury SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE CSF; biomarker; veterans; concussion C1 [Peskind, Elaine; Petrie, Eric; Mayer, Cynthia; Pagulayan, Kathleen; Huber, Bertram; Meabon, James; Raskind, Murray; Cook, David; Zhang, Jin; Banks, William] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W121 BP S549 EP S550 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002120 ER PT J AU Petryshen, T AF Petryshen, Tracey TI Function of the Ankryin 3 Bipolar Disorder Risk Gene in Brain and Behavior SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol C1 [Petryshen, Tracey] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA 49.2 BP S91 EP S91 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000174 ER PT J AU Raskind, M Peskind, E Millard, S Petrie, E AF Raskind, Murray Peskind, Elaine Millard, Steve Petrie, Eric TI Baseline Blood Pressure is Associated with PTSD Symptom Response to Prazosin in Active Duty Combat Soldiers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE prazosin; PTSD; combat; soldiers C1 [Raskind, Murray; Peskind, Elaine; Millard, Steve; Petrie, Eric] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T136 BP S384 EP S384 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001135 ER PT J AU Roffman, J AF Roffman, Joshua TI Effects of (6S)-5-Methyl-5,6,7,8-Tetrahydropteroyl-LGlutamic Acid Supplementation on Cortical Thickness in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol C1 [Roffman, Joshua] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA 3.3 BP S6 EP S6 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000012 ER PT J AU Rosenbaum, J Keefe, R Lieberman, J Romano, S McKinney, R Orf, H AF Rosenbaum, Jerrold Keefe, Richard Lieberman, Jeffrey Romano, Steven McKinney, Ross Orf, Harry TI Industry and Academic Science: Can Academia Work More Effectively and Ethically with Industry to Get New Therapies to the Market? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol C1 [Rosenbaum, Jerrold; Keefe, Richard; Lieberman, Jeffrey; Romano, Steven; McKinney, Ross; Orf, Harry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA 22 BP S37 EP S38 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000074 ER PT J AU Ross, R Krashes, M Shah, B Lowell, B AF Ross, Rachel Krashes, Michael Shah, Bhavik Lowell, Bradford TI Toward an Understanding of Eating Disorders: Are PVH PACAP Neurons an Interface Between Stress Response and Feeding Behavior? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE eating disorders; energy homeostasis; PACAP; PVH C1 [Ross, Rachel; Krashes, Michael; Shah, Bhavik; Lowell, Bradford] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T3 BP S292 EP S292 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001003 ER PT J AU Spielberg, J AF Spielberg, Jeffrey TI Anxiety Type Modulates Immediate Versus Delayed Engagement of Attention-related Brain Regions SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol C1 [Spielberg, Jeffrey] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA 39.4 BP S70 EP S70 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000136 ER PT J AU Widge, A Zorowitz, S Deckersbach, T Miller, E Dougherty, D AF Widge, Alik Zorowitz, Samuel Deckersbach, Thilo Miller, Earl Dougherty, Darin TI Increased Cognitive Flexibility as a Potential Mechanism of Ventral Capsule/Ventral Striatum Deep Brain Stimulation: A Combined Behavior/EEG Pilot Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE neuromodulation; brain stimulation; DBS; EEG C1 [Widge, Alik; Zorowitz, Samuel; Deckersbach, Thilo; Miller, Earl; Dougherty, Darin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W133 BP S558 EP S559 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002132 ER PT J AU Wynn, J Davis, M Weiner, K Maes, L Green, M Marder, S AF Wynn, Jonathan Davis, Michael Weiner, Katherine Maes, Lauryn Green, Michael Marder, Stephen TI Oxytocin Modulates EEG and Pupillary Responses to Social Stimuli in Schizophrenia: A Pilot Within-Subject Double-blind Crossover Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE oxytocin; schizophrenia; EEG; pupillometry C1 [Wynn, Jonathan; Davis, Michael; Weiner, Katherine; Maes, Lauryn; Green, Michael; Marder, Stephen] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W46 BP S502 EP S502 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002046 ER PT J AU Yang, Y Lee, J Narr, K Leaver, A Myers, AC Green, M AF Yang, Yvonne Lee, Junghee Narr, Katherine Leaver, Amber Myers, Ana Ceci Green, Michael TI GABA Assessed by Magnetic Resonance Spectroscopy in Visual Cortex in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE magnetic resonance spectroscopy; schizophrenia; GABA; visual cortex C1 [Yang, Yvonne; Lee, Junghee; Narr, Katherine; Leaver, Amber; Myers, Ana Ceci; Green, Michael] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M116 BP S186 EP S187 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000324 ER PT J AU Kebir, O Chaumette, B Fatjo-Vilas, M Ambalavanan, A Ramoz, N Xiong, L Mouaffak, F Millet, B Jaafari, N DeLisi, LE Levinson, D Joober, R Fananas, L Rouleau, G Dubertret, C Krebs, MO AF Kebir, Oussama Chaumette, Boris Fatjo-Vilas, Mar Ambalavanan, Amirthagowri Ramoz, Nicolas Xiong, Lan Mouaffak, Faycal Millet, Bruno Jaafari, Nematollah DeLisi, Lynn E. Levinson, Douglas Joober, Ridha Fananas, Lourdes Rouleau, Guy Dubertret, Caroline Krebs, Marie-Odile TI Family-based association study of common variants, raremutation study and epistatic interaction detection in HDAC genes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Epigenetics; Epistasis; Histone acetylation; Pedigree-based generalized multifactor dimensionality; Psychosis; Tag-SNP ID GENOME-WIDE SCAN; PREFRONTAL CORTEX; EXPRESSION; TRANSCRIPTION; BRAIN; POPULATION; DISORDERS; MUTATIONS; LINKAGE; NEURONS AB Background: Histone deacetylases (HDACs) are key enzymes of histone acetylation, and abnormalities in histone modifications and in the level of HDAC proteins have been reported in schizophrenia. The objective of the present study was to systematically test the HDAC genes for its association with schizophrenia. Methods: A family-based genetic association study (951 Caucasian subjects in 313 nuclear families) using 601 tag-single nucleotide polymorphisms in HDAC genes was conducted followed by a replication study of top-ranked markers in a sample of 1427 Caucasian subjects from 241 multiplex families and 176 trios. Epistasis interaction was tested by using the pedigree-based generalized multifactor dimensionality reduction (GMDR). Furthermore, we analyzed exome sequencing data of 1134 subjects for detection of rare mutations in HDAC genomic regions. Results: In the exploratory study, ten markers were in significant association with schizophrenia (P < 0.01). One maker rs14251 (HDAC3) was replicated (P = 0.04) and remained significant in the whole sample (P = 0.004). GMDR identified that a significant three-locus interaction model was detected involving rs17265596 (HDAC9), rs7290710 (HDAC10) and rs7634112 (HDAC11) with a good testing accuracy (0.58). No rare mutations were found associated with schizophrenia. Conclusion: This first exploratory systematic study of the HDAC genes provides consistent support for the involvement of the HDAC3 gene in the etiology of schizophrenia. A statistical epistatic interaction between HDAC9, HDAC10, and HDAC11 was detected and seems biologically plausible. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kebir, Oussama; Chaumette, Boris; Krebs, Marie-Odile] Univ Paris 05, Ctr Hosp St Anne, Sorbonne Paris Cite, Fac Med Paris Descartes,Serv Hosp Univ, Paris, France. [Kebir, Oussama; Chaumette, Boris; Mouaffak, Faycal; Millet, Bruno; Krebs, Marie-Odile] INSERM, U894, Ctr Psychiat & Neurosci, Lab Pathophysiol Psychiat Disorders, F-75014 Paris, France. [Kebir, Oussama; Chaumette, Boris; Mouaffak, Faycal; Millet, Bruno; Jaafari, Nematollah; Levinson, Douglas; Krebs, Marie-Odile] Inst Psychiat GDR 3557 Psychiat, Poitiers, France. [Fatjo-Vilas, Mar; Fananas, Lourdes] Univ Barcelona, Fac Biol, Dept Biol Anim, Barcelona, Spain. [Fatjo-Vilas, Mar; Fananas, Lourdes] Univ Barcelona IBUB, Ctr Biomed Researh Network Mental Hlth CIBERSAM, Inst Biomed, Inst Salud Carlos III, Madrid, Spain. [Ambalavanan, Amirthagowri; Xiong, Lan; Rouleau, Guy] Univ Montreal, CHUM Res Ctr, Ctr Excellence Neur, Montreal, PQ H2L 4M1, Canada. [Ramoz, Nicolas; Dubertret, Caroline] INSERM, U894, Ctr Psychiat & Neurosci, Team Vulnerabil Psychiat & Addict Disorders, F-75014 Paris, France. [Mouaffak, Faycal] Hop Bicetre, Psychiat Serv, Le Kremlin Bicetre, France. [Millet, Bruno] CH Guillaume Regnier, Pole Hosp Univ Psychiat Adulte, Rennes, France. [Jaafari, Nematollah] Ctr Hosp Henri Laborit, Unite Rech Clin Intersectorielle Psychiat, Poitiers, France. [Jaafari, Nematollah] CHU Poitiers, INSERM, CIC P 1402, Poitiers, France. [Jaafari, Nematollah] Univ Poitiers, INSERM, U1084, Expt & Clin Neurosci Lab, Poitiers, France. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Levinson, Douglas] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Joober, Ridha] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Rouleau, Guy] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada. [Dubertret, Caroline] Hop Louis Mourier, AP HP, Dept Psychiat, F-92701 Colombes, France. RP Krebs, MO (reprint author), INSERM, U894, Ctr Psychiat & Neurosci, Lab Pathophysiol Psychiat Disorders, 2 Ter Rue dAlesia, F-75014 Paris, France. EM marie-odile.krebs@inserm.fr RI ramoz, nicolas/K-3316-2015; Fananas Saura, Lourdes/C-7586-2017; OI Fananas Saura, Lourdes/0000-0001-6266-7706; Chaumette, Boris/0000-0002-1313-2788; Fatjo-Vilas, Mar/0000-0001-9963-6241 FU Agence Nationale de la Recherche (ANR) [08-MNP-007]; ERANET Neuron program; Institut National de la Sante et de la Recherche Medicale (INSERM); Fondation Pierre Deniker; Ministerio de Educacion y Ciencia [SAF2008-05674-C03-00]; Comissionat per a Universitats i Recerca del DIUE [2009SGR827]; Ministry of Science and Innovation [PIM2010ERM-00642]; Alicia Koplowitz Foundation; Genome Canada; Genome Quebec; Universite de Montreal; Canadian Foundation for Innovation; Fondation Charles Nicolle (Rouen, France); Accord INSERM/FRSQ FX We would like to thank all the families involved in this study. This work was supported by the Agence Nationale de la Recherche (ANR) grant no. 08-MNP-007, by the ERANET Neuron program and by the Institut National de la Sante et de la Recherche Medicale (INSERM). A portion of the schizophrenia cohort was collected through the Collaborative Network for Family Study in Psychiatry ("Reseau d'etude familiale en Psychiatrie", REFAPSY), supported by the Fondation Pierre Deniker. For the Barcelona cohort, the funding source was: i) Ministerio de Educacion y Ciencia (SAF2008-05674-C03-00), ii) the Comissionat per a Universitats i Recerca del DIUE (2009SGR827), iii) Ministry of Science and Innovation in frame of ERANET-NEURON (PIM2010ERM-00642) in frame of ERANET-NEURON and iv) Alicia Koplowitz Foundation. This work was also supported by Genome Canada and Genome Quebec, and received co-funding from Universite de Montreal for the 'Synapse to Disease' (S2D) project, as well as funding from the Canadian Foundation for Innovation Boris Chaumette receives grants from Fondation Charles Nicolle (Rouen, France). We thank Accord INSERM/FRSQ for their support. NR 47 TC 3 Z9 3 U1 5 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2014 VL 160 IS 1-3 BP 97 EP 103 DI 10.1016/j.schres.2014.09.029 PG 7 WC Psychiatry SC Psychiatry GA AW0DU UT WOS:000345961300032 PM 25445625 ER PT J AU Vakhrusheva, J Zemon, V Bar, M Weiskopf, NG Tremeau, F Petkova, E Su, Z Abeles, IY Butler, PD AF Vakhrusheva, J. Zemon, V. Bar, M. Weiskopf, N. G. Tremeau, F. Petkova, E. Su, Z. Abeles, I. Y. Butler, P. D. TI Forming first impressions of others in schizophrenia: Impairments in fast processing and in use of spatial frequency information SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Social cognition; Spatial frequency; Visual processing; First impressions; Threat ID FACIAL EMOTION RECOGNITION; SOCIAL COGNITION; OBJECT RECOGNITION; SPECTRUM DISORDERS; FACES; PERCEPTION; EXPRESSIONS; TRUSTWORTHINESS; CHLORPROMAZINE; METAANALYSIS AB Individuals form first impressions of others all the time, which affects their social functioning. Typical adults form threat impressions in faces with neutral expressions quickly, requiring less than 40 ms. These impressions appear to be mediated by low spatial frequency (LSF) content in the images. Little is known, however, about mechanisms of first impression formation in schizophrenia. The current study investigated how quickly individuals with schizophrenia can form consistent impressions of threat compared with controls and explored the mechanisms involved. Patients and controls were presented intact, LSF-or high spatial frequency (HSF)-filtered faces with durations that varied from 39 to 1703 ms and were asked to rate how threatening each face was on a scale from 1 to 5. In order to assess the speed of impression formation for intact faces, correlations were calculated for ratings made at each duration compared to a reference duration of 1703 ms for each group. Controls demonstrated a significant relation for intact faces presented for 39 ms, whereas patients required 390 ms to demonstrate a significant relation with the reference duration. For controls, LSFs primarily contributed to the formation of consistent threat impressions at 39 ms, whereas patients showed a trend for utilizing both LSF and HSF information to form consistent threat impressions at 390 ms. Results indicate that individuals with schizophrenia require a greater integration time to form a stable "first impression" of threat, which may be related to the need to utilize compensatory mechanisms such as HSF, as well as LSF, information. (C) 2014 Elsevier B.V. All rights reserved. C1 [Vakhrusheva, J.; Zemon, V.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. [Zemon, V.; Weiskopf, N. G.; Tremeau, F.; Petkova, E.; Abeles, I. Y.; Butler, P. D.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Bar, M.] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-5290002 Ramat Gan, Israel. [Bar, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA USA. [Weiskopf, N. G.] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Petkova, E.; Su, Z.] NYU, Langone Med Ctr, Dept Child & Adolescent Psychiat, New York, NY USA. [Abeles, I. Y.; Butler, P. D.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Abeles, I. Y.; Butler, P. D.] CUNY, Dept Psychol, New York, NY 10021 USA. RP Bar, M (reprint author), Bar Ilan Univ, IL-5290002 Ramat Gan, Israel. EM Moshe.bar@biu.ac.il OI Petkova, Eva/0000-0001-5129-9442 FU National Institutes of Health [RO1 MH084848] FX This work was supported by the National Institutes of Health (RO1 MH084848 to PDB). NR 55 TC 2 Z9 2 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2014 VL 160 IS 1-3 BP 142 EP 149 DI 10.1016/j.schres.2014.10.012 PG 8 WC Psychiatry SC Psychiatry GA AW0DU UT WOS:000345961300039 PM 25458862 ER PT J AU Seidman, LJ AF Seidman, Larry J. TI Lifespan developmental evolution of neurocognition in schizophrenia July 8, 2014 based on a talk given at Cold Spring Harbor Schizophrenia Seminar, June 5, 2014 SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT CSHL Workshop on Schizophrenia CY JUN 04-10, 2014 CL Cold Spring Harbor Lab, Cold Spring Harbor, NY HO Cold Spring Harbor Lab ID LONGITUDINAL BIRTH COHORT; 1ST PSYCHOTIC EPISODE; 1ST-EPISODE PSYCHOSIS; COGNITIVE PERFORMANCE; ADULT SCHIZOPHRENIA; CHILDHOOD; RISK; DEFICITS; DECLINE; METAANALYSIS C1 [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr Publ Psychiat Div,B, Cambridge, MA 02138 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lseidman@bidmc.harvard.edu NR 35 TC 0 Z9 0 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2014 VL 160 IS 1-3 BP E4 EP E6 DI 10.1016/j.schres.2014.09.067 PG 5 WC Psychiatry SC Psychiatry GA AW0DU UT WOS:000345961300008 ER PT J AU Bianchi, MT Alameddine, Y Mojica, J AF Bianchi, Matt T. Alameddine, Yvonne Mojica, James TI Apnea burden: efficacy versus effectiveness in patients using positive airway pressure SO SLEEP MEDICINE LA English DT Article DE Compliance; Management; Efficacy; Effectiveness; Apnea burden ID OBSTRUCTIVE SLEEP-APNEA; HYPOPNEA INDEX; THERAPY WITHDRAWAL; CPAP THERAPY; ADHERENCE; POLYSOMNOGRAPHY AB Background: Modern continuous positive airway pressure (PAP) machines track hours of use and residual respiratory events while on treatment. A substantial portion of sleep apnea patients are partially compliant, emphasizing the need to distinguish between PAP efficacy and PAP effectiveness in chronic management of patients with sleep apnea. Methods: We used a combination of three data sources to estimate the sleep apnea burden in a convenience cohort of PAP users from our clinics that were compliant based on Medicare criteria: self-reported habitual total sleep time, and PAP usage times with residual apnea-hypopnea index (AHI) from compliance downloads. Results: Assuming that the off-PAP time consists of baseline AHI severity, an estimated apnea burden was calculated to estimate PAP effectiveness. Whereas 70% of patients in our cohort showed machine AHI values <5/h, the apnea burden calculations revealed that only one-third of patients are predicted to have an effective AHI <5. Conclusion: Estimating PAP effectiveness through the concept of apnea burden has implications for clinical care as well as research trials. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bianchi, Matt T.; Alameddine, Yvonne] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Bianchi, Matt T.; Mojica, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Young Clinician Award from the Center for Integration of Medicine and Innovative Technology FX Dr Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital, and a Young Clinician Award from the Center for Integration of Medicine and Innovative Technology. Dr Bianchi has a patent pending on a home sleep monitoring device, consultation agreement with Sunovion, and is on the clinical advisory board for Foramis. NR 25 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD DEC PY 2014 VL 15 IS 12 BP 1579 EP 1581 DI 10.1016/j.sleep.2014.07.015 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YG UT WOS:000346084100022 PM 25441743 ER PT J AU Malmstrom, E Davidova, A Morgelin, M Linder, A Larsen, M Qvortrup, K Nordenfelt, P Shannon, O Dzupova, O Holub, M Malmstrom, J Herwald, H AF Malmstrom, Erik Davidova, Alzbeta Morgelin, Matthias Linder, Adam Larsen, Michael Qvortrup, Klaus Nordenfelt, Pontus Shannon, Oonagh Dzupova, Olga Holub, Michel Malmstrom, Johan Herwald, Heiko TI Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Coagulation; infectious diseases; innate immunity; neutrophils; mass spectrometry; proteomics ID HEPARIN-BINDING PROTEIN; SEPTIC SHOCK; GRANULES; PHAGOCYTOSIS; INFLAMMATION; MECHANISMS; PROTEOMICS; RESISTIN; PATHWAY; DISEASE AB Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation, an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil-derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis. C1 [Malmstrom, Erik; Morgelin, Matthias; Linder, Adam; Nordenfelt, Pontus; Shannon, Oonagh; Malmstrom, Johan; Herwald, Heiko] Lund Univ, Sect Clin & Expt Infect Med, Dept Clin Sci, SE-22184 Lund, Sweden. [Davidova, Alzbeta; Holub, Michel] Charles Univ Prague, Fac Med 1, Dept Infect & Trop Dis, Prague, Czech Republic. [Davidova, Alzbeta; Dzupova, Olga; Holub, Michel] Na Bulovce Hosp, Prague, Czech Republic. [Davidova, Alzbeta; Holub, Michel] Mil Univ Hosp, Fac Med 1, Dept Infect Dis, Prague, Czech Republic. [Davidova, Alzbeta; Holub, Michel] Charles Univ Prague, Prague, Czech Republic. [Linder, Adam] Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V5Z 1M9, Canada. [Larsen, Michael; Qvortrup, Klaus] Univ Copenhagen, Fac Hlth & Med Sci, CFIM, Dept Biomed Sci, Copenhagen, Denmark. [Nordenfelt, Pontus] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Springer Lab,Program Cellular & Mol Med,Childrens, Boston, MA 02115 USA. [Dzupova, Olga] Charles Univ Prague, Fac Med 3, Dept Infect Dis, Prague, Czech Republic. RP Malmstrom, E (reprint author), Lund Univ, Div Infect Med, Dept Clin Sci, BMC B14,Tornavagen 10, SE-22184 Lund, Sweden. EM erik.malmstrom@med.lu.se RI Malmstrom, Johan/B-7660-2009; OI Malmstrom, Johan/0000-0002-2889-7169; Shannon, Oonagh/0000-0001-8291-8189; Holub, Michal/0000-0003-1894-2605; Herwald, Heiko/0000-0002-8111-2842; Nordenfelt, Pontus/0000-0002-9481-9951 FU Royal Swedish Physiographic Society in Lund; European research council (Marie Curie fellowship); foundation of Alfred Osterlund; foundation of Crafoord; foundation of Greta; foundation of Johan Kock; Knut and Alice Wallenberg Foundation; Ragnar Soderberg Foundation; Medical Faculty, Lund University; Swedish Research Council [IGA NT 11390-5, 2008:3356, 621-2012-3559]; Swedish Foundation for Strategic Research [FFL4]; Crafoord Foundation [20100892]; Wallenberg Academy Fellow KAW [2012.0178]; European research council starting grant [ERC-2012-StG-309831] FX We wish to thank Monica Heidenholm and Maria Baumgarten for excellent technical assistance. This work was supported in part by the Royal Swedish Physiographic Society in Lund, the European research council (Marie Curie fellowship), the foundations of Alfred Osterlund, Crafoord, Greta and Johan Kock, Knut and Alice Wallenberg Foundation, Ragnar Soderberg Foundation, the Medical Faculty, Lund University, the Swedish Research Council, the grant IGA NT 11390-5, Swedish Research Council (projects 2008:3356 and 621-2012-3559), the Swedish Foundation for Strategic Research (grant FFL4), the Crafoord Foundation (grant 20100892), the Wallenberg Academy Fellow KAW (2012.0178) and European research council starting grant (ERC-2012-StG-309831). Core Facilty for Integrated Microscopy, CFIM, is acknowledged for access to the Quanta 3D SEM. NR 43 TC 1 Z9 1 U1 1 U2 9 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD DEC PY 2014 VL 112 IS 6 BP 1230 EP 1243 DI 10.1160/TH14-04-0312 PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AW1HJ UT WOS:000346040500020 PM 25104417 ER PT J AU Nguyen, C Wang, M AF Chau Nguyen Wang, Marilene TI Practice Patterns in the Surgical Treatment of Papillary Thyroid Microcarcinoma SO THYROID LA English DT Letter ID GUIDELINES; CANCER C1 [Chau Nguyen] Ventura Cty Med Ctr, Div Otolaryngol Head & Neck Surg, Ventura, CA 93003 USA. [Wang, Marilene] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Wang, Marilene] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Nguyen, C (reprint author), Ventura Cty Med Ctr, Div Otolaryngol Head & Neck Surg, 3291 Loma Vista Rd Ste 401, Ventura, CA 93003 USA. EM chau.nguyen@ventura.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD DEC 1 PY 2014 VL 24 IS 12 BP 1816 EP 1817 DI 10.1089/thy.2014.0388 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AW4KL UT WOS:000346249900013 PM 25232803 ER PT J AU Chan, ED Kinney, WH Honda, JR Bishwakarma, R Gangavelli, A Mya, J Bai, XY Ordway, DJ AF Chan, Edward D. Kinney, William H. Honda, Jennifer R. Bishwakarma, Raju Gangavelli, Avani Mya, Jenny Bai, Xiyuan Ordway, Diane J. TI Tobacco exposure and susceptibility to tuberculosis: Is there a smoking gun? SO TUBERCULOSIS LA English DT Review DE Cigarette smoke; Mycobacterium tuberculosis; Host-defense; Air-pollution ID OBSTRUCTIVE PULMONARY-DISEASE; REGULATORY T-CELLS; NICOTINIC ACETYLCHOLINE-RECEPTOR; CIGARETTE-SMOKE; MYCOBACTERIUM-TUBERCULOSIS; ALVEOLAR MACROPHAGES; IN-VITRO; INCREASES SUSCEPTIBILITY; ACTIVE TUBERCULOSIS; CYTOKINE RESPONSES AB In many regions of the world, there is a great overlap between the prevalence of cigarette smoke exposure and tuberculosis. Despite the large body of epidemiologic evidence that tobacco smoke exposure is associated with increased tuberculosis infection, active disease, severity of disease, and mortality from tuberculosis, these studies cannot distinguish whether the mechanism is principally through direct impairment of anti-tuberculosis immunity by cigarette smoke or due to potential confounders that increase risk for tuberculosis and are commonly associated with smoking - such as poverty, malnutrition, and crowded living conditions. While there are several in vivo murine and in vitro macrophage studies showing cigarette smoke impairs control of tuberculous infection, little is known of the molecular and cellular mechanisms by which this impairment occurs. Herein, we highlight the key findings of these studies. Additionally, we review key immune cells that play critical roles in host-defense or pathogenesis of tuberculosis and generate a hypothesis-driven discussion of the possible mechanisms by which cigarette smoke impairs or enhances their functions, respectively, ultimately resulting in compromised immunity against tuberculosis. Published by Elsevier Ltd. C1 [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Chan, Edward D.; Kinney, William H.; Bishwakarma, Raju; Gangavelli, Avani; Mya, Jenny; Bai, Xiyuan] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chan, Edward D.; Kinney, William H.; Bishwakarma, Raju; Gangavelli, Avani; Mya, Jenny; Bai, Xiyuan] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Chan, Edward D.; Honda, Jennifer R.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, but this funding had no influence in the content of the manuscript. NR 89 TC 10 Z9 10 U1 0 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD DEC PY 2014 VL 94 IS 6 BP 544 EP 550 DI 10.1016/j.tube.2014.08.010 PG 7 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA AW0KB UT WOS:000345979900003 PM 25305002 ER PT J AU Stanford, KI Goodyear, LJ AF Stanford, Kristin I. Goodyear, Laurie J. TI Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle SO ADVANCES IN PHYSIOLOGY EDUCATION LA English DT Article DE exercise; type 2 diabetes ID ACTIVATED PROTEIN-KINASE; INSULIN-STIMULATED PHOSPHORYLATION; LIFE-STYLE INTERVENTION; GLUT4 TRANSLOCATION; AS160 PHOSPHORYLATION; CONTRACTILE ACTIVITY; 3-KINASE ACTIVITY; AKT SUBSTRATE; TRANSPORT; AMPK AB Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial function, increases mitochondrial biogenesis, and increases the expression of glucose transporter proteins and numerous metabolic genes. This review focuses on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle. C1 [Stanford, Kristin I.; Goodyear, Laurie J.] Harvard Univ, Brigham & Womens Hosp, Sect Integrat Physiol & Metab, Joslin Diabet Ctr,Dept Med,Med Sch, Boston, MA 02215 USA. RP Stanford, KI (reprint author), Harvard Univ, Brigham & Womens Hosp, Sect Integrat Physiol & Metab, Joslin Diabet Ctr,Dept Med,Med Sch, Boston, MA 02215 USA. EM kristin.stanford@joslin.harvard.edu FU American College of Sports Medicine Research Endowment Grant; Mary K. Iacocca Fellowship; National Institutes of Health [R01-AR-42238, R01-DK-101043, 5-P30-DK-36836] FX This work was supported by an American College of Sports Medicine Research Endowment Grant (to K. I. Stanford), Mary K. Iacocca Fellowship (to K. I. Stanford), and National Institutes of Health Grants R01-AR-42238 (to L. J. Goodyear), R01-DK-101043 (to L. J. Goodyear), and 5-P30-DK-36836 (Diabetes Research Center, Joslin Diabetes Center). NR 87 TC 19 Z9 21 U1 4 U2 28 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1043-4046 EI 1522-1229 J9 ADV PHYSIOL EDUC JI Adv. Physiol. Educ. PD DEC 1 PY 2014 VL 38 IS 4 BP 308 EP 314 DI 10.1152/advan.00080.2014 PG 7 WC Education, Scientific Disciplines; Physiology SC Education & Educational Research; Physiology GA AU9GA UT WOS:000345898500004 PM 25434013 ER PT J AU Vaduganathan, M Greene, SJ Ambrosy, AP Mentz, RJ Subacius, HP Chioncel, O Maggioni, AP Swedberg, K Zannad, F Konstam, MA Senni, M Givertz, MM Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Greene, Stephen J. Ambrosy, Andrew P. Mentz, Robert J. Subacius, Hans P. Chioncel, Ovidiu Maggioni, Aldo P. Swedberg, Karl Zannad, Faiez Konstam, Marvin A. Senni, Michele Givertz, Michael M. Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Relation of Serum Uric Acid Levels and Outcomes Among Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; PROGNOSTIC MARKER; RENAL-FUNCTION; DOUBLE-BLIND; HYPERURICEMIA; EVEREST; RISK; METAANALYSIS; ASSOCIATION; METABOLISM AB We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) <= 40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles: The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 +/- 2.8 mg/dl and was higher in men than in women (9.3 +/- 2.7 vs 8.7 +/- 3.0 mg/dl, p <0.001) and in blacks than in whites (10.0 +/- 2.7 vs 9.0 +/- 2.8 mg/dl, p <0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate >= 30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44,95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Ambrosy, Andrew P.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Durham, NC USA. [Subacius, Hans P.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Chioncel, Ovidiu] Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest, Romania. [Maggioni, Aldo P.] Hosp Cardiologists ANMCO, Italian Assoc, Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Gothenburg, Sweden. [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France. [Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA. [Senni, Michele] Azienda Ospedaliera Papa Giovanni XXIII, Dipartimento Cardiovasc, Bergamo, Italy. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Vaduganathan, M (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM muthu@md.northwestern.edu OI chioncel, ovidiu/0000-0002-3197-3628; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka Inc. (Rockville, Maryland) FX Otsuka Inc. (Rockville, Maryland) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. NR 30 TC 7 Z9 10 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2014 VL 114 IS 11 BP 1713 EP 1721 DI 10.1016/j.amjcard.2014.09.008 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU6RJ UT WOS:000345729300014 PM 25312638 ER PT J AU Yeo, KK Maddox, TM Carey, E Low, RI Shunk, KA AF Yeo, Khung Keong Maddox, Thomas M. Carey, Evan Low, Reginald I. Shunk, Kendrick A. TI Right- and Left-Sided Heart Catheterization as a Quality Marker for Catheterization Laboratories (from the National Veterans Affairs Clinical Assessment Reporting and Tracking Program) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-CATHETERIZATION; PULMONARY-HYPERTENSION; CORONARY-ANGIOGRAPHY; DISEASE AB The rate of concurrent right-heart catheterization (RHC) in patients undergoing left-heart catheterization (LHC) for coronary artery disease (CAD) indications or bilateral heart catheterization (BHC) is recommended as a measure of hospital quality, with higher rates suggesting over utilization. Our aim was to describe the prevalence of BHC and abnormal RHC findings in patients undergoing BHC with a primary indication for LHC. A retrospective analysis was performed for patients undergoing cardiac catheterization for CAD indications using the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Program. Patients undergoing catheterization from October 2007 to September 2011 in 76 Veterans Affairs hospitals were included. Among 95,656 patients undergoing catheterization for CAD, 6,611 (6.9%) underwent BHC and 88,929 (93.0%) LHC. Among the patients undergoing BHC, 61.3% had at least 1 of the following abnormal RHC values: mean pulmonary artery (PA) pressure >25 mm Hg, pulmonary capillary wedge pressure (PCWP) >15 mm Hg, or pulmonary vascular resistance (PVR) >3 Woods units. A total of 37.5% of patients had mean PA pressures of 26 to 40 mm Hg and 11.1% had mean PA pressures >40 mm Hg. A total of 34.4% of patients had mean PCWP of 16 to 25 mm Hg and 13.6% had mean PAWP >25 mm Hg. A total of 16.5% of patients had PVR between 3 and 6 WU and 2.9% had PVR >6 WU. A total of 4.3% of patients met formal criteria for pulmonary arterial hypertension (defined as the combination of PA mean >25 mm Hg, PCWP <= 15 mm Hg, and PVR >3). In conclusion, these findings suggest that most BHC were performed for appropriate clinical reasons. Future studies should further explore BHC rate as an effective quality indicator. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yeo, Khung Keong; Low, Reginald I.] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Yeo, Khung Keong] Natl Heart Ctr Singapore, Dept Cardiol, Singapore, Singapore. [Maddox, Thomas M.] Vet Affairs Eastern Colorado Hlth Care Syst, Cardiol Sect, Denver, CO USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Div Cardiol, Denver, CO USA. [Carey, Evan] Vet Affairs Clin Assessment Reporting & Tracking, Denver, CO USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, Dept Cardiol, San Francisco, CA USA. [Shunk, Kendrick A.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. RP Yeo, KK (reprint author), Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. EM khung.yeo@ucdmc.ucdavis.edu FU VA Health Services Research and Development FX Dr Maddox is supported by a VA Health Services Research and Development career development award. The other authors have no relevant conflicts of interest. NR 11 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2014 VL 114 IS 11 BP 1758 EP 1762 DI 10.1016/j.amjcard.2014.08.047 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU6RJ UT WOS:000345729300021 PM 25316348 ER PT J AU Maan, A Mansour, M McManus, DD Patel, VV Cheng, A Ruskin, JN Heist, EK AF Maan, Abhishek Mansour, Moussa McManus, David D. Patel, Vickas V. Cheng, Alan Ruskin, Jeremy N. Heist, E. Kevin TI Novel Therapeutic Targets in the Management of Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS LA English DT Review ID CONGESTIVE-HEART-FAILURE; POLYUNSATURATED FATTY-ACIDS; CONVERTING ENZYME-INHIBITION; RANDOMIZED CONTROLLED-TRIALS; ACTIVATED PROTEIN-KINASES; BLEOMYCIN-HAMSTER MODEL; RAT CARDIAC FIBROBLASTS; GUINEA-PIG HEARTS; ANGIOTENSIN-II; GENE-EXPRESSION AB Atrial fibrillation (AF) is the most common cardiac arrhythmia, contributing to increased morbidity and reduced survival through its associations with stroke and heart failure. AF contributes to a four- to fivefold increase in the risk of stroke in the general population and is responsible for 10-15 % of all ischemic strokes. Diagnosis and treatment of AF require considerable health care resources. Current therapies to restore sinus rhythm in AF are suboptimal and are limited either by their pro-arrhythmic effects or by their procedure-related complications. These limitations have necessitated identification of newer therapeutic targets to expand the treatment options. There has been a considerable amount of research interest in investigating the mechanisms of initiation and propagation of AF. Despite extensive research focused on the pathogenesis of AF, a thorough understanding of various pathways mediating initiation and propagation of AF still remains limited. Research efforts focused on the identification of these pathways and molecular mediators have generated a great degree of interest for developing more targeted therapies. This review discusses the potential therapeutic targets and the results from experimental and clinical research investigating these targets. C1 [Maan, Abhishek; Mansour, Moussa; Ruskin, Jeremy N.; Heist, E. Kevin] Massachusetts Gen Hosp, Div Electrophysiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [McManus, David D.] Univ Massachusetts, Div Cardiol, Dept Electrophysiol, Worcester, MA 01605 USA. [Patel, Vickas V.] Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Patel, Vickas V.] Univ Penn, Sect Cardiac Electrophysiol, Philadelphia, PA 19104 USA. [Cheng, Alan] Johns Hopkins Univ, Div Electrophysiol, Baltimore, MD USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, Div Electrophysiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM kheist@mgh.harvard.edu FU Deane Institute for Integrative Research in Atrial Fibrillation at Massachusetts General Hospital FX Supported in part by The Deane Institute for Integrative Research in Atrial Fibrillation at Massachusetts General Hospital. NR 172 TC 1 Z9 3 U1 0 U2 6 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1175-3277 EI 1179-187X J9 AM J CARDIOVASC DRUG JI Am. J. Cardiovasc. Drugs PD DEC PY 2014 VL 14 IS 6 BP 403 EP 421 DI 10.1007/s40256-014-0085-0 PG 19 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA AU6YC UT WOS:000345746600001 PM 25090973 ER PT J AU Shlyankevich, J Mehta, NN Krueger, JG Strober, B Gudjonsson, JE Qureshi, AA Tebbey, PW Kimball, AB AF Shlyankevich, Julia Mehta, Nehal N. Krueger, James G. Strober, Bruce Gudjonsson, Johann E. Qureshi, Abrar A. Tebbey, Paul W. Kimball, Alexandra Boer TI Accumulating Evidence for the Association and Shared Pathogenic Mechanisms Between Psoriasis and Cardiovascular-related Comorbidities SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Atherosclerosis; Cardiovascular; Cardiovascular disease; Inflammation; Inflammatory pathway; Interleukin-17; Metabolic syndrome; Psoriasis ID POSITRON-EMISSION-TOMOGRAPHY; VASCULAR INFLAMMATION; MYOCARDIAL-INFARCTION; DISEASE; RISK; SKIN; MODERATE; FLUORODEOXYGLUCOSE; ATHEROSCLEROSIS; COHORT AB The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, Mass. By assembling a panel of global dermatology, immunology, and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. The International Psoriasis Council has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity. Published by Elsevier Inc. C1 [Shlyankevich, Julia; Kimball, Alexandra Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA. [Krueger, James G.] Rockefeller Univ, New York, NY 10021 USA. [Strober, Bruce] Univ Connecticut, Dept Dermatol, Ctr Hlth, Farmington, CT USA. [Strober, Bruce] Prob Med Res, Waterloo, ON, Canada. [Gudjonsson, Johann E.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Qureshi, Abrar A.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Tebbey, Paul W.] Int Psoriasis Council, St Louis, MO USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov FU AbbVie; Amgen FX International Psoriasis Council is a nonprofit charity organization that received unrestricted sponsorship from AbbVie and Amgen to support the workshop. The sponsors had no influence on the content of the program or the viewpoints in this manuscript. NR 28 TC 22 Z9 23 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2014 VL 127 IS 12 BP 1148 EP 1153 DI 10.1016/j.amjmed.2014.08.008 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AW1CY UT WOS:000346029400028 PM 25149424 ER PT J AU Vaduganathan, M Greene, SJ Fonarow, GC Voors, AA Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Greene, Stephen J. Fonarow, Gregg C. Voors, Adriaan A. Butler, Javed Gheorghiade, Mihai TI Hemoconcentration-guided Diuresis in Heart Failure SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Diuresis; Heart Failure; Readmission ID EMERGENCY-DEPARTMENT PRIDE; RENAL-FUNCTION; EVEREST TRIAL; CLINICAL CHARACTERISTICS; 30-DAY READMISSIONS; PREDICTIVE-VALUE; DYSPNEA RELIEF; HF REGISTRY; OUTCOMES; HOSPITALIZATION AB One quarter of patients hospitalized for heart failure are readmitted within 30 days, perhaps related to ineffective decongestion. Limited data exist guiding the extent and duration of diuresis in patients hospitalized for heart failure. The objective of this review was to determine the prognostic value of hemoconcentration, or the relative increase in the cellular elements in blood, in patients hospitalized for heart failure and to clarify its role in guiding inpatient diuretic practices. Six post hoc retrospective studies from 2010 to 2013 were available for review. Hemoconcentration was consistently associated with markers of aggressive fluid removal, including higher diuretic dosing and reduced body weight, but increased risk of in-hospital worsening renal function. Despite this, hemoconcentration was associated with improved short-term mortality and rehospitalization. Hemoconcentration is a practical, readily available, noninvasive, economically feasible strategy to help guide diuresis and monitor congestion relief in patients hospitalized for worsening heart failure. Clinicians should strongly consider using changes in hemoglobin and hematocrit as an adjunct to other available measures of decongestion and clinical acumen in inpatient heart failure care. (C) 2014 Elsevier Inc. All rights reserved. C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Butler, Javed] Emory Univ Hosp, Div Cardiol, Atlanta, GA 30322 USA. RP Vaduganathan, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM muthu@md.northwestern.edu FU Agency for Healthcare Research and Quality; Alere; AstraZeneca; Bayer; Boehringer Ingelheim; Cardio3 Biosciences; Celladon; Johnson Johnson; Merck/MSD; Novartis; Servier; Torrent; Trevena; Vifor; National Institutes of Health; European Union; Health Resources and Services Administration; U.S. Food and Drug Administration FX MV and SJG: None. GCF receives research support from the Agency for Healthcare Research and Quality (significant) and is a consultant to Medtronic (modest), Gambro (significant), and Novartis (significant). AAV receives consultancy fees and research grants from Alere, AstraZeneca, Bayer, Boehringer Ingelheim, Cardio3 Biosciences, Celladon, Johnson & Johnson, Merck/MSD, Novartis, Servier, Torrent, Trevena, and Vifor. JB receives research support from the National Institutes of Health, European Union, Health Resources and Services Administration, and U.S. Food and Drug Administration; is a consultant to Amgen, Bayer, Celladon, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, and Trevena; and has stock options in Stemedica. MG is a consultant to Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S. A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics. NR 43 TC 6 Z9 6 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2014 VL 127 IS 12 BP 1154 EP 1159 DI 10.1016/j.amjmed.2014.06.009 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AW1CY UT WOS:000346029400029 PM 24937157 ER PT J AU Chaudhry, SI Lien, C Ehrlich, J Lane, S Cordasco, K McDonald, FS Arora, VM Steinmann, A AF Chaudhry, Saima I. Lien, Cynthia Ehrlich, Jason Lane, Susan Cordasco, Kristina McDonald, Furman S. Arora, Vineet M. Steinmann, Alwin TI Curricular Content of Internal Medicine Residency Programs: A Nationwide Report SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID PREPAREDNESS; EDUCATION C1 [Chaudhry, Saima I.; Lien, Cynthia; Ehrlich, Jason] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Lane, Susan] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Cordasco, Kristina] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cordasco, Kristina] RAND Corp, Santa Monica, CA USA. [McDonald, Furman S.] Mayo Clin, Coll Med, Rochester, MN USA. [Arora, Vineet M.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Steinmann, Alwin] Exempla St Joseph Hosp, Denver, CO USA. [Steinmann, Alwin] Univ Colorado, Sch Med, Denver, CO USA. RP Chaudhry, SI (reprint author), Dept Med, 270-05 76th Ave,Res Bldg,2nd Fl, New Hyde Pk, NY 11040 USA. EM schaudhr@nshs.edu OI Arora, Vineet/0000-0002-4745-7599 NR 22 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2014 VL 127 IS 12 BP 1247 EP 1254 DI 10.1016/j.amjmed.2014.08.009 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AW1CY UT WOS:000346029400044 PM 25168079 ER PT J AU Jakobiec, FA Trief, D Rashid, A Rose, MF Minckler, D Vanderveen, D Mukai, S AF Jakobiec, Frederick A. Trief, Danielle Rashid, Alia Rose, Matthew F. Minckler, Don Vanderveen, Deborah Mukai, Shizuo TI New Insights Into the Development of Infantile Intraocular Medulloepithelioma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CILIARY BODY MEDULLOEPITHELIOMA; MALIGNANT TERATOID MEDULLOEPITHELIOMA; OF-THE-LITERATURE; ABUNDANT NEUROPIL; TRUE ROSETTES; OPTIC-NERVE; PERIPHERAL MEDULLOEPITHELIOMA; PIGMENTED MEDULLOEPITHELIOMA; CEREBRAL MEDULLOEPITHELIOMA; HISTOPATHOLOGIC CORRELATION AB PURPOSE: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas. DESIGN: Retrospective clinicohistopathologic and immunohistochemical study. METHODS: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins. RESULTS: Three infants (aged 1, 6, and 8 months) had iris neovascularization, 2 had anterior ciliary body tumors, and 1 a posterior tumor associated with a retinochoroidal coloboma. Each tumor displayed a premedullary monolayer of cuboidal epithelium that was S100(+), NeuN(-), and CRX- and that transitioned into a multilaminar medullary epithelium forming neurotubules with adluminal cells that were CRX+. NeuN first appeared in ablumenal neurotubular cells in 1 tumor and was also discovered among neuroblast-appearing cells in another. The third tumor associated with a coloboma was CRX- and NeuN(-). CONCLUSIONS: A simple premedullary epithelial monolayer appears to be the fundamental source for the tumor and its multilaminar medullary epithelium. CRX+ and NeuN(+) cells within the multilayered medullary layer approximate expression patterns similar to those found in retinal development and differentiation. Discovery of these biomarkers in the neoplastic ciliary epithelium in a small number of tumors indicates preliminarily that the most anterior layers of the optic cup have a retained retinal and neuroglial differentiation potentiality. The third case was CRX- and NeuN(-) and possibly arose from embryonic pigment epithelium at the edge of the retinochoroidal coloboma. These immunohistochemical findings offer histogenetic and potential diagnostic insights. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Trief, Danielle; Rashid, Alia; Vanderveen, Deborah; Mukai, Shizuo] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Rose, Matthew F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Minckler, Don] Univ Calif Irvine, Sch Med, Dept Ophthalmol, Irvine, CA 92717 USA. [Vanderveen, Deborah] Childrens Hosp, Dept Ophthalmol, Childrens Refract Serv, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Suite 328,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu OI Rose, Matthew/0000-0002-1148-4130 FU Mukai Fund of the Massachusetts Eye and Ear Infirmary FX S.M. reports partial funding from the Mukai Fund of the Massachusetts Eye and Ear Infirmary. NR 57 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2014 VL 158 IS 6 BP 1275 EP 1296 DI 10.1016/j.ajo.2014.08.036 PG 22 WC Ophthalmology SC Ophthalmology GA AU8AZ UT WOS:000345820400025 PM 25174896 ER PT J AU Beamer, G Major, S Das, B Campos-Neto, A AF Beamer, Gillian Major, Samuel Das, Bikul Campos-Neto, Antonio TI Bone Marrow Mesenchymal Stem Cells Provide an Antibiotic-Protective Niche for Persistent Viable Mycobacterium tuberculosis that Survive Antibiotic Treatment SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MICROBIAL ENUMERATION TECHNIQUE; IN-VIVO; LATENT TUBERCULOSIS; MOUSE TISSUES; INFECTION; FATE; REACTIVATION; RESPONSES; BACILLI; TARGET AB During tuberculosis (TB), some Mycobacterium tuberculosis bacilli persist in the presence of an active immunity and antibiotics that are used to treat the disease. Herein, by using the Cornell model of TB persistence, we further explored our recent finding that suggested that M. tuberculosis can escape therapy by residing in the bone marrow (BM) mesenchymal stem cells. We initially showed that M. tuberculosis rapidly disseminates to the mouse BM after aerosol exposure and maintained a stable burden for at least 220 days. In contrast, in the Lungs, the M. tuberculosis burden peaked at 28 days and subsequently declined approximately 10-fold. More important, treatment of the mice with the antibiotics rifampicin and isoniazid, as expected, resulted in effective clearance of M. tuberculosis from the lungs and spleen. In contrast, M. tuberculosis persisted, albeit at low numbers, in the BM of antibiotic-treated mice. Moreover, most viable M. tuberculosis was recovered from the bone marrow CD271(+)CD45(-)-enriched cell fraction, and only few viable bacteria could be isolated from the CD271(-)CD45(+) cell fraction. These results clearly show that BM mesenchymal stem cells provide an antibiotic-protective niche for M. tuberculosis and suggest that unraveling the mechanisms underlying this phenomenon will enhance our understanding of M. tuberculosis persistence in treated TB patients. C1 [Beamer, Gillian; Major, Samuel] Tufts Univ, Cummings Sch Vet Med, Dept Infect Dis & Global Hlth, Grafton, MA USA. [Das, Bikul; Campos-Neto, Antonio] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA USA. [Das, Bikul] Indian Inst Technol, KaviKrishna Lab, Gauhati, India. RP Beamer, G (reprint author), Cummings Sch Vet Med, 200 Westboro Rd, Grafton, MA 01581 USA. EM gillian.beamer@tufts.edu; acampos@forsyth.org FU NIH grants [R01AI076425, R56 AI111823]; Cummings School of Veterinary Medicine (Tufts University); KaviKrishna Foundation (Sualkuchi, Assam, India) FX Supported by NIH grants R01AI076425 (A.C-N.) and R56 AI111823 (A.C.-N. and G.B.), The Cummings School of Veterinary Medicine (Tufts University), and by the KaviKrishna Foundation (Sualkuchi, Assam, India). NR 24 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2014 VL 184 IS 12 BP 3170 EP 3175 DI 10.1016/j.ajpath.2014.08.024 PG 6 WC Pathology SC Pathology GA AW0AQ UT WOS:000345953300003 PM 25451154 ER PT J AU Bakirtzi, K West, G Fiocchi, C Law, IKM Iliopoulos, D Pothoulakis, C AF Bakirtzi, Kyriaki West, Gail Fiocchi, Claudio Law, Ivy Ka Man Iliopoulos, Dimitrios Pothoulakis, Charalabos TI The Neurotensin-HIF-1 alpha-VEGF alpha Axis Orchestrates Hypoxia, Colonic Inflammation, and Intestinal Angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BOWEL-DISEASE PATHOGENESIS; ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR PROTEIN; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; EPITHELIAL-CELLS; CROHNS-DISEASE; FACTOR-I; NEUROTENSIN; EXPRESSION AB The expression of neurotensin (NT) and its receptor (NTR1) is up-regulated in experimental colitis and inflammatory bowel disease; NT/NTR1 interactions regulate gut inflammation. During active inflammation, metabolic shifts toward hypoxia lead to the activation of hypoxia-inducible factor (HIF)-1, which enhances vascular endothelial growth factor (VEGF) expression, promoting angiogenesis. We hypothesized that NT/NTR1 signaling regulates intestinal manifestations of hypoxia and angiogenesis by promoting HIF-1 transcriptional activity and VEGF alpha expression in experimental colitis. We studied NTR1 signaling in colitis-associated angiogenesis using 2,4,6-trinitrobenzenesulfonic acid-treated wild-type and NTR1-knockout mice. The effects of NT on HIF-1 alpha and VEGF alpha were assessed on human colonic epithelial cells overexpressing NTR1 (NCM460-NTR1) and human intestinal microvascutar-endothelial cells. NTR1-knockout mice had reduced microvascular density and mucosal integrity score compared with wild-type mice after 2,4,6-trinitrobenzenesulfonic acid treatment. VEGFa mRNA levels were increased in NCM460-NTR1 cells treated with 10(-7) mol/L NT, at 1 and 6 hours post-treatment. NT exposure in NCM460-NTR1 cells caused stabilization, nuclear translocation, and transcriptional activity of HIF-1 alpha in a diacylglycerol kinase-dependent manner. NT did not stimulate tube formation in isolated human intestinal macrovascular endothelial cells but did so in human intestinal macrovascular endothelial cells cocultured with NCM460-NTR1 cells. Our results demonstrate the importance of an NTR1-HIF1 alpha VEGF alpha axis in intestinal angiogenic responses and in the pathophysiology of colitis and inflammatory bowel disease. C1 [Bakirtzi, Kyriaki; Law, Ivy Ka Man; Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90095 USA. [West, Gail; Fiocchi, Claudio] Cleveland Clin Fdn, Dept Pathobiol, Lerner Res Inst, Cleveland, OH 44195 USA. [West, Gail; Fiocchi, Claudio] Cleveland Clin Fdn, Dept Gastroenterol & Hepatol, Inst Digest Dis, Cleveland, OH 44195 USA. [Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Pothoulakis, C (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, 675 Charles E Young Dr,S MRL Bldg 1240, Los Angeles, CA 90095 USA. EM cpothoulakis@mdenet.ucla.edu FU NIH [DK60729, 1P50 DK64539, 47373, DK50984, DK69854]; Crohn's and Colitis Foundation of America, Inc.; Blinder Research Foundation for Crohn's Disease; Morphology and Cell Imaging Core of the CURE Center [CURE:DDRCC DK41301] FX Supported by grants from the NIH (DK60729, 1P50 DK64539, and DK 47373 to C.P.; DK50984 and DK69854 to C.F.), a fellowship grant award from the Crohn's and Colitis Foundation of America, Inc. (K.B.), the Blinder Research Foundation for Crohn's Disease (I.K.M.L.), and the Morphology and Cell Imaging Core of the CURE Center (CURE:DDRCC DK41301). NR 54 TC 8 Z9 8 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2014 VL 184 IS 12 BP 3405 EP 3414 DI 10.1016/j.ajpath.2014.08.015 PG 10 WC Pathology SC Pathology GA AW0AQ UT WOS:000345953300023 PM 25307345 ER PT J AU Perlis, RH AF Perlis, Roy H. TI From Bench to Bedlam SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. EM rperlis@chgr.mgh.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2014 VL 171 IS 12 BP 1233 EP 1235 DI 10.1176/appi.ajp.2014.14091198 PG 3 WC Psychiatry SC Psychiatry GA AU7ZU UT WOS:000345817500001 PM 25756761 ER PT J AU Simon, KC Eberly, S Gao, X Oakes, D Tanner, CM Shoulson, I Fahn, S Schwarzschild, MA Ascherio, A AF Simon, Kelly Claire Eberly, Shirley Gao, Xiang Oakes, David Tanner, Caroline M. Shoulson, Ira Fahn, Stanley Schwarzschild, Michael A. Ascherio, Alberto CA Parkinson Study Grp TI Mendelian Randomization of Serum Urate and Parkinson Disease Progression SO ANNALS OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; URIC-ACID CONCENTRATION; BLOOD-BRAIN-BARRIER; CLINICAL-TRIAL; RISK; TRANSPORTER; SLC2A9; GOUT; GENES; ABCG2 AB ObjectiveHigher serum urate concentrations predict more favorable prognosis in individuals with Parkinson disease (PD). The purpose of this study was to test the causality of this association using a Mendelian randomization approach. MethodsThe study was conducted among participants in DATATOP and PRECEPT, 2 randomized trials among patients with early PD. The 808 patients with available DNA were genotyped for 3 SLC2A9 single nucleotide polymorphisms (SNPs) that identify an allele associated with lower urate concentrations, and for selected SNPs in other genes encoding urate transporters that have modest or no effect on serum urate levels. An SLC2A9 score was created based on the total number of minor alleles at the 3 SLC2A9 loci. Primary outcome was disability requiring dopaminergic treatment. ResultsSerum urate concentrations were 0.69mg/dl lower among individuals with 4 SLC2A9 minor alleles as compared to those with 2 (p=0.0002). The hazard ratio (HR) for progression to disability requiring dopaminergic treatment increased with increasing SLC2A9 score (HR=1.16, 95% confidence interval [CI]=1.00-1.35, p=0.056). In a comparative analysis, the HR was 1.27 (95% CI=1.00-1.61, p=0.0497) for a 0.5mg/dl genetically conferred decrease in serum urate, and 1.05 (95% CI=1.01-1.10, p=0.0133) for a 0.5mg/dl decrease in measured serum urate. No associations were found between polymorphisms in other genes associated with urate that do not affect serum urate and PD progression. InterpretationThis Mendelian randomization analysis adds to the evidence of a causal protective effect of high urate levels. Ann Neurol 2014;76:862-868 C1 [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Eberly, Shirley; Oakes, David] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Shoulson, Ira] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Fahn, Stanley] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 667 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02115 USA. EM aascherio@hsph.harvard.edu FU NIH National Institute of Neurological Diseases and Stroke [K24NS060991, R01NS061858]; Department of Defense [W81XWH-11-1-0150]; Parkinson Study Group, University of Rochester; Lundbeck Pharmaceuticals; Parkinson Disease Foundation FX This work was supported by the NIH National Institute of Neurological Diseases and Stroke (K24NS060991, M.A.S.; R01NS061858, A.A.); the Department of Defense (W81XWH-11-1-0150, M.A.S.); the Parkinson Study Group, University of Rochester; Lundbeck Pharmaceuticals; and the Parkinson Disease Foundation. We thank Cephalon (Teva Pharmaceutical Industries) and Lundbeck for providing access to the data from PRECEPT and technical support. NR 38 TC 17 Z9 17 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2014 VL 76 IS 6 BP 862 EP 868 DI 10.1002/ana.24281 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU6BN UT WOS:000345687600010 PM 25257975 ER PT J AU Fullerton, DA Sundt, TM AF Fullerton, David A. Sundt, Thoralf M. TI Process Versus Outcome: The Sugar Window SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID CARE IMPROVEMENT PROJECT; CRITICALLY-ILL PATIENTS; GLUCOSE CONTROL; GLYCEMIC CONTROL; CARDIAC-SURGERY; WOUND-INFECTION; QUALITY C1 [Fullerton, David A.] Univ Colorado, Div Cardiothorac Surg, Sch Med, Aurora, CO 80045 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Fullerton, DA (reprint author), Univ Colorado, Div Cardiothorac Surg, Sch Med, 12631 E 17th Ave,MS C-310,Rm 6602, Aurora, CO 80045 USA. EM david.fullerton@ucdenver.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 1902 EP 1904 DI 10.1016/j.athoracsur.2014.09.039 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200010 PM 25468080 ER PT J AU Backhus, LM Farjah, F Zeliadt, SB Varghese, TK Cheng, A Kessler, L Au, DH Flum, DR AF Backhus, Leah M. Farjah, Farhood Zeliadt, Steven B. Varghese, Thomas K. Cheng, Aaron Kessler, Larry Au, David H. Flum, David R. TI Predictors of Imaging Surveillance for Surgically Treated Early-Stage Lung Cancer SO ANNALS OF THORACIC SURGERY LA English DT Article ID FOLLOW-UP; CURATIVE INTENT; UNITED-STATES; COLORECTAL-CANCER; CLINICAL-PRACTICE; SURVIVORS; RESECTION; ROUTINE; RECURRENCE; SURGERY AB Background. Current guidelines recommend routine imaging surveillance for patients with non-small cell lung cancer (NSCLC) after treatment. Little is known about surveillance patterns for patients with surgically resected early-stage lung cancer in the community at large. We sought to characterize surveillance patterns in a national cohort. Methods. We conducted a retrospective study using the Surveillance, Epidemiology, and End-Results (SEER)Medicare database (1995-2010). Patients with stage I/II NSCLC treated with surgical resection were included. Our primary outcome was receipt of imaging between 4 and 8 months after the surgical procedure. Covariates included demographics and comorbidities. Results. Chest radiography (CXR) was the most frequent initial modality (60%), followed by chest computed tomography (CT) (25%). Positron emission tomography (PET) was least frequent as an initial imaging modality (3%). A total of 13% of patients received no imaging within the initial surveillance period. Adherence to National Comprehensive Cancer Network (NCCN) guidelines for imaging by overall prevalence was 47% for receipt of CT; however, rates of CT increased over time from 28% to 61% (p < 0.01). Reduced rates of CT were associated with stage I disease and surgical resection as the sole treatment modality. Conclusions. Imaging after definitive surgical treatment for NSCLC predominantly used CXR rather than CT. Most of this imaging is likely for surveillance, and in that context CXR has inferior detection rates for recurrence and new cancers. Adherence to guideline-recommended CT surveillance after surgical treatment is poor, but the reasons are multifactorial. Efforts to improve adherence to imaging surveillance must be coupled with greater evidence demonstrating improved long-term outcomes. (C) 2014 by The Society of Thoracic Surgeons C1 VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Univ Washington, Dept Surg, Div Cardiothorac Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Sch Publ Hlth, Dept Med, Dept Hlth Serv,Div Pulm & Crit Care, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. RP Backhus, LM (reprint author), Univ Washington, Dept Surg, Div Cardiothorac Surg, 1959 NE Pacific St, Seattle, WA 98195 USA. EM lbackhus@u.washington.edu FU NIH/NCATS National Center for Research Resources [2 KL2 TR000421-06 KL2] FX This work was funded by NIH/NCATS National Center for Research Resources 2 KL2 TR000421-06 KL2 Scholar ITHS Multidisciplinary Clinical Research Training Program. Views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. NR 41 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 1944 EP 1952 DI 10.1016/j.athoracsur.2014.06.067 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200017 PM 25282167 ER PT J AU Calhoon, JH Baisden, C Holler, B Hicks, GL Bove, EL Wright, CD Merrill, WH Fullerton, DA AF Calhoon, John H. Baisden, Clint Holler, Ben Hicks, George L. Bove, Ed L. Wright, Cameron D. Merrill, Walter H. Fullerton, Dave A. TI Thoracic Surgical Resident Education: A Costly Endeavor SO ANNALS OF THORACIC SURGERY LA English DT Article ID PRICE AB Background. We sought to define an accurate measure of thoracic surgical education costs. Methods. Program directors from six distinct and differently sized and geographically located thoracic surgical training programs used a common template to provide estimates of resident educational costs. These data were reviewed, clarifying questions or discrepancies when noted and using best estimates when exact data were unavailable. Subsequently, a composite of previously published cost-estimation products was used to capture accurate cost data. Data were then compiled and averaged to provide an accurate picture of all costs associated with thoracic surgical education. Results. Before formal accounting was performed, the estimated average for all programs was approximately $ 250,000 per year per resident. However, when formal evaluations by the six programs were performed, the annual cost of resident education ranged from $ 330,000 to $ 667,000 per year per resident. The average cost of $ 483,000 per year was almost double the initial estimates. Variability was noted by region and size of program. Faculty teaching costs varied from $ 208,000 to $ 346,000 per year. Simulation costs ranged from $ 0 to $ 80,000 per year. Resident savings to program ranged from $ 0 to $ 135,000 per year and averaged $ 37,000 per year per resident. Conclusions. Thoracic surgical education costs are considerably higher than initial estimates from program directors and probably represent an unappreciated source of financial burden for cardiothoracic surgical educational programs. (C) 2014 by The Society of Thoracic Surgeons. C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Cardiothorac Surg, San Antonio, TX 78229 USA. Univ Rochester, Div Cardiothorac Surg, Rochester, NY USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Univ Mississippi, Div Cardiothorac Surg, Jackson, MS 39216 USA. Univ Colorado, Div Cardiothorac Surg, Denver, CO 80202 USA. RP Calhoon, JH (reprint author), Dept Cardiothorac Surg, UTHSCSA,7703 Floyd Curl Dr,MC 7841,Ste 211L, San Antonio, TX 78229 USA. EM calhoon@uthscsa.edu NR 5 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 2012 EP 2015 DI 10.1016/j.athoracsur.2014.07.044 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200026 PM 25443008 ER PT J AU Brennan, JM Holmes, DR Sherwood, MW Edwards, FH Carroll, JD Grover, FL Tuzcu, M Thourani, V Brindis, RG Shahian, DM Svensson, LG O'Brien, SM Shewan, CM Hewitt, K Gammie, JS Rumsfeld, JS Peterson, ED Mack, MJ AF Brennan, J. Matthew Holmes, David R. Sherwood, Matthew W. Edwards, Fred H. Carroll, John D. Grover, Fred L. Tuzcu, Murat Thourani, Vinod Brindis, Ralph G. Shahian, David M. Svensson, Lars G. O'Brien, Sean M. Shewan, Cynthia M. Hewitt, Kathleen Gammie, James S. Rumsfeld, John S. Peterson, Eric D. Mack, Michael J. TI The Association of Transcatheter Aortic Valve Replacement Availability and Hospital Aortic Valve Replacement Volume and Mortality in the United States SO ANNALS OF THORACIC SURGERY LA English DT Article ID LEARNING-CURVE; IMPLANTATION; STENOSIS; OUTCOMES; THERAPY; IMPACT AB Background. Whether the introduction of transcatheter aortic valve replacement (TAVR) has affected hospitals' surgical aortic valve replacement (SAVR) and overall aortic valve replacement (AVR) case volumes and outcomes in the United States is unknown. Methods. We utilized data from The Society of Thoracic Surgeons (STS) adult cardiac surgery database and the STS/American College of Cardiology (ACC) transcatheter valve therapies registry to examine SAVR and TAVR procedures. Temporal trends in total case volume (SAVR plus TAVR), and observed and risk-adjusted in-hospital mortality rates were assessed among low-risk cases (STS predicted risk of operative mortality < 4%), intermediaterisk cases (4% to 8%), and high-risk cases (> 8%). A contemporary control was provided by non-TAVR centers. Results. From 2008 to 2013, the total annual volume of AVR among 246 TAVR-performing hospitals increased from 19,578 to 33,004, with a 22% growth in SAVR volumes; non-TAVR hospital (n = 555) increases were more modest (16,563 to 19,134; 16% growth). Expanded volumes at TAVR hospitals included increased SAVR use in low and intermediate-risk cases, and TAVR use in high-risk cases. In parallel, in-hospital mortality for all AVR procedures at TAVR sites declined from 3.4% to 2.9% (observed to expected [O:E] ratio 0.75 to 0.58, p < 0.001); the greatest declines were among intermediate-and high-risk SAVR patients. Owing to reduced SAVR mortality, TAVR centers experienced a significantly greater decline in O:E ratio for high-risk patient in-hospital mortality than non-TAVR centers (TAVR center O:E ratio, 0.81 to 0.61; non-TAVR center O:E ratio, 0.85 to 0.76; p < 0.001). After approval of TAVR for clinical use, a trend toward higher in-hospital mortality rates and O:E ratios for TAVR procedures was observed at new (but not at established) TAVR centers (O:E ratio, 0.41 to 0.67; p = 0.08). Conclusions. Since the introduction of TAVR, the total volume of AVR procedures, including higher overall use of SAVR, at TAVR sites has significantly increased in the United States. Overall, in-hospital survival of patients undergoing treatment for aortic valve stenosis continues to improve. (C) 2014 by The Society of Thoracic Surgeons. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Mayo Clin, Rochester, MN USA. Univ Florida, Jacksonville, FL USA. Denver VA Med Ctr, Denver, CO USA. Cleveland Clin, Cleveland, OH 44106 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Soc Thorac Surg, Chicago, IL USA. Amer Coll Cardiol, Washington, DC USA. Univ Maryland, Baltimore, MD 21201 USA. Baylor Healthcare Syst, Heart Hosp Baylor Plano, Plano, TX USA. RP Brennan, JM (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27715 USA. EM j.matthew.brennan@dm.duke.edu FU Society of Thoracic Surgeons; American College of Cardiology Foundation Research and Publications Committee FX The authors would like to thank Sarah Milford-Beland, MS, who served as the primary data analyst, and Erin Hanley, MS, who provided editorial support. Neither Ms Milford-Beland nor Ms Hanley received compensation for their contributions, apart from their employment at the institution where this study was conducted. This research was supported by The Society of Thoracic Surgeons and the American College of Cardiology Foundation Research and Publications Committee. The views expressed in this manuscript represent those of the authors, and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. NR 13 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 2016 EP 2022 DI 10.1016/j.athoracsur.2014.07.051 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200027 PM 25443009 ER PT J AU Di Eusanio, M Trimarchi, S Peterson, MD Myrmel, T Hughes, GC Korach, A Sundt, TM Di Bartolomeo, R Greason, K Khoynezhad, A Appoo, JJ Folesani, G De Vincentiis, C Montgomery, DG Isselbacher, EM Eagle, KA Nienaber, CA Patel, HJ AF Di Eusanio, Marco Trimarchi, Santi Peterson, Mark D. Myrmel, Truls Hughes, G. Chad Korach, Amit Sundt, Thoralf M. Di Bartolomeo, Roberto Greason, Kevin Khoynezhad, Ali Appoo, Jehangir J. Folesani, Gianluca De Vincentiis, Carlo Montgomery, Daniel G. Isselbacher, Eric M. Eagle, Kim A. Nienaber, Christoph A. Patel, Himanshu J. TI Root Replacement Surgery Versus More Conservative Management During Type A Acute Aortic Dissection Repair SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTERNATIONAL REGISTRY; VALVE; RECONSTRUCTION; PRESERVATION; REOPERATION; IRAD; FATE AB Background. Aortic root management in type A acute aortic dissection is controversial. This study compared outcomes of root replacement (RR) interventions versus more conservative root (CR) management. Methods. Of 1,995 type A acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection, 699 (35%) underwent RR interventions and 1,296 (65%) underwent CR management. Independent predictors of hospital and 3-year survival were identified using multivariable logistic and Cox regression models. Results. Compared with CR patients, RR patients were younger (56.9 versus 62.3 years; p = 0.023) and more likely to present with larger root diameter (4.7 cm versus 4.0 cm; p < 0.001), Marfan syndrome (8.7% versus 2.5%; p < 0.001), aortic insufficiency (64.0% versus 50.3%; p < 0.001), and hypotension, shock, or tamponade (33.0% versus 26.5%; p = 0.003). Root replacement management did not increase hospital mortality (propensity score-adjusted odds ratio, 1.14; p = 0.674). On Kaplan-Meier analysis, 3-year survival (RR, 92.5% +/- 1.7% versus CR, 91.6% +/- 1.3%; log-rank p = 0.623) and freedom from aortic root reintervention (RR, 99.2% +/- 0.1% versus CR, 99.3% +/- 0.1%; log-rank p = 0.770) were similar. Only 2 patients (1 per group) underwent follow-up root reintervention. Propensity score-adjusted Cox regression excluded a relationship between root treatment and follow-up survival (hazard ratio, 1.5; 95% confidence interval, 0.502 to 5.010; p = 0.432). Conclusions. In type A acute aortic dissection patients more-extensive RR interventions are not associated with increased hospital mortality. This supports such an approach in young patients and patients with connective tissue diseases and bicuspid aortic valves. Excellent midterm survival and freedom from root reintervention in both groups suggest stable behavior of the nonreplaced aortic sinuses at 3 years. Thus, pending studies with longer follow-up, the use of aggressive RR techniques can be determined by patient-specific and dissection-related factors. (C) 2014 by The Society of Thoracic Surgeons C1 Univ Hosp S Orsola, Dept Cardiac Surg, Bologna, Italy. IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. Univ Tromso Hosp, Dept Thorac & Cardiovasc Surg, N-9012 Tromso, Norway. Duke Univ, Med Ctr, Div Thorac & Cardiovasc Surg, Durham, NC USA. Hadassah Hebrew Univ, Med Ctr, Dept Cardiothorac Surg, Jerusalem, Israel. Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Cedars Sinai Med Ctr, Div Cardiothorac Surg, Los Angeles, CA 90048 USA. Univ Calgary, Med Ctr, Div Cardiac Surg, Calgary, AB, Canada. Univ Michigan Hlth Syst, Ctr Cardiovasc, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. RP Di Eusanio, M (reprint author), Univ Bologna, Alma Mater Studiorum, St Orsola Malpighi Hosp, Cardiac Surg Div,Dept Expt Diagnost & Specialty M, Via Massarenti 9,PAD 25, I-40128 Bologna, Italy. EM marco.dieusanio2@unibo.it RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; di bartolomeo, roberto/0000-0003-3965-5779 FU W.L. Gore & Associates, Inc; Medtronic; Varbedian Aortic Research Fund; Hewlett Foundation; Mardigian Foundation; UM Faculty Group Practice; Terumo; Robert; Anne Aikens FX IRAD is funded by W.L. Gore & Associates, Inc, Medtronic, Varbedian Aortic Research Fund, Hewlett Foundation, Mardigian Foundation, UM Faculty Group Practice, Terumo, Robert and Anne Aikens. Authors had full control of the design of the study, methods used, outcome parameters and results, analysis of data, and the production of the written report. NR 23 TC 14 Z9 14 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 2078 EP 2085 DI 10.1016/j.athoracsur.2014.06.070 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200035 PM 25282163 ER PT J AU Sayegh, P Arentoft, A Thaler, NS Dean, AC Thames, AD AF Sayegh, Philip Arentoft, Alyssa Thaler, Nicholas S. Dean, Andy C. Thames, April D. TI Quality of Education Predicts Performance on the Wide Range Achievement Test-4th Edition Word Reading Subtest SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Literacy; Academic achievement; Neurocognition; High schools; Multiple regression; Test validity ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; AFRICAN-AMERICAN ELDERS; LEVEL AB The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature. C1 [Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.; Dean, Andy C.; Thames, April D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,C8-226, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu OI Arentoft, Alyssa/0000-0002-4235-4638 FU National Institutes of Health (National Institute of Mental Health) [K23 MH095661] FX This work was supported by the National Institutes of Health (National Institute of Mental Health) Career Development Award (grant number K23 MH095661) to A.D.T. NR 17 TC 4 Z9 4 U1 4 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 731 EP 736 DI 10.1093/arclin/acu059 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900001 PM 25404004 ER PT J AU Harrison, AG Armstrong, IT Harrison, LE Lange, RT Iverson, GL AF Harrison, Allyson G. Armstrong, Irene T. Harrison, Laura E. Lange, Rael T. Iverson, Grant L. TI Comparing Canadian and American Normative Scores on the Wechsler Adult Intelligence Scale-Fourth Edition SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Wechsler adult intelligence scale-IV; Normative systems; Canadian norms; Assessment ID WAIS-III; PERFORMANCE; IV; INDIVIDUALS; LEVEL AB Psychologists practicing in Canada must decide which set of normative data to use for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). The purpose of this study was to compare the interpretive effects of applying American versus Canadian normative systems in a sample of 432 Canadian postsecondary-level students who were administered the WAIS-IV as part of an evaluation for a learning disability, attention-deficit hyperactivity disorder, or other mental health problems. Employing the Canadian normative system yielded IQ, Index, and subtest scores that were systematically lower than those obtained using the American norms. Furthermore, the percentage agreement in normative classifications, defined as American and Canadian index scores within five points or within the same classification range, was between 49% and 76%. Substantial differences are present between the American and Canadian WAIS-IV norms. Clinicians should consider carefully the implications regarding which normative system is most appropriate for specific types of evaluations. C1 [Harrison, Allyson G.; Armstrong, Irene T.; Harrison, Laura E.] Queens Univ, Reg Assessment & Resource Ctr, Kingston, ON K7L 3N6, Canada. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Lange, Rael T.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Iverson, Grant L.] Copeman Healthcare Ctr, Vancouver, BC, Canada. RP Harrison, AG (reprint author), Queens Univ, Reg Assessment & Resource Ctr, Mackintosh Corry Hall,B10068,Univ Ave, Kingston, ON K7L 3N6, Canada. EM harrisna@queensu.ca FU Ministry of Training, Colleges, and Universities (MTCU) of Ontario FX This work was supported in part by funding from the Ministry of Training, Colleges, and Universities (MTCU) of Ontario. The views expressed in this paper do not necessarily reflect those of MTCU. NR 37 TC 4 Z9 4 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 737 EP 746 DI 10.1093/arclin/acu048 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900002 PM 25313225 ER PT J AU Patrick, RE Horner, MD AF Patrick, Regan E. Horner, Michael D. TI Psychological Characteristics of Individuals Who Put Forth Inadequate Cognitive Effort in a Secondary Gain Context SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Malingering; Test validity; Neuropsychological assessment; Behavioral economics; Minnesota multiphasic personality inventory; Personality processes ID SYMPTOM VALIDITY TESTS; MALINGERED NEUROCOGNITIVE DYSFUNCTION; RESPONSE BIAS SCALE; MMPI-2-RF VALIDITY; MENTAL-RETARDATION; FORENSIC SETTINGS; MILITARY SAMPLE; TEST FAILURE; CHRONIC PAIN; RC SCALES AB The current study sought to characterize the psychological architecture of individuals who put forth inadequate effort. The Minnesota Multiphasic Personality Inventory, 2nd Edition-Restructured Form was used to identify dimensions of psychological functioning in a mixed outpatient sample of U.S. Veterans referred for neuropsychological evaluation as part of their clinical care. After accounting for external financial incentive and symptom overreporting, results showed that the inadequate effort group (n = 23, mean age = 42.48) scored higher than the adequate effort group (n = 29, mean age = 44.31) on neurologic complaints (NUC) and lower on behavioral/externalizing dysfunction (BXD), antisocial behaviors (RC4), and disconstraint (DISC-r). Lower scores on BXD, RC4, and DISC-r could indicate higher behavioral constraint-a psychological characteristic that has been linked to the pursuit of high-value future rewards. Alternatively, lower scores on these scales could have reflected a self-presentation strategy aimed at minimizing externalizing and RC4 in order to appear more psychological healthy. Implications of each of these interpretations are discussed. C1 [Patrick, Regan E.; Horner, Michael D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Patrick, Regan E.; Horner, Michael D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Patrick, RE (reprint author), McLean Hosp, Dept Neuropsychol, 115 Mill St,Mailstop 234, Belmont, MA 02452 USA. EM rpatrick@partners.org NR 60 TC 0 Z9 0 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 754 EP 766 DI 10.1093/arclin/acu054 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900004 PM 25318597 ER PT J AU Barsuglia, JP Kaiser, NC Wilkins, SS Joshi, A Barrows, RJ Paholpak, P Panchal, HV Jimenez, EE Mather, MJ Mendez, MF AF Barsuglia, Joseph P. Kaiser, Natalie C. Wilkins, Stacy Schantz Joshi, Aditi Barrows, Robin J. Paholpak, Pongsatorn Panchal, Hemali Vijay Jimenez, Elvira E. Mather, Michelle J. Mendez, Mario F. TI A Scale of Socioemotional Dysfunction in Frontotemporal Dementia SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Dementia; Neurodegenerative diseases; Social behavior; Behavioral assessment; Semantic dementia; Presenile dementia ID ONSET ALZHEIMERS-DISEASE; BEHAVIORAL VARIANT; DIAGNOSTIC-CRITERIA; SOCIAL COGNITION; CLINICAL-DIAGNOSIS; LOBAR DEGENERATION; EMOTIONAL ASSESSMENT; OLDER-ADULTS; SENSITIVITY; INVENTORY AB Early social dysfunction is a hallmark symptom of behavioral variant frontotemporal dementia (bvFTD); however, validated measures for assessing social deficits in dementia are needed. The purpose of the current study was to examine the utility of a novel informant-based measure of social impairment, the Socioemotional Dysfunction Scale (SDS) in early-onset dementia. Sixteen bvFTD and 18 early-onset Alzheimer's disease (EOAD) participants received standard clinical neuropsychological measures and neuroimaging. Caregiver informants were administered the SDS. Individuals with bvFTD exhibited greater social dysfunction on the SDS compared with the EOAD group; t(32) = 6.32, p < .001. The scale demonstrated preliminary evidence for discriminating these frequently misdiagnosed groups (area under the curve = 0.920, p = < .001) and internal consistency alpha = 0.977. The SDS demonstrated initial evidence as an effective measure for detecting abnormal social behavior and discriminating bvFTD from EOAD. Future validation is recommended in larger and more diverse patient groups. C1 [Barsuglia, Joseph P.; Kaiser, Natalie C.; Wilkins, Stacy Schantz; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Panchal, Hemali Vijay; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barsuglia, Joseph P.; Kaiser, Natalie C.; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Wilkins, Stacy Schantz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Barsuglia, JP (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM joseph.barsuglia@va.gov FU National Institutes of Health [R01AG034499-04]; VA Geriatric Research Education and Clinical Centers (GRECC) FX This work was supported by the National Institutes of Health (grant number R01AG034499-04); and JPB and NCK were funded through VA Geriatric Research Education and Clinical Centers (GRECC) Advanced Fellowship in Geriatrics Awards. NR 73 TC 5 Z9 5 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 793 EP 805 DI 10.1093/arclin/acu050 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900007 PM 25331776 ER PT J AU Weisberg, E Nonami, A Griffin, JD AF Weisberg, Ellen Nonami, Atsushi Griffin, James D. TI Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies SO ARCHIVES OF TOXICOLOGY LA English DT Review DE ABL inhibitor; Nilotinib; Combination therapy; Leukemia; CML; Ph plus ALL ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; SMALL INTERFERING RNA; IMATINIB-RESISTANT; DASATINIB BMS-354825; CLINICAL RESISTANCE; CHRONIC-PHASE; BLAST CRISIS AB Despite the clinical efficacy achieved with frontline therapies for BCR-ABL-positive disease, such as imatinib and second-generation ABL inhibitors like nilotinib or dasatinib that were originally designed to override insensitivity to imatinib, drug resistance still remains a challenge, especially for patients with advanced-stage chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. The discovery of BCR-ABL point mutations has been a great asset to furthering our understanding of a major cause of drug resistance, as has discovery of multidrug resistance proteins, dysregulation of signaling molecules downstream of BCR-ABL, and insights into the underlying causes of stromal-mediated chemoresistance. Such elucidation of mechanisms of resistance associated with leukemic cell survival is essential for the optimization of current therapies and enhancement of patient survival via delaying or preventing disease recurrence. Here, we present an overview of the use of nilotinib in combination with other agents against BCR-ABL-positive leukemia, as well as solid tumors, for the purpose of increasing clinical efficacy and overriding drug resistance. C1 [Weisberg, Ellen; Nonami, Atsushi; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Ellen_Weisberg@dfci.harvard.edu NR 105 TC 0 Z9 0 U1 1 U2 16 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 EI 1432-0738 J9 ARCH TOXICOL JI Arch. Toxicol. PD DEC PY 2014 VL 88 IS 12 BP 2233 EP 2242 DI 10.1007/s00204-014-1385-5 PG 10 WC Toxicology SC Toxicology GA AU6GG UT WOS:000345701100014 PM 25331939 ER PT J AU Sato, S Richard, ML Brandon, D Buie, JNJ Oates, JC Gilkeson, GS Zhang, XK AF Sato, Shuzo Richard, Mara Lennard Brandon, Danielle Buie, Joy N. Jones Oates, Jim C. Gilkeson, Gary S. Zhang, Xian K. TI A Critical Role of the Transcription Factor Fli-1 in Murine Lupus Development by Regulation of Interleukin-6 Expression SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID MESENCHYMAL STEM-CELLS; B-CELLS; BONE-MARROW; ANTIBODY-PRODUCTION; STROMAL CELLS; ERYTHEMATOSUS; DIFFERENTIATION; MECHANISMS; OAZ; DNA AB Objective. The Fli-1 transcription factor is implicated in the pathogenesis of systemic lupus erythematosus (SLE), both in humans and in animal models. Dysregulation of interleukin-6 (IL-6) is also associated with SLE. The purpose of this study was to investigate whether Fli-1 directly regulates the expression of IL-6. Methods. Sera were collected from wild-type and Fli-1-heterozygous (Fli-1 /) MRL/lpr mice, and the concentration of IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 in the kidney was measured by real-time polymerase chain reaction analysis. T cells were isolated from wild-type and Fli-1 / MRL/lpr mice and stimulated with CD3/CD28 beads, and the concentration of IL-6 in the supernatants was measured by ELISA. MS1 endothelial cells were transfected with Fli-1 and control small interfering RNA, and the production of IL-6 was compared after lipopolysaccharide stimulation. A chromatin immunoprecipitation (ChIP) assay was performed to determine whether Fli-1 binds to the IL-6 promoter region. Transient transfections with the NIH3T3 cell line were performed to examine whether Fli-1 regulates the expression of IL-6. Results. Fli-1 / MRL/lpr mice had significantly decreased IL-6 levels in sera and reduced expression of IL-6 in kidneys as compared to their wild-type littermates. T cells isolated from Fli-1 / MRL/lpr mice produced less IL-6 than did those from wild-type mice. Inhibiting the expression of Fli-1 in endothelial cells resulted in reduced production of IL-6. The ChIP assay revealed direct binding of Fli-1 to 3 regions within the IL-6 promoter. Fli-1 activated transcription from the IL-6 promoter in a dose-dependent manner. Conclusion. The direct regulation of IL-6 expression by Fli-1 represents one possible mechanism for the protective effect of decreased Fli-1 expression in lupus. C1 [Sato, Shuzo; Richard, Mara Lennard; Brandon, Danielle; Buie, Joy N. Jones; Oates, Jim C.; Gilkeson, Gary S.; Zhang, Xian K.] Med Univ S Carolina, Charleston, SC 29425 USA. [Oates, Jim C.; Gilkeson, Gary S.; Zhang, Xian K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU Medical Research Service, Department of Veterans Affairs; NIH [AR-056670] FX Supported in part by the Medical Research Service, Department of Veterans Affairs (grant to Drs. Gilkeson and Zhang) and the NIH (grant AR-056670 to Dr. Zhang). NR 38 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD DEC PY 2014 VL 66 IS 12 BP 3436 EP 3444 DI 10.1002/art.38818 PG 9 WC Rheumatology SC Rheumatology GA AU4HK UT WOS:000345571200021 PM 25155007 ER PT J AU Khamashta, M Merrill, JT Werth, VP Furie, R Kalunian, K Illei, GG Drappa, J Wang, LW Greth, W AF Khamashta, Munther Merrill, Joan T. Werth, Victoria P. Furie, Richard Kalunian, Kenneth Illei, Gabor G. Drappa, Jorn Wang, Liangwei Greth, Warren TI Safety and Efficacy of Sifalimumab, an Anti IFN-Alpha Monoclonal Antibody, in a Phase 2b Study of Moderate to Severe Systemic Lupus Erythematosus (SLE) SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Khamashta, Munther] Kings Coll London, Graham Hughes Lupus Res Lab, London, England. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Furie, Richard] North Shore LIJ Hlth Syst, Lake Success, NY USA. [Kalunian, Kenneth] UCSD, Sch Med, La Jolla, CA USA. [Illei, Gabor G.; Drappa, Jorn; Wang, Liangwei; Greth, Warren] MedImmune LLC, Gaithersburg, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD DEC PY 2014 VL 66 IS 12 MA L4 BP 3530 EP 3531 PG 2 WC Rheumatology SC Rheumatology GA AU4HK UT WOS:000345571200041 ER PT J AU Huang, JT Duncan, CN Boyer, D Khosravi, H Lehmann, LE Saavedra, A AF Huang, J. T. Duncan, C. N. Boyer, D. Khosravi, H. Lehmann, L. E. Saavedra, A. TI Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children SO BONE MARROW TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC GRAFT; CELL TRANSPLANTATION; IMMUNE PRIVILEGE; STEM-CELL; FASCIITIS; MORTALITY; PATIENT AB The prognostic value of adnexal findings in chronic GVHD (cGVHD) has not been investigated in children. Dermatologic examinations were performed in a severe cohort of 11 children with skin cGVHD seen over a 2-year period. Findings were compared with 25 additional patients with skin cGVHD and 97 control patients. In 36 patients with skin cGVHD, nail dystrophy was present in 45% of patients, and was significantly associated with sclerotic disease and lung cGVHD. Pterygium inversum unguis (PIU) was associated with severe lung disease, with significantly lower % predicted FVC and FEV1 in those with PIU than those without. Forty-four percent of GVHD patients had preceding peripheral edema and 56% had preceding peripheral eosinophilia. Peripheral edema and eosinophilia were significantly associated with sclerotic cGVHD and persisted until the diagnosis of cGVHD in all patients. Comparison of data with control patients showed that incidence of nail dystrophy, incidence of peripheral edema and mean peak peripheral eosinophil count of patients with skin cGVHD was significantly higher than those without cGVHD. This study suggests that nail dystrophy, persistent peripheral edema and persistent peripheral eosinophilia are harbingers of severe cGVHD of the skin in children. The presence of PIU may be a harbinger of severe lung involvement. C1 [Huang, J. T.] Boston Childrens Hosp, Dermatol Program, Boston, MA 02115 USA. [Duncan, C. N.; Lehmann, L. E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Boyer, D.] Boston Childrens Hosp, Div Resp Dis, Boston, MA 02115 USA. [Khosravi, H.] Harvard Univ, Sch Med, Boston, MA USA. [Saavedra, A.] Boston Childrens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Huang, JT (reprint author), Boston Childrens Hosp, Dermatol Program, Fegan 6,300 Longwood Ave, Boston, MA 02115 USA. EM jennifer.huang@childrens.harvard.edu NR 20 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2014 VL 49 IS 12 BP 1521 EP 1527 DI 10.1038/bmt.2014.194 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AU9IM UT WOS:000345905300012 PM 25243619 ER PT J AU Andersen, RE Lim, DA AF Andersen, Rebecca E. Lim, Daniel A. TI An ingredient for the elixir of youth SO CELL RESEARCH LA English DT Editorial Material ID COGNITIVE FUNCTION; REJUVENATION; MUSCLE; CELLS AB Emerging evidence indicates that there are factors within the blood of young animals that have the ability to restore youthful characteristics to a number of organ systems in older animals. Growth/differentiation factor 11 (GDF11) is the first of such factors to be identified, and two new studies demonstrate that this "factor of youth" rejuvenates stem cells found in the skeletal muscle and brain of aged mice. C1 [Andersen, Rebecca E.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Andersen, Rebecca E.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Andersen, Rebecca E.] Univ Calif San Francisco, Dev & Stem Cell Biol Grad Program, San Francisco, CA 94143 USA. [Lim, Daniel A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. EM LimD@neurosurg.ucsf.edu FU NICHD NIH HHS [T32 HD007470] NR 10 TC 3 Z9 3 U1 1 U2 27 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD DEC PY 2014 VL 24 IS 12 BP 1381 EP 1382 DI 10.1038/cr.2014.107 PG 2 WC Cell Biology SC Cell Biology GA AU9EP UT WOS:000345894800002 PM 25112712 ER PT J AU Soh, BS Buac, K Xu, HS Li, E Ng, SY Wu, H Chmielowiec, J Jiang, X Bu, L Li, RA Cowan, C Chien, KR AF Soh, Boon-Seng Buac, Kristina Xu, Huansheng Li, Edward Ng, Shi-Yan Wu, Hao Chmielowiec, Jolanta Jiang, Xin Bu, Lei Li, Ronald A. Cowan, Chad Chien, Kenneth R. TI N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment SO CELL RESEARCH LA English DT Article DE N-cadherin; anterior heart field; cardiac progenitor cells; premature differentiation; Wnt signaling; microenvironment ID BETA-CATENIN; STEM-CELLS; CARDIOVASCULAR PROGENITORS; CARDIAC PROGENITORS; OUTFLOW TRACT; ARTERIAL POLE; 2ND HEART; PATHWAY; MUSCLE; EXPRESSION AB The cardiac progenitor cells (CPCs) in the anterior heart field (AHF) are located in the pharyngeal mesoderm (PM), where they expand, migrate and eventually differentiate into major cell types found in the heart, including cardiomyocytes. The mechanisms by which these progenitors are able to expand within the PM microenvironment without premature differentiation remain largely unknown. Through in silico data mining, genetic loss-of-function studies, and in vivo genetic rescue studies, we identified N-cadherin and interaction with canonical Wnt signals as a critical component of the microenvironment that facilitates the expansion of AHF-CPCs in the PM. CPCs in N-cadherin mutant embryos were observed to be less proliferative and undergo premature differentiation in the PM. Notably, the phenotype of N-cadherin deficiency could be partially rescued by activating Wnt signaling, suggesting a delicate functional interaction between the adhesion role of N-cadherin and Wnt signaling in the early PM microenvironment. This study suggests a new mechanism for the early renewal of AHF progenitors where N-cadherin provides additional adhesion for progenitor cells in the PM, thereby allowing Wnt paracrine signals to expand the cells without premature differentiation. C1 [Soh, Boon-Seng; Buac, Kristina; Xu, Huansheng; Li, Edward; Wu, Hao; Chmielowiec, Jolanta; Jiang, Xin; Bu, Lei; Cowan, Chad; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Soh, Boon-Seng; Buac, Kristina; Xu, Huansheng; Ng, Shi-Yan; Wu, Hao; Chmielowiec, Jolanta; Jiang, Xin; Bu, Lei; Cowan, Chad; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Soh, Boon-Seng; Buac, Kristina; Xu, Huansheng; Ng, Shi-Yan; Wu, Hao; Chmielowiec, Jolanta; Jiang, Xin; Bu, Lei; Cowan, Chad; Chien, Kenneth R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Soh, Boon-Seng; Xu, Huansheng; Bu, Lei; Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Hong Kong, Hong Kong, Peoples R China. [Soh, Boon-Seng; Xu, Huansheng; Bu, Lei; Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Dept Physiol, Hong Kong, Hong Kong, Peoples R China. [Soh, Boon-Seng; 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. [Li, Ronald A.] Mt Sinai Sch Med, Ctr Cardiovasc Res, New York, NY 10029 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM kenneth.chien@ki.se 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 28 TC 5 Z9 5 U1 1 U2 10 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD DEC PY 2014 VL 24 IS 12 BP 1420 EP 1432 DI 10.1038/cr.2014.142 PG 13 WC Cell Biology SC Cell Biology GA AU9EP UT WOS:000345894800007 PM 25367124 ER PT J AU Robertson, JFR Lindemann, J Garnett, S Anderson, E Nicholson, RI Kuter, I Gee, JMW AF Robertson, John F. R. Lindemann, Justin Garnett, Sally Anderson, Elizabeth Nicholson, Robert I. Kuter, Irene Gee, Julia M. W. TI A Good Drug Made Better: The Fulvestrant Dose-Response Story SO CLINICAL BREAST CANCER LA English DT Review DE Advanced breast cancer; Endocrine therapy; Estrogen receptor; Postmenopausal; Tumor biomarkers ID ADVANCED BREAST-CANCER; FIRST-LINE THERAPY; NONSTEROIDAL AROMATASE INHIBITOR; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ENDOCRINE THERAPY; DOUBLE-BLIND; PHASE-III; 500 MG; PHARMACOKINETIC PROFILE AB Sequential use of endocrine therapies remains the cornerstone of treatment for hormone receptor-positive advanced breast cancer, before the use of cytotoxic chemotherapy for unresponsive disease. Fulvestrant is an estrogen receptor (ER) antagonist approved for the treatment of postmenopausal women with ER+ advanced breast cancer after failure of prior antiestrogen therapy. Initially approved at a monthly dose of 250 mg, the recommended fulvestrant dose was revised to 500 mg (500 mg/mo plus 500 mg on day 14 of month 1) after demonstration of improved progression-free survival versus fulvestrant 250 mg. We have reviewed the dose-dependent effects of fulvestrant, both from a retrospective combined analysis of dose-dependent reduction of tumor biomarkers in the presurgical setting (3 previously reported studies: Study 18, Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors, and Trial 57) and from a review of clinical studies for advanced breast cancer in postmenopausal women. Analysis of presurgical data revealed a consistent dose-dependent effect for fulvestrant on tumor biomarkers, with increasing fulvestrant dose resulting in greater reductions in ER, progesterone receptor, and Ki67 labeling index. The dose-dependent biological effect corresponds with the dose-dependent clinical efficacy observed in the treatment of advanced breast cancer after failure of prior antiestrogen therapy. Although it remains to be determined in a phase III trial, crosstrial comparisons suggest a dose-dependent relationship for fulvestrant as first-line treatment for advanced breast cancer. Overall, biological and clinical data demonstrate a strong dose-dependent relationship for fulvestrant, supporting the efficacy benefit seen with fulvestrant 500 mg over the 250 mg dose. C1 [Robertson, John F. R.] Univ Nottingham, Grad Entry Med & Hlth Sch GEMS, Derby, England. [Lindemann, Justin; Garnett, Sally; Anderson, Elizabeth] AstraZeneca, Macclesfield, Cheshire, England. [Nicholson, Robert I.; Gee, Julia M. W.] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Breast Canc Mol Pharmacol Grp, Cardiff CF10 3AX, S Glam, Wales. [Kuter, Irene] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Robertson, JFR (reprint author), Univ Nottingham, Royal Derby Hosp Ctr, Div Med Sci & Grad Entry Med, Sch Med,Fac Med & Hlth Sci, Derby DE22 3DT, England. EM john.robertson@nottingham.ac.uk FU AstraZeneca FX The authors thank Simon Vass, PhD, of Complete Medical Communications, who provided medical writing support, funded by AstraZeneca. NR 42 TC 9 Z9 9 U1 4 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 EI 1938-0666 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD DEC PY 2014 VL 14 IS 6 BP 381 EP 389 DI 10.1016/j.clbc.2014.06.005 PG 9 WC Oncology SC Oncology GA AU8ZZ UT WOS:000345883000002 PM 25457991 ER PT J AU Ruddy, KJ DeSantis, SD Barry, W Guo, H Block, CC Borges, V Winer, EP Partridge, AH AF Ruddy, Kathryn J. DeSantis, Stephen D. Barry, William Guo, Hao Block, Caroline C. Borges, Virginia Winer, Eric P. Partridge, Ann H. TI Extended Therapy With Letrozole and Ovarian Suppression in Premenopausal Patients With Breast Cancer After Tamoxifen SO CLINICAL BREAST CANCER LA English DT Article DE Dyspareunia; Endocrine therapy; Hot flashes; Pain; Toxicity ID RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; ANASTROZOLE; RECURRENCE; RATES AB A single-arm phase II study (goal, n = 50) evaluated the feasibility of administering 2 years of ovarian suppression with letrozole to patients with breast cancer who remained premenopausal after adjuvant tamoxifen. This study closed owing to poor accrual (actual patients treated, n = 16) over 3.5 years, and a quarter of enrollees stopped treatment owing to toxicity. Future studies of this approach may be challenging. Introduction: In premenopausal women with breast cancer, standard adjuvant endocrine therapy has been 5 years of tannoxifen. This study sought to investigate the safety and feasibility of treating patients who remain premenopausal after adjuvant tamoxifen with gonadotropin-releasing hormone agonist (GnRH-a) concurrent with an aromatase inhibitor, mimicking the strategy that has proven effective in postmenopausal patients. Patients and Methods: This phase II single-arm clinical trial aimed to enroll 50 premenopausal women who had completed > 4.5 years of adjuvant tamoxifen for a 2-year course of leuprolide (7.5 mg intramuscularly monthly or 22.5 mg intramuscularly every 3 months) and letrozole (2.5 mg orally daily). Zoledronic acid (4 mg intravenously every 6 months) was offered optionally to help prevent bone loss. Results: Despite aggressive recruitment strategies at the 3 participating sites (including Dana-Farber Cancer Institute), poor accrual over 3.5 years ultimately led to early study closure after only 16 patients began therapy. Of the 16, 4 stopped treatment before 1 year, owing to toxicity; 5 completed 2 years of protocol-directed therapy; and 7 remained on treatment as of September 1, 2013, for an average of 53.5 weeks (SD, 17.2 weeks). Hot flashes, vaginal dryness, and pain were common toxicities. Conclusion: Extended therapy with GnRH-a and an aromatase inhibitor (plus optional bisphosphonate) is associated with substantial side effects in premenopausal women who have already completed > 4.5 years of adjuvant tamoxifen. This study's poor accrual suggests that young women may not be highly motivated to pursue lengthier courses of endocrine therapy and that future studies of this approach may be challenging. C1 [Ruddy, Kathryn J.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [DeSantis, Stephen D.; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Barry, William; Guo, Hao] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Block, Caroline C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Borges, Virginia] Univ Colorado, Div Med Oncol, Denver, CO 80202 USA. RP Ruddy, KJ (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM ruddy.kathryn@mayo.edu RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 NR 13 TC 5 Z9 5 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 EI 1938-0666 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD DEC PY 2014 VL 14 IS 6 BP 413 EP 416 DI 10.1016/j.clbc.2014.04.007 PG 4 WC Oncology SC Oncology GA AU8ZZ UT WOS:000345883000006 PM 24970714 ER PT J AU Wright, AJ Fishman, JA AF Wright, Alissa J. Fishman, Jay A. TI Diagnosis of Central Nervous System Mycoses in Solid Organ Transplant Recipients Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID INFECTIONS C1 [Wright, Alissa J.; Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,WH510A, Boston, MA 02114 USA. EM jfishman@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2014 VL 59 IS 11 BP 1653 EP 1654 DI 10.1093/cid/ciu669 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU8JG UT WOS:000345841900028 PM 25139965 ER PT J AU Yenchek, R Ix, JH Rifkin, DE Shlipak, MG Sarnak, MJ Garcia, M Patel, KV Satterfield, S Harris, TB Newman, AB Fried, LF AF Yenchek, Robert Ix, Joachim H. Rifkin, Dena E. Shlipak, Michael G. Sarnak, Mark J. Garcia, Melissa Patel, Kashang V. Satterfield, Suzanne Harris, Tamara B. Newman, Anne B. Fried, Linda F. CA Hlth Aging Body Composition Study TI Association of Serum Bicarbonate with Incident Functional Limitation in Older Adults SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; METABOLIC-ACIDOSIS; DISABILITY; PERFORMANCE; INCREASES; HUMANS; PEOPLE; FALLS AB Background and objectives Cross-sectional studies have found that low serum bicarbonate is associated with slower gait speed. Whether bicarbonate levels independently predict the development of functional limitation has not been previously studied. Whether bicarbonate was associated with incident persistent lower extremity functional limitation and whether the relationship differed in individuals with and without CKD were assessed in participants in the Health, Aging, and Body Composition study, a prospective study of well functioning older individuals Design, setting, participants, & measurements Functional limitation was defined as difficulty in walking 0.25 miles or up 10 stairs on two consecutive reports 6 months apart in the same activity (stairs or walking). Kidney function was measured using eGFR by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and CKD was defined as an eGFR<60 ml/min per 1.73 m(2). Serum bicarbonate was measured using arterialized venous blood gas. Cox proportional hazards analysis was used to assess the association of bicarbonate (<23, 23-25.9, and >= 26 mEq/L) with functional limitation. Mixed model linear regression was performed to assess the association of serum bicarbonate on change in gait speed over time. Results Of 1544 participants, 412 participants developed incident persistent functional limitation events over a median 4.4 years (interquartile range, 3.1 to 4.5). Compared with >= 26 mEq/L, lower serum bicarbonate was associated with functional limitation. After adjustment for demographics, CKD, diabetes, body mass index, smoking, diuretic use, and gait speed, lower serum bicarbonate was significantly associated with functional limitation (hazard ratio, 1.35; 95% confidence interval, 1.08 to.1.68 and hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.22 for bicarbonate levels from 23 to 25.9 and <23, respectively). There was not a significant interaction of bicarbonate with CKD. In addition, bicarbonate was not significantly associated with change in gait speed. Conclusions Lower serum bicarbonate was associated with greater risk of incident, persistent functional limitation. This association was present in individuals with and without CKD. C1 [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Fried, LF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, R01-AG029364]; National Institute of Nursing Research (NINR) [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T3-2DK061296] FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grants R01-AG028050 and R01-AG029364; and National Institute of Nursing Research (NINR) Grant R01-NR012459. This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. R.Y. was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant T3-2DK061296. NR 21 TC 3 Z9 3 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2111 EP 2116 DI 10.2215/CJN.05480614 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800015 PM 25381341 ER PT J AU Subramanya, AR Ellison, DH AF Subramanya, Arohan R. Ellison, David H. TI Distal Convoluted Tubule SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NA-CL COTRANSPORTER; SODIUM-CHLORIDE COTRANSPORTER; FAMILIAL HYPERKALEMIC HYPERTENSION; CORTICAL COLLECTING DUCT; RETICULUM-ASSOCIATED DEGRADATION; PSEUDOHYPOALDOSTERONISM TYPE-II; CELL-SURFACE EXPRESSION; RECTIFIER K+ CHANNEL; KELCH-LIKE 3; SENSORINEURAL DEAFNESS AB The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. C1 [Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Subramanya, AR (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, S828A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM ars129@pitt.edu FU National Institutes of Health [R01-DK51496, R01-DK095841, P30-DK079307, R01-DK098145]; Mid-Level Veterans Affairs Career Development Grant FX This work was supported, in part, by the National Institutes of Health Grants R01-DK51496 (to D.H.E.), R01-DK095841 (to D.H.E.), and P30-DK079307 (to the Pittsburgh Center for Kidney Research), R01-DK098145 (to A.R.S.), and a Mid-Level Veterans Affairs Career Development Grant (to A.R.S.). NR 120 TC 23 Z9 23 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2147 EP 2163 DI 10.2215/CJN.05920613 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800020 PM 24855283 ER PT J AU O'Hare, AM Armistead, N Schrag, WLF Diamond, L Moss, AH AF O'Hare, Ann M. Armistead, Nancy Schrag, Wendy L. Funk Diamond, Louis Moss, Alvin H. TI Patient-Centered Care: An Opportunity to Accomplish the "Three Aims" of the National Quality Strategy in the Medicare ESRD Program SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; OF-LIFE CARE; PALLIATIVE CARE; UNITED-STATES; CONSERVATIVE CARE; DECISION-MAKING; DIALYSIS INITIATION; STARTING DIALYSIS; OLDER-ADULTS; END AB In light of mounting federal government debt and levels of Medicare spending that are widely viewed as unsustainable, commentators have called for a transformation of the United States health care system to deliver better care at lower costs. This article presents the priorities of the Coalition for Supportive Care of Kidney Patients for how clinicians might achieve this transformation for patients with advanced CKD and their families. The authors suspect that much of the high-intensity, high-cost care currently delivered to patients with advanced kidney disease may be unwanted and that the "Three Aims" put forth by the National Quality Strategy of better care for the individual, better health for populations, and reduced health care costs may be within reach for patients with CKD and ESRD. This work describes the coalition's vision for a more patient-centered approach to the care of patients with kidney disease and argues for more concerted efforts to align their treatments with their goals, values, and preferences. Key priorities to achieve this vision include using improved prognostic models and decision science to help patients, their families, and their providers better understand what to expect in the future; engaging patients and their families in shared decision-making before the initiation of dialysis and during the course of dialysis treatment; and tailoring treatment strategies throughout the continuum of their care to address what matters most to individual patients. C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Armistead, Nancy] Midatlantic Renal Coalit, Richmond, VA USA. [Schrag, Wendy L. Funk] Fresenius Med Care, Newton, KS USA. [Diamond, Louis] Qual Hlth Care Advisory Grp, Rockville, MD USA. [Moss, Alvin H.] W Virginia Univ, Sch Med, Nephrol Sect, Morgantown, WV 26506 USA. RP Moss, AH (reprint author), W Virginia Univ, Sch Med, Nephrol Sect, POB 9022, Morgantown, WV 26506 USA. EM amoss@hsc.wvu.edu FU MARC FX In 2007, the Mid-Atlantic Renal Coalition (MARC) established the Coalition for Supportive Care of Kidney Patients (CSCKP; formerly the Kidney End-of-Life Coalition) in recognition that end-of-life care is an essential component of the continuum of quality care. The coalition maintains a resource-rich website that encourages active engagement in meaningful shared decision-making. MARC is a nonprofit subsidiary of West Virginia Medical Institute/Quality Insights Holdings and serves as an ESRD Network organization. The CSCKP is supported by MARC from reserve funds. NR 63 TC 17 Z9 17 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2189 EP 2194 DI 10.2215/CJN.01930214 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800023 PM 25035275 ER PT J AU O'Neill, AC Shinagare, AB Rosenthal, MH Tirumani, SH Jagannathan, JP Ramaiya, NH AF O'Neill, A. C. Shinagare, A. B. Rosenthal, M. H. Tirumani, S. H. Jagannathan, J. P. Ramaiya, N. H. TI Differences in CT features of peritoneal carcinomatosis, sarcomatosis, and lymphomatosis: Retrospective analysis of 122 cases at a tertiary cancer institution SO CLINICAL RADIOLOGY LA English DT Article ID IMAGING FINDINGS; ABDOMINAL MANIFESTATIONS; OVARIAN-CANCER; SOLID TUMORS; MALIGNANCY; TOXICITIES; MRI; PET AB AIMS: To study the differences in the imaging features of spread from the three cancer cell lines, namely epithelial, sarcomatoid, and lymphoid, resulting in peritoneal carcinomatosis, peritoneal sarcomatosis, and peritoneal lymphomatosis, respectively. MATERIALS AND METHODS: In this institutional review board-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study, an electronic radiology database was searched to identify patients with peritoneal tumour spread who underwent CT imaging at Dana-Farber Cancer Institute, a tertiary cancer institution, between January 2011 and December 2012. Out of 1214 patients with possible peritoneal tumour spread on the radiology reports, 122 patients were included with histopathologically confirmed peritoneal disease (50 randomly selected patients with peritoneal carcinomatosis and sarcomatosis each, and all 22 patients with lymphomatosis). Two blinded, fellowship-trained radiologists in consensus reviewed the CT images in random order and recorded the imaging findings of peritoneal tumour spread. The statistical analysis was performed in two steps: the first comparing incidence of various features in each group and the second step was a pairwise analysis between each cohort. RESULTS: Peritoneal carcinomatosis more frequently had ascites, peritoneal thickening, and omental cake (all p <= 0.001). Measurable nodules were less common in peritoneal carcinomatosis (p < 0.001), and when present, were ill-defined and had an irregular outline (p <= 0.002). Peritoneal sarcomatosis more often had discrete nodules that were well defined and had a smooth outline and less frequently had ascites, peritoneal thickening, omental caking, serosal implants, and lymphadenopathy (all p <= 0.005). Peritoneal lymphomatosis frequently involved the omentum, and mesentery, and often had associated lymphadenopathy and splenomegaly (all p <= 0.002). CONCLUSION: Peritoneal carcinomatosis, sarcomatosis, and lymphomatosis have distinctive patterns on imaging, which can help the radiologists to differentiate between them. (C) 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [O'Neill, A. C.; Shinagare, A. B.; Rosenthal, M. H.; Tirumani, S. H.; Jagannathan, J. P.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Canc Imaging, Brookline, MA 02215 USA. RP O'Neill, AC (reprint author), Dana Farber Canc Inst, Dept Canc Imaging, 450 Brookline Ave, Brookline, MA 02215 USA. EM aoneill9@partners.org RI Rosenthal, Michael/D-4080-2015 NR 28 TC 5 Z9 5 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 DEC PY 2014 VL 69 IS 12 BP 1219 EP 1227 DI 10.1016/j.crad.2014.06.019 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU6QN UT WOS:000345727200003 PM 25308238 ER PT J AU Shaqdan, K Aran, S Thrall, J Abujudeh, H AF Shaqdan, K. Aran, S. Thrall, J. Abujudeh, H. TI Incidence of contrast medium extravasation for CT and MRI in a large academic medical centre: A report on 502,391 injections SO CLINICAL RADIOLOGY LA English DT Article ID ENHANCED CT; PREVENTION; MANAGEMENT; FREQUENCY AB AIM: To present the authors' experience of contrast medium extravasation (CME) during both CT and MRI examinations in a large academic medical centre. MATERIALS AND METHODS: The present retrospective investigation was conducted between June 2008 and June 2013. The radiology data and medical records of patients in whom CME had occurred were reviewed. RESULTS: The extravasation rate for CT and MRI was 0.11% (541/502 391); the % was 0.13% during CT and 0.06% during MR'. There was a statistically significant difference between females and males in the overall % (p = 0.0062), and the number of extravasations between CT and MRI (p < 0.0001). At MRI, the incidence of CME in patients >60 years was statistically significant when compared to the 18760 year age group (p = 0.0072). Of 90 MRI patients with extravasation, CME occurred in 51 (0.048%, 51/105,578) patients from manual injections, and 39 (0.087%, 39/44,688) patients from automated injection with statistical significance (p = 0.0048). A statistical significance was found between females receiving automatic injections and,males receiving manual injections (p = 0.0161). The majority of CME during CT and MRI occurred in the outpatient department [64.5% (291/451) and 64.4% (58/90), respectively], but the overall incidence of CME was highest in inpatients [0.29%, (160/54,664) in CT and 0.16% (32/20,048) in MRI]. CONCLUSION: Patients undergoing CT are at higher risk of developing CME than MRI patients. Females and inpatients were also were more likely to develop CME at both CT and MM. At MRI CME is more likely in patients above the age of 60 years and for those receiving automated power injections. (C) 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Shaqdan, K.; Aran, S.; Thrall, J.; Abujudeh, H.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Abujudeh, H (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. EM Habujudeh@partners.org NR 22 TC 5 Z9 6 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 DEC PY 2014 VL 69 IS 12 BP 1264 EP 1272 DI 10.1016/j.crad.2014.08.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU6QN UT WOS:000345727200009 PM 25248291 ER PT J AU Cotter, G Metra, M Davison, BA Senger, S Bourge, RC Cleland, JGF Jondeau, G Krum, H O'Connor, CM Parker, JD Torre-Amione, G van Veldhuisen, DJ Milo, O Kobrin, I Rainisio, M McMurray, JJV Teerlink, JR AF Cotter, Gad Metra, Marco Davison, Beth A. Senger, Stefanie Bourge, Robert C. Cleland, John G. F. Jondeau, Guillaume Krum, Henry O'Connor, Christopher M. Parker, John D. Torre-Amione, Guillermo van Veldhuisen, Dirk J. Milo, Olga Kobrin, Isaac Rainisio, Maurizio McMurray, John J. V. Teerlink, John R. CA VERITAS Investigators TI Worsening heart failure, a critical event during hospital admission for acute heart failure: results from the VERITAS study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Outcome; VERITAS study; Worsening heart failure; Death ID TASK-FORCE; GUIDELINES AB AimsWorsening heart failure (WHF) in the first 7 days after an admission for acute HF (AHF) has been proposed as a therapeutic target in several recent AHF studies and was a co-primary endpoint of the VERITAS studies. Methods and resultsPatients were randomized within 24h of admission for AHF. WHF was defined as worsening or persistent signs and symptoms of HF requiring additional intravenous or mechanical therapy for HF or death within 7 days of randomization. Multivariable models were developed to predict the time to WHF through day 7. Unadjusted and multivariable-adjusted associations of WHF with the length of stay (LOS) of the index hospitalization, and 30- and 90-day outcomes were estimated. WHF occurred by day 7 in 27% of the 1347 patients enrolled. Age, co-morbidities, and markers of HF severity were moderately predictive of WHF; the C-index for a multivariable model for WHF was 0.66. After multivariable adjustment for baseline characteristics, WHF was associated with an increase in LOS of 4.33days [95% confidence interval (CI) 3.54-5.13days], a hazard ratio (HR) for 30-day HF readmission or death of 2.43 (95% CI 1.75-3.40), and a HR for 90-day mortality of 2.57 (95% CI 1.81-3.65), all with P < 0.0001.The associations of WHF with these outcomes remained largely unchanged after adjustment for both baseline characteristics and changes in markers of renal and hepatic dysfunction during the first day of admission. ConclusionsIn patients admitted for AHF, WHF is a significant clinical event that is associated with delays in discharge and higher rates for readmission and death. C1 [Cotter, Gad; Davison, Beth A.; Senger, Stefanie; Milo, Olga] Momentum Res, Durham, NC 27707 USA. [Metra, Marco] Univ Brescia, Piazza Spedali Civili, Brescia, Italy. [Bourge, Robert C.] Univ Alabama Birmingham, Birmingham, AL USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield Hosp NHS Trust, Natl Heart & Lung Inst, London, England. [Jondeau, Guillaume] Hop Bichat Claude Bernard, Serv Cardiol, F-75877 Paris 18, France. [Krum, Henry] Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3181, Australia. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Parker, John D.] Mt Sinai Hosp, Div Cardiol, Toronto, ON M5G 1X5, Canada. [Torre-Amione, Guillermo] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kobrin, Isaac] Kobrin Associates GmbH, Basel, Switzerland. [Rainisio, Maurizio] Abanovus Srl, San Remo, Imperia, Italy. [McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Cotter, G (reprint author), Momentum Res, 3100 Tower Blvd, Durham, NC 27707 USA. EM gadcotter@momentum-research.com OI Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Parker, John/0000-0003-1949-2669; Senger, Stefanie/0000-0003-4144-1040; mcmurray, john/0000-0002-6317-3975 FU Novartis; Corthera; Novocardia; Trevena; Merck; Angen; ChanRX; Cardio 3; Sorbent; Singulex; Actelion; Gilead; Amgen; Cytokinetics FX O.M.C., G.C., B.A.D., and S.S. are employees of Momentum Research Inc. which has received research grants from Novartis, Corthera, Novocardia, Trevena, Merck, Angen, ChanRX, Cardio 3, Sorbent, and Singulex. M.M. has received honoraria from Bayer as DMC Chairman, Novartis as EC Co-chairman. and Servier as a steering committee member. R.B. has conducted research sponsored by Actelion, has ongoing research sponsored by Gilead, a competitor of Actelion, and has served on Gilead's speaker's bureau. J.C., H.K., and J.D.P. have received honoraria from Actelion for steering committee activities. J.T. has received funds from Actelion and is currently conducting research funded by Amgen, Cytokinetics, Novartis, and Trevena. All other authors report no potential conflict of interest. NR 19 TC 10 Z9 10 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2014 VL 16 IS 12 BP 1362 EP 1371 DI 10.1002/ejhf.186 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU7BJ UT WOS:000345755200015 PM 25371147 ER PT J AU Reddy, AT Lakshmi, SP Zhang, YZ Reddy, RC AF Reddy, Aravind T. Lakshmi, Sowmya P. Zhang, Yingze Reddy, Raju C. TI Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages SO FASEB JOURNAL LA English DT Article DE TGF; collagen; MFG-E8 ID ACTIVATED-RECEPTOR-GAMMA; GROWTH-FACTOR-BETA; HEPATIC STELLATE CELLS; GENE-EXPRESSION; LUNG FIBROSIS; MURINE MODEL; INFLAMMATION; INJURY; DIFFERENTIATION; MECHANISMS AB Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease, thought to be largely transforming growth factor beta (TGF beta) driven, for which there is no effective therapy. We assessed the potential benefits in IPF of nitrated fatty acids (NFAs), which are unique endogenous agonists of peroxisome proliferator- activated receptor gamma (PPAR gamma), a nuclear hormone receptor that exhibits wound-healing and antifibrotic properties potentially useful for IPF therapy. We found that pulmonary PPAR gamma is down-regulated in patients with IPF. In vitro, knockdown or knockout of PPAR gamma expression in isolated human and mouse lung fibroblasts induced a profibrotic phenotype, whereas treating human fibroblasts with NFAs up-regulated PPAR gamma and blocked TGF beta signaling and actions. NFAs also converted TGF beta to inactive monomers in cell-free solution, suggesting an additional mechanism through which they may inhibit TGF beta. In vivo, treating mice bearing experimental pulmonary fibrosis with NFAs reduced disease severity. Also, NFAs up-regulated the collagen-targeting factor milk fat globule-EGF factor 8 (MFG-E8), stimulated collagen uptake and degradation by alveolar macrophages, and promoted myofibroblast dedifferentiation. Moreover, treating mice with established pulmonary fibrosis using NFAs reversed their existing myofibroblast differentiation and collagen deposition. These findings raise the prospect of treating IPF with NFAs to halt and perhaps even reverse the progress of IPF. C1 [Reddy, Aravind T.; Lakshmi, Sowmya P.; Zhang, Yingze; Reddy, Raju C.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Reddy, Aravind T.; Lakshmi, Sowmya P.; Reddy, Raju C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Reddy, RC (reprint author), Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, 3459 Fifth Ave, Pittsburgh, PA 15213 USA. EM reddyrc@upmc.edu FU U.S. Department of Veterans Affairs; U.S. National Institutes of Health [HL-093196] FX This work was supported by a Merit Review Award from the U.S. Department of Veterans Affairs and by U.S. National Institutes of Health grant HL-093196 (to R.C.R). NR 38 TC 7 Z9 7 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2014 VL 28 IS 12 BP 5299 EP 5310 DI 10.1096/fj.14-256263 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AU9EN UT WOS:000345894500024 PM 25252739 ER PT J AU Erhardt, I Levy, RA Ablon, JS Ackerman, JA Seybert, C Vosshagen, I Kachele, H AF Erhardt, Ingrid Levy, Raymond A. Ablon, J. Stuart Ackerman, Julie A. Seybert, Carolina Vosshagen, Iris Kaechele, Horst TI Amalie Xs specimen case - Analyzed with the Psychotherapy Process Q-set SO FORUM DER PSYCHOANALYSE LA German DT Article ID COLLABORATIVE RESEARCH-PROGRAM; PSYCHOANALYSIS; REFLECTIONS; TERM AB The Psychotherapy Process Q-set (PQS) of Enrico Jones will be described and its application in analyzing an analytic session will be demonstrated with the specimen case of Amalie X's session 152. Additionally, a method to analyze therapy adherence based on the PQS will be presented to demonstrate how this session conforms to an ideal analytic session. Furthermore, it will be illustrated that psychoanalytic process can be demonstrated with the PQS systematically and empirically although the full complexity of an analytic session cannot be captured. The importance of the PQS and potential further developments and uses will be discussed. C1 [Erhardt, Ingrid] Klinikum Rechts Der Isar, Klin & Poliklin Psychiat & Psychotherapie, D-81675 Munich, Germany. [Levy, Raymond A.; Ablon, J. Stuart] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ackerman, Julie A.] CCNY, Psychol Ctr, Dept Psychol, New York, NY 10031 USA. [Seybert, Carolina; Vosshagen, Iris; Kaechele, Horst] Int Psychoanalyt Univ, D-10555 Berlin, Germany. RP Erhardt, I (reprint author), Klinikum Rechts Der Isar, Klin & Poliklin Psychiat & Psychotherapie, Ismaninges Str 22, D-81675 Munich, Germany. EM erhardt.ingrid@gmail.com NR 35 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0178-7667 EI 1437-0751 J9 FORUM PSYCHOANAL JI Forum Psychoanal. PD DEC PY 2014 VL 30 IS 4 BP 441 EP 458 DI 10.1007/s00451-013-0163-y PG 18 WC Psychology, Psychoanalysis SC Psychology GA AU5IF UT WOS:000345639500006 ER PT J AU Zeitels, LR Acharya, A Shi, G Chivukula, D Chivukula, RR Anandam, JL Abdelnaby, AA Balch, GC Mansour, JC Yopp, AC Richardson, JA Mendell, JT AF Zeitels, Lauren R. Acharya, Asha Shi, Guanglu Chivukula, Divya Chivukula, Raghu R. Anandam, Joselin L. Abdelnaby, Abier A. Balch, Glen C. Mansour, John C. Yopp, Adam C. Richardson, James A. Mendell, Joshua T. TI Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis SO GENES & DEVELOPMENT LA English DT Article DE microRNA; miR-26; intestine; colon cancer ID EMBRYONIC STEM-CELLS; MICRORNA EXPRESSION; COLORECTAL-CANCER; BINDING-PROTEIN; LIVER-CANCER; COLON-CANCER; C-MYC; PTEN; REPRESSION; MOUSE AB Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type. C1 [Zeitels, Lauren R.] Johns Hopkins Univ, Med Scientist Training Program, Sch Med, Baltimore, MD 21205 USA. [Zeitels, Lauren R.; Acharya, Asha; Shi, Guanglu; Chivukula, Divya; Richardson, James A.; Mendell, Joshua T.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Chivukula, Divya] Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Anandam, Joselin L.; Abdelnaby, Abier A.; Balch, Glen C.; Mansour, John C.; Yopp, Adam C.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Richardson, James A.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Mendell, Joshua T.] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA. [Mendell, Joshua T.] Univ Texas SW Med Ctr Dallas, Ctr Regenerat Sci & Med, Dallas, TX 75390 USA. RP Mendell, JT (reprint author), Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. EM joshua.mendell@utsouthwestern.edu RI Shi, Guanglu/G-1641-2013 OI Shi, Guanglu/0000-0001-5562-111X FU Cancer Prevention Research Institute of Texas (CPRIT) [R1008]; National Institutes of Health [R01CA120185, P01CA134292, 5P30CA142543, 5T32GM007309] FX We thank Chip Hawkins in the Johns Hopkins Transgenic Core for assistance with generation of LSL.eGFP.miR-26a mice, John Shelton in the University of Texas Southwestern Molecular Pathology Core for assistance with histopathology, Cheryl Lewis in the University of Texas Southwestern Tissue Resource Core for assistance with human tissue specimens, Quan-Zhen Li in the University of Texas Southwestern Microarray Core for assistance with gene expression profiling, and Jeanetta Marshburn-Wynn for mouse colony maintenance. Kathryn O'Donnell, Tsung-Cheng Chang, and Kenneth Chen provided valuable technical assistance and advice. This work was supported by grants from Cancer Prevention Research Institute of Texas (CPRIT) (R1008 to J.T.M.) and the National Institutes of Health (R01CA120185 and P01CA134292 to J.T.M., 5P30CA142543 to the University of Texas Southwestern Simmons Cancer Center, and 5T32GM007309 to L.R.Z. and R.R.C.). J.T.M. is a CPRIT Scholar in Cancer Research. NR 40 TC 18 Z9 18 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2014 VL 28 IS 23 BP 2585 EP 2590 DI 10.1101/gad.250951.114 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA AU7XP UT WOS:000345812000002 PM 25395662 ER PT J AU Li, Y Esain, V Teng, L Xu, J Kwan, W Frost, IM Yzaguirre, AD Cai, XW Cortes, M Maijenburg, MW Tober, J Dzierzak, E Orkin, SH Tan, K North, TE Speck, NA AF Li, Yan Esain, Virginie Teng, Li Xu, Jian Kwan, Wanda Frost, Isaura M. Yzaguirre, Amanda D. Cai, Xiongwei Cortes, Mauricio Maijenburg, Marijke W. Tober, Joanna Dzierzak, Elaine Orkin, Stuart H. Tan, Kai North, Trista E. Speck, Nancy A. TI Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production SO GENES & DEVELOPMENT LA English DT Article DE interferon; hematopoiesis; lymphoid progenitor; hematopoietic stem cell; mouse; zebrafish ID YOLK-SAC; GENE-EXPRESSION; MOUSE EMBRYO; DEFINITIVE HEMATOPOIESIS; MYELOID PROGENITORS; CLASS DISCOVERY; ZEBRAFISH; EMERGENCE; RECEPTOR; SYSTEM AB Identifying signaling pathways that regulate hematopoietic stem and progenitor cell (HSPC) formation in the embryo will guide efforts to produce and expand HSPCs ex vivo. Here we show that sterile tonic inflammatory signaling regulates embryonic HSPC formation. Expression profiling of progenitors with lymphoid potential and hematopoietic stem cells (HSCs) from aorta/gonad/mesonephros (AGM) regions of midgestation mouse embryos revealed a robust innate immune/inflammatory signature. Mouse embryos lacking interferon gamma (IFN-gamma) or IFN-alpha signaling and zebrafish morphants lacking IFN-gamma and IFN-phi activity had significantly fewer AGM HSPCs. Conversely, knockdown of IFN regulatory factor 2 (IRF2), a negative regulator of IFN signaling, increased expression of IFN target genes and HSPC production in zebrafish. Chromatin immunoprecipitation (ChIP) combined with sequencing (ChIP-seq) and expression analyses demonstrated that IRF2-occupied genes identified in human fetal liver CD34(+) HSPCs are actively transcribed in human and mouse HSPCs. Furthermore, we demonstrate that the primitive myeloid population contributes to the local inflammatory response to impact the scale of HSPC production in the AGM region. Thus, sterile inflammatory signaling is an evolutionarily conserved pathway regulating the production of HSPCs during embryonic development. C1 [Li, Yan; Yzaguirre, Amanda D.; Cai, Xiongwei; Maijenburg, Marijke W.; Tober, Joanna; Speck, Nancy A.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19014 USA. [Li, Yan; Yzaguirre, Amanda D.; Cai, Xiongwei; Maijenburg, Marijke W.; Tober, Joanna; Speck, Nancy A.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19014 USA. [Esain, Virginie; Kwan, Wanda; Frost, Isaura M.; Cortes, Mauricio; North, Trista E.] Harvard Univ, Dept Pathol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Teng, Li; Tan, Kai] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Xu, Jian; Orkin, Stuart H.] Boston Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Dzierzak, Elaine] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Tan, Kai] Univ Iowa, Dept Bioengn, Iowa City, IA 52242 USA. RP Speck, NA (reprint author), Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19014 USA. EM tnorth@bidmc.harvard.edu; nancyas@exchange.upenn.edu RI Cai, Xiongwei/G-3169-2015 FU National Institutes of Health (NIH) [R01HL091724, R01HG006130, P01-HL032259, U01HL100405]; Leukemia and Lymphoma Society; NIH [1F31HL120615, 1R01DK098241]; Rubicon [825.12.003]; American Society of Hematology; [K01DK093543] FX We thank B. Black for explant culture protocols, V. Mulero (University of Murcia) for ifng expression construct, and B. van Handel and H. Mikkola (University of California at Los Angeles) for hCD34+ FL cells. This work was supported by National Institutes of Health (NIH) R01HL091724 (N.A.S.), U01HL100405 (N.A.S.), R01HG006130 (K.T.), and P01-HL032259 (S.H.O.). Y.L. and J.T. are supported by the Leukemia and Lymphoma Society, A.D.Y. is supported by NIH 1F31HL120615, M.W.M. is supported by Rubicon grant 825.12.003, and J.X. is supported by K01DK093543. T.E.N. is supported by NIH 1R01DK098241 and the American Society of Hematology. Core services were provided by the Abramson Cancer Center (mice), the Harvard Stem Cell Institute, and Beth Israel Deaconess Medical Center (zebrafish). NR 58 TC 51 Z9 51 U1 3 U2 20 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2014 VL 28 IS 23 BP 2597 EP 2612 DI 10.1101/gad.253302.114 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA AU7XP UT WOS:000345812000004 PM 25395663 ER PT J AU Cooper, VS Staples, RK Traverse, CC Ellis, CN AF Cooper, Vaughn S. Staples, Rachel K. Traverse, Charles C. Ellis, Crystal N. TI Parallel evolution of small colony variants in Burkholderia cenocepacia biofilms SO GENOMICS LA English DT Article DE Biofilm; Experimental evolution; Bacteria ID CYSTIC-FIBROSIS LUNG; PSEUDOMONAS-AERUGINOSA; CEPACIA COMPLEX; EXPERIMENTAL POPULATIONS; ADAPTIVE DIVERGENCE; DI-GMP; FLUORESCENS; ADAPTATION; DIVERSITY; INFECTION AB A common phenotype within bacterial biofilms is the small, "wrinkly" colony, which may associate with worse prognoses from biofilm-associated infections. The mechanisms that produce these variants in Burkholderia are undefined. Here we report the mutational and ecological causes of wrinkly (W) colonies that evolved during experimental biofilm evolution of Burkholderia cenocepacia. Mutations clustered in a homologous pathway to the Pseudomonas wsp operon but with a distinct terminal signaling mechanism, and their parallel evolution suggested that they inhabited an equivalent biofilm niche. We tested this hypothesis of niche complementarity by measuring effects of substituting different W variants in the same evolved biofilm community. Despite phenotypic differences among W mutants growing alone, fitness of reconstituted mixed biofilms did not differ significantly. In conclusion, the evolution of small-colony variants in Burkholderia biofilms appears to be driven by an ecological opportunity that generates strong selection for constitutive wsp mutants to inhabit a common niche. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Cooper, Vaughn S.] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03820 USA. [Staples, Rachel K.] Univ Houston, Dept Biol & Biochem, Houston, TX USA. [Traverse, Charles C.] Univ Texas Austin, Dept Microbiol, Austin, TX 78712 USA. [Ellis, Crystal N.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Cooper, VS (reprint author), Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03820 USA. EM vaughn.cooper@unh.edu OI Cooper, Vaughn/0000-0001-7726-0765 FU NSF [DEB-0845851] FX This work was supported by NSF CAREER award DEB-0845851 to VSC. We thank L. Mayo-Smith and D. Morejon for the technical assistance. NR 38 TC 9 Z9 9 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD DEC PY 2014 VL 104 IS 6 BP 447 EP 452 DI 10.1016/j.ygeno.2014.09.007 PN A PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW1OP UT WOS:000346059200009 PM 25263109 ER PT J AU Hoeppner, BB Kahler, CW Gwaltney, CJ AF Hoeppner, Bettina B. Kahler, Christopher W. Gwaltney, Chad J. TI Relationship Between Momentary Affect States and Self-Efficacy in Adolescent Smokers SO HEALTH PSYCHOLOGY LA English DT Article DE adolescent smokers; self-efficacy; mood; stages of smoking cessation; ecological momentary assessment ID RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; NEGATIVE AFFECT; PSYCHOLOGICAL INTERVENTION; DEPRESSIVE SYMPTOMS; MAJOR DEPRESSION; MOOD VARIABILITY; CUE REACTIVITY AB Objective: Relapse to smoking after making a quit attempt is both common and rapid in adolescent smokers. Momentary self-efficacy (SE)-that is, momentary shifts in one's confidence in the ability to abstain from smoking-predicts the occurrence and timing of relapse among adolescent smokers. Therefore, it is important to identify factors that are associated with changes in momentary SE early in a quit attempt. This study examined the relationship between affect states (including positive, negative, and nicotine withdrawal states) and momentary SE at various stages of a quit attempt. Method: Adolescent daily smokers interested in making a quit attempt (n = 202) completed ecological momentary assessments (EMA) each day for 1 week leading up to and 2 weeks after a quit attempt. In each assessment, they reported current SE and affect state. Results: Results of linear mixed models indicated that most of the examined affect states were related to momentary SE. Contrary to expectation, they were related to momentary SE both immediately before and after the quit attempt. Moderation effects were observed for select affect states, where higher baseline SE was related to lower momentary SE in the presence of increasing negative high activation, boredom, and difficulty concentrating. Conclusions: Our findings suggest that both positive and negative affect states are related to SE, and that thereby positive affect enhancement may be a promising, underutilized treatment target. C1 [Hoeppner, Bettina B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA 02114 USA. [Kahler, Christopher W.; Gwaltney, Chad J.] Brown Sch Publ Hlth, Dept Behav & Social Sci, Providence, RI USA. [Kahler, Christopher W.; Gwaltney, Chad J.] Brown Sch Publ Hlth, Ctr Alcohol & Addict Studies, Providence, RI USA. [Gwaltney, Chad J.] ERT Inc, Philadelphia, PA USA. RP Hoeppner, BB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA 02114 USA. EM bhoeppner@mgh.harvard.edu FU National Institute on Drug Abuse [R01 DA021677, K01 DA027097] FX This study was supported by grants from the National Institute on Drug Abuse R01 DA021677 (CJG) and K01 DA027097 (BBH). We thank Jessica Emerson, Kathryn Story, Linda Brazil, Robert Dvorak, Suzanne Sales, Julia Pleet, Rachel Bartolomei, Sam Klugman, and Timothy Souza for their assistance with data collection and management. NR 63 TC 2 Z9 2 U1 6 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD DEC PY 2014 VL 33 IS 12 BP 1507 EP 1517 DI 10.1037/hea0000075 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA AU6WK UT WOS:000345741900007 PM 25020151 ER PT J AU Buchan, SL Manzo, T Flutter, B Rogel, A Edwards, N Zhang, L Sivakumaran, S Ghorashian, S Carpenter, B Bennett, C Freeman, G Sykes, M Croft, M Al-Shamkhani, A Chakraverty, R AF Buchan, S. L. Manzo, T. Flutter, B. Rogel, A. Edwards, N. Zhang, L. Sivakumaran, S. Ghorashian, S. Carpenter, B. Bennett, C. Freeman, G. Sykes, M. Croft, M. Al-Shamkhani, A. Chakraverty, R. TI CD27 co-stimulation and co-inhibitory checkpoint blockade synergise by forcing exhausted CD8+T-cells to exit quiescence SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Buchan, S. L.; Rogel, A.; Al-Shamkhani, A.] Univ Southampton, Canc Sci Unit, Southampton, Hants, England. [Manzo, T.; Flutter, B.; Edwards, N.; Zhang, L.; Sivakumaran, S.; Ghorashian, S.; Carpenter, B.; Bennett, C.; Chakraverty, R.] UCL, Inst Canc, Transplantat Immunol Grp, London, England. [Manzo, T.; Flutter, B.; Edwards, N.; Zhang, L.; Sivakumaran, S.; Ghorashian, S.; Carpenter, B.; Bennett, C.; Chakraverty, R.] UCL, Inst Immun & Transplantat, London, England. [Freeman, G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sykes, M.] Columbia Univ Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. [Croft, M.] Inst Allergy & Immunol, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 429 BP 134 EP 134 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600397 ER PT J AU Lee, JS Fine, MJ AF Lee, Jonathan S. Fine, Michael J. TI The Debate on Antibiotic Therapy for Patients Hospitalized for Pneumonia Where Should We Go From Here? SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID AZITHROMYCIN C1 [Lee, Jonathan S.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Fine, MJ (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM michael.fine@va.gov NR 8 TC 2 Z9 2 U1 0 U2 7 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 DEC PY 2014 VL 174 IS 12 BP 1901 EP 1903 DI 10.1001/jamainternmed.2014.3996 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KI UT WOS:000345911000008 PM 25285980 ER PT J AU Berkowitz, SA Krumme, AA Avorn, J Brennan, T Matlin, OS Spettell, CM Pezalla, EJ Brill, G Shrank, WH Choudhry, NK AF Berkowitz, Seth A. Krumme, Alexis A. Avorn, Jerry Brennan, Troyen Matlin, Olga S. Spettell, Claire M. Pezalla, Edmund J. Brill, Gregory Shrank, William H. Choudhry, Niteesh K. TI Initial Choice of Oral Glucose-Lowering Medication for Diabetes Mellitus A Patient-Centered Comparative Effectiveness Study SO JAMA INTERNAL MEDICINE LA English DT Article ID CARDIOVASCULAR OUTCOMES; METFORMIN; ROSIGLITAZONE; EVENTS; COMPLICATIONS; MONOTHERAPY; THERAPY; DRUGS AB IMPORTANCE Although many classes of oral glucose-lowering medications have been approved for use, little comparative effectiveness evidence exists to guide initial selection of therapy for diabetes mellitus. OBJECTIVE To determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification and 4 short-term adverse clinical events. DESIGN, SETTING, AND PARTICIPANTS This study was a retrospective cohort study of patients who were fully insured members of Aetna (a large national health insurer) who had been prescribed an oral glucose-lowering medication from July 1, 2009, through June 30, 2013. Individuals newly prescribed an oral glucose-lowering agent who filled a second prescription for a medication in the same class and with a dosage at or above the World Health Organization's defined daily dose within 90 days of the end-of-day's supply of the first prescription were studied. Individuals with interim prescriptions for other oral glucose-lowering medications were excluded. EXPOSURES Initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor. MAIN OUTCOMES AND MEASURES Time to addition of a second oral agent or insulin, each component separately, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events. RESULTS A total of 15 516 patients met the inclusion criteria, of whom 8964 (57.8%) started therapy with metformin. In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events. CONCLUSIONS AND RELEVANCE Despite guidelines, only 57.8% of individuals began diabetes treatment with metformin. Beginning treatment with metformin was associated with reduced subsequent treatment intensification, without differences in rates of hypoglycemia or other adverse clinical events. These findings have significant implications for quality of life and medication costs. C1 [Berkowitz, Seth A.; Krumme, Alexis A.; Avorn, Jerry; Brill, Gregory; Choudhry, Niteesh K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol,Dept Med, Boston, MA 02120 USA. [Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Brennan, Troyen; Matlin, Olga S.; Shrank, William H.] CVS Hlth, Woonsocket, RI USA. [Spettell, Claire M.; Pezalla, Edmund J.] Aetna Informat, Blue Bell, PA USA. RP Choudhry, NK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol,Dept Med, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM nchoudhry@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU CVS Health FX This work was supported by an unrestricted grant from CVS Health to Brigham and Women's Hospital. NR 28 TC 21 Z9 22 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 DEC PY 2014 VL 174 IS 12 BP 1955 EP 1962 DI 10.1001/jamainternmed.2014.5294 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KI UT WOS:000345911000021 PM 25347323 ER PT J AU Bernacki, RE Block, SD AF Bernacki, Rachelle E. Block, Susan D. CA Amer Coll Phys High Value Care TI Communication About Serious Illness Care Goals A Review and Synthesis of Best Practices SO JAMA INTERNAL MEDICINE LA English DT Review ID END-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; TERMINALLY-ILL PATIENTS; FACULTY-DEVELOPMENT PROGRAM; ADVANCED CANCER-PATIENTS; CELL LUNG-CANCER; PALLIATIVE CARE; HEALTH-CARE; ADVANCE DIRECTIVES; MEDICARE BENEFICIARIES AB An understanding of patients' care goals in the context of a serious illness is an essential element of high-quality care, allowing clinicians to align the care provided with what is most important to the patient. Early discussions about goals of care are associated with better quality of life, reduced use of nonbeneficial medical care near death, enhanced goal-consistent care, positive family outcomes, and reduced costs. Existing evidence does not support the commonly held belief that communication about end-of-life issues increases patient distress. However, conversations about care goals are often conducted by physicians who do not know the patient, do not routinely address patients' nonmedical goals, and often fail to provide patients with sufficient information about prognosis to allow appropriate decisions; in addition, they tend to occur so late in the patient's illness that their impact on care processes is reduced. This article (1) reviews the evidence and describes best practices in conversations about serious illness care goals and (2) offers practical advice for clinicians and health care systems about developing a systematic approach to quality and timing of such communication to assure that each patient has a personalized serious illness care plan. Best practices in discussing goals of care include the following: sharing prognostic information, eliciting decision-making preferences, understanding fears and goals, exploring views on trade-offs and impaired function, and wishes for family involvement. Several interventions hold promise in systematizing conversations with patients about serious illness care goals: better education of physicians; systems to identify and trigger early discussions for appropriate patients; patient and family education; structured formats to guide discussions; dedicated, structured sections in the electronic health record for recording information; and continuous measurement. We conclude that communication about serious illness care goals is an intervention that should be systematically integrated into our clinical care structures and processes. C1 [Bernacki, Rachelle E.; Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Adult Palliat Care, Boston, MA 02215 USA. [Bernacki, Rachelle E.; Block, Susan D.] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA. [Bernacki, Rachelle E.; Block, Susan D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bernacki, Rachelle E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Bernacki, Rachelle E.; Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Bernacki, RE (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Adult Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM rbernacki@partners.org FU American College of Physicians (ACP); Partners Healthcare; Charina Foundation FX Financial support for the development of this guideline comes exclusively from the American College of Physicians (ACP) operating budget. This work was supported by Partners Healthcare and the Charina Foundation. NR 106 TC 79 Z9 79 U1 14 U2 45 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 DEC PY 2014 VL 174 IS 12 BP 1994 EP 2003 DI 10.1001/jamainternmed.2014.5271 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KI UT WOS:000345911000027 PM 25330167 ER PT J AU Linder, JA Doctor, JN Friedberg, MW Nieva, HR Birks, C Meeker, D Fox, CR AF Linder, Jeffrey A. Doctor, Jason N. Friedberg, Mark W. Nieva, Harry Reyes Birks, Caroline Meeker, Daniella Fox, Craig R. TI Time of Day and the Decision to Prescribe Antibiotics SO JAMA INTERNAL MEDICINE LA English DT Letter ID SELF-REGULATION; INFECTIONS C1 [Linder, Jeffrey A.; Friedberg, Mark W.; Nieva, Harry Reyes] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Linder, Jeffrey A.; Friedberg, Mark W.; Nieva, Harry Reyes; Birks, Caroline] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Doctor, Jason N.] Univ So Calif, Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Friedberg, Mark W.] RAND, Boston, MA USA. [Birks, Caroline] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meeker, Daniella] RAND, Santa Monica, CA USA. [Fox, Craig R.] Univ Calif Los Angeles, Anderson Sch Management, Los Angeles, CA USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St,BC-3-2X, Boston, MA 02120 USA. EM jlinder@partners.org OI Meeker, Daniella/0000-0002-1034-7628; Reyes Nieva, Harry/0000-0001-7774-2561 FU NIA NIH HHS [RC4 AG039115] NR 6 TC 13 Z9 13 U1 1 U2 2 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 DEC PY 2014 VL 174 IS 12 BP 2029 EP 2031 DI 10.1001/jamainternmed.2014.5225 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KI UT WOS:000345911000036 PM 25286067 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI Pain Terminology SO JAMA PEDIATRICS LA English DT Letter ID SMALL-FIBER POLYNEUROPATHY C1 [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Boston, MA USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, 275 Charles St Warren 310, Boston, MA 02114 USA. EM aloaklander@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD DEC PY 2014 VL 168 IS 12 BP 1167 EP 1167 PG 1 WC Pediatrics SC Pediatrics GA AU9GO UT WOS:000345900000016 PM 25436847 ER PT J AU Jones, M Huttner, B Leecaster, M Huttner, A Damal, K Tanner, W Nielson, C Rubin, MA Goetz, MB Madaras-Kelly, K Samore, MH AF Jones, Makoto Huttner, Benedikt Leecaster, Molly Huttner, Angela Damal, Kavitha Tanner, Windy Nielson, Christopher Rubin, Michael A. Goetz, Matthew Bidwell Madaras-Kelly, Karl Samore, Matthew H. TI Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010 SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE vancomycin; empirical treatment; definitive treatment ID RESISTANT STAPHYLOCOCCUS-AUREUS; SOFT-TISSUE INFECTIONS; INTENSIVE-CARE UNITS; ANTIMICROBIAL SUSCEPTIBILITY; LATIN-AMERICA; THERAPY; SKIN; TRANSMISSION; PERFORMANCE; PNEUMONIA AB After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. Among 569aEuroS815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2-8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%-97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1-3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy. C1 [Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Rubin, Michael A.; Samore, Matthew H.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA. [Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Rubin, Michael A.; Samore, Matthew H.] Univ Utah, Salt Lake City, UT USA. [Tanner, Windy] Univ Utah, Dept Family & Preventat Med, Salt Lake City, UT USA. [Nielson, Christopher] VA Reno Med Ctr, Reno, NV USA. [Nielson, Christopher] Univ Nevada, Reno, NV 89557 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Madaras-Kelly, Karl] Vet Affairs Med Ctr, Clin Pharm Serv, Boise, ID USA. RP Jones, M (reprint author), VA Salt Lake City Hlth Care Syst, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM makoto.jones@va.gov RI Huttner, Benedikt/M-5616-2014 OI Huttner, Benedikt/0000-0002-1749-9464 FU VA Consortium for Health Informatics Research (CHIR) [HIR 09-001, HIR 09-003]; VA Informatics and Computing Infrastructure (VINCI) [HIR 08-204]; Centers for Disease Control and Prevention Epicenter [5U01CI000334, 07FED706504]; Geneva University Hospitals, Switzerland; [CDA 10-030-02] FX This work was supported by using resources and facilities at the VA Salt Lake City Health Care System. Funding was provided by the VA Consortium for Health Informatics Research (CHIR) (grant numbers HIR 09-001 and HIR 09-003), the VA Informatics and Computing Infrastructure (VINCI) (HIR 08-204) and the Centers for Disease Control and Prevention Epicenter (5U01CI000334 and 07FED706504). In addition, M. J. was supported by a career development award (CDA 10-030-02) and B. H. was supported in part by a fellowship grant from Geneva University Hospitals, Switzerland. NR 29 TC 2 Z9 2 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2014 VL 69 IS 12 BP 3401 EP 3408 DI 10.1093/jac/dku299 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AU7FX UT WOS:000345767300032 PM 25103488 ER PT J AU Doyle, JO Lee, HJ Selesniemi, K Styer, AK Rueda, BR AF Doyle, Joseph O. Lee, Ho Joon Selesniemi, Kaisa Styer, Aaron K. Rueda, Bo R. TI The impact of vitrification on murine germinal vesicle oocyte In vitro maturation and aurora kinase A protein expression SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Vitrification; Aurora kinase; Oocyte; In vitro maturation ID MICROTUBULE-ORGANIZING CENTER; MEIOTIC SPINDLE; MOUSE OOCYTES; MEIOSIS-I; BOVINE OOCYTES; MATURE OOCYTES; C KINASE; CRYOPRESERVATION; CHROMOSOME; IMMATURE AB Purpose Investigate the effect of vitrification on in vitro maturation (IVM) and expression of Aurora kinases A, B, and C in germinal vesicle (GV)-stage oocytes. Methods GV-stage oocytes from B6D2F1 female mice 711 weeks of age were vitrified after collection, thawed, and matured in vitro for 0, 4, 8, and 12 h (hrs). The rate of germinal vesicle breakdown (GVBD), spindle apparatus assembly, and Aurora kinase mRNA and protein expression during IVM was measured. Results Oocyte vitrification was associated with significant delays in both GVBD and normal spindle apparatus assembly at 4 and 8 h of IVM (p<0.05). There was no difference in mRNA levels between control and vitrified oocytes for any of the Aurora kinases. Aurora A protein levels were reduced in vitrified compared to control oocytes at 0 h (p=0.008), and there was no difference at 4 and 8 h (p=0.08 and 0.69, respectively) of IVM. Conclusions Vitrified oocytes have delayed GVBD and normal spindle assembly during in vitro maturation. Reduced levels of Aurora A protein immediately post-thaw may be associated with the impaired oocyte maturation manifested by the delayed progression through meiosis I and II, and the atypical timing of the formation of meiotic spindles in vitrified GV-stage oocytes. C1 [Doyle, Joseph O.; Lee, Ho Joon; Selesniemi, Kaisa; Styer, Aaron K.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, MGH Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Doyle, Joseph O.; Styer, Aaron K.; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, MGH Vincent Dept Obstet & Gynecol, Thier 9,55 Fruit St, Boston, MA 02114 USA. EM brueda@MGH.Harvard.edu FU Vincent Memorial Research Funds FX The authors would like to express their gratitude to the Tang lab for providing Aurora C antibody and to Thomas Toth, M.D. for editorial support. We appreciate the technical efforts of Sanaz Ghazal, M.D. The authors would also like to thank Jonathan L. Tilly, PhD for his contributions related to the design of the experiments and interpretation of the results. This work was funded by the Vincent Memorial Research Funds. NR 32 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 EI 1573-7330 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD DEC PY 2014 VL 31 IS 12 BP 1695 EP 1702 DI 10.1007/s10815-014-0336-7 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA AU7FK UT WOS:000345766000017 PM 25318984 ER PT J AU Neill, US Nathan, D AF Neill, Ushma S. Nathan, David TI A conversation with David Nathan SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 [Nathan, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nathan, David] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2014 VL 124 IS 12 BP 5090 EP 5091 DI 10.1172/JCI78143 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200002 ER PT J AU Le, MTN Hamar, P Guo, CY Basar, E Perdigao-Henriques, R Balaj, L Lieberman, J AF Le, Minh T. N. Hamar, Peter Guo, Changying Basar, Emre Perdigao-Henriques, Ricardo Balaj, Leonora Lieberman, Judy TI miR-200-containing extracellular vesicles promote breast cancer cell metastasis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MIRNA-200 FAMILY; MIR-200 FAMILY; TUMOR; MICRORNA; COLONIZATION; PROGRESSION; BIOMARKER; REQUIRES; MARKERS; FLUID AB Metastasis is associated with poor prognosis in breast cancer patients. Not all cancer cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family, which regulates the mesenchymal-to-epithelial transition, is enriched in the serum of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic ability to poorly metastatic tumor cells in some settings. Here, we investigated whether metastatic capability could be transferred between metastatic and nonmetastatic cancer cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from metastatic murine and human breast cancer cell lines, and miR-200 levels were increased in sera of mice bearing metastatic tumors. In culture, murine and human metastatic breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic cells, altering gene expression and promoting mesenchymal-to-epithelial transition. In murine cancer and human xenograft models, miR-200 expressing tumors and extracellular vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells either nearby or at distant sites and conferred to these cells the ability to colonize distant tissues in a miR-200 dependent manner. Together, our results demonstrate that metastatic capability can be transferred by the uptake of extracellular vesicles. C1 [Le, Minh T. N.; Hamar, Peter; Guo, Changying; Basar, Emre; Perdigao-Henriques, Ricardo; Lieberman, Judy] Boston Childrens Hosp, Cellular & Mol Med Program, Boston, MA 02115 USA. [Le, Minh T. N.; Hamar, Peter; Guo, Changying; Basar, Emre; Perdigao-Henriques, Ricardo; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hamar, Peter] Semmelweis Univ, Inst Pathophysiol, H-1085 Budapest, Hungary. [Perdigao-Henriques, Ricardo] Univ Nova Lisboa, Inst Tecnol Quim & Biol, Anim Cell Technol Unit, Oeiras, Portugal. [Perdigao-Henriques, Ricardo] Inst Biol Expt & Tecnol, Oeiras, Portugal. [Balaj, Leonora] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci, Boston, MA USA. RP Lieberman, J (reprint author), Boston Childrens Hosp, Cellular & Mol Med Program, 200 Longwood Ave,WAB Room 255, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015; OI LE, Thi Nguyet Minh/0000-0002-6077-1566 FU Jane Coffin Childs Fund [61-1465]; Fulbright Visiting Scholar grant [1213204]; Portuguese Ministry of Science and Technology [SFRH/BD/37188/2007] FX This work was supported by the Jane Coffin Childs Fund (project no. 61-1465 to M.T.N. Le), a Fulbright Visiting Scholar grant (1213204 to P. Hamar), and a Portuguese Ministry of Science and Technology Ph.D. fellowship (SFRH/BD/37188/2007 to R. Perdigao-Henriques). The authors thank members of the Lieberman and Breakefield labs, Daniel Pregibon (Firefly BioWorks), Wai Leong Tam (Whitehead Institute), Andrew Kung (Columbia University), and Pierre-Yves Mantel (Harvard School of Public Health) for helpful suggestions. NR 29 TC 49 Z9 51 U1 2 U2 18 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 DEC PY 2014 VL 124 IS 12 BP 5109 EP 5128 DI 10.1172/JCI75695 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200008 PM 25401471 ER PT J AU Kim, J Fox, C Peng, S Pusung, M Pectasides, E Matthee, E Hong, YS Do, IG Jang, J Thorner, AR Van Hummelen, P Rustgi, AK Wong, KK Zhou, ZR Tang, P Kim, KM Lee, J Bass, AJ AF Kim, Jihun Fox, Cameron Peng, Shouyong Pusung, Mark Pectasides, Eirini Matthee, Eric Hong, Yong Sang Do, In-Gu Jang, Jiryeon Thorner, Aaron R. Van Hummelen, Paul Rustgi, Anil K. Wong, Kwok-Kin Zhou, Zhongren Tang, Ping Kim, Kyoung-Mee Lee, Jeeyun Bass, Adam J. TI Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; UTERINE SEROUS CARCINOMA; COPY-NUMBER ALTERATION; LABEL PHASE-3 TRIAL; GASTRIC-CANCER; BREAST-CANCER; ESOPHAGEAL ADENOCARCINOMA; TYROSINE KINASE; GENOMIC ALTERATIONS; LUNG-CANCER AB Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials. C1 [Kim, Jihun; Fox, Cameron; Peng, Shouyong; Pusung, Mark; Pectasides, Eirini; Matthee, Eric; Hong, Yong Sang; Van Hummelen, Paul; Wong, Kwok-Kin; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kim, Jihun; Peng, Shouyong; Bass, Adam J.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Kim, Jihun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. [Pectasides, Eirini] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Matthee, Eric] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Hong, Yong Sang] Univ Ulsan, Sch Med, Dept Internal Med, Seoul, South Korea. [Do, In-Gu; Kim, Kyoung-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Jang, Jiryeon; Lee, Jeeyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med, Seoul, South Korea. [Thorner, Aaron R.; Van Hummelen, Paul] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Rustgi, Anil K.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Wong, Kwok-Kin; Bass, Adam J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zhou, Zhongren] Univ Rochester, Dept Surg, Rochester, NY USA. [Tang, Ping] Univ Rochester, Dept Pathol & Lab Med, Rochester, NY USA. [Bass, Adam J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM adam_bass@dfci.harvard.edu FU AGA-Funberburg Award in Gastric Cancer Biology; Phi Beta Psi Sorority; American Cancer Society; NIH [P01 CA098101, R01 DK060694, R01 DK056645, P30 DK050306] FX A.J. Bass was supported by the AGA-Funberburg Award in Gastric Cancer Biology, the Phi Beta Psi Sorority, and a Research Scholar Grant from the American Cancer Society. A.K. Rustgi, K.K. Wong, and A.J. Bass were supported by NIH grant P01 CA098101. A.K. Rustgi was also supported by NIH grants R01 DK060694, R01 DK056645, and P30 DK050306. NR 55 TC 12 Z9 13 U1 0 U2 7 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 DEC PY 2014 VL 124 IS 12 BP 5145 EP 5158 DI 10.1172/JCI75200 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200010 PM 25401468 ER PT J AU Howarth, MM Simpson, D Ngok, SP Nieves, B Chen, R Siprashvili, Z Vaka, D Breese, MR Crompton, BD Alexe, G Hawkins, DS Jacobson, D Brunner, AL West, R Mora, J Stegmaier, K Khavari, P Sweet-Cordero, EA AF Howarth, Michelle Marques Simpson, David Ngok, Siu P. Nieves, Bethsaida Chen, Ron Siprashvili, Zurab Vaka, Dedeepya Breese, Marcus R. Crompton, Brian D. Alexe, Gabriela Hawkins, Doug S. Jacobson, Damon Brunner, Alayne L. West, Robert Mora, Jaume Stegmaier, Kimberly Khavari, Paul Sweet-Cordero, E. Alejandro TI Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIFFERENTIAL EXPRESSION ANALYSIS; DAVID BIOINFORMATICS RESOURCES; MESENCHYMAL STEM-CELLS; TARGET GENE; TRANSCRIPTIONAL REPRESSION; PROGENITOR CELLS; PROSTATE-CANCER; FUSION GENE; HNRNP-K; IN-VIVO AB Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma-associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes. C1 [Howarth, Michelle Marques; Simpson, David; Ngok, Siu P.; Nieves, Bethsaida; Chen, Ron; Vaka, Dedeepya; Breese, Marcus R.; Sweet-Cordero, E. Alejandro] Stanford Univ, Sch Med, Div Hematol Oncol Stem Cell Transplantat & Canc B, Dept Pediat, Stanford, CA 94305 USA. [Siprashvili, Zurab; Khavari, Paul] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA. [Crompton, Brian D.; Alexe, Gabriela; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Crompton, Brian D.; Alexe, Gabriela; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Hawkins, Doug S.; Jacobson, Damon] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Div Hematol Oncol, Seattle, WA 98195 USA. [Brunner, Alayne L.; West, Robert] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Mora, Jaume] Hosp San Juan Dios, Dept Pediat Oncol, Barcelona, Spain. [Khavari, Paul] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. RP Sweet-Cordero, EA (reprint author), 265 Campus Dr,LLSCRB 2078B, Stanford, CA 94305 USA. EM ascor@stanford.edu; ascor@stanford.edu RI Vaka, Dedeepya/L-9041-2016; OI Breese, Marcus/0000-0002-6870-0228; Vaka, Dedeepya/0000-0001-7951-5514 FU Doris Duke Clinical Scientist Development Fund; St. Baldrick's Foundation; Kavner Family Fund; Hope Street Kids Foundation; Sunbeam Foundation; Elsa U. Pardee Foundation; Bear Necessities Foundation; Hyundai Hope on Wheels; National Cancer Institute of the NIH [T32CA009302]; Stanford Graduate Fellowship FX We thank the members of the Sweet-Cordero lab and the labs of Laura Attardi, Steven Artandi, and Julien Sage for useful comments and advice. We thank Howard Chang, Arend Sidow, Javed Khan, and Maite Huarte for protocols and useful discussions. We thank Fernando Lecanda for the inducible EWS-FLI1 vector. We thank Jonathan Pollack, Jae Cho, and Michael Clark for their generous gift of cancer cell lines. E.A. Sweet-Cordero received grant support from the Doris Duke Clinical Scientist Development Fund, the St. Baldrick's Foundation, the Kavner Family Fund, the Hope Street Kids Foundation, the Sunbeam Foundation, the Elsa U. Pardee Foundation, the Bear Necessities Foundation, and Hyundai Hope on Wheels. M.M. Howarth and D. Simpson were funded in part by the National Cancer Institute of the NIH under award number T32CA009302. R. Chen was funded by a Stanford Graduate Fellowship. NR 78 TC 8 Z9 8 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 DEC PY 2014 VL 124 IS 12 BP 5275 EP 5290 DI 10.1172/JC172124 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200020 ER PT J AU Barbie, TU Alexe, G Aref, AR Li, SQ Zhu, ZH Zhang, XL Imamura, Y Thai, TC Huang, Y Bowden, M Herndon, J Cohoon, TJ Fleming, T Tamayo, P Mesirov, JP Ogino, S Wong, KK Ellis, MJ Hahn, WC Barbie, DA Gillanders, WE AF Barbie, Thanh U. Alexe, Gabriela Aref, Amir R. Li, Shunqiang Zhu, Zehua Zhang, Xiuli Imamura, Yu Thai, Tran C. Huang, Ying Bowden, Michaela Herndon, John Cohoon, Travis J. Fleming, Timothy Tamayo, Pablo Mesirov, Jill P. Ogino, Shuji Wong, Kwok-Kin Ellis, Matthew J. Hahn, William C. Barbie, David A. Gillanders, William E. TI Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; IKK-EPSILON; INFLAMMATORY CYTOKINES; CELL-TRANSFORMATION; SIGNALING PATHWAY; VIRAL-INFECTION; JAK2 INHIBITOR; KINASE; STAT3; IDENTIFICATION AB Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible I kappa B kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK a lone does not. CYT387 treatment inhibited activation of both NF-kappa B and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. C1 [Barbie, Thanh U.; Zhang, Xiuli; Herndon, John; Fleming, Timothy; Gillanders, William E.] Washington Univ, Dept Surg, Div Biol & Biomed Sci, St Louis, MO USA. [Barbie, Thanh U.; Li, Shunqiang; Fleming, Timothy; Ellis, Matthew J.; Gillanders, William E.] Washington Univ, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Alexe, Gabriela; Zhu, Zehua; Thai, Tran C.; Tamayo, Pablo; Mesirov, Jill P.; Hahn, William C.; Barbie, David A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Alexe, Gabriela] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Alexe, Gabriela] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Alexe, Gabriela] Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA. [Aref, Amir R.; Zhu, Zehua; Imamura, Yu; Thai, Tran C.; Huang, Ying; Bowden, Michaela; Cohoon, Travis J.; Ogino, Shuji; Wong, Kwok-Kin; Hahn, William C.; Barbie, David A.] Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, Boston, MA 02115 USA. [Li, Shunqiang; Ellis, Matthew J.] Washington Univ, Div Med Oncol, St Louis, MO USA. RP Gillanders, WE (reprint author), 660 S Euclid Ave,Box 8109, St Louis, MO 63110 USA. EM William_Hahn@dfci.harvard.edu; dbarbie@partners.org; gillandersw@wudosis.wustl.edu OI Huang, Ying/0000-0003-1145-3606 FU NIH [T32 CA009621, P01 CA154303, R01 CA130988, K08 CA13891801A1]; US Department of Defense Breast Cancer Award [W81XWH-13-1-0029]; V Scholar, Gloria Spivak Faculty, GTM Fund for Lung Cancer Research, and Friends of the Dana-Farber Cancer Institute Awards FX We thank the HAMLET core for assistance with WHIM tumor propagation and the shRNA facility (RNAi Consortium, Children's Discovery Institute, and the Genome Institute) at Washington University School of Medicine. We thank Mahjobeh Rahimian Mashhadi and Yaser Masoudnia for assistance with 3D culture imaging. This work was supported in part by NIH grant T32 CA009621 and the US Department of Defense Breast Cancer Award W81XWH-13-1-0029 (to T.U. Barbie), NIH grants P01 CA154303 and R01 CA130988 (to W.C. Hahn), and NIH grant K08 CA13891801A1 (to D.A. Barbie). D.A. Barbie is supported by V Scholar, Gloria Spivak Faculty, GTM Fund for Lung Cancer Research, and Friends of the Dana-Farber Cancer Institute Awards. NR 53 TC 18 Z9 18 U1 2 U2 9 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 DEC PY 2014 VL 124 IS 12 BP 5411 EP 5423 DI 10.1172/JCI5661 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200030 PM 25365225 ER PT J AU Mak, RH Hunt, D Shipley, WU Efstathiou, JA Tester, WJ Hagan, MP Kaufman, DS Heney, NM Zietman, AL AF Mak, Raymond H. Hunt, Daniel Shipley, William U. Efstathiou, Jason A. Tester, William J. Hagan, Michael P. Kaufman, Donald S. Heney, Niall M. Zietman, Anthony L. TI Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; RADICAL CYSTECTOMY; TRANSURETHRAL SURGERY; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; ORGAN PRESERVATION; SPARING THERAPY; II TRIAL; RADIOTHERAPY; CISPLATIN AB Purpose Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies. Patients and Methods Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method. Results The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively. Conclusion This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery. (C) 2014 by American Society of Clinical Oncology C1 [Mak, Raymond H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mak, Raymond H.; Shipley, William U.; Efstathiou, Jason A.; Kaufman, Donald S.; Heney, Niall M.; Zietman, Anthony L.] Harvard Univ, Sch Med, Boston, MA USA. [Shipley, William U.; Efstathiou, Jason A.; Kaufman, Donald S.; Heney, Niall M.; Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hunt, Daniel] Radiat Therapy Oncol Grp Stat Ctr, Philadelphia, PA USA. [Tester, William J.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Hagan, Michael P.] Vet Hlth Adm, Richmond, VA USA. RP Mak, RH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM rmak@lroc.harvard.edu FU Radiation Therapy Oncology Group Grant from the National Cancer Institute [U10 CA21661]; Community Clinical Oncology Program from the National Cancer Institute [U10 CA37422] FX Supported by Radiation Therapy Oncology Group Grant No. U10 CA21661 and Community Clinical Oncology Program Grant No. U10 CA37422 from the National Cancer Institute. NR 34 TC 43 Z9 44 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2014 VL 32 IS 34 BP 3801 EP U188 DI 10.1200/JCO.2014.57.5548 PG 11 WC Oncology SC Oncology GA AU9ID UT WOS:000345904300007 PM 25366678 ER PT J AU O'Shaughnessy, J Schwartzberg, L Danso, MA Miller, KD Rugo, HS Neubauer, M Robert, N Hellerstedt, B Saleh, M Richards, P Specht, JM Yardley, DA Carlson, RW Finn, RS Charpentier, E Garcia-Ribas, I Winer, EP AF O'Shaughnessy, Joyce Schwartzberg, Lee Danso, Michael A. Miller, Kathy D. Rugo, Hope S. Neubauer, Marcus Robert, Nicholas Hellerstedt, Beth Saleh, Mansoor Richards, Paul Specht, Jennifer M. Yardley, Denise A. Carlson, Robert W. Finn, Richard S. Charpentier, Eric Garcia-Ribas, Ignacio Winer, Eric P. TI Phase III Study of Iniparib Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin in Patients With Metastatic Triple-Negative Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CISPLATIN; SUBTYPES; TRIAL; GEMCITABINE/CARBOPLATIN; CHEMOSENSITIVITY; TRASTUZUMAB; SURVIVAL; THERAPY AB Purpose There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients and Methods Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Results Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. Conclusion The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation. (C) 2014 by American Society of Clinical Oncology C1 [O'Shaughnessy, Joyce] Baylor Charles A Sammons Canc Ctr, Dallas, TX 75246 USA. [O'Shaughnessy, Joyce] US Oncol, Dallas, TX USA. [O'Shaughnessy, Joyce] Beth Hellerstedt Texas Oncol Round Rock, Austin, TX USA. [Schwartzberg, Lee] Accelerated Community Oncol Res Network, Memphis, TN USA. [Schwartzberg, Lee] West Clin, Memphis, TN USA. [Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Yardley, Denise A.] Tennessee Oncol, Nashville, TN USA. [Danso, Michael A.] Virginia Oncol Assoc, Norfolk, VA USA. [Robert, Nicholas] Virginia Canc Specialists, Fairfax, VA USA. [Richards, Paul] Blue Ridge Canc Care, Salem, VA USA. [Miller, Kathy D.] Indiana Univ Melvin, Indianapolis, IN USA. [Miller, Kathy D.] Bren Simon Canc Ctr, Indianapolis, IN USA. [Rugo, Hope S.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Carlson, Robert W.] Stanford Comprehens Canc Ctr, Palo Alto, CA USA. [Finn, Richard S.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. [Finn, Richard S.] Translat Res Oncol, Los Angeles, CA USA. [Neubauer, Marcus] Kansas City Canc City, Overland Pk, KS USA. [Saleh, Mansoor] Georgia Canc Specialists, Sandy Springs, GA USA. [Specht, Jennifer M.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Charpentier, Eric; Garcia-Ribas, Ignacio] Sanofi, Cambridge, England. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP O'Shaughnessy, J (reprint author), Baylor Charles A Sammons Canc Ctr, 3410 Worth St, Dallas, TX 75246 USA. EM joyce.oshaughnessy@usoncology.com OI Specht, Jennifer/0000-0003-1484-2113 FU Sanofi FX We thank the patients, their families, and the investigators who participated in this study. We also thank Matthew Naylor, who provided medical writing support funded by Sanofi. We also thank Wenjuan Zhang for programming support. NR 24 TC 62 Z9 64 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2014 VL 32 IS 34 BP 3840 EP U232 DI 10.1200/JCO.2014.55.2984 PG 9 WC Oncology SC Oncology GA AU9ID UT WOS:000345904300012 PM 25349301 ER PT J AU McAllister, C Leykum, LK Lanham, H Reisinger, HS Kohn, JL Palmer, R Pezzia, C Agar, M Parchman, M Pugh, J McDaniel, RR AF McAllister, Caitlin Leykum, Luci K. Lanham, Holly Reisinger, Heather Schacht Kohn, Jamie L. Palmer, Ray Pezzia, Carla Agar, Michael Parchman, Michael Pugh, Jacqueline McDaniel, Reuben R., Jr. TI Relationships Within Inpatient Physician Housestaff Teams and Their Association With Hospitalized Patient Outcomes SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID HEALTH-CARE; QUALITY; IMPLEMENTATION; KNOWLEDGE; MORTALITY; FAILURE; PROGRAM AB IMPORTANCEImproving inpatient care delivery has historically focused on improving individual components of the system. Applying the complexity science framework to clinical systems highlights the important role of relationships among providers in influencing system function and clinical outcomes. OBJECTIVETo understand whether inpatient medical physician teams can be differentiated based on the relationships among team members, and whether these relationships are associated with patient outcomes, including length of stay (LOS), unnecessary length of stay (ULOS), and complication rates. DESIGNEleven inpatient medicine teams were observed daily during attending rounds for 2- to 4-week periods from September 2008 through June 2011. Detailed field notes were taken regarding patient care activities, team behaviors, and patient characteristics and outcomes. Behaviors were categorized using the Lanham relationship framework, giving each team a relationship score. We used factor analysis to assess the pattern of relationship characteristics and assessed the association between relationship characteristics and patient outcomes. SETTINGObservations occurred at the Audie L. Murphy Veterans Affairs Hospital and University Hospital in San Antonio, Texas. PARTICIPANTSPhysicians were chosen based on rotation schedules, experience, and time of year. Patients were included based on their admission to the inpatient medicine teams that were being observed. MAIN MEASURESRelationship scores were based on the presence or absence of 7 relationship characteristics. LOS, ULOS, and complication rates were assessed based on team discussions and chart review. The association between relationships and outcomes was assessed using the Kruskal-Wallis rank sum test. RESULTSWe observed 11 teams over 352.9 hours, observing 1941 discussions of 576 individual patients. Teams exhibited a range of 0 to 7 relationship characteristics. Relationship scores were significantly associated with complication rates, and presence of trust and mindfulness among teams was significantly associated with ULOS and complication rates. CONCLUSIONSOur findings are an important step in understanding the impact of relationships on the outcomes of hospitalized medical patients. This understanding could expand the scope of interventions to improve hospital care to include not only process improvement but also relationships among providers. Journal of Hospital Medicine 2014;9:764-771. (c) 2014 Society of Hospital Medicine C1 [McAllister, Caitlin] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly; Pezzia, Carla; Pugh, Jacqueline] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Leykum, Luci K.; Pezzia, Carla; Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Lanham, Holly; McDaniel, Reuben R., Jr.] Univ Texas Austin, McCombs Sch Business, Dept Management Sci & Informat Syst, Austin, TX 78712 USA. [Reisinger, Heather Schacht] Iowa City VA Hlth Care Syst, Dept Med, Iowa City, IA USA. [Reisinger, Heather Schacht] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Kohn, Jamie L.] Univ N Carolina, Kenan Flagler Business Sch, Chapel Hill, NC USA. [Palmer, Ray] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Agar, Michael] Ethknoworks LLC, Santa Fe, NM USA. [Parchman, Michael] Grp Hlth Res Inst, MacColl Ctr Hlth Care Innovat, Seattle, WA USA. RP Leykum, LK (reprint author), 7400 Merton Minter, San Antonio, TX 78229 USA. EM leykum@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 07-022] FX The research reported herein was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 07-022). Investigator salary support was provided through this funding, and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. Dr. McDaniel receives support from the IC2 Institute of the University of Texas at Austin. Dr. Luci Leykum had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no conflicts of interest. NR 35 TC 7 Z9 7 U1 0 U2 8 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 DEC PY 2014 VL 9 IS 12 BP 764 EP 771 DI 10.1002/jhm.2274 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AU9LE UT WOS:000345913400004 PM 25355652 ER PT J AU Jenkins, TC Knepper, BC Moore, SJ Saveli, CC Pawlowski, SW Perlman, DM McCollister, BD Burman, WJ AF Jenkins, Timothy C. Knepper, Bryan C. Moore, S. Jason Saveli, Carla C. Pawlowski, Sean W. Perlman, Daniel M. McCollister, Bruce D. Burman, William J. TI Comparison of the Microbiology and Antibiotic Treatment Among Diabetic and Nondiabetic Patients Hospitalized for Cellulitis or Cutaneous Abscess SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SOFT-TISSUE INFECTIONS; DISEASES SOCIETY; COMPLICATED SKIN; PRACTICE GUIDELINES; FOOT INFECTIONS; AMERICA; MULTICENTER; MANAGEMENT; DIAGNOSIS; MORTALITY AB BACKGROUNDAmong diabetics, complicated skin infections may involve gram-negative pathogens; however, the microbiology of cellulitis and cutaneous abscess is not well established. OBJECTIVETo compare the microbiology and prescribing patterns between diabetics and nondiabetics hospitalized for cellulitis or abscess. DESIGNSecondary analysis of 2 published retrospective cohorts. SETTING/PATIENTSAdults hospitalized for cellulitis or abscess, excluding infected ulcers or deep tissue infections, at 7 academic and community facilities. METHODSMicrobiological findings and antibiotic use were compared among diabetics and nondiabetics. Multivariable logistic regression was performed to identify factors associated with exposure to broad gram-negative therapy, defined as receipt of at least 2 calendar days of -lactamase inhibitors, second- to fifth-generation cephalosporins, fluoroquinolones, carbapenems, tigecycline, aminoglycosides, or colistin. RESULTSOf 770 total patients with cellulitis or abscess, 167 (22%) had diabetes mellitus. Among the 38% of cases with a positive culture, an aerobic gram-positive organism was isolated in 90% of diabetics and 92% of nondiabetics (P=0.59); aerobic gram-negative organisms were isolated in 7% and 12%, respectively (P=0.28). Overall, diabetics were more likely than nondiabetics to be exposed to broad gram-negative therapy (54% vs 44% of cases, P=0.02). By logistic regression, diabetes mellitus was independently associated with exposure to broad gram-negative therapy (odds ratio: 1.66, 95% confidence interval: 1.15-2.40). CONCLUSIONIn cases of cellulitis or abscess associated with a positive culture, gram-negative pathogens were not more common among diabetics compared with nondiabetics. However, diabetics were overall more likely to be exposed to broad gram-negative therapy suggesting this prescribing practice may not be not warranted. Journal of Hospital Medicine 2014;9:788-794. (c) 2014 Society of Hospital Medicine C1 [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Dept Med, Denver, CO USA. [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Div Infect Dis, Denver, CO USA. [Jenkins, Timothy C.; Saveli, Carla C.; McCollister, Bruce D.; Burman, William J.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Jenkins, Timothy C.; Saveli, Carla C.; McCollister, Bruce D.; Burman, William J.] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA. [Knepper, Bryan C.] Denver Hlth, Dept Patient Safety & Qual, Denver, CO USA. [Moore, S. Jason] Vail Valley Med Ctr, Dept Trauma & Crit Care Serv, Vail, CO USA. [Pawlowski, Sean W.] Colorado Infect Dis Associates, Denver, CO USA. [Perlman, Daniel M.] Porter Adventist Med Ctr, Dept Med, Denver, CO USA. [McCollister, Bruce D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [McCollister, Bruce D.] Denver Vet Affairs Med Ctr, Div Infect Dis, Denver, CO USA. [Burman, William J.] Denver Hlth, Denver Publ Hlth, Denver, CO USA. RP Jenkins, TC (reprint author), 660 Bannock St, Denver, CO 80204 USA. EM timothy.jenkins@dhha.org FU National Institute of Allergy and Infectious Diseases, National Institute of Health [TCJ: K23 AI099082] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institute of Health (TCJ: K23 AI099082). D.M.P. reports potential conflicts of interests with Optimer, Cubist, and Forest Pharmaceuticals. The authors report no other conflicts of interest. NR 16 TC 1 Z9 1 U1 0 U2 2 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 DEC PY 2014 VL 9 IS 12 BP 788 EP 794 DI 10.1002/jhm.2267 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AU9LE UT WOS:000345913400007 PM 25266293 ER PT J AU Wang, C Abdel-Mohsen, M Strain, MC Lada, SM Yukl, S Cockerham, LR Pilcher, CD Hecht, FM Sinclair, E Liegler, T Richman, DD Deeks, SG Pillai, SK AF Wang, Charlene Abdel-Mohsen, Mohamed Strain, Matthew C. Lada, Steven M. Yukl, Steven Cockerham, Leslie R. Pilcher, Christopher D. Hecht, Frederick M. Sinclair, Elizabeth Liegler, Teri Richman, Douglas D. Deeks, Steven G. Pillai, Satish K. TI Decreased HIV Type 1 Transcription in CCR5-Delta 32 Heterozygotes During Suppressive Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; CCR5; Delta 32; coreceptor; reservoir; latency; eradication; NF-kappa B; HIV transcription; HIV replication ID T-CELL-ACTIVATION; DISEASE PROGRESSION; CCR5; REPLICATION; INFECTION; RNA AB Individuals who are heterozygous for the CCR5-Delta 32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Delta 32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P = .035), RNA to DNA transcriptional ratios (P = .013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P = .013) were significantly lower in CD4(+) T cells from CCR5-Delta 32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4(+) T cells (r(2) = 0.136; P = .002). Our findings suggest that curative strategies should further explore manipulation of CCR5. C1 [Wang, Charlene] Emory Univ, Atlanta, GA 30322 USA. [Wang, Charlene; Abdel-Mohsen, Mohamed; Pillai, Satish K.] Blood Syst Res Inst, San Francisco, CA USA. [Abdel-Mohsen, Mohamed; Yukl, Steven; Cockerham, Leslie R.; Pilcher, Christopher D.; Hecht, Frederick M.; Sinclair, Elizabeth; Liegler, Teri; Deeks, Steven G.; Pillai, Satish K.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Yukl, Steven] San Francisco VA Med Ctr, San Francisco, CA USA. [Strain, Matthew C.; Lada, Steven M.; Richman, Douglas D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Strain, Matthew C.; Lada, Steven M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Pillai, SK (reprint author), Univ Calif San Francisco, Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM satish.pillai@ucsf.edu FU American Foundation for AIDS Research; FAIR [108545]; National Institutes of Health [R21 AI108503, R01 HD074511]; University of California-San Francisco Gladstone Institute of Virology and Immunology Center for AIDS Research [P30 AI027763]; Delaney AIDS Research Enterprise [U19 AI096109]; Collaboratory of AIDS Researchers for Eradication [U19 AI096113]; University of California-San Diego Center for AIDS Research [P30 AI036214]; James Pendleton Charitable Trust; U.S. Department of Veterans Affairs [1 IK2 CX000520-01] FX This work was supported by American Foundation for AIDS Research, with support from FAIR (grant 108545 to S. K. P.) and the National Institutes of Health (grants R21 AI108503 [to S. K. P.] and R01 HD074511 [to C. D. P.]); the University of California-San Francisco Gladstone Institute of Virology and Immunology Center for AIDS Research (grant P30 AI027763); the Delaney AIDS Research Enterprise (grant U19 AI096109); the Collaboratory of AIDS Researchers for Eradication (grant U19 AI096113); the University of California-San Diego Center for AIDS Research (grant P30 AI036214 to D. D. R.); the James Pendleton Charitable Trust (support to D. D. R.); and the U.S. Department of Veterans Affairs (grant 1 IK2 CX000520-01 to S. Y.). NR 15 TC 5 Z9 5 U1 0 U2 5 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 DEC 1 PY 2014 VL 210 IS 11 BP 1838 EP 1843 DI 10.1093/infdis/jiu338 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HI UT WOS:000345771000018 PM 24935955 ER PT J AU Tam, JM Mansour, MK Khan, NS Seward, M Puranam, S Tanne, A Sokolovska, A Becker, CE Acharya, M Baird, MA Choi, AMK Davidson, MW Segal, BH Lacy-Hulbert, A Stuart, LM Xavier, RJ Vyas, JM AF Tam, Jenny M. Mansour, Michael K. Khan, Nida S. Seward, Michael Puranam, Sravanthi Tanne, Antoine Sokolovska, Anna Becker, Christine E. Acharya, Mridu Baird, Michelle A. Choi, Augustine M. K. Davidson, Michael W. Segal, Brahm H. Lacy-Hulbert, Adam Stuart, Lynda M. Xavier, Ramnik J. Vyas, Jatin M. TI Dectin-1-Dependent LC3 Recruitment to Phagosomes Enhances Fungicidal Activity in Macrophages SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE dectin-1; autophagy; LC3; Candida albicans; ROS; NADPH oxidase ID NADPH OXIDASE; INFLAMMATORY RESPONSES; ASPERGILLUS-FUMIGATUS; FUNGAL-INFECTIONS; INNATE IMMUNITY; DECTIN-1; AUTOPHAGY; RECOGNITION; INDUCTION; RECEPTOR AB Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages. C1 [Tam, Jenny M.; Mansour, Michael K.; Khan, Nida S.; Seward, Michael; Puranam, Sravanthi; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Sokolovska, Anna] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Becker, Christine E.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Becker, Christine E.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Becker, Christine E.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Tam, Jenny M.; Mansour, Michael K.; Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Becker, Christine E.; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Tanne, Antoine] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Choi, Augustine M. K.] Weill Cornell Med Coll, New York, NY USA. [Segal, Brahm H.] SUNY Buffalo, Sch Med, Roswell Pk Canc Inst, New York, NY USA. [Acharya, Mridu; Lacy-Hulbert, Adam; Stuart, Lynda M.] Benaroya Res Inst, Seattle, WA USA. [Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. RP Vyas, JM (reprint author), 55 Fruit St,GRJ 5-504, Boston, MA 02114 USA. EM jvyas@partners.org FU National Institute of Allergy and Infectious Diseases [1R01AI092084, 1R01AI097519, R01AI079253]; National Heart, Lung, and Blood Institute [R01HL055330] FX This work was supported by the National Institute of Allergy and Infectious Diseases (grants 1R01AI092084 and 1R01AI097519; grant R01AI079253 to B. H. S.) and the National Heart, Lung, and Blood Institute (grant R01HL055330 to A. M. K. C.). NR 48 TC 16 Z9 16 U1 0 U2 5 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 DEC 1 PY 2014 VL 210 IS 11 BP 1844 EP 1854 DI 10.1093/infdis/jiu290 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HI UT WOS:000345771000019 PM 24842831 ER PT J AU Hughes, MS Atkins, EJ Cestari, DM Stacy, RC Hochberg, F AF Hughes, Michael S. Atkins, Edward J. Cestari, Dean M. Stacy, Rebecca C. Hochberg, Fred TI Isolated Optic Nerve, Chiasm, and Tract Involvement in Bing-Neel Syndrome SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID WALDENSTROMS MACROGLOBULINEMIA; NEUROMYELITIS-OPTICA; ORBITAL INVOLVEMENT; LYMPHOMA; AUTOIMMUNITY; ASSOCIATION; ANTIBODIES; COMPLEMENT; NEUROPATHY; IGM AB Central nervous system infiltration of Waldenstrom's macroglobulinemia is referred to as Bing-Neel Syndrome. We describe 2 patients whose clinical presentation was due to isolated involvement of the anterior visual pathways. The mechanism of visual failure in Bing-Neel Syndrome may involve both infiltrative and autoimmune processes. (C) 2014 by North American Neuro-Ophthalmology Society C1 [Hughes, Michael S.] Harvard Univ, Cambridge, MA 02138 USA. [Atkins, Edward J.] Univ Saskatchewan, Saskatoon, SK S7N 0W0, Canada. [Cestari, Dean M.; Stacy, Rebecca C.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hochberg, Fred] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hochberg, F (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 27 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2014 VL 34 IS 4 BP 340 EP 345 DI 10.1097/WNO.0000000000000138 PG 6 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AU8QL UT WOS:000345861100008 PM 25409481 ER PT J AU Yoon, MK Piluek, WJ Ruggiero, JP McDermott, MW McCulley, TJ AF Yoon, Michael K. Piluek, Wachirapon Jordan Ruggiero, Jason P. McDermott, Michael W. McCulley, Timothy J. TI Orbital Cerebrospinal Fluid Accumulation After Complicated Pterional-Orbitozygomatic Craniotomy SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID SKULL BASE; SURGERY; PRESSURE; TEARS; SINUS; CYST AB We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure. (C) 2014 by North American Neuro-Ophthalmology Society C1 [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Piluek, Wachirapon Jordan; McCulley, Timothy J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Ruggiero, Jason P.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [McDermott, Michael W.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. RP McCulley, TJ (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 North Wolfe St,Wilmer 110, Baltimore, MD 21287 USA. EM tmccull5@jhmi.edu FU Research to Prevent Blindness, Inc. FX Supported in part by an unrestricted grant to the Wilmer Ophthalmological Institute by Research to Prevent Blindness, Inc. NR 20 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2014 VL 34 IS 4 BP 346 EP 349 DI 10.1097/WNO.0000000000000125 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AU8QL UT WOS:000345861100009 PM 24699141 ER PT J AU Murthy, VL Lee, BC Sitek, A Naya, M Moody, J Polavarapu, V Ficaro, EP Di Carli, MF AF Murthy, Venkatesh L. Lee, Benjamin C. Sitek, Arkadiusz Naya, Masanao Moody, Jonathan Polavarapu, Vivek Ficaro, Edward P. Di Carli, Marcelo F. TI Comparison and Prognostic Validation of Multiple Methods of Quantification of Myocardial Blood Flow with Rb-82 PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE myocardial perfusion imaging; myocardial flow reserve; Rb-82 ID POSITRON-EMISSION-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; VASCULAR DYSFUNCTION; N-13-AMMONIA PET; RESERVE; PERFUSION; REPRODUCIBILITY; ASSOCIATION; OUTCOMES; HEART AB The quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) using PET with Rb-82 in patients with known or suspected coronary artery disease has been demonstrated to have substantial prognostic and diagnostic value. However, multiple methods for estimation of an image-derived input function and several models for the nonlinear first-pass extraction of Rb-82 by myocardium have been used. We sought to compare the differences in these methods and models and their impact on prognostic assessment in a large clinical dataset. Methods: Consecutive patients (n = 2,783) underwent clinically indicated rest-stress myocardial perfusion PET with Rb-82. The input function was derived using a region of interest (ROI) semiautomatically placed in the region of the mitral valve, factor analysis, and a hybrid method that creates an ROI from factor analysis. We used 5 commonly used extraction models for Rb-82 to estimate MBF and MFR. Pearson correlations, bias, and Cohen. were computed for the various measures. The relationship between MFR/stress MBF and annual rate of cardiac mortality was estimated with spline fits using Poisson regression. Finally, incremental value was assessed with the net reclassification improvement using Cox proportional hazards regression. Results: Correlations between MFR or stress MBF measures made with the same input function derivation method were generally high, regardless of extraction model used (Pearson r > 0.90). However, correlations between measures derived with the ROI method and other methods were only moderate (Pearson r = 0.42-0.62). Importantly, substantial biases were seen for most combinations. We saw that the relationship between cardiac mortality and stress MBF was variable depending on the input function method and extraction model, whereas the relationship between MFR and risk was highly consistent. Net reclassification improvement was comparable for most methods and models for MFR but was highly variable for stress MBF. Conclusion: Although both stress MBF and MFR can improve prognostic assessment, MFR is substantially more consistent, regardless of choice of input function derivation method and extraction model used. C1 [Murthy, Venkatesh L.; Naya, Masanao; Di Carli, Marcelo F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Murthy, Venkatesh L.; Naya, Masanao; Di Carli, Marcelo F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Murthy, Venkatesh L.; Polavarapu, Vivek; Ficaro, Edward P.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. [Lee, Benjamin C.; Moody, Jonathan; Ficaro, Edward P.] INVIA Med Imaging Solut, Ann Arbor, MI USA. [Sitek, Arkadiusz] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Murthy, VL (reprint author), Univ Michigan, 1500 E Med Ctr Dr,SPC 5873, Ann Arbor, MI 48109 USA. EM vlmurthy@med.umich.edu RI Murthy, Venkatesh/B-3448-2013; OI Murthy, Venkatesh/0000-0002-7901-1321; Sitek, Arkadiusz/0000-0002-0677-4002 FU National Institutes of Health [T32HL094301-02]; Blahd Research grant from the Society of Nuclear Medicine and Molecular Imaging; Intersocietal Accreditation Council; INVIA Medical Imaging Solutions FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported in part by National Institutes of Health grant T32HL094301-02, the Blahd Research grant from the Society of Nuclear Medicine and Molecular Imaging, and research grants from the Intersocietal Accreditation Council and INVIA Medical Imaging Solutions. Dr. Ficaro owns equity in INVIA Medical Imaging Solutions. Dr. Sitek receives royalties related to factor analysis. Drs. Lee and Moody are employed by INVIA Medical Imaging Solutions. NR 34 TC 16 Z9 16 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2014 VL 55 IS 12 BP 1952 EP 1958 DI 10.2967/jnumed.114.145342 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU8EC UT WOS:000345828300010 PM 25429160 ER PT J AU Grace, PJ Robinson, EM Jurchak, M Zollfrank, AA Lee, SM AF Grace, Pamela J. Robinson, Ellen M. Jurchak, Martha Zollfrank, Angelika A. Lee, Susan M. TI Clinical Ethics Residency for Nurses An Education Model to Decrease Moral Distress and Strengthen Nurse Retention in Acute Care SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID WORK AB The experience of unaddressed moral distress can lead to nurse attrition and/or distancing from patients, compromising patient care. Nurses who are confident in their ethical decision making abilities and moral agency have the antidote to moral distress for themselves and their colleagues and can act as local or institutional ethics resources. We describe a grant-funded model education program designed to increase ethics competence throughout the institution. C1 [Grace, Pamela J.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02467 USA. [Robinson, Ellen M.; Zollfrank, Angelika A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jurchak, Martha] Brigham & Womens Hosp, Ctr Nursing Excellence, Eth Serv, Boston, MA 02115 USA. [Lee, Susan M.] Brigham & Womens Hosp, Ctr Nursing Excellence, Boston, MA 02115 USA. RP Grace, PJ (reprint author), Boston Coll, William F Connell Sch Nursing, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM Pamela.grace.2@bc.edu FU Division of Nursing (DN), Bureau of Health Professions (BHPr), Health Resources and Services Administration (HRSA), Department of Health and Human Services (DHHS) under Nurse Education, Practice, Quality, and Retention [D11HP18974] FX This project was supported by funds from the Division of Nursing (DN), Bureau of Health Professions (BHPr), Health Resources and Services Administration (HRSA), Department of Health and Human Services (DHHS) under D11HP18974, Nurse Education, Practice, Quality, and Retention. The information, content, and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any official endorsement be inferred by the DN, BHPr, HRSA, DHHS, or US Government. NR 25 TC 6 Z9 6 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD DEC PY 2014 VL 44 IS 12 BP 640 EP 646 DI 10.1097/NNA.0000000000000141 PG 7 WC Nursing SC Nursing GA AU8PT UT WOS:000345859400007 PM 25393140 ER PT J AU Winter, HS Krzeski, P Heyman, MB Ibarguen-Secchia, E Iwanczak, B Kaczmarski, M Kierkus, J Kolacek, S Osuntokun, B Quiros, JA Shah, M Yacyshyn, B Dunnmon, PM AF Winter, Harland S. Krzeski, Piotr Heyman, Melvin B. Ibarguen-Secchia, Eduardo Iwanczak, Barbara Kaczmarski, Maciej Kierkus, Jaroslaw Kolacek, Sanja Osuntokun, Bankole Quiros, J. Antonio Shah, Manoj Yacyshyn, Bruce Dunnmon, Preston M. TI High- and Low-Dose Oral Delayed-Release Mesalamine in Children With Mild-to-Moderately Active Ulcerative Colitis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE children; inflammatory bowel disease; mild-to-moderate ulcerative colitis; oral mesalamine; Pediatric Ulcerative Colitis Activity Index ID INFLAMMATORY-BOWEL-DISEASE; MULTICENTER; MANAGEMENT; TRIAL; G/DAY AB Objective: The aim of the study was to assess the safety and efficacy of high-and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of >= 10 to <= 55 and a truncated Mayo Score of >= 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg . g(-1) . day(-1)) or high-dose group (53-118 mg . g(-1) . day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score >= 10 with a decrease from baseline by >= 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low-and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Conclusions: Both low-and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose. C1 [Winter, Harland S.] MassGen Hosp Children, Boston, MA 02114 USA. [Krzeski, Piotr] Medpace, Warsaw, Poland. [Heyman, Melvin B.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Ibarguen-Secchia, Eduardo] Methodist Childrens Hosp, San Antonio, TX USA. [Iwanczak, Barbara] Med Acad Wroclaw, Dept Pediat Gastroenterol & Nutr, Wroclaw, Poland. [Kaczmarski, Maciej] Med Univ Bialystok, Dept Pediat Gastroenterol & Allergol, Bialystok, Poland. [Kierkus, Jaroslaw] Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol & Immunol, Warsaw, Poland. [Kolacek, Sanja] Univ Childrens Hosp Zagreb, Zagreb, Croatia. [Osuntokun, Bankole] Cook Childrens Med Ctr, Ft Worth, TX USA. [Quiros, J. Antonio] MUSC Pediat Ctr Inflammatory Bowel Disorders, Charleston, SC USA. [Shah, Manoj] Loma Linda Univ Childrens Hosp, Loma Linda, CA USA. [Yacyshyn, Bruce] Univ Cincinnati, Div Digest Dis, Cincinnati, OH USA. [Dunnmon, Preston M.] US FDA, Silver Spring, MD USA. RP Winter, HS (reprint author), MassGen Hosp Children, 175 Cambridge St,CRPZ 5-560, Boston, MA 02114 USA. EM hwinter@mgh.harvard.edu FU Warner Chilcott (US) LLC.; Janssen Pharmaceuticals; Prometheus Laboratories; UCB Pharmaceuticals; Autism Research Institute; Pediatric IBD Foundation; Nutricia; Shire; Salix Pharmaceuticals; Procter&Gamble Pharmaceuticals; CCFA; NIH [DK060617]; Chr. Hansen; FALK; Abbott; BioGaia; Nestle; Merck FX Financial support for the study and for writing and editorial services was provided by Warner Chilcott (US) LLC.; H.S.W.: consultant for Janssen Pharmaceuticals, Prometheus Laboratories, Mead Johnson, Salix, Shire, and AstraZeneca; grant support from Janssen Pharmaceuticals, Prometheus Laboratories, UCB Pharmaceuticals, Autism Research Institute, Pediatric IBD Foundation, and Nutricia. P.K.: employee of Procter&Gamble Pharmaceuticals and Warner Chilcott at the time of the study. M.B.H.: grant support from Shire, Salix Pharmaceuticals, Procter&Gamble Pharmaceuticals, UCB Pharmaceuticals, Janssen Pharmaceuticals, CCFA, and NIH (DK060617). M.K.: scientific board member of Mead Johnson Nutrition research grant "ALERNI Education Programme." S.K.: sponsored research for Chr. Hansen; lectures provided for Abbott, Arla Foods, BioGaia, JGL, Nestle, Nutricia, and MSD; grant support from FALK, Abbott, BioGaia, and Nestle. J.A.Q.: consultant for Sigma-Tau, Prometheus Laboratories, and Santarus. B.Y.: employee of Procter&Gamble Pharmaceuticals at time of study; speakers bureau for Optimer, Santarus, and Forest; consultant to N-8, GlaxoSmithKline, Sucampo, and Procter&Gamble Pharmaceuticals; and grant funding (ISP) from Merck. The remaining authors report no conflicts of interest. NR 16 TC 1 Z9 1 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD DEC PY 2014 VL 59 IS 6 BP 767 EP 772 DI 10.1097/MPG.0000000000000530 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AU8NS UT WOS:000345853800021 PM 25419597 ER PT J AU Wald, C Patti, JW Tilkin, M Dreyer, K AF Wald, Christoph Patti, Jay W. Tilkin, Michael Dreyer, Keith TI ACR Introduction to the ACR Imaging IT Reference Guide SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Wald, Christoph] Lahey Hosp & Med Ctr, Dept Radiol, Burlington, MA 01805 USA. [Wald, Christoph] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Patti, Jay W.] Mecklenburg Radiol Associates, Charlotte, NC USA. [Tilkin, Michael] Amer Coll Radiol, Reston, VA USA. [Dreyer, Keith] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wald, C (reprint author), Lahey Hosp & Med Ctr, Dept Radiol, Burlington, MA 01805 USA. EM christoph.wald@lahey.org NR 12 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2014 VL 11 IS 12 SI SI BP 1195 EP 1196 DI 10.1016/j.jacr.2014.09.006 PN B PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW0AS UT WOS:000345953500001 PM 25467894 ER PT J AU Krishnaraj, A Siddiqui, A Goldszal, A AF Krishnaraj, Arun Siddiqui, Adeel Goldszal, Alberto TI Meaningful Use: Participating in the Federal Incentive Program SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Meaningful use; electronic health record; eligible provider; stage 1 AB Meaningful use legislation was first introduced in the American Recovery and Reinvestment Act of 2009 as a multistaged program to incentivize adoption of electronic health record technology. Since that time, numerous eligible providers and eligible hospitals have captured incentive payments by installing certified electronic health record technology and capturing and reporting on key elements for patients whose health records are stored in an electronic format. Although the question of whether radiologists should participate in the program was initially debated, the evidence is now clear that lack of participation leaves a significant amount of money at risk. This article provides an overview of how the program is structured, what technology needs to be installed, the necessary data elements to capture in an electronic format, and how radiologists can effectively participate in the program to capture their maximum incentive payment. C1 [Krishnaraj, Arun] Univ Virginia Hlth Syst, Dept Radiol & Med Imaging, Charlottesville, VA 22908 USA. [Siddiqui, Adeel] Univ Tennessee, Ctr Hlth Sci, Dept Neuroradiol, Memphis, TN 38163 USA. [Siddiqui, Adeel] Massachusetts Gen Hosp, Enterprise Med Imaging, Boston, MA 02114 USA. [Goldszal, Alberto] Univ Radiol Grp, Robert Wood Johnson Med Sch, East Brunswick, NJ USA. RP Krishnaraj, A (reprint author), Univ Virginia Hlth Syst, Div Body Imaging, 1215 Lee St,POB 800170, Charlottesville, VA 22908 USA. EM ak8jj@virginia.edu NR 10 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2014 VL 11 IS 12 SI SI BP 1205 EP 1211 DI 10.1016/j.jacr.2014.09.012 PN B PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW0AS UT WOS:000345953500003 PM 25467896 ER PT J AU Mendelson, DS Erickson, BJ Choy, G AF Mendelson, David S. Erickson, Bradley J. Choy, Garry TI Image Sharing: Evolving Solutions in the Age of Interoperability SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Cloud; CDs; THE; data security; inappropriate utilization AB Interoperability is a major focus of the quickly evolving world of Health IT. Easy, yet secure and confidential exchange of imaging exams and the associated reports must be a part of the solutions that are implemented. The availability of historical exams is essential in providing a quality interpretation and reducing inappropriate utilization of imaging services. Today, the exchange of imaging exams is most often achieved via a compact disc. We describe the virtues of this solution as well as challenges that have surfaced. Internet- and cloud-based technologies employed for many consumer services can provide a better solution. Vendors are making these solutions available. Standards for Internet-based exchange are emerging. Just as radiology converged on DICOM as a standard to store and view images, we need a common exchange standard. We will review the existing standards and how they are organized into useful workflows through Integrating the Healthcare Enterprise profiles. Integrating the Healthcare Enterprise and standards development processes are discussed. Health care and the domain of radiology must stay current with quickly evolving Internet standards. The successful use of the "cloud" will depend on both the technologies and the policies put into place around them, both of which we discuss. The radiology community must lead the way and provide a solution that works for radiologists and clinicians with use of the electronic medical record. We describe features we believe radiologists should consider when adding Internet-based exchange solutions to their practice. C1 [Mendelson, David S.] Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA. [Erickson, Bradley J.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Choy, Garry] Massachusetts Gen Hosp, Div Cardiac Imaging & Emergency Imaging, Informat Imaging Trials Ctr, Boston, MA 02114 USA. RP Mendelson, DS (reprint author), Mt Sinai Med Ctr, Dept Radiol, 1 Gustave Levy Pl, New York, NY 10029 USA. EM david.mendelson@mountsinai.org FU NHLBI NIH HHS [HHSN268201200078C] NR 7 TC 11 Z9 11 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2014 VL 11 IS 12 SI SI BP 1260 EP 1269 DI 10.1016/j.jacr.2014.09.013 PN B PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW0AS UT WOS:000345953500010 PM 25467903 ER PT J AU Zong, P Zhang, LL Shaban, NM Pena, J Jiang, L Taub, CC AF Zong, Pu Zhang, Lili Shaban, Nada M. Pena, Jessica Jiang, Leng Taub, Cynthia C. TI Left Heart Chamber Quantification in Obese Patients: How Does Larger Body Size Affect Echocardiographic Measurements? SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Left heart; Obesity; Isometric scaling; Allometric scaling ID LEFT ATRIAL VOLUME; LEFT-VENTRICULAR MASS; SURFACE-AREA; CARDIAC DIMENSIONS; WEIGHT; CHILDREN; HEIGHT; ADULTS; ASSOCIATION; POPULATION AB Background: Accurate normalization of cardiac chamber size in the obese population is a challenge. The aim of this study was to develop and assess the performance of allometric models for scaling left heart chamber sizes, including left atrial anteroposterior dimension (LAD(AP)), left atrial volume (LAV), left ventricular end-diastolic volume (LVEDV), and left ventricular end-diastolic dimension (LVEDD), in an obese population. Methods: To normalize left heart chamber measurements (Y: LAD(AP), LAV, LVEDV, and LVEDD) to body size variables (X: height, weight, body mass index, and body surface area), both isometric models (Y = aX) and optimal allometric models (Y = aX(b)) were tested. A logarithmic transformation (LnY = Lna + b x LnX) and ordinary least squares linear regression was performed to estimate the allometric scaling exponents. Pearson's correlation coefficients were obtained for measured and indexed left chamber sizes using both isometric and allometric models against body size variables. Gender-specific allometric models were also derived as sensitivity analyses. Results: A total of 717 healthy obese subjects were included in the analysis. The mean body surface area and body mass index were 2.3 m(2) and 42.2 kg/m(2), respectively. Measured LAD(AP), LAV, LVEDD, and LVEDV were positively correlated with body size variables. Allometric scaling of LAD(AP), LAV, LVEDD, and LVEDV showed stronger correlation with measured chamber sizes compared with isometric scaling. The overcorrection caused by isometric scaling significantly improved after allometric models were used. The sensitivity analysis showed no significant differences in scaling exponents between men and women. Conclusions: Normalizing cardiac chamber measurements with allometric scaling methods is superior to the use of isometric methods in removing the effects of body size and minimizing overcorrection in the obese population. Using an allometric model with height provides the most accurate results. C1 [Zong, Pu] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. [Zhang, Lili] Jacobi Med Ctr, Dept Med, Bronx, NY USA. [Shaban, Nada M.; Pena, Jessica; Taub, Cynthia C.] Montefiore Med Ctr, Dept Cardiol, Bronx, NY 10467 USA. [Jiang, Leng] Baystate Med Ctr, Dept Cardiol, Springfield, MA USA. RP Taub, CC (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 1845 Eastchester Rd, Bronx, NY 10461 USA. EM ctaub@montefiore.org OI Zhang, Lili/0000-0002-9341-5832 NR 24 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2014 VL 27 IS 12 BP 1267 EP 1274 DI 10.1016/j.echo.2014.07.015 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU9GI UT WOS:000345899400003 PM 25193637 ER PT J AU Eisner, BH Goldfarb, DS AF Eisner, Brian H. Goldfarb, David S. TI A Nomogram for the Prediction of Kidney Stone Recurrence SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CALCIUM NEPHROLITHIASIS; AMBIENT-TEMPERATURE; PREVENTION C1 [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Goldfarb, David S.] New York Harbor Vet Affairs Healthcare Syst, New York, NY USA. [Goldfarb, David S.] NYU, Sch Med, New York, NY USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org OI Goldfarb, David/0000-0002-9215-1273 NR 15 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2685 EP 2687 DI 10.1681/ASN.2014060631 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500004 PM 25104802 ER PT J AU Andeen, NK Lann, DY de Boer, IH Nicosia, RF AF Andeen, Nicole K. Lann, Daniel Y. de Boer, Ian H. Nicosia, Roberto F. TI Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID APOLIPOPROTEIN-A-I; HIGH-DENSITY-LIPOPROTEIN; HEREDITARY AMYLOIDOSIS; VARIANT; RECEPTOR; CUBILIN AB Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in atherosclerotic plaques, but it can also manifest as a hereditary disorder caused by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with diverse organ involvement based on the position of the mutation. We describe a case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival, and renal involvement; and the notable finding of lipid deposition within the amyloid deposits. C1 [Andeen, Nicole K.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Lann, Daniel Y.; de Boer, Ian H.] Vet Affairs Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA. [Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Andeen, NK (reprint author), Univ Washington, Dept Pathol, 1959 NE Pacific St,Box 356100, Seattle, WA 98195 USA. EM nandeen@u.washington.edu NR 19 TC 0 Z9 2 U1 2 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2703 EP 2705 DI 10.1681/ASN.2013060651 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500006 PM 24925720 ER PT J AU Chung, SA Brown, EE Williams, AH Ramos, PS Berthier, CC Bhangale, T Alarcon-Riquelme, ME Behrens, TW Criswell, LA Graham, DC Demirci, FY Edberg, JC Gaffney, PM Harley, JB Jacob, CO Kamboh, MI Kelly, JA Manzi, S Moser-Sivils, KL Russell, LP Petri, M Tsao, BP Vyse, TJ Zidovetzki, R Kretzler, M Kimberly, RP Freedman, BI Graham, RR Langefeld, CD AF Chung, Sharon A. Brown, Elizabeth E. Williams, Adrienne H. Ramos, Paula S. Berthier, Celine C. Bhangale, Tushar Alarcon-Riquelme, Marta E. Behrens, Timothy W. Criswell, Lindsey A. Graham, Deborah Cunninghame Demirci, F. Yesim Edberg, Jeffrey C. Gaffney, Patrick M. Harley, John B. Jacob, Chaim O. Kamboh, M. Ilyas Kelly, Jennifer A. Manzi, Susan Moser-Sivils, Kathy L. Russell, Laurie P. Petri, Michelle Tsao, Betty P. Vyse, Tim J. Zidovetzki, Raphael Kretzler, Matthias Kimberly, Robert P. Freedman, Barry I. Graham, Robert R. Langefeld, Carl D. CA Int Consortium Systemic TI Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; RENAL-DISEASE; GENE-EXPRESSION; GROWTH-FACTOR; METAANALYSIS; POLYMORPHISM; POPULATIONS; VARIANTS; ITGAM; SCANS AB Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5 X 10(-7)), 16p12 (SLC5A11; P=5.1 X 10(-7)), 6p22 (ID4; P=7.4 X 10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1 X 10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7 X 10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5 X 10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. C1 [Chung, Sharon A.; Criswell, Lindsey A.] Univ Calif San Francisco, Div Rheumatol, Rosalind Russell Ephraim P Engleman Med Res Ctr A, San Francisco, CA USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Brown, Elizabeth E.; Edberg, Jeffrey C.; Kimberly, Robert P.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Williams, Adrienne H.; Russell, Laurie P.; Langefeld, Carl D.] Wake Forest Sch Med, Ctr Publ Hlth Gen, Dept Biostatist Sci, Winston Salem, NC USA. [Ramos, Paula S.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Berthier, Celine C.; Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Harley, John B.; Kelly, Jennifer A.; Moser-Sivils, Kathy L.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Andalusian, Ctr Genom & Oncol Res, Granada, Spain. [Bhangale, Tushar] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA. [Behrens, Timothy W.] Genentech Inc, Immunol Tissue Growth & Repair Human Genet Grp, San Francisco, CA 94080 USA. [Demirci, F. Yesim; Kamboh, M. Ilyas] Kings Coll London, Div Genet & Mol Med & Immunol Infect & Inflammato, London, England. [Harley, John B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Div Rheumatol, Cincinnati, OH USA. [Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Jacob, Chaim O.] Univ So Calif, Dept Med, Los Angeles, CA USA. [Manzi, Susan] W Penn Allegheny Hlth Syst, Dept Med, Pittsburgh, PA USA. [Manzi, Susan] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Moser-Sivils, Kathy L.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Tsao, Betty P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Zidovetzki, Raphael] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Nephrol Sect, Winston Salem, NC USA. RP Langefeld, CD (reprint author), Wake Forest Sch Med, Dept Biostatist Sci, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM clangefe@wakehealth.edu OI Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Kimberly, Robert/0000-0002-5330-3086 FU Genentech; International Consortium for Systemic Lupus Erythematosus Genetics; National Institutes of Health [AI063274, AR052125, AR043247, KL2-TR000143, R01-AR033062, N01-AR062277, RC2-AR058951, UL1-TR000165, P60-AR053308, K24-AR02175]; National Institutes of Health (National Research Service) [5F32-AR50927]; Lupus Foundation of Minnesota; Arthritis Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK079912, P30-DK081943]; Alliance for Lupus Research; Swedish Research Council of Medicine; National Kidney Foundation [FLB1245]; Arthritis Research UK Special Strategic Award [19289]; Kirkland Scholar Award; National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] Progression of Cardiovascular Disease in Lupus) [K24-AR002213, AR43727, UL1-RR025005, R01-AR043814, R01-AR057172, R01-HL56266, R01-DK070941]; National Institutes of Health. [R01-AR057172, R01-AR052300, UL1-TR000004, AR057028, IMMA9, 5R37AI024717-25, 5P01AI083194, 5P01AR049084, PR094002, 3R37AI024717-23S1, HL092397, R01-AR046588] FX The authors gratefully acknowledge the following funding sources for this research. Genotyping funds for set I were provided by Genentech. The Alliance for Lupus Research funded the International Consortium for Systemic Lupus Erythematosus Genetics and the genotyping for set II. Set III was funded by grants from the National Institutes of Health (AI063274 and AR052125 to P.M.G. and AR043247 to K.L.M.; National Research Service Award 5F32-AR50927 to R.R.G.), the Lupus Foundation of Minnesota (to P.M.G. and K.L.M.-S.), and the Arthritis Foundation (to K.L.M.-S.). This study Was also supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK079912 and P30-DK081943 to M.K.), the Alliance for Lupus Research (M.K., B.P.T., L.A.C., and M.K.), and the Swedish Research Council of Medicine (to M.E.A.-R.), as well as a research fellowship from the National Kidney Foundation (FLB1245 to C.C.B.), an Arthritis Research UK Special Strategic Award (19289 to T.J.V.), and a Kirkland Scholar Award (to L.A.C). Sample collections and additional financial support were also obtained from grants from the National Institutes of Health (KL2-TR000143 to S.A.C.; R01-AR033062, N01-AR062277, RC2-AR058951, and UL1-TR000165 to E.E.B. and R.P.K.; P60-AR053308, K24-AR02175, R01-AR052300, and UL1-TR000004 to L.A.C.; AR057028 to F.Y.D.; IMMA9, 5R37AI024717-25, 5P01AI083194, 5P01AR049084, PR094002, and 3R37AI024717-23S1 to J.B.H.; R01-AR057172 to C.O.J.; HL092397 to M.I.K.; R01-AR046588, National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] Progression of Cardiovascular Disease in Lupus K24-AR002213 to S.M.; AR43727 and UL1-RR025005 to M.P.; R01-AR043814 to B.P.T.; R01-AR057172 to C.O.J.; and R01-HL56266 and R01-DK070941 to B.I.F.). NR 47 TC 18 Z9 19 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2859 EP 2870 DI 10.1681/ASN.2013050446 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500020 PM 24925725 ER PT J AU Skupien, J Warram, JH Smiles, A Galecki, A Stanton, RC Krolewski, AS AF Skupien, Jan Warram, James H. Smiles, Adam Galecki, Andrzej Stanton, Robert C. Krolewski, Andrzej S. TI Improved Glycemic Control and Risk of ESRD in Patients with Type 1 Diabetes and Proteinuria SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RENAL-FUNCTION; PANCREAS TRANSPLANTATION; INTENSIVE TREATMENT; BLOOD-PRESSURE; NEPHROPATHY; PROGRESSION; MELLITUS; GLUCOSE; DECLINE AB Most patients with type 1 diabetes (T1D) and proteinuria have poor glycemic control and a high risk of ESRD. We investigated whether long-term improvement of glycemic control reduces risk of ESRD in a prospective 7- to 15-year follow-up observation of 349 patients with CKD stages 1-3 enrolled in the Joslin Proteinuria Cohort of adults with T1D. All patients developed proteinuria between 1990 and 2004 and were followed until 2011 to ascertain onset of ESRD and deaths unrelated to ESRD. Furthermore, we analyzed data from 279 patients with >= 3 years of clinic follow-up available to assess the level of glycemic control after enrollment. Average HbA(1c) during the 5 years before study enrollment (prebaseline) was compared with HbA(1c) (postbaseline) averaged during the first half of follow-up (median, 5.1 years). Median prebaseline HbA(1c) was 9.3%, decreasing to 8.7% postbaseline. Cumulative risk of ESRD after 15 years was significantly lower for patients whose HbA(1c) decreased than for those whose HbA(1c) increased or remained poor (29% versus 42%; P<0.001). The difference between these groups was not visible at 5 years of follow-up but became visible at 10 and 15 years of follow-up. In multivariate Cox regression analysis of ESRD risk, the hazard ratio corresponding to a 1 percentage point improvement in postbaseline HbA(1c) was 0.76 (95% confidence interval, 0.63 to 0.91; P=0.003). In conclusion, results of this study suggest that long-term sustained improvement in HbA(1c) decelerates eGFR loss and delays the onset of ESRD in patients with T1D and proteinuria. C1 [Skupien, Jan; Warram, James H.; Smiles, Adam; Stanton, Robert C.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Skupien, Jan; Warram, James H.; Smiles, Adam; Stanton, Robert C.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Clin Div, Boston, MA 02115 USA. [Skupien, Jan; Krolewski, Andrzej S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Skupien, Jan] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Galecki, Andrzej] Univ Michigan, Sch Med, Inst Gerontol, Ann Arbor, MI USA. [Galecki, Andrzej] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Stanton, Robert C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Renal Div, Boston, MA 02215 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU Juvenile Diabetes Research Foundation [1-2008-1018, 3-2009-397]; National Institutes of Health [DK41526] FX This project was supported through Juvenile Diabetes Research Foundation research grant 1-2008-1018 (A.S.K.), National Institutes of Health grant DK41526 (A.S.K.), and Juvenile Diabetes Research Foundation fellowship grant 3-2009-397 (J.S.). NR 26 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2916 EP 2925 DI 10.1681/ASN.2013091002 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500026 PM 24904086 ER PT J AU Fullerton, DA Sundt, TM AF Fullerton, David A. Sundt, Thoralf M. TI Process versus outcome: The sugar window SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID CARE IMPROVEMENT PROJECT; CRITICALLY-ILL PATIENTS; GLUCOSE CONTROL; GLYCEMIC CONTROL; CARDIAC-SURGERY; WOUND-INFECTION; QUALITY C1 [Fullerton, David A.] Univ Colorado, Sch Med, Div Cardiothorac Surg, Aurora, CO 80045 USA. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Fullerton, DA (reprint author), Univ Colorado, Sch Med, Div Cardiothorac Surg, 12631 E 17th Ave,MS C-310,Rm 6602, Aurora, CO 80045 USA. EM david.fullerton@ucdenver.edu NR 16 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2014 VL 148 IS 6 BP 2458 EP 2460 DI 10.1016/j.jtcvs.2014.10.076 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6BD UT WOS:000345686100004 PM 25433864 ER PT J AU Weisel, RD Nussmeier, N Newman, MF Pearl, RG Wechsler, AS Ambrosio, G Pitt, B Clare, RM Pieper, KS Mongero, L Reece, TL Yau, TM Fremes, S Menasche, P Lira, A Harrington, RA Ferguson, TB AF Weisel, Richard D. Nussmeier, Nancy Newman, Mark F. Pearl, Ronald G. Wechsler, Andrew S. Ambrosio, Giuseppe Pitt, Bertram Clare, Robert M. Pieper, Karen S. Mongero, Linda Reece, Tammy L. Yau, Terrence M. Fremes, Stephen Menasche, Philippe Lira, Armando Harrington, Robert A. Ferguson, T. Bruce CA RED-CABG Executive Steering Comm TI Predictors of contemporary coronary artery bypass grafting outcomes SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; PRESERVED EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CARDIAC-OUTPUT SYNDROME; HEART-FAILURE; PREOPERATIVE ASPIRIN; BONE-MARROW; SURGERY; MORTALITY; CELLS AB Objectives: The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes. Methods: The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates. Results: The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes. Conclusions: Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes. C1 [Weisel, Richard D.; Yau, Terrence M.] Toronto Gen Hosp, Div Cardiac Surg, Toronto, ON M5G 2C4, Canada. [Weisel, Richard D.; Yau, Terrence M.; Fremes, Stephen] Univ Toronto, Toronto, ON, Canada. [Nussmeier, Nancy] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Newman, Mark F.; Clare, Robert M.; Pieper, Karen S.; Reece, Tammy L.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Pearl, Ronald G.; Harrington, Robert A.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Wechsler, Andrew S.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Ambrosio, Giuseppe] Univ Perugia, Sch Med, Div Cardiol, I-06100 Perugia, Italy. [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Mongero, Linda] New York Presbyterian Columbia Univ, Med Ctr, New York, NY USA. [Fremes, Stephen] Sunnybrook Hlth Sci Ctr, Div Cardiac Surg, Toronto, ON M4N 3M5, Canada. [Menasche, Philippe] Univ Paris 05, Sorbonne Paris Cite, Assistance Publ Hop Europeen Georges Pompidou, Dept Chirurg Cardiovasc,Hop Paris, Paris, France. [Lira, Armando] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Ferguson, T. Bruce] East Carolina Heart Inst, Greenville, NC USA. RP Weisel, RD (reprint author), Toronto Gen Hosp, 4N-466, Toronto, ON M5G 2C4, Canada. EM rweisel@uhnresearch.ca RI Fremes, Stephen/P-7928-2015 OI LIVI, Ugolino/0000-0003-1394-736X; Fremes, Stephen/0000-0003-1723-3049 FU Schering-Plough (Merck Sharp & Dohme Corp, Whitehouse Station, NJ) FX The RED-CABG study was funded by Schering-Plough (subsequently Merck Sharp & Dohme Corp, Whitehouse Station, NJ). NR 26 TC 5 Z9 5 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2014 VL 148 IS 6 BP 2720 EP U1368 DI 10.1016/j.jtcvs.2014.08.018 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6BD UT WOS:000345686100064 PM 25218533 ER PT J AU Dariushnia, SR Gill, AE Martin, LG Saad, WE Baskin, KM Caplin, DM Kalva, SP Hogan, MJ Midia, M Siddiqi, NH Walker, TG Nikolic, B AF Dariushnia, Sean R. Gill, Anne E. Martin, Louis G. Saad, Wael E. Baskin, Kevin M. Caplin, Drew M. Kalva, Sanjeeva P. Hogan, Mark J. Midia, Mehran Siddiqi, Nasir H. Walker, T. Gregory Nikolic, Boris CA Soc Interventional Radiology Stand TI Quality Improvement Guidelines for Diagnostic Arteriography SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CONTRAST-INDUCED NEPHROPATHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; UNRESECTABLE HEPATOCELLULAR-CARCINOMA; PERCUTANEOUS CORONARY INTERVENTION; PRACTICE MANAGEMENT GUIDELINE; ANESTHESIOLOGISTS TASK-FORCE; PERIPHERAL ARTERIAL-DISEASE; CHEST COMPUTED-TOMOGRAPHY; SINGLE-CENTER EXPERIENCE C1 [Dariushnia, Sean R.; Gill, Anne E.; Martin, Louis G.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Dariushnia, Sean R.; Gill, Anne E.; Martin, Louis G.] Emory Univ, Div Intervent Radiol & Image Guided Med, Atlanta, GA 30322 USA. [Saad, Wael E.] Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA. [Baskin, Kevin M.] Adv Intervent Inst, Dept Radiol, Pittsburgh, PA USA. [Caplin, Drew M.] Northshore Univ Hosp, Dept Radiol, Manhasset, NY USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. [Hogan, Mark J.] Ohio State Univ, Nationwide Childrens Hosp, Sect Vasc & Intervent Radiol, Columbus, OH 43210 USA. [Hogan, Mark J.] Ohio State Univ, Nationwide Childrens Hosp, Dept Radiol, Columbus, OH 43210 USA. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Siddiqi, Nasir H.] Northwest Vasc Care St Louis, Dept Intervent Radiol, St Louis, MO USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Midia, Mehran] McMaster Univ, Med Ctr, Dept Diagnost Imaging, Hamilton, ON, Canada. RP Dariushnia, SR (reprint author), Emory Univ, Dept Radiol & Imaging Sci, 1364 Clfiton Rd NE, Atlanta, GA 30322 USA. EM dariushnia1@yahoo.com NR 128 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2014 VL 25 IS 12 BP 1873 EP 1881 DI 10.1016/j.jvir.2014.07.020 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AU5XK UT WOS:000345676700006 PM 25241301 ER PT J AU Thabet, A Somarouthu, B Oliva, E Gervais, DA Hahn, PF Lee, SI AF Thabet, Ashraf Somarouthu, Bhanusupriya Oliva, Esther Gervais, Debra A. Hahn, Peter F. Lee, Susanna I. TI Image-Guided Ovarian Mass Biopsy: Efficacy and Safety SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ADNEXAL MASSES; CANCER; CHEMOTHERAPY; CT; MANAGEMENT; CARCINOMA; CYTOLOGY; LESIONS AB Purpose: Image-guided needle biopsy represents a minimally invasive method for pathologic diagnosis of a mass. This study evaluates the diagnostic yield, accuracy, and safety of ovarian mass biopsy with combined core and fine-needle technique. Materials and Methods: Medical records of all women at least 18 years of age, referred from gynecologic oncology, who underwent image-guided ovarian mass biopsy from 2001 through 2011 were reviewed. Among 27 patients, ultrasound guidance was used in 13 (48%), six transabdominal and seven transvaginal; computed tomography guidance was used in 14 (52%), nine transabdominal and five transgluteal. Biopsy indications were suspected metastasis (n = 15; 56%), suspected ovarian cancer to be treated with neoadjuvant chemotherapy (n = 10; 37%), and relative contraindication to surgery (n = 2; 7%). Mean maximum lesion dimension was 9.9 cm (range, 2-23 cm), with solid composition in nine (33%), cystic in six (22%), and mixed in 12 (44%). Biopsy pathologic findings were compared versus those of the surgical specimen or, for masses that were not resected, versus the stability of benign masses and response to chemotherapy of malignant masses on follow-up. Results: All biopsies yielded a diagnosis. No biopsy-related complications were noted. Eleven patients (41%) did not undergo lesion resection and were followed for an average of 28.8 months (range, 0.3-118.4 mo). In no patient did malignancy develop during clinical follow-up after a benign biopsy diagnosis. Sensitivity and specificity for diagnosis of malignancy were 100% +/- 0 (19 of 19) and 88% +/- 26 (seven of eight), respectively, for cancer detection. In nine patients (33%) with final pathologic diagnosis of epithelial ovarian cancer, tumor seeding was not observed during a mean follow-up of 44.6 months (range, 1.3-110.2 mo). Conclusions: Image-guided ovarian mass core needle biopsy results in a pathologic diagnosis of benign and malignant masses with high yield, accuracy, and safety. C1 [Thabet, Ashraf; Somarouthu, Bhanusupriya; Gervais, Debra A.; Hahn, Peter F.; Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Oliva, Esther] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Somarouthu, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 25 New Chardon St,Suite 501, Boston, MA 02114 USA. EM bsomarouthu@mgh.harvard.edu FU Covidien FX A.T. is a paid consultant for Covidien (Mansfield, Massachusetts) and D.A G. received a research grant from Covidien. None of the other authors have identified a conflict of interest. NR 27 TC 1 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2014 VL 25 IS 12 BP 1922 EP 1927 DI 10.1016/j.jvir.2014.08.009 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AU5XK UT WOS:000345676700014 PM 25241300 ER PT J AU McWilliams, SR Murphy, KP Golestaneh, S O'Regan, KN Arellano, RS Maher, MM O'Connor, OJ AF McWilliams, Sebastian R. Murphy, Kevin P. Golestaneh, Safieh O'Regan, Kevin N. Arellano, Ronald S. Maher, Michael M. O'Connor, Owen J. TI Reduction of Guide Needle Streak Artifact in CT-Guided Biopsy SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID LIVER-LESIONS AB Purpose: Computed tomography (CT)-guided core needle biopsy (CNB) can be affected by streak artifact obscuring the needle tip. This study investigates factors that influence the occurrence and severity of streak artifact during CNB. Materials and Methods: Eight coaxial guide needles of two sizes from two manufacturers with and without stylets were imaged in a CT phantom, with CT reconstructed with adaptive statistical iterative reconstruction and filtered back projection. CNB-related streak artifact was quantified with profile analysis in an image-processing program. Differences between maximum attenuation at the needle tip and minimum attenuation in the streak artifact were compared for each variable. Diagnostic acceptability and streak artifact were subjectively assessed on each phantom image and on 40 clinical CNB procedures by three independent blinded reviewers following training case review. Results: Artifact was significantly less with the central stylet removed versus in situ (median, 1,145 HU vs 3,390 HU; P < .001) for all needles, and less for 19-gauge needles versus 17-gauge needles (median, 1,334 HU vs 2,780 HU, respectively; P = .006). There were no differences based on manufacturer (P = .906) or reconstruction algorithm (P = .524). Independent reviews found that streak artifact was significantly reduced when the central stylet was removed (kappa = 0.8751.0; P < .001), and needle tip position was better in cases in which the stylet was removed (kappa = 0.2310.711; P < .001). Conclusions: Streak artifact can be reduced and needle tip visualization improved by confirming final biopsy needle position with the central stylet removed on CT and using smaller-gauge guide needles. C1 [McWilliams, Sebastian R.; Murphy, Kevin P.; Golestaneh, Safieh; O'Regan, Kevin N.; Maher, Michael M.; O'Connor, Owen J.] Natl Univ Ireland Univ Coll Cork, Dept Radiol, Cork Univ Hosp, Cork, Ireland. [McWilliams, Sebastian R.; Murphy, Kevin P.; Golestaneh, Safieh; O'Regan, Kevin N.; Maher, Michael M.; O'Connor, Owen J.] Mercy Univ Hosp, Cork, Ireland. [Arellano, Ronald S.; O'Connor, Owen J.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP O'Connor, OJ (reprint author), Natl Univ Ireland Univ Coll Cork, Dept Radiol, Cork Univ Hosp, Cork, Ireland. NR 9 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2014 VL 25 IS 12 BP 1929 EP 1935 DI 10.1016/j.jvir.2014.08.028 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AU5XK UT WOS:000345676700015 PM 25311968 ER PT J AU Crowley, JJ Hogan, MJ Towbin, RB Saad, WE Baskin, KM Cahill, AM Caplin, DM Connolly, BL Kalva, SP Krishnamurthy, V Marshalleck, FE Roebuck, DJ Saad, NE Salazar, GM Stokes, LS Temple, MJ Walker, TG Nikolic, B AF Crowley, John J. Hogan, Mark J. Towbin, Richard B. Saad, Wael E. Baskin, Kevin M. Cahill, Anne Marie Caplin, Drew M. Connolly, Bairbre L. Kalva, Sanjeeva P. Krishnamurthy, Venkataramu Marshalleck, Francis E. Roebuck, Derek J. Saad, Nael E. Salazar, Gloria M. Stokes, Leann S. Temple, Michael J. Walker, T. Gregory Nikolic, Boris CA Soc Interventional Radiology Stand Soc Pediat Radiology Interventiona TI Quality Improvement Guidelines for Pediatric Gastrostomy and Gastrojejunostomy Tube Placement SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RETROGRADE PERCUTANEOUS GASTROSTOMY; TOTAL PARENTERAL-NUTRITION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; INTERVENTIONAL RADIOLOGY; GASTROESOPHAGEAL-REFLUX; CONTROLLED-TRIAL; DEEP SEDATION; CHILDREN; COMPLICATIONS C1 [Crowley, John J.] Childrens Hosp Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Hogan, Mark J.] Nationwide Childrens Hosp, Dept Vasc & Intervent Radiol, Columbus, OH USA. [Hogan, Mark J.] Ohio State Univ, Columbus, OH 43210 USA. [Towbin, Richard B.] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA. [Saad, Wael E.; Krishnamurthy, Venkataramu] Univ Michigan, Med Ctr, Dept Radiol, Ctr Cardiovasc,Div Vasc & Intervent Radiol, Ann Arbor, MI 48109 USA. [Baskin, Kevin M.] Adv Intervent Inst, Pittsburgh, PA USA. [Cahill, Anne Marie] Childrens Hosp Philadelphia, Dept Intervent Radiol, Philadelphia, PA 19104 USA. [Caplin, Drew M.] Northshore Univ Hosp, Dept Radiol, Div Intervent Radiol, Manhasset, NY USA. [Connolly, Bairbre L.; Temple, Michael J.] Univ Toronto, Hosp Sick Children, Ctr Image Guided Therapy, Toronto, ON M5G 1X8, Canada. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Marshalleck, Francis E.] Indiana Univ Sch Med, Riley Hosp Children, Indianapolis, IN 46202 USA. [Roebuck, Derek J.] Great Ormond St Hosp Sick Children, Dept Radiol, London, England. [Saad, Nael E.] Washington Univ, Sch Med, Dept Radiol, Div Vasc & Intervent Radiol, St Louis, MO 63110 USA. [Saad, Nael E.] Washington Univ, Sch Med, Dept Surg, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Salazar, Gloria M.; Walker, T. Gregory] Massachusetts Gen Hosp, Dept Radiol, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Stokes, Leann S.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Nikolic, Boris] Stratton Med Ctr, Albany, NY USA. RP Saad, WE (reprint author), Univ Michigan, Med Ctr, Dept Radiol, Ctr Cardiovasc,Div Vasc & Intervent Radiol, 1500 E Med Dr,SPC 5868,5588, Ann Arbor, MI 48109 USA. NR 63 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2014 VL 25 IS 12 BP 1983 EP 1991 DI 10.1016/j.jvir.2014.08.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AU5XK UT WOS:000345676700022 PM 25439676 ER PT J AU Shin, MH Sullivan, JL Rosen, AK Solomon, JL Dunn, EJ Shimada, SL Hayes, J Rivard, PE AF Shin, Marlena H. Sullivan, Jennifer L. Rosen, Amy K. Solomon, Jeffrey L. Dunn, Edward J. Shimada, Stephanie L. Hayes, Jennifer Rivard, Peter E. TI Examining the Validity of AHRQ's Patient Safety Indicators (PSIs): Is Variation in PSI Composite Score Related to Hospital Organizational Factors? SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE hospital; Patient Safety Indicators; criterion validity; qualitative methods; organizational factors ID SURGICAL SERVICES; CARE-DELIVERY; OUTCOMES; PERFORMANCE; QUALITY; LEADERSHIP; IMPLEMENTATION; COORDINATION; MORTALITY; PROGRAM AB Increasing use of Agency for Healthcare Research and Quality's Patient Safety Indicators (PSIs) for hospital performance measurement intensifies the need to critically assess their validity. Our study examined the extent to which variation in PSI composite score is related to differences in hospital organizational structures or processes (i.e., criterion validity). In site visits to three Veterans Health Administration hospitals with high and three with low PSI composite scores (low performers and high performers, respectively), we interviewed a cross-section of hospital staff. We then coded interview transcripts for evidence in 13 safety-related domains and assessed variation across high and low performers. Evidence of leadership and coordination of work/communication (organizational process domains) was predominantly favorable for high performers only. Evidence in the other domains was either mixed, or there were insufficient data to rate the domains. While we found some evidence of criterion validity, the extent to which variation in PSI rates is related to differences in hospitals' organizational structures/processes needs further study. C1 [Shin, Marlena H.; Sullivan, Jennifer L.; Rosen, Amy K.; Hayes, Jennifer; Rivard, Peter E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Sullivan, Jennifer L.; Shimada, Stephanie L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Solomon, Jeffrey L.; Shimada, Stephanie L.] Edith Nourse Rogers Mem VA Med Ctr, Bedford, MA USA. [Dunn, Edward J.] Lexington VA Med Ctr, Lexington, KY USA. [Shimada, Stephanie L.] VA eHlth Qual Enhancement Res Initiat, Bedford, MA USA. [Shimada, Stephanie L.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Hayes, Jennifer] VA Off Acad Affiliat Evaluat & Analyt, San Francisco, CA USA. [Rivard, Peter E.] Suffolk Univ, Sawyer Business Sch, Boston, MA 02114 USA. RP Shin, MH (reprint author), VA Boston Healthcare Syst, CHOIR, 150 South Huntington Ave 152M, Boston, MA 02130 USA. EM marlena.shin@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, and Quality Enhancement Research Initiative as Service Directed Research [07-002] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research reported in this article was funded by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, and Quality Enhancement Research Initiative as Service Directed Research #07-002 (Dr. Amy K. Rosen, PI). NR 47 TC 3 Z9 3 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD DEC PY 2014 VL 71 IS 6 BP 599 EP 618 DI 10.1177/1077558714556894 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AU4RY UT WOS:000345600400003 PM 25380608 ER PT J AU Woods, NF Cohen, L Freeman, EW Hohensee, C Joffe, H LaCroix, A Cochrane, B AF Woods, Nancy F. Cohen, Lee Freeman, Ellen W. Hohensee, Chancellor Joffe, Hadine LaCroix, Andrea Cochrane, Barbara TI Symptom Clusters Among MS-FLASH Clinical Trial Participants SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 25th Annual Meeting of the North-American-Menopause-Society CY OCT 15-18, 2014 CL Washington, DC SP N Amer Menopause Soc C1 [Woods, Nancy F.] Univ Washington, Seattle, WA 98195 USA. [Cohen, Lee] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Cohen, Lee] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [Freeman, Ellen W.] Univ Penn, Philadelphia, PA 19104 USA. [Hohensee, Chancellor] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Joffe, Hadine] Brigham & Womens Hosp, Womens Hormone & Aging Res Program, Boston, MA 02115 USA. [Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [LaCroix, Andrea] Univ Calif San Diego, San Diego, CA 92103 USA. [Cochrane, Barbara] Univ Washington, Seattle, WA 98195 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2014 VL 21 IS 12 MA S-21 BP 1333 EP 1333 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AU8KY UT WOS:000345846600060 ER PT J AU Looby, S Shifren, JL Grinspoon, S Joffe, H AF Looby, Sara Shifren, Jan L. Grinspoon, Steven Joffe, Hadine TI Longitudinal Assessment of Menopause Symptoms in Perimenopausal Women with HIV SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 25th Annual Meeting of the North-American-Menopause-Society CY OCT 15-18, 2014 CL Washington, DC SP N Amer Menopause Soc C1 [Looby, Sara; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Looby, Sara; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Looby, Sara; Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Looby, Sara] MGH, Munn Ctr Nursing Res, Boston, MA USA. [Shifren, Jan L.] HMS, MGH, Boston, MA USA. [Joffe, Hadine] HMS, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. [Joffe, Hadine] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2014 VL 21 IS 12 MA P-71 BP 1354 EP 1354 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AU8KY UT WOS:000345846600132 ER PT J AU Ono, N Ono, W Nagasawa, T Kronenberg, HM AF Ono, Noriaki Ono, Wanida Nagasawa, Takashi Kronenberg, Henry M. TI A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones SO NATURE CELL BIOLOGY LA English DT Article ID OSTEO-CHONDROPROGENITOR CELLS; STEM-CELLS; TRANSGENIC MICE; GROWTH-PLATE; CRE ACTIVITY; MARROW; DIFFERENTIATION; PRECURSORS; EXPRESSION; CARTILAGE AB The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals. C1 [Ono, Noriaki; Ono, Wanida; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Ono, Noriaki; Ono, Wanida; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ono, Noriaki; Ono, Wanida] Univ Michigan, Dept Orthodont & Pediat Dent, Sch Dent, Ann Arbor, MI 48109 USA. [Nagasawa, Takashi] Kyoto Univ, Inst Frontier Med Sci, Dept Immunobiol & Hematol, Kyoto 6068507, Japan. [Nagasawa, Takashi] Japan Sci & Technol Agcy JST, Core Res Evolut Sci & Technol, Tokyo 1020076, Japan. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@mgh.harvard.edu FU National Institutes of Health [DE022564, DK056246] FX The authors thank D. Rowe (University of Connecticut, USA) for Col2.3-GFP and Oc-GFP mice and S. Mackem (National Cancer Institute, USA) for Col2a1-creERT2 mice, H. Akiyama (Kyoto University, Japan) and B. de Crombrugghe (MD Anderson Cancer Center, USA) for Sox9-creERT2 and Acan-creERT2 mice, and L. Prickett, K. Folz-Donahue and M. Weglarz of Harvard Stem Cell Institute/Massachusetts General Hospital flow cytometry core and T. Diefenbach of Ragon Institute imaging core for their expert assistance. This work was supported by National Institutes of Health Grants DE022564 to N.O. and DK056246 to H.M.K. NR 31 TC 48 Z9 48 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2014 VL 16 IS 12 BP 1157 EP U73 DI 10.1038/ncb3067 PG 19 WC Cell Biology SC Cell Biology GA AU7JR UT WOS:000345777300007 PM 25419849 ER PT J AU Shulman, LN Mpunga, T Tapea, N Wagner, CM Fadelu, T Binagwaho, A AF Shulman, Lawrence N. Mpunga, Tharcisse Tapea, Neo Wagner, Claire M. Fadelu, Temidayo Binagwaho, Agnes TI Bringing cancer care to the poor: experiences from Rwanda SO NATURE REVIEWS CANCER LA English DT Review ID MIDDLE-INCOME COUNTRIES; CHRONIC MYELOGENOUS LEUKEMIA; HIV TREATMENT; AFRICA; RADIOTHERAPY; LYMPHOMA; SURVIVAL; PROGRAM; WORLD; NEED AB The knowledge and tools to cure many cancer patients exist in developed countries but are unavailable to many who live in the developing world, resulting in unnecessary loss of life. Bringing cancer care to the poor, particularly to low-income countries, is a great challenge, but it is one that we believe can be met through partnerships, careful planning and a set of guiding principles. Alongside vaccinations, screening and other cancer-prevention efforts, treatment must be a central component of any cancer programme from the start. It is also critical that these programmes include implementation research to determine programmatic efficacy, where gaps in care still exist and where improvements can be made. This article discusses these issues using the example of Rwanda's expanding national cancer programme. C1 [Shulman, Lawrence N.; Wagner, Claire M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Shulman, Lawrence N.] Partners Heath, Boston, MA 02215 USA. [Mpunga, Tharcisse; Binagwaho, Agnes] Govt Rwanda, Minist Hlth, Kigali, Rwanda. [Mpunga, Tharcisse] Univ Rwanda, Coll Med & Hlth Sci, Musanze, Rwanda. [Tapea, Neo; Fadelu, Temidayo] Partners Hlth Inshuti Mu Buzima, Kigali, Rwanda. [Tapea, Neo] Brigham & Womens Hosp, Boston, MA 02115 USA. [Binagwaho, Agnes] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Binagwaho, Agnes] Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM lawrence_shulman@dfci.harvard.edu NR 50 TC 16 Z9 16 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2014 VL 14 IS 12 BP 815 EP 821 DI 10.1038/nrc3848 PG 7 WC Oncology SC Oncology GA AU8AE UT WOS:000345818400010 PM 25355378 ER PT J AU Bird, GH Irimia, A Ofek, G Kwong, PD Wilson, IA Walensky, LD AF Bird, Gregory H. Irimia, Adriana Ofek, Gilad Kwong, Peter D. Wilson, Ian A. Walensky, Loren D. TI Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; EPITOPE-SCAFFOLDS; VACCINE DESIGN; GP41; MEMBRANE; 4E10; 2F5 AB Hydrocarbon stapling can restore bioactive a-helical structure to natural peptides, yielding research tools and prototype therapeutics to dissect and target protein interactions. Here we explore the capacity of peptide stapling to generate high-fidelity, protease-resistant mimics of antigenic structures for vaccine development. HIV-1 has been refractory to vaccine technologies thus far, although select human antibodies can broadly neutralize HIV-1 by targeting sequences of the gp41 juxtamembrane fusion apparatus. To develop candidate HIV-1 immunogens, we generated and characterized stabilized alpha-helices of the membrane-proximal external region (SAH-MPER) of gp41. SAH-MPER peptides were remarkably protease resistant and bound to the broadly neutralizing 4E10 and 10E8 antibodies with high affinity, recapitulating the structure of the MPER epitope when differentially engaged by the two anti-HIV Fabs. Thus, stapled peptides may provide a new opportunity to develop chemically stabilized antigens for vaccination. C1 [Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bird, Gregory H.; Walensky, Loren D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Bird, Gregory H.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Irimia, Adriana; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Irimia, Adriana; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Irimia, Adriana; Wilson, Ian A.] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA. [Ofek, Gilad; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu FU NIH [1R01 AI084102, R01 AI084817]; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [UM1 AI100663]; International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, IAVI Collaboration for AIDS Vaccine Discovery; Bill and Melinda Gates Foundation; Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-39, DE-AC02-06CH11357] FX We thank E. Smith for graphics assistance, D. Ekiert and E. Reinherz for insightful discussions, M. Connors (National Institute of Allergy and Infectious Diseases) for his generosity in providing us with a sample of 10E8 antibody and Y. Yang and P. Acharya for technical support. We are grateful to the US National Institutes of Health (NIH) AIDS Reagent Program for providing us with 4E10 and 10E8 antibodies. This work was supported by NIH grants 1R01 AI084102 (L.D.W.) and R01 AI084817 (I.A.W.); Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) grant UM1 AI100663 (I.A.W.); the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, IAVI Collaboration for AIDS Vaccine Discovery; the Bill and Melinda Gates Foundation; and the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. Use of the 22-ID and 23-ID sectors at Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract nos. W-31-109-Eng-39 and DE-AC02-06CH11357. NR 57 TC 18 Z9 18 U1 4 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2014 VL 21 IS 12 BP 1058 EP 1067 DI 10.1038/nsmb.2922 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AU9EC UT WOS:000345893300009 PM 25420104 ER PT J AU Kozin, ED Gliklich, RE AF Kozin, Elliott D. Gliklich, Richard E. TI Voldemort Deformity: Nasolabial Transposition Technique for Severe Nasal Inlet Stenosis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE nasal stenosis; rhinoplasty; cocaine C1 [Kozin, Elliott D.; Gliklich, Richard E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Kozin, ED (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Elliott_Kozin@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 5 TC 0 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2014 VL 151 IS 6 BP 1078 EP 1080 DI 10.1177/0194599814545745 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AU8PS UT WOS:000345859300031 PM 25104815 ER PT J AU Shrime, MG AF Shrime, Mark G. TI Cost-Effectiveness of Transoral Robotic Surgery in the Unknown Primary: The Problem of Extended Dominance SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Letter C1 [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02138 USA. [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Shrime, MG (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02138 USA. EM shrime@mail.harvard.edu FU NCI NIH HHS [NIH/NCI R25CA92203, R25 CA092203] NR 4 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2014 VL 151 IS 6 BP 1093 EP 1093 DI 10.1177/0194599814553931 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AU8PS UT WOS:000345859300037 PM 25452331 ER PT J AU Klick, JC Friebert, S Hutton, N Osenga, K Pituch, KJ Vesel, T Weidner, N Block, SD Morrison, LJ AF Klick, Jeffrey C. Friebert, Sarah Hutton, Nancy Osenga, Kaci Pituch, Kenneth J. Vesel, Tamara Weidner, Norbert Block, Susan D. Morrison, Laura J. CA Hosp Palliat Med Competencies W TI Developing Competencies for Pediatric Hospice and Palliative Medicine SO PEDIATRICS LA English DT Article DE competencies; hospice and palliative medicine; milestones; pediatric palliative care; fellowship training ID CARE; EDUCATION; OUTCOMES AB In 2006, hospice and palliative medicine (HPM) became an officially recognized subspecialty. This designation helped initiate the Accreditation Council of Graduate Medical Education Outcomes Project in HPM. As part of this process, a group of expert clinician-educators in HPM defined the initial competency-based outcomes for HPM fellows (General HPM Competencies). Concurrently, these experts recognized and acknowledged that additional expertise in pediatric HPM would ensure that the competencies for pediatric HPM were optimally represented. To fill this gap, a group of pediatric HPM experts used a product development method to define specific Pediatric HPM Competencies. This article describes the development process. With the ongoing evolution of HPM, these competencies will evolve. As part of the Next Accreditation System, the Accreditation Council of Graduate Medical Education uses milestones as a framework to better define competency-based, measurable outcomes for trainees. Currently, there are no milestones specific to HPM, although the field is designing curricular milestones with multispecialty involvement, including pediatrics. These competencies are the conceptual framework for the pediatric content in the HPM milestones. They are specific to the pediatric HPM subspecialist and should be integrated into the training of pediatric HPM subspecialists. They will serve a foundational role in HPM and should inform a wide range of emerging innovations, including the next evolution of HPM Competencies, development of HPM curricular milestones, and training of adult HPM and other pediatric subspecialists. They may also inform pediatric HPM outcome measures, as well as standards of practice and performance for pediatric HPM interdisciplinary teams. C1 [Klick, Jeffrey C.] Emory Univ, Childrens Healthcare Atlanta, Sch Med, Atlanta, GA 30322 USA. [Friebert, Sarah] Northeast Ohio Med Univ, Akron Childrens Hosp, Rootstown, OH USA. [Osenga, Kaci] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Osenga, Kaci] Childrens Hosp, Minneapolis, MN USA. [Osenga, Kaci] Clin Minnesota, Minneapolis, MN USA. [Pituch, Kenneth J.] Univ Michigan, Sch Med, Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Vesel, Tamara] Hosp North Shore & Greater Boston, Danvers, MA USA. [Weidner, Norbert] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Block, Susan D.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Morrison, Laura J.] Yale Univ, Sch Med, Yale New Haven Hosp, New Haven, CT USA. RP Klick, JC (reprint author), Childrens Healthcare Atlanta, 1001 Johnson Ferry Rd, Atlanta, GA 30342 USA. EM jeffrey.klick@choa.org FU Y.C. Ho/Helen and Michael Chiang Foundation at Children's Hospital of Philadelphia; Fraser/Parker Foundation at Children's Healthcare of Atlanta; Arthur Vining Davis Foundation FX The Y.C. Ho/Helen and Michael Chiang Foundation helped fund work on this project at the Children's Hospital of Philadelphia. The Fraser/Parker Foundation helped fund work on this project at Children's Healthcare of Atlanta. The Arthur Vining Davis Foundation supported the development of the original Hospice and Palliative Medicine Competencies by the American Board of Hospice and Palliative Medicine Competencies Work Group, on which much of the pediatric competencies content is based. NR 18 TC 5 Z9 5 U1 1 U2 6 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 DEC PY 2014 VL 134 IS 6 BP E1670 EP E1677 DI 10.1542/peds.2014-0748 PG 8 WC Pediatrics SC Pediatrics GA AU8KB UT WOS:000345844200018 PM 25404726 ER PT J AU Sui, YT Bullock, KM Erickson, MA Zhang, J Banks, WA AF Sui, Yu-Ting Bullock, Kristin M. Erickson, Michelle A. Zhang, Jing Banks, W. A. TI Alpha synuclein is transported into and out of the brain by the blood-brain barrier SO PEPTIDES LA English DT Article DE Blood-brain barrier; Alpha-synuclein; LRP-1; p-Glycoprotein; Parkinson's disease ID CARRIER-MEDIATED TRANSPORT; DOPAMINERGIC NEURON LOSS; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; MOUSE MODEL; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; LOCUS TRIPLICATION; HUMAN PLASMA AB Alpha-synuclein (alpha-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, alpha-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of alpha-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of alpha-Syn to cross the blood-brain barrier (BBB). Here, we found that radioactively labeled alpha-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in alpha-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase alpha-Syn uptake by the brain by disrupting the BBB. Published by Elsevier Inc. C1 [Sui, Yu-Ting; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Bullock, Kristin M.; Erickson, Michelle A.; Banks, W. A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, W. A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Room 810 Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU NIN [U01 N5082137]; VA Merit Review; NIH [AG029834 (WAB)] FX This study was supported by NIN U01 N5082137 (JZ), VA Merit Review (WAB) and NIH RO-1 AG029834 (WAB). NR 62 TC 8 Z9 8 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD DEC PY 2014 VL 62 BP 197 EP 202 DI 10.1016/j.peptides.2014.09.018 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA AU4YQ UT WOS:000345614700020 PM 25278492 ER PT J AU Pemp, B Deak, G Prager, S Mitsch, C Lammer, J Schmidinger, G Scholda, C Schmidt-Erfurth, U Bolz, M AF Pemp, Berthold Deak, Gabor Prager, Sonja Mitsch, Christoph Lammer, Jan Schmidinger, Gerald Scholda, Christoph Schmidt-Erfurth, Ursula Bolz, Matthias CA Diabetic Retinopathy Res Grp TI DISTRIBUTION OF INTRARETINAL EXUDATES IN DIABETIC MACULAR EDEMA DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY OBSERVED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AND FUNDUS PHOTOGRAPHY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE anti-VEGF therapy; diabetes mellitus; diabetic macular edema; hard exudates; lipids; microexudates; optical coherence tomography ID RETINOPATHY; ASSOCIATION; MANAGEMENT AB Purpose: To evaluate changes in the distribution and morphology of intraretinal microexudates and hard exudates (HEs) during intravitreal anti-vascular endothelial growth factor therapy in patients with persistent diabetic macular edema. Methods: Twenty-four patients with persistent diabetic macular edema after photocoagulation were investigated in this prospective cohort study. Each eye was assigned to a loading dose of three anti-vascular endothelial growth factor treatments at monthly intervals. Additional single treatments were performed if diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed over 6 months using spectral domain optical coherence tomography (SD-OCT) and fundus photography. Results: Before treatment, microexudates were detected by SD-OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During therapy, HE increased significantly in number and size. This was accompanied by accumulation of microexudates in the outer retina. Enlargement of hyperreflective structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus locations. A rapid reduction in diabetic macular edema was seen in all patients, but to varying degrees. Patients with hemoglobin A1c levels <7% and serum cholesterol <200 mg/dL formed fewer HEs and featured more edema reduction and visual acuity gain. Conclusion: Diabetic macular edema reduction during intravitreal anti-vascular endothelial growth factor therapy was accompanied by dynamic rearrangement of intraretinal exudates at corresponding locations in fundus photography and SD-OCT. Intraretinal aggregates of microexudates detectable as hyperreflective foci by SD-OCT may compose and precede HE before they become clinically visible. C1 [Pemp, Berthold; Deak, Gabor; Prager, Sonja; Mitsch, Christoph; Schmidinger, Gerald; Scholda, Christoph; Schmidt-Erfurth, Ursula; Bolz, Matthias] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria. [Lammer, Jan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. RP Pemp, B (reprint author), Med Univ Vienna, Dept Ophthalmol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM berthold.pemp@meduniwien.ac.at NR 24 TC 4 Z9 5 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD DEC PY 2014 VL 34 IS 12 BP 2407 EP 2415 PG 9 WC Ophthalmology SC Ophthalmology GA AU9KK UT WOS:000345911300016 PM 25062440 ER PT J AU Atwood, CW AF Atwood, Charles W., Jr. TI How Few Signals are Needed to Diagnose Sleep Apnea? SO SLEEP LA English DT Editorial Material ID POLYSOMNOGRAPHY; AUTOTITRATION; HOME C1 [Atwood, Charles W., Jr.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, 3459 Fifth Ave,NW628 MUH, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2014 VL 37 IS 12 BP 1883 EP 1884 DI 10.5665/sleep.4232 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU8DW UT WOS:000345827600004 PM 25406117 ER PT J AU Jeon, HJ Kim, JH Kim, BN Park, SJ Fava, M Mischoulon, D Choi, H Roh, S Lee, D AF Jeon, Hong Jin Kim, Ji-Hae Kim, Bin-Na Park, Seung Jin Fava, Maurizio Mischoulon, David Choi, Hong Roh, Sungwon Lee, Dongsoo TI Sleep Quality, Posttraumatic Stress, Depression, and Human Errors in Train Drivers: A Population-Based Nationwide Study in South Korea SO SLEEP LA English DT Article DE depression; human error; sleep quality; train drivers; trauma ID MAJOR DEPRESSION; SHIFT WORK; DISORDER; HEALTH; ACCIDENTS; INSOMNIA; ANXIETY; ADULTS; DISTURBANCES; COMORBIDITY AB Study Objectives: Human error is defined as an unintended error that is attributable to humans rather than machines, and that is important to avoid to prevent accidents. We aimed to investigate the association between sleep quality and human errors among train drivers. Design: Cross-sectional. Setting: Population-based. Participants: A sample of 5,480 subjects who were actively working as train drivers were recruited in South Korea. The participants were 4,634 drivers who completed all questionnaires (response rate 84.6%). Interventions: None Measurements: The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Impact of Event Scale-Revised (IES-R), the State-Trait Anxiety Inventory (STAI), and the Korean Occupational Stress Scale (KOSS). Results: Of 4,634 train drivers, 349 (7.5%) showed more than one human error per 5 y. Human errors were associated with poor sleep quality, higher PSQI total scores, short sleep duration at night, and longer sleep latency. Among train drivers with poor sleep quality, those who experienced severe posttraumatic stress showed a significantly higher number of human errors than those without. Multiple logistic regression analysis showed that human errors were significantly associated with poor sleep quality and posttraumatic stress, whereas there were no significant associations with depression, trait and state anxiety, and work stress after adjusting for age, sex, education years, marital status, and career duration. Conclusions: Poor sleep quality was found to be associated with more human errors in train drivers, especially in those who experienced severe posttraumatic stress. C1 [Jeon, Hong Jin; Kim, Ji-Hae; Choi, Hong; Lee, Dongsoo] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat, Seoul 135710, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Kim, Bin-Na; Park, Seung Jin] Seoul Natl Univ, Seoul, South Korea. [Roh, Sungwon] Seoul Natl Hosp, Dept Mental Hlth Res, Seoul, South Korea. RP Lee, D (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, 50 Irwon Dong, Seoul 135710, South Korea. EM dongsoolee@skku.edu FU Korean National Railroad Corporation (KORAIL); National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461]; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; BioResearch; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc; PamLab, LLC; Pfizer Inc.; Pharmavite; Roche; Wyeth-Ayerst Laboratories; Bowman Family Foundation; FisherWallace; Nordic Naturals; Methylation Sciences, Inc. (MSI) FX This study was supported by the Korean National Railroad Corporation (KORAIL). This study was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064), and the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461. Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, EnVivo Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories. He has served as an advisor and consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc., BioMarin Pharmaceuticals, Inc., Biovail Pharmaceuticals, Inc., BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Inc., Eli Lilly & Company, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc., Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc., PharmaStar, Pharmavite, Precision Human Biolaboratory, Prexa Pharmaceuticals, Inc., PsychoGenics, Psylin Neurosciences, Inc., Ridge Diagnostics, Inc., Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc., Wyeth-Ayerst Laboratories. He has received speaking and publishing honoraria from Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc., PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, and Wyeth-Ayerst Laboratories. He holds equity in Compellis. He currently holds a patent for SPCD and a patent application for a combination of azapirones and bupropion in MDD, and has received copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER diagnostic instruments. Dr Mischoulon has received research support from the Bowman Family Foundation, FisherWallace, Ganeden, Nordic Naturals, and Methylation Sciences, Inc. (MSI). He has received honoraria for consulting, speaking, and writing from the Massachusetts General Hospital Psychiatry Academy. He has received royalties from Lippincott Williams & Wilkins for published book "Natural Medications for Psychiatric Disorders: Considering the Alternatives." The other authors have indicated no financial conflicts of interest.; The work was performed at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. NR 35 TC 1 Z9 1 U1 4 U2 16 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2014 VL 37 IS 12 BP 1969 EP 1975 DI 10.5665/sleep.4252 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU8DW UT WOS:000345827600014 PM 25325495 ER PT J AU Roguski, M Benzel, EC Curran, JN Magge, SN Bisson, EF Krishnaney, AA Steinmetz, MP Butler, WE Heary, RF Ghogawala, Z AF Roguski, Marie Benzel, Edward C. Curran, Jill N. Magge, Subu N. Bisson, Erica F. Krishnaney, Ajit A. Steinmetz, Michael P. Butler, William E. Heary, Robert F. Ghogawala, Zoher TI Postoperative Cervical Sagittal Imbalance Negatively Affects Outcomes After Surgery for Cervical Spondylotic Myelopathy SO SPINE LA English DT Article DE cervical spondylotic myelopathy; CSM; sagittal balance; sagittal vertical axis; prospective study; comparative effectiveness; health-related quality of life; functional outcome; SF-36; mJOA ID NECK-DISABILITY-INDEX; POSTERIOR DECOMPRESSION; KYPHOTIC DEFORMITY; CONTROLLED-TRIAL; GRAVITY LINE; ALIGNMENT; ANTERIOR; BALANCE; KYPHOSIS; IMPACT AB Study Design. Prospective observational cohort study. Objective. To determine if postoperative cervical sagittal balance is an independent predictor of health-related quality of life outcome after surgery for cervical spondylotic myelopathy. Summary of Background Data. Both ventral and dorsal fusion procedures for CSM are effective at reducing the symptoms of myelopathy. The importance of cervical sagittal balance in predicting overall health-related quality of life outcome after ventral versus dorsal surgery for CSM has not been previously explored. Methods. A prospective, nonrandomized cohort of 49 patients undergoing dorsal and ventral fusion surgery for CSM was examined. Preoperative and postoperative C2-C7 sagittal vertical axis was measured on standing lateral cervical spine radiographs. Outcome was assessed with 2 disease-specific measures-the modified Japanese Orthopedic Association scale and the Oswestry Neck Disability Index and 2 generalized outcome measures-the Short-Form 36 physical component summary (SF-36 PCS) and Euro-QOL-5D. Assessments were performed preoperatively, and at 3 months, 6 months, and 1 year postoperatively. Statistical analyses were performed using SAS version 9.3 (SAS Institute). Results. Most patients experienced improvement in all outcome measures regardless of approach. Both preoperative and postoperative C2-C7 sagittal vertical axis measurements were independent predictors of clinically significant improvement in SF-36 PCS scores (P = 0.03 and P = 0.02). The majority of patients with C2-C7 sagittal vertical axis values greater than 40 mm did not improve from an overall health-related quality of life perspective (SF-36 PCS) despite improvement in myelopathy. The postoperative sagittal balance value was inversely correlated with a clinically significant improvement of SF-36 PCS scores in patients undergoing dorsal surgery but not ventral surgery (P = 0.03 vs. P = 0.93). Conclusion. Preoperative and postoperative sagittal balance measurements independently predict clinical outcomes after surgery for CSM. C1 [Roguski, Marie; Curran, Jill N.; Magge, Subu N.; Ghogawala, Zoher] Lahey Hosp & Med Ctr, Alan & Jacqueline Stuart Spine Res Ctr, Dept Neurosurg, Burlington, MA 01805 USA. [Roguski, Marie; Ghogawala, Zoher] Tufts Univ, Sch Med, Dept Neurosurg, Boston, MA 02111 USA. [Roguski, Marie] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Benzel, Edward C.; Krishnaney, Ajit A.] Cleveland Clin, Ctr Spine Hlth, Cleveland, OH 44106 USA. [Benzel, Edward C.; Krishnaney, Ajit A.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Bisson, Erica F.] Univ Utah, Dept Neurosurg, Salt Lake City, UT USA. [Steinmetz, Michael P.] Case Western Reserve Univ, Sch Med, MetroHlth Spine Ctr, Cleveland, OH USA. [Steinmetz, Michael P.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA. [Butler, William E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Heary, Robert F.] Rutgers State Univ, New Jersey Med Sch, Dept Neurosurg, Newark, NJ 07102 USA. RP Ghogawala, Z (reprint author), Lahey Hosp & Med Ctr, Alan & Jacqueline Stuart Spine Res Ctr, Dept Neurosurg, 41 Mall Rd, Burlington, MA 01805 USA. EM Zoher.Ghogawala@lahey.org FU Jean and David Wallace Foundation FX Jean and David Wallace Foundation funds were received in support of this work. NR 38 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD DEC PY 2014 VL 39 IS 25 BP 2070 EP 2077 DI 10.1097/BRS.0000000000000641 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AU5CU UT WOS:000345625600012 PM 25419682 ER PT J AU Holliday, EG Traylor, M Malik, R Bevan, S Maguire, J Koblar, SA Sturm, J Hankey, GJ Oldmeadow, C McEvoy, M Sudlow, C Rothwell, PM Coresh, J Hamet, P Tremblay, J Turner, ST de Andrade, M Rao, M Schmidt, R Crick, PA Robino, A Peralta, CA Jukema, JW Mitchell, P Rosas, SE Wang, JJ Scott, RJ Dichgans, M Mitchell, BD Kao, WHL Fox, CS Levi, C Attia, J Markus, HS AF Holliday, Elizabeth G. Traylor, Matthew Malik, Rainer Bevan, Stephen Maguire, Jane Koblar, Simon A. Sturm, Jonathan Hankey, Graeme J. Oldmeadow, Christopher McEvoy, Mark Sudlow, Cathie Rothwell, Peter M. Coresh, Josef Hamet, Pavel Tremblay, Johanne Turner, Stephen T. de Andrade, Mariza Rao, Madhumathi Schmidt, Reinhold Crick, Peter A. Robino, Antonietta Peralta, Carmen A. Jukema, J. Wouter Mitchell, Paul Rosas, Sylvia E. Wang, Jie Jin Scott, Rodney J. Dichgans, Martin Mitchell, Braxton D. Kao, W. H. Linda Fox, Caroline S. Levi, Christopher Attia, John Markus, Hugh S. CA CKDGen Consortium Int Stroke Genetics Consortium TI Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke SO STROKE LA English DT Article DE genetic epidemiology; kidney; stroke ID GLOMERULAR-FILTRATION-RATE; GENOME-WIDE ASSOCIATION; INTIMA-MEDIA THICKNESS; ATRIAL-FIBRILLATION; ISCHEMIC-STROKE; RENAL-FUNCTION; CARDIOVASCULAR-DISEASE; RISK; METAANALYSIS; TRAITS AB Background and Purpose-Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes. Methods-Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease. Results-Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). Conclusions-This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited. C1 [Holliday, Elizabeth G.; Sturm, Jonathan; McEvoy, Mark; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Maguire, Jane] Univ Newcastle, Sch Nursing & Midwifery, Callaghan, NSW 2308, Australia. [Holliday, Elizabeth G.; Oldmeadow, Christopher; Attia, John] Clin Res Design IT & Stat Support Unit, Newcastle, NSW, Australia. [Maguire, Jane; Scott, Rodney J.; Levi, Christopher] Hunter Med Res Inst, Newcastle, NSW, Australia. [Traylor, Matthew; Bevan, Stephen; Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Koblar, Simon A.] Univ Adelaide, Stroke Res Program, Sch Med, Adelaide, SA 5005, Australia. [Koblar, Simon A.] Univ Adelaide, Adelaide Ctr Neurosci Res, Adelaide, SA 5005, Australia. [Sturm, Jonathan] Gosford Hosp, Dept Neurol, Gosford, NSW, Australia. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Hankey, Graeme J.] Sir Charles Gairdner Hosp, Dept Neurol, Perth, WA, Australia. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford OX1 2JD, England. [Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hamet, Pavel; Tremblay, Johanne] Univ Montreal, Res Ctr, Univ Montreal Hosp Hlth Ctr, Montreal, PQ, Canada. [Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN USA. [de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Rao, Madhumathi] Tufts Univ, Sch Med, Div Nephrol, Tufts Evidence Practice Ctr, Boston, MA 02111 USA. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria. [Robino, Antonietta] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Peralta, Carmen A.] Univ Calif San Francisco, Sch Med, Div Nephrol, San Francisco, CA USA. [Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Kidney & Hypertens Unit, Boston, MA 02115 USA. [Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia. [Scott, Rodney J.] John Hunter Hosp, NSW Pathol, Newcastle, NSW, Australia. [Levi, Christopher] John Hunter Hosp, Dept Neurol, Newcastle, NSW, Australia. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Div Endocrinol Nutr & Metab, Baltimore, MD 21201 USA. [Fox, Caroline S.] NHLBIs Framingham Heart Study & Ctr Populat Studi, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Holliday, EG (reprint author), HMRI, CReDITSS, C Univ Dr, Callaghan, NSW 2308, Australia. EM liz.holliday@newcastle.edu.au RI Hankey, Graeme /H-4968-2014; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; OI Hankey, Graeme /0000-0002-6044-7328; Mitchell, Braxton/0000-0003-4920-4744; Wang, Jie Jin/0000-0001-9491-4898; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Koblar, Simon/0000-0002-8667-203X FU Canadian Institutes of Health Research; Intramural NIH HHS [Z99 HL999999, ZIA HL006094-01, ZIA HL006094-03, ZIA HL006094-04, ZIA HL006094-05]; NCATS NIH HHS [UL1 TR000135]; NHGRI NIH HHS [U01 HG004436]; NHLBI NIH HHS [U01 HL054464, U01 HL096812]; NIDDK NIH HHS [K01 DK067207, P30 DK072488, R01 DK073537]; Wellcome Trust [, 095626] NR 46 TC 3 Z9 4 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3508 EP + DI 10.1161/STROKEAHA.114.006609 PG 17 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600237 PM 25352485 ER PT J AU Lord, AS Langefeld, CD Sekar, P Moomaw, CJ Badjatia, N Vashkevich, A Rosand, J Osborne, J Woo, D Elkind, MSV AF Lord, Aaron S. Langefeld, Carl D. Sekar, Padmini Moomaw, Charles J. Badjatia, Neeraj Vashkevich, Anastasia Rosand, Jonathan Osborne, Jennifer Woo, Daniel Elkind, Mitchell S. V. TI Infection After Intracerebral Hemorrhage Risk Factors and Association With Outcomes in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study SO STROKE LA English DT Article DE cerebral hemorrhage; infection; outcomes assessment (health care); risk factors ID ACUTE ISCHEMIC-STROKE; TRIALS; COMPLICATIONS; SCALE AB Background and Purpose-Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes. Methods-We determined prevalence of infections in a multicenter, triethnic study of ICH. We performed univariate and multivariate analyses to determine the association of infection with admission characteristics and hospital complications. We performed logistic regression on association of infection with outcomes after controlling for known determinants of prognosis after ICH (volume, age, infratentorial location, intraventricular hemorrhage, and Glasgow Coma Scale). Results-Among 800 patients, infections occurred in 245 (31%). Admission characteristics associated with infection in multivariable models were ICH volume (odds ratio [OR], 1.02/mL; 95% confidence interval [CI], 1.01-1.03), lower Glasgow Coma Scale (OR, 0.91 per point; 95% CI, 0.87-0.95), deep location (reference lobar: OR, 1.90; 95% CI, 1.28-2.88), and black race (reference white: OR, 1.53; 95% CI, 1.01-2.32). In a logistic regression of admission and hospital factors, infections were associated with intubation (OR, 3.1; 95% CI, 2.1-4.5), dysphagia (with percutaneous endoscopic gastrostomy: OR, 3.19; 95% CI, 2.03-5.05 and without percutaneous endoscopic gastrostomy: OR, 2.11; 95% CI, 1.04-4.23), pulmonary edema (OR, 3.71; 95% CI, 1.29-12.33), and deep vein thrombosis (OR, 5.6; 95% CI, 1.86-21.02), but not ICH volume or Glasgow Coma Scale. Infected patients had higher discharge mortality (16% versus 8%; P=0.001) and worse 3-month outcomes (modified Rankin Scale >= 3; 80% versus 51%; P<0.001). Infection was an independent predictor of poor 3-month outcome (OR, 2.6; 95% CI, 1.8-3.9). Conclusions-There are identifiable risk factors for infection after ICH, and infections predict poor outcomes. C1 [Lord, Aaron S.] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. [Langefeld, Carl D.] Wake Forest Univ, Ctr Publ Hlth Genom, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Sekar, Padmini; Moomaw, Charles J.; Osborne, Jennifer; Woo, Daniel] Univ Cincinnati, Dept Neurol & Rehabil Med, Coll Med, Cincinnati, OH 45221 USA. [Badjatia, Neeraj] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Vashkevich, Anastasia; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Elkind, Mitchell S. V.] Columbia Univ, Dept Neurol, New York, NY USA. Columbia Univ, Dept Neurol, New York, NY USA. [Elkind, Mitchell S. V.] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Lord, AS (reprint author), NYU, Dept Neurol, Sch Med, 530 1st Ave,Suite 5A, New York, NY 10016 USA. EM Aaron.Lord@Nyumc.org OI Lord, Aaron/0000-0001-8755-7773 FU NINDS NIH HHS [U01 NS069763, U10 NS077311]; PHS HHS [U01-069763] NR 23 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3535 EP + DI 10.1161/STROKEAHA.114.006435 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600241 PM 25316275 ER PT J AU Schroder, J Cheng, B Ebinger, M Kohrmann, M Wu, O Kang, DW Liebeskind, DS Tourdias, T Singer, OC Christensen, S Campbell, B Luby, M Warach, S Fiehler, J Fiebach, JB Gerloff, C Thomalla, G AF Schroeder, Julian Cheng, Bastian Ebinger, Martin Koehrmann, Martin Wu, Ona Kang, Dong-Wha Liebeskind, David S. Tourdias, Thomas Singer, Oliver C. Christensen, Soren Campbell, Bruce Luby, Marie Warach, Steven Fiehler, Jens Fiebach, Jochen B. Gerloff, Christian Thomalla, Goetz CA STIR Vista Imaging Investigators TI Validity of Acute Stroke Lesion Volume Estimation by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomographic Score Depends on Lesion Location in 496 Patients With Middle Cerebral Artery Stroke SO STROKE LA English DT Article DE brain ischemia; diffusion magnetic resonance imaging; magnetic resonance imaging; middle cerebral artery; neuroimaging; severity of illness index; stroke ID ACUTE ISCHEMIC-STROKE; DWI-ASPECTS; PREDICTS; ONSET; CT AB Background and Purpose-Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume >= 100 mL. Methods-We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for >= 100-mL lesion volume. Results-A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (r=-0.78; P<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (r=-0.19; P=0.038) when compared with superficial (r=-0.72; P<0.001) or combined superficial and deep MCA lesions (r=-0.72; P<0.001). Receiver-operating characteristics analysis revealed ASPECTS <= 6 as best cutoff to identify >= 100-mL DWI lesion volume; however, positive predictive value was low (0.35). Conclusions-ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps. C1 [Schroeder, Julian; Cheng, Bastian; Gerloff, Christian; Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, Hamburg, Germany. [Ebinger, Martin; Fiebach, Jochen B.] Charite, Ctr Schlaganfallforsch Berlin, D-13353 Berlin, Germany. [Koehrmann, Martin] Univ Erlangen Nurnberg, Neurol Klin, Erlangen, Germany. [Wu, Ona] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02115 USA. [Kang, Dong-Wha] Univ Ulsan, Coll Med, Dept Neurol, Asan Med Ctr, Seoul, South Korea. [Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Tourdias, Thomas] Univ Bordeaux, CHU Bordeaux, Serv NeuroImagerie Diagnost Therapeut, Bordeaux, France. [Singer, Oliver C.] Univ Frankfurt Klinikum, Neurol Klin, Frankfurt, Germany. [Christensen, Soren; Campbell, Bruce] Univ Melbourne, Royal Melbourne Hosp, Dept Med & Neurol, Melbourne Brain Ctr, Parkville, Vic, Australia. [Luby, Marie] NINDS, Bethesda, MD 20892 USA. [Warach, Steven] UT SW Med Ctr, Dept Neurol & Neurotherapeut, Seton UT SW Clin Res Inst Austin, Austin, TX USA. [Fiehler, Jens] Unv Klinikum Hamburg Eppendorf, Klin & Poliklin Neuroradiol Diagnost & Intervent, Hamburg, Germany. RP Schroder, J (reprint author), Martinistr 52, D-20246 Hamburg, Germany. EM jul.schroeder@uke.de RI Thijs, Vincent/C-3647-2009; OI Thijs, Vincent/0000-0002-6614-8417; Fiebach, Jochen B./0000-0002-7936-6958; Campbell, Bruce/0000-0003-3632-9433; DOUSSET, VINCENT/0000-0003-0427-3236; Donnan, Geoffrey/0000-0001-6324-3403 FU Intramural NIH HHS [Z99 NS999999]; NINDS NIH HHS [P50 NS051343, R01 NS059775, R01 NS063925] NR 14 TC 4 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3583 EP 3588 DI 10.1161/STROKEAHA.114.006694 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600248 PM 25316278 ER PT J AU Ay, H Arsava, EM Andsberg, G Benner, T Brown, RD Chapman, SN Cole, JW Delavaran, H Dichgans, M Engstrom, G Giralt-Steinhauer, E Grewal, RP Gwinn, K Jern, C Jimenez-Conde, J Jood, K Katsnelson, M Kissela, B Kittner, SJ Kleindorfer, DO Labovitz, DL Lanfranconi, S Lee, JM Lehm, M Lemmens, R Levi, C Li, LX Lindgren, A Markus, HS McArdle, PF Melander, O Norrving, B Peddareddygari, LR Pedersen, A Pera, J Rannikmae, K Rexrode, KM Rhodes, D Rich, SS Roquer, J Rosand, J Rothwell, PM Rundek, T Sacco, RL Schmidt, R Schurks, M Seiler, S Sharma, P Slowik, A Sudlow, C Thijs, V Woodfield, R Worrall, BB Meschia, JF AF Ay, Hakan Arsava, Ethem Murat Andsberg, Gunnar Benner, Thomas Brown, Robert D., Jr. Chapman, Sherita N. Cole, John W. Delavaran, Hossein Dichgans, Martin Engstroem, Gunnar Giralt-Steinhauer, Eva Grewal, Raji P. Gwinn, Katrina Jern, Christina Jimenez-Conde, Jordi Jood, Katarina Katsnelson, Michael Kissela, Brett Kittner, Steven J. Kleindorfer, Dawn O. Labovitz, Daniel L. Lanfranconi, Silvia Lee, Jin-Moo Lehm, Manuel Lemmens, Robin Levi, Chris Li, Linxin Lindgren, Arne Markus, Hugh S. McArdle, Patrick F. Melander, Olle Norrving, Bo Peddareddygari, Leema Reddy Pedersen, Annie Pera, Joanna Rannikmaee, Kristiina Rexrode, Kathryn M. Rhodes, David Rich, Stephen S. Roquer, Jaume Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Sacco, Ralph L. Schmidt, Reinhold Schuerks, Markus Seiler, Stephan Sharma, Pankaj Slowik, Agnieszka Sudlow, Cathie Thijs, Vincent Woodfield, Rebecca Worrall, Bradford B. Meschia, James F. TI Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network SO STROKE LA English DT Article DE classification; pathogenesis; phenotype ID CAUSATIVE CLASSIFICATION; INTEROBSERVER RELIABILITY; ATHEROSCLEROTIC STROKE; AGREEMENT; VARIANTS; SYSTEM; SUBTYPES; RISK AB Background and Purpose-NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods-Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. Results-The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (kappa 0.73; 95% confidence interval, 0.70-0.75). Conclusions-This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke. C1 [Ay, Hakan; Arsava, Ethem Murat; Benner, Thomas] Harvard Univ, AA Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. [Ay, Hakan; Roquer, Jaume] Harvard Univ, Stroke Serv, Massachusetts Gen Hosp, Dept Neurol,Med Sch, Charlestown, MA 02129 USA. [Roquer, Jaume] Harvard Univ, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Andsberg, Gunnar; Delavaran, Hossein; Lindgren, Arne; Melander, Olle; Norrving, Bo] Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chapman, Sherita N.; Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Cole, John W.; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [McArdle, Patrick F.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA. [Dichgans, Martin; Lehm, Manuel] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany. [Engstroem, Gunnar; Norrving, Bo] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Giralt-Steinhauer, Eva; Jimenez-Conde, Jordi; Rosand, Jonathan] Univ Pompeu Fabra, Dept Neurol, Neurovasc Res Grp, IMIM,Hosp del Mar,Univ Autonoma Barcelona,DCEXS, Barcelona, Spain. [Grewal, Raji P.; Peddareddygari, Leema Reddy] St Francis Med Ctr, Neurosci Inst, Trenton, NJ USA. [Gwinn, Katrina] NINDS, NIH, Bethesda, MD 20892 USA. [Jern, Christina; Pedersen, Annie] Univ Gothenburg, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden. [Jood, Katarina] Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden. [Katsnelson, Michael; Rundek, Tatjana; Sacco, Ralph L.] Univ Miami, Dept Neurol, Miller Sch Med, Coral Gables, FL 33124 USA. [Kissela, Brett; Kleindorfer, Dawn O.] Univ Cincinnati, Dept Neurol, Coll Med, Cincinnati, OH 45221 USA. [Labovitz, Daniel L.] Albert Einstein Coll Med, Stern Stroke Ctr, Dept Neurol, Bronx, NY 10467 USA. [Lanfranconi, Silvia] Policlin Hosp Fdn IRCCS Ca Granda, Dept Neurosci & Sensory Organs, Milan, Italy. [Lee, Jin-Moo] Washington Univ, Dept Neurol, St Louis, MO USA. [Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Levi, Chris] Univ Newcastle, John Hunter Hosp, Dept Neurol, Callaghan, NSW 2308, Australia. [Li, Linxin; Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England. [Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. [Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Coll Med, Krakow, Poland. [Rannikmaee, Kristiina; Sudlow, Cathie; Woodfield, Rebecca] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Rexrode, Kathryn M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Rhodes, David] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL USA. [Schmidt, Reinhold; Seiler, Stephan] Med Univ Graz, Dept Neurol, Graz, Austria. [Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Sharma, Pankaj] Imperial Coll London, Dept Med, Cerebrovasc Res Unit, London, England. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Ay, H (reprint author), Harvard Univ, AA Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@mgh.harvard.edu RI Thijs, Vincent/C-3647-2009; Lee, Jin-Moo/K-2024-2015; JIMENEZ-CONDE, JORDI/C-1941-2012; OI Gwinn, Katrina/0000-0002-8277-651X; Kissela, Brett/0000-0002-9773-4013; Thijs, Vincent/0000-0002-6614-8417; Lee, Jin-Moo/0000-0002-3979-0906; Engstrom, Gunnar/0000-0002-8618-9152; Rexrode, Kathryn/0000-0003-3387-8429 FU Austrian Science Fund FWF [I 904]; NCI NIH HHS [P01 CA087969, R01 CA049449, U01 CA049449]; NCRR NIH HHS [U54 RR020278]; NHGRI NIH HHS [HHSN268200782096C, U01 HG004436, U01 HG004446]; NHLBI NIH HHS [R01 HL034594, R01 HL088521]; NIA NIH HHS [Z01 AG000015, Z01 AG000954]; NIDDK NIH HHS [P30 DK072488]; NINDS NIH HHS [R01 NS059727, K23 NS042695, K23 NS042720, P50 NS055977, R01 NS030678, R01 NS039987, R01 NS042618, R01 NS042733, R01 NS045012, R01 NS073346, R01 NS085419, R37 NS029993, U01 NS038529, U01 NS041588, U01 NS069208]; The Dunhill Medical Trust [OSRP2/1006]; WHI NIH HHS [N01WH22110]; Wellcome Trust [084724, 095626] NR 16 TC 3 Z9 4 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3589 EP + DI 10.1161/STROKEAHA.114.007362 PG 14 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600249 PM 25378430 ER PT J AU Castonguay, AC Zaidat, OO Novakovic, R Nguyen, TN Taqi, MA Gupta, R Sun, CHJ Martin, C Holloway, WE Mueller-Kronast, N English, JE Linfante, I Dabus, G Malisch, TW Marden, FA Bozorgchami, H Xavier, A Rai, AT Froehler, MT Badruddin, A Abraham, MG Janardhan, V Shaltoni, H Yoo, AJ Abou-Chebl, A Chen, PR Britz, GW Kaushal, R Nanda, A Issa, MA Nogueira, RG AF Castonguay, Alicia C. Zaidat, Osama O. Novakovic, Roberta Nguyen, Thanh N. Taqi, M. Asif Gupta, Rishi Sun, Chung-Huan J. Martin, Coleman Holloway, William E. Mueller-Kronast, Nils English, Joey E. Linfante, Italo Dabus, Guilherme Malisch, Tim W. Marden, Franklin A. Bozorgchami, Hormozd Xavier, Andrew Rai, Ansaar T. Froehler, Michael T. Badruddin, Aamir Abraham, Michael G. Janardhan, Vallabh Shaltoni, Hashem Yoo, Albert J. Abou-Chebl, Alex Chen, Peng R. Britz, Gavin W. Kaushal, Ritesh Nanda, Ashish Issa, Mohammad A. Nogueira, Raul G. TI Influence of Age on Clinical and Revascularization Outcomes in the North American Solitaire Stent-Retriever Acute Stroke Registry SO STROKE LA English DT Article DE age groups; aged; stroke; thrombectomy ID ACUTE ISCHEMIC-STROKE; INFARCT VOLUME; INTRAARTERIAL THROMBOLYSIS; MECHANICAL THROMBECTOMY; ENDOVASCULAR THERAPY; RECANALIZATION; OCTOGENARIANS; MORTALITY; OCCLUSION; DEVICE AB Background and Purpose-The Solitaire With the Intention for Thrombectomy (SWIFT) and thrombectomy revascularization of large vessel occlusions in acute ischemic stroke (TREVO 2) trial results demonstrated improved recanalization rates with mechanical thrombectomy; however, outcomes in the elderly population remain poorly understood. Here, we report the effect of age on clinical and angiographic outcome within the North American Solitaire-FR Stent-Retriever Acute Stroke (NASA) Registry. Methods-The NASA Registry recruited sites to submit data on consecutive patients treated with Solitaire-FR. Influence of age on clinical and angiographic outcomes was assessed by dichotomizing the cohort into <= 80 and >80 years of age. Results-Three hundred fifty-four patients underwent treatment in 24 centers; 276 patients were <= 80 years and 78 were >80 years of age. Mean age in the <= 80 and >80 cohorts was 62.2 +/- 13.2 and 85.2 +/- 3.8 years, respectively. Of patients >80 years, 27.3% had a 90-day modified Rankin Score <= 2 versus 45.4% <= 80 years (P=0.02). Mortality was 43.9% and 27.3% in the >80 and <= 80 years cohorts, respectively (P=0.01). There was no significant difference in time to revascularization, revascularization success, or symptomatic intracranial hemorrhage between the groups. Multivariate analysis showed age >80 years as an independent predictor of poor clinical outcome and mortality. Within the >80 cohort, National Institutes of Health Stroke Scale (NIHSS), revascularization rate, rescue therapy use, and symptomatic intracranial hemorrhage were independent predictors of mortality. Conclusion-Greater than 80 years of age is predictive of poor clinical outcome and increased mortality compared with younger patients in the NASA registry. However, intravenous tissue-type plasminogen activator use, lower NIHSS, and shorter revascularization time are associated with better outcomes. Further studies are needed to understand the endovascular therapy role in this cohort compared with medical therapy. C1 [Castonguay, Alicia C.; Zaidat, Osama O.; Issa, Mohammad A.] Med Coll Wisconsin, Dept Neurol, Froedtert Hosp, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Froedtert Hosp, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Froedtert Hosp, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Froedtert Hosp, Milwaukee, WI 53226 USA. [Novakovic, Roberta] UT Suthwestern Med Ctr, Dept Radiol, Dallas, TX USA. [Novakovic, Roberta] UT Suthwestern Med Ctr, Dept Neurol, Dallas, TX USA. [Nguyen, Thanh N.] Boston Med Ctr, Dept Neurol, Boston, MA USA. [Nguyen, Thanh N.] Boston Med Ctr, Dept Neurosurg, Boston, MA USA. [Nguyen, Thanh N.] Boston Med Ctr, Dept Radiol, Boston, MA USA. [Taqi, M. Asif] Desert Reg Med Ctr, Palm Springs, CA USA. [Gupta, Rishi] Wellstar Neurosurg Kennestone Hosp, Atlanta, GA USA. [Sun, Chung-Huan J.; Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Martin, Coleman; Holloway, William E.] St Lukes Kansas City, Kansas City, MO USA. [Mueller-Kronast, Nils] Delray Med Ctr, Dept Neurol, Delray Beach, FL USA. [English, Joey E.] Calif Pacific Med Ctr, San Francisco, CA USA. [Linfante, Italo; Dabus, Guilherme] Baptist Cardiac & Vasc Inst, Div Intervent Neuroradiol, Miami, FL USA. [Malisch, Tim W.; Marden, Franklin A.] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Bozorgchami, Hormozd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Xavier, Andrew] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Rai, Ansaar T.] West Virginia Univ Hosp, Dept Radiol, Morgantown, WV USA. [Froehler, Michael T.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN USA. [Froehler, Michael T.] Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN USA. [Froehler, Michael T.] Vanderbilt Univ, Med Ctr, Dept Radiol, Nashville, TN USA. [Badruddin, Aamir] Provena St Joseph Med Ctr, Joliet, IL USA. [Abraham, Michael G.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Janardhan, Vallabh; Abou-Chebl, Alex] Texas Stroke Inst, Plano, TX USA. [Shaltoni, Hashem] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Chen, Peng R.] Univ Texas Houston, Houston, TX USA. [Britz, Gavin W.] Methodist Neurol Inst, Dept Neurosurg, Houston, TX USA. [Kaushal, Ritesh] St Louis Univ, St Louis, MO 63103 USA. [Nanda, Ashish] Univ Missouri, Columbia, MO USA. RP Zaidat, OO (reprint author), Med Coll Wisconsin, Dept Neurol Radiol & Neurosurg, Neurointervent Div, Froedtert Hosp, Milwaukee, WI 53226 USA. EM szaidat@mcw.edu NR 29 TC 14 Z9 15 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3631 EP + DI 10.1161/STROKEAHA.114.006487 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600255 PM 25358699 ER PT J AU McGrath, ER Kapral, MK Fang, JM Eikelboom, JW Conghaile, AO Canavan, M O'Donnell, MJ AF McGrath, Emer R. Kapral, Moira K. Fang, Jiming Eikelboom, John W. Conghaile, Aengus O. Canavan, Michelle O'Donnell, Martin J. CA Investigators Ontario Stroke Regis TI Antithrombotic Therapy After Acute Ischemic Stroke in Patients With Atrial Fibrillation SO STROKE LA English DT Article DE atrial fibrillation; secondary prevention; stroke ID ASPIRIN THERAPY; DOSE WARFARIN; PREVENTION; RISK; ANTICOAGULATION; TRIALS; METAANALYSIS; ASSOCIATION; INTENSITY; REGISTRY AB Background and Purpose-For patients with atrial fibrillation and ischemic stroke (IS), current guidelines recommend oral anticoagulation (OAC) alone for secondary prevention of IS. In a large prospective cohort of patients with acute IS and atrial fibrillation, we determine the association between antithrombotic regimen on discharge and risk of major vascular events. Methods-Prospective cohort of consecutive patients included in the Ontario Stroke Registry. Multivariable Cox proportional hazard models were used to determine the association between antithrombotic regimen on discharge and time to death or admission for recurrent IS, myocardial infarction, or major bleeding. Results-Two thousand one hundred sixty-two patients were hospitalized atrial fibrillation and acute IS. At discharge, 8.0% were prescribed no antithrombotic therapy, 21.6% antiplatelet therapy alone, 39.3% OAC (warfarin) alone, and 31.1% combination OAC and antiplatelet therapy. Compared with OAC alone (hazard ratio [HR], 1.0), no antithrombotic therapy (HR, 1.51; 95% confidence interval, 1.23-1.86) and antiplatelet therapy (HR, 1.31; 95% confidence interval, 1.14-1.50) were associated with an increased risk of the primary composite outcome, whereas combination OAC and antiplatelet therapy was associated with a trend toward a reduced risk (HR, 0.91; 95% confidence interval, 0.80-1.04 overall and HR, 0.79; 95% confidence interval, 0.61-1.02 in those with coronary heart disease). Results were consistent in those with severe stroke: HR 1.58 (95% CI, 1.21-2.06), 1.34 (95% CI, 1.09-1.63), and 0.91 (95% CI, 0.74-1.11), respectively. Conclusions-Contrary to current guidelines, 30% of patients with atrial fibrillation and recent IS are not prescribed any OAC therapy on discharge, whereas a further 30% are prescribed combination OAC and antiplatelet therapy. Combination OAC and antiplatelet therapy in patients at high cardiovascular risk requires evaluation in clinical trials, particularly with the newer OACs, given their more favorable risk-benefit ratio compared with warfarin. C1 [McGrath, Emer R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McGrath, Emer R.] Natl Univ Ireland, Galway, Ireland. [Kapral, Moira K.] Univ Toronto, Toronto, ON, Canada. [Kapral, Moira K.; Fang, Jiming] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Eikelboom, John W.] McMaster Univ, Hamilton, ON, Canada. [Conghaile, Aengus O.; Canavan, Michelle; O'Donnell, Martin J.] Natl Univ Ireland, Galway, Ireland. RP McGrath, ER (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM emcgrath2@partners.org OI O'Donnell, Martin/0000-0002-7347-7761; McGrath, Emer/0000-0002-3589-2964 NR 21 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3637 EP + DI 10.1161/STROKEAHA.114.006929 PG 18 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600256 PM 25378422 ER PT J AU Battey, TWK Karki, M Singhal, AB Wu, O Sadaghiani, S Campbell, BCV Davis, SM Donnan, GA Sheth, KN Kimberly, WT AF Battey, Thomas W. K. Karki, Mahima Singhal, Aneesh B. Wu, Ona Sadaghiani, Saloomeh Campbell, Bruce C. V. Davis, Stephen M. Donnan, Geoffrey A. Sheth, Kevin N. Kimberly, W. Taylor TI Brain Edema Predicts Outcome After Nonlacunar Ischemic Stroke SO STROKE LA English DT Article DE brain edema; magnetic resonance imaging; stroke; swelling ID MIDDLE-CEREBRAL-ARTERY; HEMORRHAGIC TRANSFORMATION; TERRITORY INFARCTION; SIGNAL INTENSITY; RELIABILITY; RECOVERY; CT; HYPERINTENSITY; THROMBOLYSIS; REPERFUSION AB Background and Purpose-In malignant infarction, brain edema leads to secondary neurological deterioration and poor outcome. We sought to determine whether swelling is associated with outcome in smaller volume strokes. Methods-Two research cohorts of acute stroke subjects with serial brain MRI were analyzed. The categorical presence of swelling and infarct growth was assessed on diffusion-weighted imaging (DWI) by comparing baseline and follow-up scans. The increase in stroke volume (Delta DWI) was then subdivided into swelling and infarct growth volumes using region-of-interest analysis. The relationship of these imaging markers with outcome was evaluated in univariable and multivariable regression. Results-The presence of swelling independently predicted worse outcome after adjustment for age, National Institutes of Health Stroke Scale, admission glucose, and baseline DWI volume (odds ratio, 4.55; 95% confidence interval, 1.21-18.9; P<0.02). Volumetric analysis confirmed that Delta DWI was associated with outcome (odds ratio, 4.29; 95% confidence interval, 2.00-11.5; P<0.001). After partitioning Delta DWI into swelling and infarct growth volumetrically, swelling remained an independent predictor of poor outcome (odds ratio, 1.09; 95% confidence interval, 1.03-1.17; P<0.005). Larger infarct growth was also associated with poor outcome (odds ratio, 7.05; 95% confidence interval, 1.04-143; P<0.045), although small infarct growth was not. The severity of cytotoxic injury measured on apparent diffusion coefficient maps was associated with swelling, whereas the perfusion deficit volume was associated with infarct growth. Conclusions-Swelling and infarct growth each contribute to total stroke lesion growth in the days after stroke. Swelling is an independent predictor of poor outcome, with a brain swelling volume of >= 11 mL identified as the threshold with greatest sensitivity and specificity for predicting poor outcome. C1 [Battey, Thomas W. K.; Karki, Mahima; Kimberly, W. Taylor] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Battey, Thomas W. K.; Karki, Mahima; Kimberly, W. Taylor] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Battey, Thomas W. K.; Karki, Mahima; Singhal, Aneesh B.; Wu, Ona; Sadaghiani, Saloomeh; Kimberly, W. Taylor] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Campbell, Bruce C. V.; Davis, Stephen M.] Royal Melbourne Hosp, Dept Radiol, Parkville, Vic 3050, Australia. [Campbell, Bruce C. V.; Donnan, Geoffrey A.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Sheth, Kevin N.] Yale New Haven Med Ctr, Div Neurocrit Care & Emergency Neurol, New Haven, CT USA. RP Kimberly, WT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Lunder 644, Boston, MA 02114 USA. EM wtkimberly@mgh.harvard.edu OI Campbell, Bruce/0000-0003-3632-9433; Donnan, Geoffrey/0000-0001-6324-3403 FU NINDS NIH HHS [K23 NS076597, K23NS076597, P50 NS051343, R01 NS051412, R01 NS059775, R01NS051412, R21 NS077442] NR 32 TC 10 Z9 10 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP 3643 EP + DI 10.1161/STROKEAHA.114.006884 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600257 PM 25336512 ER PT J AU Hakimelahi, R Schwamm, LH Gonzalez, RG AF Hakimelahi, Reza Schwamm, Lee H. Gonzalez, R. Gilberto TI Response to Letter Regarding Article, "Time and Diffusion Lesion Size in Major Anterior Circulation Ischemic Strokes" SO STROKE LA English DT Letter C1 [Hakimelahi, Reza] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02163 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA. RP Hakimelahi, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02163 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 BP E306 EP E306 DI 10.1161/STROKEAHA.114.007766 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600229 PM 25378428 ER PT J AU Lanthier, S Ferro, JM Calabrese, LH Putaala, J Strbian, D Letourneau-Guillon, L Chagnon, M Singhal, AB Salvarani, C Frosch, MP Guilbert, F Raymond, J AF Lanthier, S. Ferro, J. M. Calabrese, L. H. Putaala, J. Strbian, D. Letourneau-Guillon, L. Chagnon, M. Singhal, A. B. Salvarani, C. Frosch, M. P. Guilbert, F. Raymond, J. TI The International Study on Primary Angiitis of the Central Nervous System (INTERSPACE) Needs More Study Sites: a Special Invitation to Canada SO STROKE LA English DT Meeting Abstract CT Canadian Stroke Congress CY OCT 04-07, 2014 CL Vancouver, CANADA C1 [Calabrese, L. H.] Cleveland Clin, Cleveland, OH 44106 USA. [Ferro, J. M.] Univ Lisbon, Hosp Santa Maria, P-1699 Lisbon, Portugal. [Putaala, J.; Strbian, D.] Helsinki Univ Hosp, Dept Med 4, Helsinki, Finland. [Lanthier, S.; Letourneau-Guillon, L.] Univ Montreal, Montreal, PQ, Canada. [Singhal, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salvarani, C.; Frosch, M. P.] Azienda Ospedaliera ASMN, Ist Ricovero & Cura Carattere Sci, Reggio Emilia, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2014 VL 45 IS 12 MA P.057 BP E279 EP E280 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU3ME UT WOS:000345516600118 ER PT J AU Luciano, JA Zuckerbraun, BS AF Luciano, Jason A. Zuckerbraun, Brian S. TI Clostridium Difficile Infection Prevention, Treatment, and Surgical Management SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Vancomycin; Fecal microbiota therapy; Ileostomy; Colectomy ID FULMINANT PSEUDOMEMBRANOUS COLITIS; FECAL MICROBIOTA TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; RISK-FACTORS; BINARY TOXIN; MONOCLONAL-ANTIBODIES; CARE FACILITIES; UNITED-STATES; DISEASE; DIARRHEA AB Clostridium difficile is increasing in both incidence and severity. Although metronidazole and vancomycin remain the gold standard for medical management, and surgical colectomy remains the gold standard for surgical management, new treatment alternatives, including the creation of a diverting loop ileostomy along with colonic lavage and vancomycin enemas, are being investigated. These alternatives may lead to changes in the current treatment algorithms. The most exciting development in the treatment options for C difficile infection, however, is likely to be novel immunologic agents, which hold the potential to reduce the incidence, mortality, and costs associated with C difficile. C1 [Luciano, Jason A.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. RP Zuckerbraun, BS (reprint author), F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 90 TC 4 Z9 4 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 2014 VL 94 IS 6 BP 1335 EP + DI 10.1016/j.suc.2014.08.006 PG 16 WC Surgery SC Surgery GA AU7YO UT WOS:000345814400015 PM 25440127 ER PT J AU Monteiro, IP Gabriel, D Timko, BP Hashimoto, M Karajanagi, S Tong, R Marques, AP Reis, RL Kohane, DS AF Monteiro, I. P. Gabriel, D. Timko, B. P. Hashimoto, M. Karajanagi, S. Tong, R. Marques, A. P. Reis, R. L. Kohane, D. S. TI A two-component pre-seeded dermal-epidermal scaffold SO ACTA BIOMATERIALIA LA English DT Article DE Skin defects; Bilayered; Hyaluronic acid; Amine-aldehyde bonding ID HYALURONIC-ACID HYDROGELS; TISSUE ENGINEERING APPLICATIONS; ENDOTHELIAL-CELLS; BURN INJURIES; FIBRIN GELS; MATRIX; SKIN; KERATINOCYTES; ANGIOGENESIS; FIBRONECTIN AB We have developed a bilayered dermal-epidermal scaffold for application in the treatment of full-thickness skin defects. The dermal component gels in situ and adapts to the lesion shape, delivering human dermal fibroblasts in a matrix of fibrin and cross-linked hyaluronic acid modified with a cell adhesion-promoting peptide. Fibroblasts were able to form a tridimensional matrix due to material features such as tailored mechanical properties, presence of protease-degradable elements and cell-binding ligands. The epidermal component is a robust membrane containing cross-linked hyaluronic acid and poly-L-lysine, on which keratinocytes were able to attach and to form a monolayer. Amine-aldehyde bonding at the interface between the two components allows the formation of a tightly bound composite scaffold. Both parts of the scaffold were designed to provide cell-type-specific cues to allow for cell proliferation and form a construct that mimics the skin environment. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Monteiro, I. P.; Gabriel, D.; Timko, B. P.; Hashimoto, M.; Tong, R.; Kohane, D. S.] Harvard Univ, Div Crit Care Med, Lab Biomat & Drug Delivery, Dept Anesthesiol,Childrens Hosp Boston,Med Sch, Boston, MA 02115 USA. [Monteiro, I. P.; Gabriel, D.; Timko, B. P.; Hashimoto, M.; Karajanagi, S.; Tong, R.; Kohane, D. S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Monteiro, I. P.; Marques, A. P.; Reis, R. L.] Univ Minho, Res Grp Biomat Biodegradables & Biomimet 3Bs, Headquarters European Inst Excellence Tissue Engn, P-4806909 Taipas, Guimaraes, Portugal. [Monteiro, I. P.; Marques, A. P.; Reis, R. L.] Univ Minho, PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal. [Karajanagi, S.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Harvard Univ, Div Crit Care Med, Lab Biomat & Drug Delivery, Dept Anesthesiol,Childrens Hosp Boston,Med Sch, 300 Longwood Ave, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu RI Reis, Rui L./A-8938-2008; Marques, Alexandra/B-1238-2012; Tong, Rong/A-4100-2013; Group, 3Bs/E-4374-2012 OI Reis, Rui L./0000-0002-4295-6129; Marques, Alexandra/0000-0002-3222-0310; Tong, Rong/0000-0002-2034-9272; Group, 3Bs/0000-0002-5195-3456 FU Biotechnology Research Endowment from the Department of Anesthesiology at Boston Children's Hospital; Portuguese Foundation for Science and Technology [BD/39396/2007]; Swiss National Science Foundation [PBGEP3-129111] FX D.S.K. acknowledges funding from the Biotechnology Research Endowment from the Department of Anesthesiology at Boston Children's Hospital. I.P.M. acknowledges the Portuguese Foundation for Science and Technology for the grant BD/39396/2007 and the MIT-Portugal Program. D.G. acknowledges the Swiss National Science Foundation for a post-doctoral fellowship (PBGEP3-129111). B.P.T. acknowledges an NIR Ruth L. Kirschstein National Research Service Award (F32GM096546). NR 61 TC 5 Z9 5 U1 2 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD DEC PY 2014 VL 10 IS 12 BP 4928 EP 4938 DI 10.1016/j.actbio.2014.08.029 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AU2SQ UT WOS:000345468300001 PM 25192821 ER PT J AU Kim, SC Glynn, RJ Liu, J Everett, BM Goldfine, AB AF Kim, Seoyoung C. Glynn, Robert J. Liu, Jun Everett, Brendan M. Goldfine, Allison B. TI Dipeptidyl peptidase-4 inhibitors do not increase the risk of cardiovascular events in type 2 diabetes: a cohort study SO ACTA DIABETOLOGICA LA English DT Article DE Dipeptidyl peptidase-4 inhibitor; Type 2 diabetes; Cardiovascular disease; Heart failure ID ADMINISTRATIVE DATA; VALIDATED METHODS; GLYCEMIC CONTROL; DOUBLE-BLIND; MELLITUS; SAFETY; METAANALYSIS; EFFICACY; PANCREATITIS; PERFORMANCE AB Aims Two recent randomized controlled trials of type 2 diabetes mellitus (T2DM) patients with history of, or at high risk of, cardiovascular disease (CVD) showed no risk of ischemic cardiovascular events associated with dipeptidyl peptidase-4 inhibitors (DPP4i), but an increased risk of heart failure (HF) with saxagliptin. We evaluated the risk of CVD including myocardial infarction (MI), stroke, coronary revascularization, and HF associated with DPP4i in T2DM patients with and without baseline CVD as used in the community. Methods Using US commercial insurance claims data (2005-2012), we conducted a cohort study that included initiators of DPP4i and non-DPP4i treatments. Composite CVD endpoints including MI, stroke, coronary revascularization, and HF were defined with a hospital discharge diagnosis or procedure code. Cox proportional hazards models compared the risk of composite and individual CVD endpoints in propensity score (PS)-matched initiators of DPP4 versus non-DPP4i. Results We included 79,538 (18 % with baseline CVD) persons in PS-matched pairs of DPP4i and non-DPP4i initiators. The incidence rate per 1,000 person-years for composite CVD was 30.30 (95 % CI 28.24-32.51) in DPP4i and 34.76 (95 % CI 32.34-37.36) in non-DPP4i. The PS-matched hazard ratio (HR) for composite CVD was 0.87 (95 % CI 0.79-0.96) in DPP4i versus non-DPP4i. The PS-matched HR for HF was 0.81 (95 % CI 0.70-0.94) in DPP4i versus non-DPP4i. Among patients with baseline CVD, there was no increased risk of CVD or HF associated with DPP4i use. Conclusions Among T2DM patients, initiating DPP4i was not associated with a greater risk of CVD or HF compared to non-DPP4i initiators. C1 [Kim, Seoyoung C.; Glynn, Robert J.; Liu, Jun] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Kim, Seoyoung C.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Everett, Brendan M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kim, SC (reprint author), 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM skim62@partners.org; rglynn@rics.bwh.harvard.edu; jliu3@partners.org; beverett@partners.org; Allison.Goldfine@joslin.harvard.edu OI Kim, Seoyoung/0000-0002-2517-3579 FU NIH [K23 AR059677, R56 DK095451, P50 HL083813, R01 DK088214, U01 HL101422, P30-DK03836]; American Diabetes Association [7-13-CE-17] FX Kim was supported by the NIH grant K23 AR059677. Goldfine is supported by the NIH grants R56 DK095451, P50 HL083813, R01 DK088214, U01 HL101422, P30-DK03836, and American Diabetes Association 7-13-CE-17. NR 29 TC 18 Z9 19 U1 0 U2 7 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 0940-5429 EI 1432-5233 J9 ACTA DIABETOL JI Acta Diabetol. PD DEC PY 2014 VL 51 IS 6 BP 1015 EP 1023 DI 10.1007/s00592-014-0663-2 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AU1PJ UT WOS:000345392300015 PM 25311055 ER PT J AU Husted, H Gromov, K Malchau, H Freiberg, A Gebuhr, P Troelsen, A AF Husted, Henrik Gromov, Kirill Malchau, Henrik Freiberg, Andrew Gebuhr, Peter Troelsen, Anders TI Traditions and myths in hip and knee arthroplasty A narrative review SO ACTA ORTHOPAEDICA LA English DT Review ID GRADED COMPRESSION STOCKINGS; RANDOMIZED CONTROLLED-TRIALS; RELEVANT CLINICAL INDICATOR; ELECTIVE ORTHOPEDIC-SURGERY; VENOUS THROMBOEMBOLISM; EARLY MOBILIZATION; TRANEXAMIC ACID; TOURNIQUET USE; REPLACEMENT; METAANALYSIS AB Background and purpose - Traditions are passed on from experienced surgeons to younger fellows and become "the right way to do it". Traditions associated with arthroplasty surgery may, however, not be evidence-based and may be potentially deleterious to both patients and society, increasing morbidity and mortality, slowing early functional recovery, and increasing cost. Methods - We identified selected traditions and performed a literature search using relevant search criteria (June 2014). We present a narrative review grading the studies according to evidence, and we suggest some lines of future research. Results - We present traditions and evaluate them against the published evidence. Preoperative removal of hair, urine testing for bacteria, use of plastic adhesive drapes intraoperatively, and pre-warming of the operation room should be abandoned-as should use of a tourniquet, a space suit, a urinary catheter, and closure of the knee in extension. The safety and efficacy of tranexamic acid is supported by meta-analyses. Postoperatively, there is no evidence to support postponement of showering or postponement of changing of dressings to after 48 h. There is no evidence to recommend routine dental antibiotic prophylaxis, continuous passive motion (CPM), the use of compression stockings, cooling for pain control or reduction of swelling, flexion of at least 90 degrees as a discharge criterion following TKA, or having restrictions after THA. We present evidence supporting the use of NSAIDs, early mobilization, allowing early travel, and a low hemoglobin trigger for transfusion. Interpretation - Revision of traditions and myths surrounding hip and knee arthroplasty towards more contemporary evidence-based principles can be expected to improve early functional recovery, thus reducing morbidity, mortality, and costs. C1 [Husted, Henrik; Gromov, Kirill; Gebuhr, Peter; Troelsen, Anders] Univ Copenhagen, Hvidovre Hosp, Dept Orthoped Surg, Copenhagen, Denmark. [Malchau, Henrik; Freiberg, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malchau, Henrik] Sahlgrens Univ Hosp, Molndal, Sweden. RP Husted, H (reprint author), Univ Copenhagen, Hvidovre Hosp, Dept Orthoped Surg, Copenhagen, Denmark. EM henrikhusted@dadlnet.dk NR 68 TC 15 Z9 15 U1 2 U2 20 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD DEC PY 2014 VL 85 IS 6 BP 548 EP 555 DI 10.3109/17453674.2014.971661 PG 8 WC Orthopedics SC Orthopedics GA AU0YH UT WOS:000345347600002 PM 25285615 ER PT J AU Moroz, N Carmona, JJ Anderson, E Hart, AC Sinclair, DA Blackwell, TK AF Moroz, Natalie Carmona, Juan J. Anderson, Edward Hart, Anne C. Sinclair, David A. Blackwell, T. Keith TI Dietary restriction involves NAD(+)-dependent mechanisms and a shift toward oxidative metabolism SO AGING CELL LA English DT Article DE aging; dietary restriction; C. elegans; stress response; sirtuins; NAD(+) ID LIFE-SPAN EXTENSION; NEMATODE CAENORHABDITIS-ELEGANS; C-ELEGANS; CALORIC RESTRICTION; NAD(+) METABOLISM; INDUCED LONGEVITY; AMPK; NICOTINAMIDE; DROSOPHILA; SIRTUINS AB Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD(+)-dependent deacylases known as sirtuins, and increases in NAD(+) that derive from higher levels of respiration. Here, we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens [DAF-16 (FOXO), SKN-1 (Nrf1/2/3), PHA-4 (FOXA), AAK-2 (AMPK)]. Complete DR lifespan extension required the sirtuin SIR-2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC-1, a key NAD(+) salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc-1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD(+)-dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD(+) salvage. Under DR conditions, NAD(+)-dependent processes may be supported by a DR-induced shift toward oxidative metabolism rather than an increase in total respiration. C1 [Moroz, Natalie] Harvard Univ, Sch Publ Hlth, Div Biol Sci, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Moroz, Natalie; Blackwell, T. Keith] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Dept Genet,Harva, Boston, MA 02115 USA. [Carmona, Juan J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Carmona, Juan J.] Harvard Univ, Sch Publ Hlth, Program Quantitat Genom, Boston, MA 02115 USA. [Anderson, Edward; Hart, Anne C.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Carmona, Juan J.; Sinclair, David A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Carmona, Juan J.; Sinclair, David A.] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA USA. [Sinclair, David A.] Univ New S Wales, Dept Pharmacol, Sch Med Sci, Sydney, NSW, Australia. RP Blackwell, TK (reprint author), 1 Joslin Pl,Rm 655B, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu OI Anderson, Edward/0000-0002-2468-0851 FU NIH [P40 OD010440, GM062891, GM078171, AG028730]; Joslin Diabetes Center [T32DK007260]; Ellison Medical Foundation; NIDDK DRC [P30DK036836]; Paul F. Glenn Foundation for Medical Research; United Mitochondrial Disease Foundation; Juvenile Diabetes Foundation FX We thank Wendy Hanna-Rose, Leonard Guarente, Robert Horvitz, Max Heiman, Brendan Manning, Jay Mitchell, and Blackwell lab members for helpful discussions or providing strains. Some strains were provided by the CGC, which is funded by the NIH (P40 OD010440). NM was supported by the Joslin Diabetes Center T32 (T32DK007260), TKB by the NIH (GM062891), the Ellison Medical Foundation and an NIDDK DRC grant to the Joslin (P30DK036836), ACH by the Ellison Medical Foundation and NIH (GM078171), and DAS by grants from NIH (AG028730), The Paul F. Glenn Foundation for Medical Research, The United Mitochondrial Disease Foundation, The Juvenile Diabetes Foundation and a gift from the Schulak Family. We declare that no competing interests exist. NR 45 TC 16 Z9 16 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD DEC PY 2014 VL 13 IS 6 BP 1075 EP 1085 DI 10.1111/acel.12273 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AU2ON UT WOS:000345457900012 PM 25257342 ER PT J AU Park, M Vittinghoff, E Shlipak, MG Mishra, R Whooley, M Bansal, N AF Park, Meyeon Vittinghoff, Eric Shlipak, Michael G. Mishra, Rakesh Whooley, Mary Bansal, Nisha TI Associations of N-terminal pro-B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY-DISEASE; SUBCLINICAL CARDIAC ABNORMALITIES; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR EVENTS; RENAL-FUNCTION; CYSTATIN-C; PLASMA; BNP; MORTALITY AB Background Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). Methods We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (>3% per year for 5 years), and (c) incident eGFR <60 mL/min per 1.73 m(2). In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function. Results Among 535 participants, medianNT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (>280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR <60 mL/min per 1.73 m(2) were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. Conclusions N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD. C1 [Park, Meyeon] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Shlipak, Michael G.; Whooley, Mary] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.; Mishra, Rakesh; Whooley, Mary] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Mishra, Rakesh] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Bansal, Nisha] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU NHLBI NIH HHS [R01 HL079235]; NIA NIH HHS [R01 AG034853, R01 AG027002]; NIDDK NIH HHS [R01 DK087961, K23 DK088865, K23 DK099238] NR 45 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2014 VL 168 IS 6 BP 931 EP + DI 10.1016/j.ahj.2014.09.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU3IN UT WOS:000345506100017 PM 25458658 ER PT J AU Ho, VT Kim, HT Kao, G Cutler, C Levine, J Rosenblatt, J Joyce, R Antin, JH Soiffer, RJ Ritz, J Avigan, D Alyea, EP AF Ho, Vincent T. Kim, Haesook T. Kao, Grace Cutler, Corey Levine, James Rosenblatt, Jacalyn Joyce, Robin Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome Avigan, David Alyea, Edwin P., III TI Sequential infusion of donor-derived dendritic cells with donor lymphocyte infusion for relapsed hematologic cancers after allogeneic hematopoietic stem cell transplantation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MELANOMA PATIENTS; IMMUNOTHERAPY; VACCINATION; GRAFT; BLOOD; GVHD AB Donor lymphocyte infusion (DLI) is often given to induce a graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). However, efficacy of DLI is limited in most hematologic cancers. As antigen presenting cells, dendritic cells (DC) bolster immune responses. We conducted a Phase I trial testing the coinfusion of DC followed by DLI. DC were generated by culturing peripheral blood mononuclear cells from HLA matched-related donors in GM-CSF and IL-4 for 7 days, followed by TNF- for 3 days. DC were administered intravenously on 3 dose levels (5 x 10(6); 1 x 10(7); 5 x 10(7) cells). DLI (3 x 10(7) CD3+ cells/kg) was administered intravenously 1 day after the DC. Sixteen patients with hematologic cancers relapsed after HSCT were treated. A maximum tolerated dose for DC was not reached. Two of 16 patients met criteria for DLT within 10 weeks of the infusion: 1 idiopathic respiratory failure, 1 ventricular cardiac arrest. None developed grade III/IV GVHD. One patient developed grade II acute intestinal graft-vs.-host disease (GVHD) and 1 chronic GVHD within 6 months of the infusion. Both resolved with corticosteroids. Four of 14 patients evaluable for disease response achieved durable remissions and are alive and cancer free 6.7, 8.4, 8.8, and 10.1 years from infusion. Sequential infusion of donor-derived DC with DLI is feasible in patients with relapsed hematologic cancers after allogeneic HSCT. Future studies may consider donor DC preloaded with tumor antigens to investigate whether DC infusion could augment the GVL effect. Am. J. Hematol. 89:1092-1096, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Ho, Vincent T.; Kim, Haesook T.; Cutler, Corey; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P., III] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Div Hematol Malignancies, Boston, MA 02115 USA. [Kao, Grace] Tufts Med Sch, Dept Hematol Oncol, Tufts Med Ctr, Boston, MA USA. [Levine, James; Rosenblatt, Jacalyn; Joyce, Robin; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Hematol Oncol, Boston, MA 02215 USA. RP Ho, VT (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D-2030, Boston, MA 02215 USA. EM Vincent_Ho@DFCI.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [P01 CA142106] NR 13 TC 4 Z9 4 U1 1 U2 8 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 DEC PY 2014 VL 89 IS 12 BP 1092 EP 1096 DI 10.1002/ajh.23825 PG 5 WC Hematology SC Hematology GA AU1CK UT WOS:000345358600007 PM 25132538 ER EF