FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Streiff, MB Holmstrom, B Ashrani, A Bockenstedt, PL Chesney, C Eby, C Fanikos, J Fenninger, RB Fogerty, AE Gao, SW Goldhaber, SZ Hendrie, P Kuderer, N Lee, A Lee, JT Lovrincevic, M Millenson, MM Neff, AT Ortel, TL Paschal, R Shattil, S Siddiqi, T Smock, KJ Soff, G Wang, TF Yee, GC Zakarija, A McMillian, N Engh, AM AF Streiff, Michael B. Holmstrom, Bjorn Ashrani, Aneel Bockenstedt, Paula L. Chesney, Carolyn Eby, Charles Fanikos, John Fenninger, Randolph B. Fogerty, Annemarie E. Gao, Shuwei Goldhaber, Samuel Z. Hendrie, Paul Kuderer, Nicole Lee, Alfred Lee, Jason T. Lovrincevic, Mirjana Millenson, Michael M. Neff, Anne T. Ortel, Thomas L. Paschal, Rita Shattil, Sanford Siddiqi, Tanya Smock, Kristi J. Soff, Gerald Wang, Tzu-Fei Yee, Gary C. Zakarija, Anaadriana McMillian, Nicole Engh, Anita M. TI Cancer-Associated Venous Thromboembolic Disease, Version 1.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID LAPAROSCOPIC BARIATRIC SURGERY; CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX; DEEP-VEIN THROMBOSIS; Y GASTRIC BYPASS; MOLECULAR-WEIGHT HEPARIN; MORBIDLY OBESE-PATIENTS; RANDOMIZED DOUBLE-BLIND; MEDICALLY-ILL PATIENTS; ANTI-XA LEVELS AB The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer. C1 [Streiff, Michael B.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Holmstrom, Bjorn] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Ashrani, Aneel] Mayo Clin, Ctr Canc, Rochester, MN USA. [Bockenstedt, Paula L.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chesney, Carolyn] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Eby, Charles] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Eby, Charles] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fanikos, John; Goldhaber, Samuel Z.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fenninger, Randolph B.] Natl Blood Clot Alliance, Strockville, MD USA. [Fogerty, Annemarie E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gao, Shuwei] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hendrie, Paul; Kuderer, Nicole] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Lee, Alfred] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Lee, Jason T.] Stanford Canc Inst, Stanford, CA USA. [Lovrincevic, Mirjana] Roswell Pk Canc Inst, Buffalo, NY USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Neff, Anne T.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ortel, Thomas L.] Duke Canc Inst, Durham, NC USA. [Paschal, Rita] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Shattil, Sanford] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Siddiqi, Tanya] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Smock, Kristi J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Soff, Gerald] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Wang, Tzu-Fei] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Wang, Tzu-Fei] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Yee, Gary C.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Zakarija, Anaadriana] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [McMillian, Nicole; Engh, Anita M.] Natl Comprehens Canc Network, Washington, DC USA. RP Streiff, MB (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RI Wang, Tzu-Fei/F-2519-2016 FU Eisai; Bristol-Myers Squibb; Genentech; BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 110 TC 11 Z9 12 U1 0 U2 1 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 SEP PY 2015 VL 13 IS 9 BP 1079 EP 1096 PG 18 WC Oncology SC Oncology GA CR5YH UT WOS:000361419800007 PM 26358792 ER PT J AU Abdollah, F Sammon, JD Majumder, K Reznor, G Gandaglia, G Sood, A Hevelone, N Kibel, AS Nguyen, PL Choueiri, TK Selvaggi, KJ Menon, M Trinh, QD AF Abdollah, Firas Sammon, Jesse D. Majumder, Kaustav Reznor, Gaily Gandaglia, Giorgio Sood, Akshay Hevelone, Nathanael Kibel, Adam S. Nguyen, Paul L. Choueiri, Toni K. Selvaggi, Kathy J. Menon, Mani Quoc-Dien Trinh TI Racial Disparities in End-of-Life Care Among Patients With Prostate Cancer: A Population-Based Study SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID MEDICARE BENEFICIARIES; AFRICAN-AMERICAN; ETHNIC-DIFFERENCES; HOSPICE CARE; LUNG-CANCER; NEAR-DEATH; ASSOCIATION; INDICATORS; INTENSITY; SURVIVAL AB Objective: To examine racial disparities in end-of-life (EOL) care among black and white patients dying of prostate cancer (PCa). Methods: Relying on the SEER-Medicare database, 3789 patients who died of metastatic PCa between 1999 and 2009 were identified. Information was assessed regarding diagnostic care, therapeutic interventions, hospitalizations, intensive care unit (ICU) admissions, and emergency department visits in the last 12 months, 3 months, and 1 month of life. Logistic regression tested the relationship between race and the receipt of diagnostic care, therapeutic interventions, and high-intensity EOL care. Results: Overall, 729 patients (19.24%) were black. In the 12-months preceding death, laboratory tests (odds ratio [OR], 0.51; 95% Cl, 0.36-0.72), prostate-specific antigen test (OR, 0.54; 95% Cl, 0.43-0.67), cystourethroscopy (OR, 0.71; 95% Cl, 0.56-0.90), imaging procedure (OR, 0.58; 95% Cl, 0.41-0.81), hormonal therapy (OR, 0.53; 95% Cl, 0.44-0.65), chemotherapy (OR, 0.59; 95% Cl, 0.48-0.72), radiotherapy (OR, 0.74; 95% Cl, 0.61-0.90), and office visit (OR, 0.38; 95% Cl, 0.28-0.50) were less frequent in black versus white patients. Conversely, high-intensity EOL care, such as ICU admission (OR, 1.27; 95% Cl, 1.04-1.58), inpatient admission (OR, 1.49; 95% Cl, 1.09-2.05), and cardiopulmonary resuscitation (OR, 1.72; 95% Cl, 1.40-2.11), was more frequent in black versus white patients. Similar trends for EOL care were observed at 3-month and 1-month end points. Conclusions: Although diagnostic and therapeutic interventions are less frequent in black patients with end-stage PCa, the rate of high-intensity and aggressive EOL care is higher in these individuals. These disparities may indicate that race plays an important role in the quality of care for men with end-stage PCa. C1 [Abdollah, Firas; Sammon, Jesse D.; Sood, Akshay; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Majumder, Kaustav] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. [Reznor, Gaily; Gandaglia, Giorgio; Hevelone, Nathanael; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. [Reznor, Gaily; Gandaglia, Giorgio; Hevelone, Nathanael; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Selvaggi, Kathy J.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Abdollah, F (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 West Grand Blvd, Detroit, MI 48202 USA. EM firas.abdollah@gmail.com NR 33 TC 6 Z9 6 U1 1 U2 1 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 SEP PY 2015 VL 13 IS 9 BP 1131 EP 1138 PG 8 WC Oncology SC Oncology GA CR5YH UT WOS:000361419800012 PM 26358797 ER PT J AU Haddad, RI Lydiatt, WM Ball, DW Busaidy, NL Byrd, D Callender, G Dickson, P Duh, QY Ehya, H Haymart, M Hoh, C Hunt, JP Iagaru, A Kandeel, F Kopp, P Lamonica, DM McCaffrey, JC Moley, JF Parks, L Raeburn, CD Ridge, JA Ringel, MD Scheri, RP Shah, JP Smallridge, RC Sturgeon, C Wang, TN Wirth, LJ Hoffmann, KG Hughes, M AF Haddad, Robert I. Lydiatt, William M. Ball, Douglas W. Busaidy, Naifa Lamki Byrd, David Callender, Glenda Dickson, Paxton Duh, Quan-Yang Ehya, Hormoz Haymart, Megan Hoh, Carl Hunt, Jason P. Iagaru, Andrei Kandeel, Fouad Kopp, Peter Lamonica, Dominick M. McCaffrey, Judith C. Moley, Jeffrey F. Parks, Lee Raeburn, Christopher D. Ridge, John A. Ringel, Matthew D. Scheri, Randall P. Shah, Jatin P. Smallridge, Robert C. Sturgeon, Cord Wang, Thomas N. Wirth, Lori J. Hoffmann, Karin G. Hughes, Miranda TI Anaplastic Thyroid Carcinoma, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID FINE-NEEDLE-ASPIRATION; PHASE-II TRIAL; PROGNOSTIC-FACTORS; UNITED-STATES; SINGLE-INSTITUTION; CANCER STATISTICS; CONSECUTIVE PATIENTS; INCREASING INCIDENCE; TREATMENT OUTCOMES; RADIATION-THERAPY AB This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer. C1 [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Lydiatt, William M.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Ball, Douglas W.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Busaidy, Naifa Lamki] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Byrd, David] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Callender, Glenda] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT 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, Ctr Comprehens Canc, 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. [McCaffrey, Judith C.] 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, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Scheri, Randall P.] Duke Canc Inst, Durham, NC USA. [Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Smallridge, Robert C.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Wang, Thomas N.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Haddad, RI (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. OI Shah, Jatin/0000-0002-6444-6592 FU NCI NIH HHS [P30 CA008748] NR 104 TC 7 Z9 7 U1 0 U2 5 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 SEP PY 2015 VL 13 IS 9 BP 1140 EP 1150 PG 11 WC Oncology SC Oncology GA CR5YH UT WOS:000361419800013 PM 26358798 ER PT J AU McCauley, HL Blosnich, JR Dichter, ME AF McCauley, Heather L. Blosnich, John R. Dichter, Melissa E. TI Adverse Childhood Experiences and Adult Health Outcomes Among Veteran and Non-Veteran Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID MILITARY SEXUAL TRAUMA; MENTAL-HEALTH; HOUSEHOLD DYSFUNCTION; US ADULTS; LIFE-SPAN; ABUSE; RISK; MORTALITY; VIOLENCE; SERVICE AB Background: Women veterans represent a vulnerable population with unique health needs and disparities in access to care. One constellation of exposures related to subsequent poor health includes adverse childhood experiences (ACEs; e.g., physical and sexual child abuse), though research on impacts of ACEs among women veterans is limited. Methods: Data were drawn from the 2010 Behavioral Risk Factor Surveillance System for the 11 states that included the ACE module (n=36,485). Weighted chi-squared tests and multivariable logistic regression were used to assess the prevalence of ACEs among women veterans compared with women non-veterans and differences in the following outcomes, controlling for ACEs: social support, inadequate sleep, life satisfaction, mental distress, smoking, heavy alcohol use, obesity, diabetes, cardiovascular disease symptoms, asthma, and disability. Results: Women veterans (1.6% of the total sample) reported a higher prevalence of 7 out of 11 childhood adversities and higher mean ACE score than women non-veterans. Women veterans were more likely to be current smokers and report a disability, associations which were attenuated when controlling for ACE. Conclusions: Despite women veterans' higher prevalence of ACE, their health outcomes did not differ substantially from non-veterans. Further research is needed to understand the intersections of traumatic experiences and sources of resilience over the lifecourse among women veterans. C1 [McCauley, Heather L.] Univ Pittsburgh, Div Adolescent & Young Adult Med, Childrens Hosp Pittsburgh UPMC, Dept Pediat,Sch Med, Pittsburgh, PA 15213 USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP McCauley, HL (reprint author), Univ Pittsburgh, Sch Med, Dept Pediat, 3414 Fifth Ave,CHOB Room 109, Pittsburgh, PA 15213 USA. EM heather.mccauley@chp.edu FU National Institutes of Health/Office of Research on Women's Health Building Interdisciplinary Research Careers in Women's Health [K12HD043441]; Office of Academic Affiliations in the Department of Veterans Affairs; Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development Service (CDA) [10-202] FX This work was supported by National Institutes of Health/Office of Research on Women's Health Building Interdisciplinary Research Careers in Women's Health K12HD043441 scholar funds to HLM; a postdoctoral fellowship to JRB from the Office of Academic Affiliations in the Department of Veterans Affairs; and a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development Service to MED (CDA No. 10-202). NR 43 TC 1 Z9 1 U1 5 U2 16 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD SEP 1 PY 2015 VL 24 IS 9 BP 723 EP 729 DI 10.1089/jwh.2014.4997 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CR6RT UT WOS:000361475700005 PM 26390379 ER PT J AU Berger, D Bradley, KA AF Berger, Douglas Bradley, Katharine A. TI Primary Care Management of Alcohol Misuse SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Alcohol misuse; Unhealthy alcohol use; Alcohol use disorder; Alcohol abuse; Alcohol dependence; Alcohol screening; Brief intervention; Alcohol treatment ID NATIONAL EPIDEMIOLOGIC SURVEY; SERVICES TASK-FORCE; SUBSTANCE USE DISORDERS; CHRONIC NONCANCER PAIN; PREVENTIVE SERVICES; UNITED-STATES; RISK DRINKING; CONTROLLED-TRIAL; DSM-IV; RECOMMENDATION STATEMENT AB More than one in four American adults consume alcohol in quantities exceeding recommended limits. One in 12 have an alcohol use disorder marked by harmful consequences. Both types of alcohol misuse contribute to acute injury and chronic disease, making alcohol the third largest cause of preventable death in the United States. Alcohol misuse alters the management of common conditions from insomnia to anemia. Primary care providers should screen adult patients to identify the full spectrum of alcohol misuse. A range of effective treatments are available from brief counselling interventions and mutual help groups to medications and behavioral therapies. C1 [Berger, Douglas] VA Puget Sound, Gen Med Serv, Seattle, WA 98108 USA. [Berger, Douglas; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Bradley, Katharine A.] VA Hlth Serv Res & Dev HSR&D, Seattle, WA USA. [Bradley, Katharine A.] CESATE, Seattle, WA USA. RP Berger, D (reprint author), S-123 PCC,1660 S Columbian Way, Seattle, WA 98108 USA. EM douglas.berger@va.gov NR 144 TC 3 Z9 3 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2015 VL 99 IS 5 BP 989 EP + DI 10.1016/j.mcna.2015.05.004 PG 29 WC Medicine, General & Internal SC General & Internal Medicine GA CS0TW UT WOS:000361776100007 PM 26320043 ER PT J AU Klein, JW Reddy, S AF Klein, Jared Wilson Reddy, Simha TI Care of the Homeless Patient SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Homelessness; Harm reduction; Housing first; Respite ID SERIOUS MENTAL-ILLNESS; HEALTH-CARE; ADULTS; PEOPLE; BARRIERS; DISEASE; PERCEPTIONS; MANAGEMENT; PROGRAMS; SAMPLE AB This article discusses the unique considerations when caring for patients who lack housing, one of the most essential human needs. Special attention is provided to diseases and conditions that are affected by homelessness as well as to particularly vulnerable populations of homeless patients. C1 [Klein, Jared Wilson] Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, Seattle, WA 98104 USA. [Reddy, Simha] Univ Washington, Dept Med, Div Gen Internal Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Klein, JW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. EM jaredwk@uw.edu NR 57 TC 0 Z9 0 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2015 VL 99 IS 5 BP 1017 EP + DI 10.1016/j.mcna.2015.05.011 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA CS0TW UT WOS:000361776100008 PM 26320044 ER PT J AU Iverson, GL Gardner, AJ McCrory, P Zafonte, R Castellani, RJ AF Iverson, Grant L. Gardner, Andrew J. McCrory, Paul Zafonte, Ross Castellani, Rudy J. TI A critical review of chronic traumatic encephalopathy SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Brain injury; Dementia pugilistica; Athletes; Dementia; Concussion ID MILD COGNITIVE IMPAIRMENT; FOOTBALL LEAGUE PLAYERS; VARIANT FRONTOTEMPORAL DEMENTIA; ALZHEIMERS ASSOCIATION GUIDELINES; MAJOR DEPRESSIVE DISORDER; REPETITIVE BRAIN TRAUMA; AMYLOID-BETA-PROTEIN; HIGH-SCHOOL FOOTBALL; QUALITY-OF-LIFE; HEAD-INJURY AB Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Iverson, Grant L.] Harvard Univ, Spaulding Rehabil Hosp, MassGeneral Hosp Children,Med Sch, Dept Phys Med & Rehabil,Sports Concuss Program, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Gardner, Andrew J.] Univ Newcastle, Hunter New England Local Hlth Dist Sports Concuss, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Gardner, Andrew J.] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [McCrory, Paul] Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. [Castellani, Rudy J.] Univ Maryland, Sch Med, Div Neuropathol, Baltimore, MD USA. [Zafonte, Ross] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA USA. [Zafonte, Ross] Spaulding Rehabil Hosp, Boston, MA USA. [Zafonte, Ross] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Iverson, GL (reprint author), Harvard Univ, Ctr Hlth & Rehabil Res, Dept Phys Med & Rehabil, Sch Med, 79-96 Thirteenth St, Charlestown, MA 02129 USA. EM giverson@mgh.harvard.edu RI Gardner, Andrew/J-5162-2013 FU INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD]; Harvard Integrated Program to Protect and Improve the Health of NFLPA; NICHD Brain and Tissue Bank at the University of Maryland; New South Wales Sporting Injuries Committee; Brain Foundation, Australia; National Health and Medical Research Council of Australia; Florey Institute of Neuroscience and Mental Health; Victorian Government FX GLI and RZ note that this work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). RZ also was supported in part by the Harvard Integrated Program to Protect and Improve the Health of NFLPA Members. RJC acknowledges support from the NICHD Brain and Tissue Bank at the University of Maryland. AJG has received funding from the New South Wales Sporting Injuries Committee, and the Brain Foundation, Australia to conduct research in current and retired rugby league players. PM receives ongoing funding from the National Health and Medical Research Council of Australia and the Florey Institute of Neuroscience and Mental Health. The Florey Institute of Neuroscience and Mental Health acknowledges support from the Victorian Government, in particular the funding from the Operational Infrastructure Support Grant. NR 220 TC 23 Z9 23 U1 10 U2 65 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD SEP PY 2015 VL 56 BP 276 EP 293 DI 10.1016/j.neubiorev.2015.05.008 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CR8CK UT WOS:000361578500021 PM 26183075 ER PT J AU Halpern, SD French, B Small, DS Saulsgiver, K Harhay, MO Audrain-McGovern, J Loewenstein, G Brennan, TA Asch, DA Volpp, KG AF Halpern, Scott D. French, Benjamin Small, Dylan S. Saulsgiver, Kathryn Harhay, Michael O. Audrain-McGovern, Janet Loewenstein, George Brennan, Troyen A. Asch, David A. Volpp, Kevin G. TI Randomized Trial of Four Financial-Incentive Programs for Smoking Cessation SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB In the 50 years since the release of the first Surgeon General's report on the harmful effects of smoking, national policies and behavioral programs as well as pharmacologic approaches have helped reduce smoking rates in the United States. Despite these interventions, the need for new approaches is clear because smoking is still the leading cause of preventable illness and death. Previous studies have demonstrated that financial incentives can promote a variety of health behaviors. However, effective ways to deliver health incentives are uncertain. A number of online and employer-based behavioral-change programs have been used. One of these programs involves use of deposit (commitment) contracts, whereby participants put some of their own money at risk and recover it if they are successful in changing their behavior. Deposit contracts should be more successful than reward programs because people are usually more motivated to avoid losses than to seek gains. The need to make deposits, however, may deter people from participating in such programs. No studies have directly compared the overall effectiveness of deposit and reward programs. This randomized controlled trial compared 4 financial-incentive programs for smoking cessation. Participants were CVS Caremark employees and their relatives and friends. The incentive programs were compared with usual care (which included informational resources and free smoking-cessation aids). Two of the incentive programs (reward based and deposit based) targeted individuals, whereas the other 2 targeted groups of 6 participants. One individual-oriented program and 1 group-oriented program provided rewards of approximately $800 for smoking cessation; the other 2 entailed refundable deposits of $150 plus $650 for successful participants. Levels of acceptance, overall effectiveness, and efficacy were assessed. The primary efficacy outcome was sustained abstinence for 6 months after the target quit date. A total of 2538 participants were randomized to 1 of the 4 incentive programs or to usual care. Participants in the 2 reward-based incentive programs were much more likely to accept the assignment (combined acceptance rate, 90.0%) than those in the 2 deposit-based programs (combined acceptance rate, 13.7%; P < 0.001). Intention-to-treat analyses using logistic regression showed that rates of sustained abstinence from smoking through 6 months were higher for each of the 4 incentive programs (range, 9.4%-16.0%) than usual care (6.0%) (P < 0.05 for all comparisons). Moreover, the superiority of reward-based programs was sustained through 12 months. The proportion of participants with sustained abstinence was similar at 6 months for participants assigned to group-oriented and individual-oriented programs (13.7% and 12.1%, respectively; P = 0.29). At 6 months, the proportion of participants with sustained abstinence was greater with reward-based incentives than with deposit-based incentives (15.7% vs 10.2%, P < 0.001). However, the rate of abstinence at 6 months in instrumental-variable analyses (accounting for differential acceptance) was 13.2 percentage points higher (95% confidence interval, 3.1-22.8) in the deposit-based programs than in the reward-based programs among the 13.7% of smokers who would accept participation in either type of program. These findings show that, among several financial-incentive programs for smoking cessation, rewards for smoking cessation achieve higher rates of sustained abstinence from smoking than deposit-based contracts owing to much higher rates of acceptance. Group-oriented programs are no more effective than the programs for individuals. C1 [Halpern, Scott D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.; French, Benjamin; Saulsgiver, Kathryn; Harhay, Michael O.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Audrain-McGovern, Janet] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Halpern, Scott D.; French, Benjamin; Small, Dylan S.; Saulsgiver, Kathryn; Audrain-McGovern, Janet; Loewenstein, George; Asch, David A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Ctr Hlth Equ Res & Promot, Dept Stat, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Ctr Hlth Equ Res & Promot, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn Hlth Syst, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn Hlth Syst, Ctr Hlth Care Innovat, Philadelphia, PA USA. [Loewenstein, George] Carnegie Mellon Univ, Ctr Behav Decis Res, Pittsburgh, PA 15213 USA. [Brennan, Troyen A.] CVS Caremark, Woonsocket, RI USA. RP Halpern, SD (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. OI Harhay, Michael/0000-0002-0553-674X NR 0 TC 0 Z9 0 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD SEP PY 2015 VL 70 IS 9 BP 566 EP 567 DI 10.1097/01.ogx.0000470840.40563.9a PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CS0LE UT WOS:000361749900012 ER PT J AU Grady, CD Dehlendorf, C Cohen, ED Schwarz, EB Borrero, S AF Grady, Cynthia D. Dehlendorf, Christine Cohen, Elan D. Schwarz, E. Bimla Borrero, Sonya TI Racial and Ethnic Differences in Contraceptive use Among Women Who Desire No Future Children, 2006-2010 National Survey of Family Growth SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Uynintended pregnancies are either mistimed pregnancies occurring sooner than desired or unwanted pregnancies occurring when no children (or no more children) are desired. Unwanted pregnancies appear to be associated with poor pregnancy outcomes, specifically higher risk of preterm delivery and premature rupture of membranes. Women from racial and ethnic minority groups are more likely than white women to experience an unwanted pregnancy. Racial/ethnic differences in contraceptive use patterns among black and Hispanic women are the most likely proximal cause of observed disparities in unintended pregnancy. Several studies have reported that black women are more likely than white women to not use contraceptives or use contraception inconsistently, to have more contraceptive failures, and to less frequently use some prescription methods. Little is known about disparities in contraceptive use among the specific subset of women who do not want any (more) children and who may be at particularly high risk for having an unwanted pregnancy. This study evaluated racial/ethnic differences in contraceptive use among women who do not desire future pregnancy. Nationally representative data were obtained from the 2006-2010 National Survey of Family Growth (NSFG) to examine the relationships between race/ethnicity and contraceptive use among a sample of sexually active, reproductive-age women who stated that they do not desire any (more) children. The primary study outcome measures were (1) use of any contraceptive method and (2) the effectiveness of contraceptive methods used by women using any method at last heterosexual intercourse. Multivariable logistic regression models were used to assess the independent effect of race/ethnicity on contraceptive use patterns, adjusting for sociodemographic factors, reproductive characteristics, and indicators of health care access and utilization. The study sample comprised 2900 sexually active women, aged 15 to 44 years, who were at risk of an unwanted pregnancy. The vast majority (91.2%) used contraception at last sex, although use varied significantly by race/ethnicity; 93.2% of white women reported use of any method, compared with 84.7% of black and 90.5% of Hispanic women; P < 0.01. In the fully adjusted model, black women were significantly less likely than whites to use any contraception at last sex (odds ratio [OR], 0.43; 95% confidence interval, 0.27-0.73); in contrast, there was no significant difference among Hispanic women (OR, 0.95; 95% confidence interval, 0.52-1.72). In bivariate analysis, the type of contraceptive method used at last sex among women who used a method at last sex varied significantly by race/ethnicity (P < 0.01), although most women (59%) used a highly effective method. In the fully adjusted model, however, racial/ethnic differences were no longer significant: There were no significant differences between white women and black or Hispanic women with regard to use of highly/moderately effective contraception. Among the subset of women who report that they do not want (more) children, black women are significantly less likely than white women to use any contraception at last intercourse; this disparity does not appear to be due to differences in sociodemographic characteristics, reproductive factors, or utilization of health care. C1 [Grady, Cynthia D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cohen, Elan D.] Univ Pittsburgh, Ctr Res Hlth, Care Data Ctr, Pittsburgh, PA USA. [Schwarz, E. Bimla] Univ Calif Davis, Sch Med, Div Gen Internal Med, Sacramento, CA 95817 USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Grady, CD (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD SEP PY 2015 VL 70 IS 9 BP 574 EP 576 DI 10.1097/01.ogx.0000470841.16800.60 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CS0LE UT WOS:000361749900017 ER PT J AU del Carmen, MG AF del Carmen, Marcela G. TI Evidence for the Relationship Between Endometriosis and Epithelial Ovarian Cancer SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Review ID CLEAR-CELL CARCINOMA; HOSPITAL DISCHARGE DIAGNOSIS; DISTINCT-HISTOLOGIC-TYPE; ESTROGEN-RECEPTOR-ALPHA; MALIGNANT-TRANSFORMATION; ATYPICAL ENDOMETRIOSIS; BREAST-CANCER; POSTMENOPAUSAL ENDOMETRIOSIS; CLINICAL CHARACTERISTICS; POOR-PROGNOSIS AB Endometriosis may be a precursor lesion for some epithelial ovarian cancers (EOCs), especially those of clear cell and endometrioid histologies. The causality of this relationship remains controversial and in need of further investigation because the high prevalence of endometriosis and high mortality of EOC carry significant public health implications if the association is real. Endometriosis-associated ovarian cancer (EAOC) often presents at an earlier stage and with lower-grade lesions than non-EAOC. After surgical resection, these patients also tend to have less residual disease than do patients with non-EAOC. Survival has been reported to be better for women with EAOC. The tumor suppression gene, ARID1A, is frequently disrupted in EAOC. The ARID1A mutation has been reported in preneoplastic lesions and may be an early marker in the transformation of endometriosis into cancer. The current evidence in respect to critical molecular pathways underscores the need to investigate possible role of targeted therapies in the treatment of EAOC. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives Endometriosis may be a precursor lesion for some EOCs, especially those of clear cell and endometrioid histologies. We review the epidemiology, pathology, pathogenesis, clinical presentation, and management of patients with EAOC. After completing this CME, physicians should be able to able to discuss the epidemiologic data supporting the association of endometriosis to certain histological subtypes of EOC, as well as describe the pathogenesis of this association. In addition, they should be able to discuss the clinical presentation and optimal management of these patients. C1 [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 117 TC 0 Z9 1 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD SEP PY 2015 VL 70 IS 9 BP 587 EP 595 DI 10.1097/OGX.0000000000000218 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CS0LE UT WOS:000361749900020 PM 26403563 ER PT J AU Campbell, AA Cunnane, ME Dunn, GP Gray, ST Lefebvre, DR AF Campbell, Ashley A. Cunnane, Mary Elizabeth Dunn, Gavin P. Gray, Stacy Tutt Lefebvre, Daniel R. TI Spontaneous Resorption of a Penetrating Orbital Bone Fracture Fragment SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB The authors describe a 20-year-old man who sustained multiple facial fractures in a high-speed motor vehicle crash, including a bone fragment from a skull base fracture that penetrated the orbital soft tissues superomedially. Serial CT scans documented spontaneous resorption over a 6-month period. While it is known that autologous bone grafts used in craniofacial reconstruction exhibit variable amounts of bone resorption, the complete resorption of an intraorbital fracture fragment has not been documented in the literature. His clinical care and the report of his case were undertaken in a fashion in accordance with the principles of the Health Insurance Portability and Accountability Act regulations. C1 [Campbell, Ashley A.; Lefebvre, Daniel R.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. [Campbell, Ashley A.; Lefebvre, Daniel R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Cunnane, Mary Elizabeth] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Cunnane, Mary Elizabeth] Harvard Univ, Sch Med, Dept Radiol Neuroradiol, Boston, MA USA. [Dunn, Gavin P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dunn, Gavin P.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Gray, Stacy Tutt] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Gray, Stacy Tutt] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Campbell, AA (reprint author), Mass Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Ashley_Campbell@MEEI.Harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2015 VL 31 IS 5 BP E123 EP E125 DI 10.1097/IOP.0000000000000146 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CR5LJ UT WOS:000361383500003 PM 24833452 ER PT J AU Jakobiec, FA Rai, R Rashid, A Sutula, FC AF Jakobiec, Frederick A. Rai, Ruju Rashid, Alia Sutula, Francis C. TI Bilateral Eyelid Pseudoptosis From Lipogranulomas of the Preaponeurotic Fat Pads SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HYALURONIC-ACID GEL; CUTANEOUS GRANULOMATOUS REACTION; MELKERSSON-ROSENTHAL-SYNDROME; INTRAOCULAR SILICONE OIL; SOFT-TISSUE AUGMENTATION; SCLEROSING LIPOGRANULOMATOSIS; INVOLUTIONAL BLEPHAROPTOSIS; PERIORBITAL LIPOGRANULOMA; ADVERSE-REACTIONS; INJECTION AB Lipogranulomas of the periocular tissues with fulminant fibrotic and lymphohistiocytic responses were initially described in cases of exogenous paraffin or petrolatum jelly injections (paraffinomas). A 49-year-old Cambodian woman slowly developed bilateral pseudoptosis with intact levator function and redundant, taut upper eyelid skin. At surgery, vesiculations or bubbles in the preaponeurotic fat were encountered and were demonstrated histopathologically to be empty locules surrounded by a thin collagenous lamina. Outside these extracellular spaces were CD68/CD163-positive mononucleated and univacuolated histiocytes simulating damaged fat cells or neoplastic lipoblasts in hematoxylin and eosin sections. Giant cells and chronic sclerosing inflammation were absent. The patient denied any previous injections. The bland character of the lipogranulomas in comparison with that of other injectable agents, the absence of any residual particles associated with other cosmetic fillers, and the distinctive histiocytic response of lipoblast-like cells that were sufficiently characteristic to compel the diagnosis of surreptitious silicone injections. Other conditions were excluded based on comparative clinicopathologic criteria. C1 [Jakobiec, Frederick A.; Rai, Ruju; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Sutula, Francis C.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast Surg, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Rai, Ruju; Rashid, Alia; Sutula, Francis C.] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 57 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2015 VL 31 IS 5 BP E125 EP E131 DI 10.1097/IOP.0000000000000157 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CR5LJ UT WOS:000361383500004 PM 24841730 ER PT J AU Costa-Mallen, P Zabetian, CP Agarwal, P Hu, SC Yearout, D Samii, A Leverenz, JB Roberts, JW Checkoway, H AF Costa-Mallen, Paola Zabetian, Cyrus P. Agarwal, Pinky Hu, Shu-Ching Yearout, Dora Samii, Ali Leverenz, James B. Roberts, John W. Checkoway, Harvey TI Haptoglobin phenotype modifies serum iron levels and the effect of smoking on Parkinson disease risk SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Idiopathic Parkinson disease; Tobacco smoking; Serum iron; Serum ferritin; Haptoglobin phenotype ID NEURODEGENERATIVE DISEASES; SUBSTANTIA-NIGRA; FERRITIN; SUSCEPTIBILITY; POLYMORPHISM; ASSOCIATION; METABOLISM AB Introduction: Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk. Methods: The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk. Results: PD cases had lower serum iron than controls (83.28 ug/100 ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity. Conclusions: Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Costa-Mallen, Paola] Bastyr Univ, Res Inst, Kenmore, WA 98028 USA. [Zabetian, Cyrus P.; Yearout, Dora; Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.; Hu, Shu-Ching; Samii, Ali] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Agarwal, Pinky] Evergreen Hlth, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Leverenz, James B.] Cleveland Clin, Neurol Inst, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Checkoway, Harvey] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Costa-Mallen, P (reprint author), Bastyr Univ, Res Inst, 14500 Juanita Dr NE, Kenmore, WA 98028 USA. EM pcostamallen@bastyr.edu FU NIH [R21 NS070202-01A1, P50 NS062684, R01 NS065070]; Department of Veterans Affairs [1I01BX000531]; Bastyr University [3, 4] FX This study was funded by grants from the NIH (R21 NS070202-01A1, P50 NS062684, R01 NS065070), Department of Veterans Affairs (1I01BX000531), and Bastyr University (Faculty Seed Grants #3 and #4 2009-2011). NR 29 TC 7 Z9 7 U1 1 U2 1 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 SEP PY 2015 VL 21 IS 9 BP 1087 EP 1092 DI 10.1016/j.parkreldis.2015.07.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CR8BR UT WOS:000361576600013 PM 26228081 ER PT J AU Chou, JJ Wang, JH AF Chou, James J. Wang, Jia-huai TI Transmembrane signaling: A multiplex problem with converging solutions SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Editorial Material ID RECEPTOR; CELLS C1 [Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wang, Jia-huai] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. [Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jwang@crystal.harvard.edu FU NHLBI NIH HHS [P01 HL103526]; NIGMS NIH HHS [U54 GM094608] NR 9 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD SEP PY 2015 VL 118 IS 3 BP 87 EP 88 DI 10.1016/j.pbiomolbio.2015.06.006 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CS0UA UT WOS:000361776500001 PM 26140997 ER PT J AU Finci, L Zhang, Y Meijers, R Wang, JH AF Finci, L. Zhang, Y. Meijers, R. Wang, J. -H. TI Signaling mechanism of the netrin-1 receptor DCC in axon guidance SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE DCC; Netrin-1; Axon guidance; Structure; UNC5 ID C-ELEGANS; COLORECTAL-CANCER; CRYSTAL-STRUCTURE; TYROSINE PHOSPHORYLATION; STRUCTURAL BASIS; SPINAL-CORD; BINDING; ADHESION; FAMILY; IMMUNOGLOBULIN AB DCC (Deleted in Colorectal Cancer) is a single-pass transmembrane protein that belongs to the immunoglobulin superfamily. It was originally identified as a prognostic tumor marker and then subsequently found to be a receptor for netrin-1. DCC plays a key role in axon guidance and also in a number of other important cellular processes. This review describes the current progress of the structural biology of DCC with an emphasis on how DCC is involved in the dual functionality of netrin-1 as a chemo-attractant as well as a repellent in axon guidance, referred to as hi-functionality. A perspective about other DCC ligands and the signaling mechanism of the cytoplasmic tail of DCC is also recapitulated. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Finci, L.; Zhang, Y.; Wang, J. -H.] Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Finci, L.; Wang, J. -H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Meijers, R.] European Mol Biol Lab, Hamburg Outstn, D-22607 Hamburg, Germany. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM r.meijers@embl-hamburg.de; jwang@crystal.harvard.edu OI Meijers, Rob/0000-0003-2872-6279 FU Ministry of Education of China; National Science Foundation of China (NSFC) [91132718]; NIH [HL48675]; Peking-Tsinghua Center for Life Sciences; short-term EMBO postdoctoral fellowship FX This work was supported by the Ministry of Education of China to J.-H.W. and Y.Z., the National Science Foundation of China (NSFC) Major Research Grant (91132718) to Y.Z., an NIH grant (HL48675) and funds from the Peking-Tsinghua Center for Life Sciences to J-H W, and a short-term EMBO postdoctoral fellowship to L. I. F. NR 48 TC 5 Z9 6 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD SEP PY 2015 VL 118 IS 3 BP 153 EP 160 DI 10.1016/j.pbiomolbio.2015.04.001 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CS0UA UT WOS:000361776500009 PM 25881791 ER PT J AU LaChance, H Cioe, PA Tooley, E Colby, SM O'Farrell, TJ Kahler, CW AF LaChance, Heather Cioe, Patricia A. Tooley, Erin Colby, Suzanne M. O'Farrell, Timothy J. Kahler, Christopher W. TI Behavioral Couples Therapy for Smoking Cessation: A Pilot Randomized Clinical Trial SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE smoking cessation; couples therapy; tobacco dependence; behavioral couples therapy ID SOCIAL SUPPORT; PARTNER SUPPORT; QUITTING SMOKING; UNITED-STATES; USE DISORDERS; SMOKERS; RELAPSE; METAANALYSIS; PREGNANCY; INTERVENTIONS AB Behavioral couples therapy (BCT) has been found to improve long-term abstinence rates in alcohol-and substance-dependent populations but has not been tested for smoking cessation. This pilot study examined the feasibility and acceptability of BCT for smoking-discordant couples. Forty-nine smokers (smoking >10 cigarettes/day) with nonsmoking partners were randomized to receive a couples social support (BCT-S) intervention or an individually delivered, standard smoking cessation treatment (ST). The couples were married or had been cohabiting for at least 1 year, with partners who had never smoked or had not used tobacco in 1 year. Both treatments included 7 weekly sessions and 8 weeks of nicotine replacement therapy. Participants were followed for 6 months posttreatment. The Partner Interaction Questionnaire was used to measure perceived smoking-specific partner support. Participants were 67% male and 88% White. Biochemically verified cessation rates were 40.9%, 50%, and 45% in BCT-S and 59.1%, 50%, and 55% in ST at end of treatment, after 3 month, and after 6 months, respectively, and did not differ significantly between treatment conditions at any time point. Perceived smoking-specific partner support at posttreatment did not significantly differ between treatment groups. Results of this pilot study do not provide support for the efficacy of BCT in smoking-discordant couples. C1 [LaChance, Heather] Natl Jewish Hlth, Denver, CO USA. [Cioe, Patricia A.; Colby, Suzanne M.; Kahler, Christopher W.] Brown Univ, Ctr Alcohol & Addict Studies, Sch Publ Hlth, Providence, RI 02912 USA. [Tooley, Erin] Brown Univ, Ctr Behav & Preventat Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Tooley, Erin] Miriam Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Families & Addict Program, Brockton, MA USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Cioe, PA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Sch Publ Hlth, 121 South Main St, Providence, RI 02912 USA. EM Patricia_Cioe@brown.edu OI CIOE, PATRICIA/0000-0003-3599-7819 FU National Institute on Drug Abuse (NIDA) at the National Institutes of Health [R01 DA021265]; NIDA [T32 DA016184]; National Heart Lung and Blood Institute at the National Institutes of Health [T32 HL076134-07]; Department of Veterans Affairs FX This work was supported by the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (Grant R01 DA021265 to Heather LaChance). This work was partially supported by NIDA (Grant T32 DA016184 to Patricia A. Cioe), the National Heart Lung and Blood Institute at the National Institutes of Health (Grant T32 HL076134-07 to Erin Tooley), and the Department of Veterans Affairs (award to Timothy J. O'Farrell). We gratefully acknowledge Suzanne Sales for her assistance with data management and data analyses. NR 55 TC 2 Z9 2 U1 3 U2 9 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2015 VL 29 IS 3 BP 643 EP 652 DI 10.1037/adb0000051 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA CS1NT UT WOS:000361833900016 PM 25642582 ER PT J AU Seltzer, EK Jean, NS Kramer-Golinkoff, E Asch, DA Merchant, RM AF Seltzer, E. K. Jean, N. S. Kramer-Golinkoff, E. Asch, D. A. Merchant, R. M. TI The content of social media's shared images about Ebola: a retrospective study SO PUBLIC HEALTH LA English DT Article DE Ebola; Social media; Public opinion; Public health; Communication ID EMERGENCY; EPIDEMIC; HEALTH AB Objective: Social media have strongly influenced awareness and perceptions of public health emergencies, but a considerable amount of social media content is now carried through images, rather than just text. This study's objective is to explore how image-sharing platforms are used for information dissemination in public health emergencies. Study design: Retrospective review of images posted on two popular image-sharing platforms to characterize public discourse about Ebola. Methods: Using the keyword '#ebola' we identified a 1% sample of images posted on Instagram and Flickr across two sequential weeks in November 2014. Images from both platforms were independently coded by two reviewers and characterized by themes. We reviewed 1217 images posted on Instagram and Flickr and identified themes. Results: Nine distinct themes were identified. These included: images of health care workers and professionals [308 (25%)], West Africa [75 (6%)], the Ebola virus [59 (5%)], and artistic renderings of Ebola [64 (5%)]. Also identified were images with accompanying embedded text related to Ebola and associated: facts [68 (6%)], fears [40 (3%)], politics [46 (4%)], and jokes [284 (23%)]. Several [273 (22%)] images were unrelated to Ebola or its sequelae. Instagram images were primarily coded as jokes [255 (42%)] or unrelated [219 (36%)], while Flickr images primarily depicted health care workers and other professionals [281 (46%)] providing care or other services for prevention or treatment. Conclusion: Image sharing platforms are being used for information exchange about public health crises, like Ebola. Use differs by platform and discerning these differences can help inform future uses for health care professionals and researchers seeking to assess public fears and misinformation or provide targeted education/awareness interventions. (C) 2015 The Royal Institute of Public Health. All rights reserved. C1 [Seltzer, E. K.; Jean, N. S.; Kramer-Golinkoff, E.; Asch, D. A.; Merchant, R. M.] Univ Penn, Penn Med Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Asch, D. A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Seltzer, EK (reprint author), 423 Blockley Hall, Philadelphia, PA 19104 USA. EM seltzer@uphs.upenn.edu FU NIH, NHLBI [K23: 10714038, R01: HL122457-01A1] FX Seltzer, Saint Jean, Kramer-Golinkoff: No conflicts to disclose; Asch: US Government employee, no conflicts to disclose; Merchant: Grant/Research support: NIH, NHLBI K23: 10714038, NIH, NHLBI, R01: HL122457-01A1. NR 23 TC 9 Z9 9 U1 6 U2 19 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 EI 1476-5616 J9 PUBLIC HEALTH JI Public Health PD SEP PY 2015 VL 129 IS 9 BP 1273 EP 1277 DI 10.1016/j.puhe.2015.07.025 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR8VI UT WOS:000361631800019 PM 26285825 ER PT J AU Sripada, RK Bohnert, ASB Teo, AR Levine, DS Pfeiffer, PN Bowersox, NW Mizruchi, MS Chermack, ST Ganoczy, D Walters, H Valenstein, M AF Sripada, Rebecca K. Bohnert, Amy S. B. Teo, Alan R. Levine, Debra S. Pfeiffer, Paul N. Bowersox, Nicholas W. Mizruchi, Mark S. Chermack, Stephen T. Ganoczy, Dara Walters, Heather Valenstein, Marcia TI Social networks, mental health problems, and mental health service utilization in OEF/OIF National Guard veterans SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Social support; Social network; PTSD; Depression; Veteran; National Guard ID POSTTRAUMATIC-STRESS-DISORDER; OPERATIONS ENDURING FREEDOM; VIETNAM VETERANS; PTSD SYMPTOMS; TREATMENT-SEEKING; CARE UTILIZATION; SUPPORT NETWORKS; PHYSICAL HEALTH; SEXUAL ASSAULT; DEPRESSED MOOD AB Low social support and small social network size have been associated with a variety of negative mental health outcomes, while their impact on mental health services use is less clear. To date, few studies have examined these associations in National Guard service members, where frequency of mental health problems is high, social support may come from military as well as other sources, and services use may be suboptimal. Surveys were administered to 1448 recently returned National Guard members. Multivariable regression models assessed the associations between social support characteristics, probable mental health conditions, and service utilization. In bivariate analyses, large social network size, high social network diversity, high perceived social support, and high military unit support were each associated with lower likelihood of having a probable mental health condition (p < .001). In adjusted analyses, high perceived social support (OR .90, CI .88-.92) and high unit support (OR .96, CI .94-.97) continued to be significantly associated with lower likelihood of mental health conditions. Two social support measures were associated with lower likelihood of receiving mental health services in bivariate analyses, but were not significant in adjusted models. General social support and military-specific support were robustly associated with reduced mental health symptoms in National Guard members. Policy makers, military leaders, and clinicians should attend to service members' level of support from both the community and their units and continue efforts to bolster these supports. Other strategies, such as focused outreach, may be needed to bring National Guard members with need into mental health care. C1 [Sripada, Rebecca K.; Bohnert, Amy S. B.; Levine, Debra S.; Pfeiffer, Paul N.; Bowersox, Nicholas W.; Chermack, Stephen T.; Ganoczy, Dara; Walters, Heather; Valenstein, Marcia] VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI 48105 USA. [Sripada, Rebecca K.; Bohnert, Amy S. B.; Levine, Debra S.; Pfeiffer, Paul N.; Bowersox, Nicholas W.; Chermack, Stephen T.; Walters, Heather; Valenstein, Marcia] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Sripada, Rebecca K.; Bohnert, Amy S. B.; Levine, Debra S.; Pfeiffer, Paul N.; Bowersox, Nicholas W.; Chermack, Stephen T.; Walters, Heather; Valenstein, Marcia] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Teo, Alan R.] Portland VA Med Ctr, Portland, OR USA. [Teo, Alan R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mizruchi, Mark S.] Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. RP Sripada, RK (reprint author), VA Serious Mental Illness Treatment Resource & Ev, 2800 Plymouth Rd Bldg 16, Ann Arbor, MI 48105 USA. EM rekaufma@umich.edu OI Sripada, Rebecca/0000-0002-2844-3458 FU Department of Veterans Affairs Health Services Research and Development Service [RRP 09-420, SDP 10-047]; Welcome Back Veterans Initiative; McCormick Foundation; Families and Communities Together Coalition of Michigan State University FX This work was supported by the Department of Veterans Affairs Health Services Research and Development Service, RRP 09-420 and SDP 10-047; the Welcome Back Veterans Initiative, the McCormick Foundation, and Families and Communities Together Coalition of Michigan State University. Writing of this manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, the Veterans Affairs Serious Mental Illness Treatment Resource and Evaluation Center (SMITREC) and the Mental Health Service of the VA Ann Arbor Healthcare System. NR 104 TC 1 Z9 1 U1 5 U2 14 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD SEP PY 2015 VL 50 IS 9 BP 1367 EP 1378 DI 10.1007/s00127-015-1078-2 PG 12 WC Psychiatry SC Psychiatry GA CS1KA UT WOS:000361821700006 PM 26032182 ER PT J AU Liang, SH Southon, AG Fraser, BH Krause-Heuer, AM Zhang, B Shoup, TM Lewis, R Volitakis, I Han, YF Greguric, I Bush, AI Vasdev, N AF Liang, Steven H. Southon, Adam G. Fraser, Benjamin H. Krause-Heuer, Anwen M. Zhang, Bo Shoup, Timothy M. Lewis, Rebecca Volitakis, Irene Han, Yifeng Greguric, Ivan Bush, Ashley I. Vasdev, Neil TI Novel Fluorinated 8-Hydroxyquinoline Based Metal Ionophores for Exploring the Metal Hypothesis of Alzheimer's Disease SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE 8-Hydroxyquinoline; metal ionophore; positron emission tomography; Alzheimer's disease ID A-BETA; TRANSGENIC MICE; ZINC; PLAQUES; COPPER; BIOMARKER; PROTEIN; AGENTS AB Zinc, copper, and iron ions are involved in amyloid-beta (A beta) deposition and stabilization in Alzheimer's disease (AD). Consequently, metal binding agents that prevent metal-A beta interaction and lead to the dissolution of A beta deposits have become well sought therapeutic and diagnostic targets. However, direct intervention between diseases and metal abnormalities has been challenging and is partially attributed to the lack of a suitable agent to determine and modify metal concentration and distribution in vivo. In the search of metal ionophores, we have identified several promising chemical entities by strategic fluorination of 8-hydroxyquinoline drugs, clioquinol, and PBT2. Compounds 15-17 and 28-30 showed exceptional metal ionophore ability (6-40-fold increase of copper uptake and >2-fold increase of zinc uptake) and inhibition of zinc induced A beta oligomerization (EC(50)s < similar to 5 mu M). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with F-18. C1 [Liang, Steven H.; Shoup, Timothy M.; Lewis, Rebecca; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.; Shoup, Timothy M.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Southon, Adam G.; Volitakis, Irene; Bush, Ashley I.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. [Fraser, Benjamin H.; Krause-Heuer, Anwen M.; Zhang, Bo; Greguric, Ivan] Australian Nucl Sci & Technol Org, Life Sci, Radiopharmaceut Res & Dev, Kirrawee, NSW 2232, Australia. [Han, Yifeng] Zhejiang Sci Tech Univ, Dept Chem, Key Lab Adv Text Mat & Mfg Technol, Hangzhou 310018, Zhejiang, Peoples R China. RP Bush, AI (reprint author), Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. EM ashleyib@unimelb.edu.au; vasdev.neil@mgh.harvard.edu FU NIDA NIH HHS [K01 DA038000] NR 24 TC 4 Z9 4 U1 9 U2 30 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 SEP PY 2015 VL 6 IS 9 BP 1025 EP 1029 DI 10.1021/acsmedchemlett.5b00281 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CR3UY UT WOS:000361259800016 PM 26396692 ER PT J AU Yaremchuk, MJ AF Yaremchuk, Michael J. TI Commentary on: The Role of Microfat Grafting in Facial Contouring SO AESTHETIC SURGERY JOURNAL LA English DT Editorial Material C1 [Yaremchuk, Michael J.] Harvard Univ, Sch Med, Surg, Boston, MA USA. [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Craniofacial Surg, Boston, MA 02114 USA. [Yaremchuk, Michael J.] Harvard Plast Surg Training Program, Boston, MA USA. RP Yaremchuk, MJ (reprint author), 170 Commonwealth Ave, Boston, MA 02116 USA. EM dr.y@dryaremchuk.com NR 2 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 1090-820X EI 1527-330X J9 AESTHET SURG J JI Aesthet. Surg. J. PD SEP-OCT PY 2015 VL 35 IS 7 BP 772 EP 773 DI 10.1093/asj/sjv084 PG 2 WC Surgery SC Surgery GA CR5PJ UT WOS:000361395100011 PM 26141672 ER PT J AU Khera, AV Qamar, A Murphy, SA Cannon, CP Sabatine, MS Rader, DJ AF Khera, Amit V. Qamar, Arman Murphy, Sabina A. Cannon, Christopher P. Sabatine, Marc S. Rader, Daniel J. TI On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RECEPTOR; ADIPONECTIN; DISEASE; OBESITY; HUMANS; WOMEN AB Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or, Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome. (C) 2015 Elsevier Inc. All rights reserved. C1 [Khera, Amit V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Qamar, Arman; Rader, Daniel J.] 11 125 Smillow Ctr Translat Res, Perelman Sch Med, Dept Med & Cardiovasc Inst, Philadelphia, PA USA. [Murphy, Sabina A.; Cannon, Christopher P.; Sabatine, Marc S.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Murphy, Sabina A.; Cannon, Christopher P.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. RP Khera, AV (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. EM avkhera@mgh.harvard.edu FU Bristol-Myers Squibb (New York, New York); Sankyo Pharmaceuticals (Parsippany, New Jersey); ACCF/Merck (Kenilworth, NJ) Research Fellowship in Cardiovascular Disease; Merck; Boehringer Ingelheim (Ridgefield, CT); Bristol-Myers Squibb; CSL Behring (King of Prussia, PA); Essentialis (Carlsbad, CA); GlaxoSmithKline (Middlesex, UK); Kowa (Montgomery, AL); Takeda (Deerfield, IL); Lipimedix (Jerusalem, Israel); Pfizer (New York, NY); Regeneron (Tarrytown, NJ); Sanofi (Bridgewater, NJ); Accumetrics (San Diego, CA); Arisaph (Boston, MA); Astra Zeneca (London, UK); Boehringer-Ingelheim; GlaxoSmithKline; Janssen (New Brunswick, NJ); Takeda; Alnylam (Cambridge, MA); Amgen (Thousand Oaks, CA); Cubist (Lexington, MA); CVS Caremark (Woonsocket, RI); Intarcia (Boston, MA); MyoKardia (San Francisco, CA); Abbott Laboratories (Chicago, IL); Amgen; AstraZeneca; Critical Diagnostics (San Diego, CA); Daiichi-Sankyo (Tokyo, Japan); Eisai (Woodcliff Lake, NJ); Gilead (Forest City, CA); Intarcia; Roche Diagnostics (Indianapolis, Indiana); Sanofi-Aventis FX The PROVE IT-TIMI 22 Study was funded by Bristol-Myers Squibb (New York, New York) and Sankyo Pharmaceuticals (Parsippany, New Jersey). The companies had no role in the analysis presented, manuscript preparation, or decision to submit for publication. An ACCF/Merck (Kenilworth, NJ) Research Fellowship in Cardiovascular Disease (awarded to AVK) provided additional project support.; Dr. Khera has received consulting fees/honoraria from Merck. Dr. Cannon has received consulting fees/honoraria from Boehringer Ingelheim (Ridgefield, CT), Bristol-Myers Squibb, CSL Behring (King of Prussia, PA), Essentialis (Carlsbad, CA), GlaxoSmithKline (Middlesex, UK), Kowa (Montgomery, AL), Merck, Takeda (Deerfield, IL), Lipimedix (Jerusalem, Israel), Pfizer (New York, NY), Regeneron (Tarrytown, NJ), and Sanofi (Bridgewater, NJ) and research grants from Accumetrics (San Diego, CA), Arisaph (Boston, MA), Astra Zeneca (London, UK), Boehringer-Ingelheim, GlaxoSmithKline, Janssen (New Brunswick, NJ), Merck, and Takeda. Dr. Sabatine has received consulting fees/honoraria from Alnylam (Cambridge, MA), Amgen (Thousand Oaks, CA), AstraZeneca, Cubist (Lexington, MA), CVS Caremark (Woonsocket, RI), Intarcia (Boston, MA), Merck, and MyoKardia (San Francisco, CA) and research grant support from Abbott Laboratories (Chicago, IL), Amgen, AstraZeneca, Critical Diagnostics (San Diego, CA), Daiichi-Sankyo (Tokyo, Japan), Eisai (Woodcliff Lake, NJ), Gilead (Forest City, CA), GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics (Indianapolis, Indiana), Sanofi-Aventis, and Takeda. NR 20 TC 3 Z9 3 U1 0 U2 4 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 SEP 1 PY 2015 VL 116 IS 5 BP 694 EP 698 DI 10.1016/j.amjcard.2015.05.038 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3YX UT WOS:000361270100004 PM 26119654 ER PT J AU Tabtabai, S Yeh, DD Stefanescu, A Kennedy, K Yeh, RW Bhatt, AB AF Tabtabai, Sara Yeh, Doreen DeFaria Stefanescu, Ada Kennedy, Kevin Yeh, Robert W. Bhatt, Ami B. TI National Trends in Hospitalizations for Patients With Single-Ventricle Anatomy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; UNITED-STATES; ADULTS; COMORBIDITY; PHYSIOLOGY; OUTCOMES; IMPACT; DEATH; RISK AB Patients with single-ventricle (SV) anatomy now live to adulthood. Little is known about the cost of care and outcomes for patients with SV anatomy, especially those who develop heart failure (HF) cared for in adult hospitals in the United States. We analyzed the Nationwide Inpatient Sample from 2000 to 2011 for patients >14 years admitted to adult hospitals with the International Classifications of Diseases, Ninth Revision, codes for SV anatomy. Demographics, outcomes, co-morbidities, and cost were assessed. From 2000 to 2011, the number of SV admissions was stable with a trend toward increased cost per admission over time. Coexistent hypertension, obesity, and liver, pulmonary, and renal diseases significantly increased over time. The most common reason for admission was atrial arrhythmia followed by HF. Patients with SV with HF had significantly higher inhospital mortality, length of stay, and more medical co-morbidities than those with SV and without HF. In conclusion, the cohort of patients with SV admitted to adult hospitals has changed in the modern era. Patients with SV have medical co-morbidities including renal and liver diseases, hypertension, and obesity at a surprisingly young age. Aggressive and proactive management of HF and arrhythmia may reduce cost of care for this challenging population. Patients with SV with HE have particularly high mortality, more medical co-morbidities, and increased cost of care and deserve more focused attention to improve outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tabtabai, Sara; Yeh, Doreen DeFaria; Stefanescu, Ada; Kennedy, Kevin; Yeh, Robert W.; Bhatt, Ami B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM abhatt@mgh.harvard.edu OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 NR 19 TC 2 Z9 2 U1 0 U2 0 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 SEP 1 PY 2015 VL 116 IS 5 BP 773 EP 778 DI 10.1016/j.amjcard.2015.05.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3YX UT WOS:000361270100017 PM 26100589 ER PT J AU Hirko, KA Kantor, ED Cohen, SS Blot, WJ Stampfer, MJ Signorello, LB AF Hirko, Kelly A. Kantor, Elizabeth D. Cohen, Sarah S. Blot, William J. Stampfer, Meir J. Signorello, Lisa B. TI Body Mass Index in Young Adulthood, Obesity Trajectory, and Premature Mortality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; mortality; obesity; young adulthood ID SOUTHERN COMMUNITY COHORT; INTENTIONAL WEIGHT-LOSS; CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; BIRTH COHORT; HEALTH DISPARITIES; CHILDHOOD OBESITY; BLACK ADULTS; US WHITE; OVERWEIGHT AB Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40-79 years and were followed through December, 2011. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years of follow-up. Participants who reported being overweight or obese as young adults had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95% confidence interval: 52, 78) higher, respectively, than those of their normal weight counterparts. The results did not significantly differ by race or sex. Participants who reported being obese in young adulthood only or in both young and middle adulthood experienced mortality rates that were 40%-90% higher than those of participants who were nonobese at either time. These results suggest that obesity in young adulthood is associated with higher mortality risk regardless of race, sex, and obesity status in later life. C1 [Hirko, Kelly A.; Stampfer, Meir J.; Signorello, Lisa B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Hirko, Kelly A.; Stampfer, Meir J.; Signorello, Lisa B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hirko, Kelly A.; Kantor, Elizabeth D.; Stampfer, Meir J.; Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cohen, Sarah S.] EpidStat Inst, Ann Arbor, MI USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Blot, William J.] Vanderbilt Univ, Med Ctr, Div Epidemiol, Dept Med, Nashville, TN 37235 USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Hirko, KA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM khirko@hsph.harvard.edu FU National Cancer Institute [R01 CA092447]; [R25T CA098566] FX The Southern Community Cohort Study is funded by grant R01 CA092447 from the National Cancer Institute. K.A.H. is supported by the R25T CA098566 training grant. NR 50 TC 9 Z9 9 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2015 VL 182 IS 5 BP 441 EP 450 DI 10.1093/aje/kwv084 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR5NB UT WOS:000361388700009 PM 25977515 ER PT J AU Gradus, JL Antonsen, S Svensson, E Lash, TL Resick, PA Hansen, JG AF Gradus, Jaimie L. Antonsen, Sussie Svensson, Elisabeth Lash, Timothy L. Resick, Patricia A. Hansen, Jens Georg TI Trauma, Comorbidity, and Mortality Following Diagnoses of Severe Stress and Adjustment Disorders: A Nationwide Cohort Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; stress disorders; traumatic; suicide ID SEXUAL REVICTIMIZATION; PSYCHIATRIC-ILLNESS; COMPLETED SUICIDE; PTSD; REGISTER; VETERANS; SYMPTOMATOLOGY; POPULATION; SYMPTOMS; MEDIATOR AB Longitudinal outcomes following stress or trauma diagnoses are receiving attention, yet population-based studies are few. The aims of the present cohort study were to examine the cumulative incidence of traumatic events and psychiatric diagnoses following diagnoses of severe stress and adjustment disorders categorized using International Classification of Diseases, Tenth Revision, codes and to examine associations of these diagnoses with all-cause mortality and suicide. Data came from a longitudinal cohort of all Danes who received a diagnosis of reaction to severe stress or adjustment disorders (International Classification of Diseases, Tenth Revision, code F43.x) between 1995 and 2011, and they were compared with data from a general-population cohort. Cumulative incidence curves were plotted to examine traumatic experiences and psychiatric diagnoses during the study period. A Cox proportional hazards regression model was used to examine the associations of the disorders with mortality and suicide. Participants with stress diagnoses had a higher incidence of traumatic events and psychiatric diagnoses than did the comparison group. Each disorder was associated with a higher rate of all-cause mortality than that seen in the comparison cohort, and strong associations with suicide were found after adjustment. This study provides a comprehensive assessment of the associations of stress disorders with a variety of outcomes, and we found that stress diagnoses may have long-lasting and potentially severe consequences. C1 [Gradus, Jaimie L.] Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Gradus, Jaimie L.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Antonsen, Sussie; Svensson, Elisabeth; Hansen, Jens Georg] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Lash, Timothy L.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Resick, Patricia A.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Resick, Patricia A.] Duke Univ, Dept Behav Sci, Durham, NC USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU National Institute of Mental Health [1R21MH094551-01A1] FX This work was supported by a National Institute of Mental Health (grant 1R21MH094551-01A1) to J.L.G. NR 27 TC 2 Z9 2 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2015 VL 182 IS 5 BP 451 EP 458 DI 10.1093/aje/kwv066 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR5NB UT WOS:000361388700010 PM 26243737 ER PT J AU Chenelle, CT Fisher, DF Kacmarek, RM Berra, L AF Chenelle, Christopher T. Fisher, Daniel F. Kacmarek, Robert M. Berra, Lorenzo TI Procedural Considerations on the Use of Polyurethane and/or Conical Cuffs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID VENTILATOR-ASSOCIATED PNEUMONIA; CRITICALLY-ILL PATIENTS; PRESSURE C1 [Chenelle, Christopher T.; Fisher, Daniel F.; Kacmarek, Robert M.; Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chenelle, Christopher T.; Fisher, Daniel F.; Kacmarek, Robert M.; Berra, Lorenzo] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chenelle, CT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 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 SEP 1 PY 2015 VL 192 IS 5 BP 639 EP 640 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CR4XX UT WOS:000361344500020 PM 26561679 ER PT J AU Dieras, V Campone, M Yardley, DA Romieu, G Valero, V Isakoff, SJ Koeppen, H Wilson, TR Xiao, Y Shames, DS Mocci, S Chen, M Schmid, P AF Dieras, V. Campone, M. Yardley, D. A. Romieu, G. Valero, V. Isakoff, S. J. Koeppen, H. Wilson, T. R. Xiao, Y. Shames, D. S. Mocci, S. Chen, M. Schmid, P. TI Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE bevacizumab; MET; triple-negative breast cancer; onartuzumab; paclitaxel; phase II ID SOLID TUMORS; C-MET; EXPRESSION; CHEMOTHERAPY; CARCINOMAS; SUBTYPES AB Increased hepatocyte growth factor/MET signaling is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer (TNBC). We evaluated the benefit of adding onartuzumab, a monoclonal anti-MET antibody, to paclitaxel with/without bevacizumab in patients with TNBC. Women with metastatic TNBC were randomized to receive onartuzumab plus placebo plus weekly paclitaxel (OP; n = 60) or onartuzumab plus bevacizumab plus paclitaxel (OBP; n = 63) or placebo plus bevacizumab plus paclitaxel (BP; n = 62). The primary end point was progression-free survival (PFS); additional end points included overall survival (OS), objective response rate (ORR), and safety. This trial was hypothesis generating and did not have power to detect minimum clinically meaningful differences between treatment arms. There was no improvement in PFS with the addition of onartuzumab to BP [hazard ratio (HR), 1.08; 95% confidence interval (CI) 0.69-1.70]; the risk of a PFS event was higher with OP than with BP (HR, 1.74; 95% CI 1.13-2.68). Most patients had MET-negative tumors (88%); PAM50 subtype analysis showed basal-like tumors in 68% of samples. ORR was higher in the bevacizumab arms (OBP: 42.2%; 95% CI 28.6-57.1; BP: 54.7%; 95% CI 41.0-68.4) compared with OP (27.5%; 95% CI 15.9-40.6). Median OS was shorter with OBP (HR, 1.36; 95% CI 0.75-2.46) and OP (HR, 1.92; 95% CI 1.03-3.59), than with BP. Peripheral edema was more frequent in the onartuzumab arms (OBP, 51.8%; OP, 58.6%) versus BP (17.7%). This study did not show a clinical benefit of the addition of onartuzumab to paclitaxel with/without bevacizumab in patients with predominantly MET-negative TNBC. C1 [Dieras, V.] Inst Curie Paris & St Cloud, Dept Clin Res, F-75248 Paris 05, France. [Campone, M.] Ctr Reg Lutte Canc CRLC Nantes, Ctr Rene Gauducheau, Atlantique, France. [Yardley, D. A.] PLLC, Sarah Cannon Res Inst & Tennessee Oncol, Nashville, TN USA. [Romieu, G.] ICM, Montpellier, France. [Valero, V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Isakoff, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koeppen, H.; Wilson, T. R.; Xiao, Y.; Shames, D. S.; Mocci, S.] Genentech Inc, San Francisco, CA 94080 USA. [Chen, M.] Roche Prod Dev, Shanghai, Peoples R China. [Schmid, P.] Queen Mary Univ London, Barts Canc Inst, London, England. RP Dieras, V (reprint author), Inst Curie Paris & St Cloud, Dept Clin Res, 26 Rue Ulm, F-75248 Paris 05, France. EM veronique.dieras@curie.fr RI campone, mario/L-4880-2015 FU Genentech, Inc. FX This study was supported by Genentech, Inc. Support for third-party writing assistance for this manuscript was provided by Genentech, Inc. Grant numbers are not applicable. NR 20 TC 15 Z9 16 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2015 VL 26 IS 9 BP 1904 EP 1910 DI 10.1093/annonc/mdv263 PG 7 WC Oncology SC Oncology GA CR5ON UT WOS:000361392700015 PM 26202594 ER PT J AU Ausiello, D Lipnick, S AF Ausiello, Dennis Lipnick, Scott TI Real-Time Assessment of Wellness and Disease in Daily Life SO BIG DATA LA English DT Article DE big data industry standards; big data architecture; big data analytics ID GUT MICROBIOTA; METAGENOME AB The next frontier in medicine involves better quantifying human traits, known as "phenotypes." Biological markers have been directly associated with disease risks, but poor measurement of behaviors such as diet and exercise limits our understanding of preventive measures. By joining together an uncommonly wide range of disciplines and expertise, the Kavli HUMAN Project will advance measurement of behavioral phenotypes, as well as environmental factors that impact behavior. By following the same individuals over time, KHP will liberate new understanding of dynamic links between behavioral phenotypes, disease, and the broader environment. As KHP advances understanding of the bio-behavioral complex, it will seed new approaches to the diagnosis, prevention, and treatment of human disease. C1 [Ausiello, Dennis; Lipnick, Scott] Massachussetts Gen Hosp, Ctr Assessment Technol & Continuous Hlth, Boston, MA USA. RP Ausiello, D (reprint author), Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM Ausiello.Dennis@mgh.harvard.edu NR 9 TC 3 Z9 3 U1 5 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2167-6461 EI 2167-647X J9 BIG DATA JI Big Data PD SEP 1 PY 2015 VL 3 IS 3 BP 203 EP 208 DI 10.1089/big.2015.0016 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA CR5FC UT WOS:000361364900010 ER PT J AU Kim, KS Hyun, H Yang, JA Lee, MY Kim, H Yun, SH Choi, HS Hahn, SK AF Kim, Ki Su Hyun, Hoon Yang, Jeong-A Lee, Min Young Kim, Hyemin Yun, Seok-Hyun Choi, Hak Soo Hahn, Sei Kwang TI Bioimaging of Hyaluronate-Interferon alpha Conjugates Using a Non-Interfering Zwitterionic Fluorophore SO BIOMACROMOLECULES LA English DT Article ID HEPATITIS-C VIRUS; NEAR-INFRARED FLUOROPHORES; QUANTUM DOTS; IN-VIVO; ACID DERIVATIVES; DELIVERY; TARGET; CELLS; CLEARANCE; DRUGS AB We conducted real-time bioimaging of the hyaluronate-interferon alpha (HA-IFN alpha) conjugate using a biologically inert zwitterionic fluorophore of ZW800-1 for the treatment of hepatitis C virus (HCV) infection. ZW800-1 was labeled on the IFN alpha molecule of the HA-IFN alpha conjugate to investigate its bio distribution and clearance without altering its physicochemical and targeting characteristics. Confocal microscopy clearly visualized the effective in vitro cellular uptake of the HA-IFN alpha conjugate to HepG2 cells. After verifying the biological activity in Daudi cells, we conducted the pharmacokinetic analysis of the HA-IFN alpha conjugate, which confirmed its target-specific delivery to the liver with a prolonged residence time longer than that of PEGylated IFN alpha. In vivo and ex vivo bioimaging of the ZW800-1-labeled HA-IFN alpha conjugate directly showed real-time biodistribution and clearance of the conjugate that are consistent with the biological behaviors analyzed by an enzyme-linked immunosorbent assay. Furthermore, the elevated level of OAS1 mRNA in the liver confirmed in vivo antiviral activity of HA-IFN alpha conjugates. With the data taken together, we could confirm the feasibility of ZW800-1 as a biologically inert fluorophore and target-specific HA-IFN alpha conjugate for the treatment of HCV infection. C1 [Kim, Ki Su; Yun, Seok-Hyun; Hahn, Sei Kwang] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Ki Su; Yun, Seok-Hyun; Hahn, Sei Kwang] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Yang, Jeong-A; Lee, Min Young; Kim, Hyemin; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Hyun, Hoon; Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Hyun, Hoon; Choi, Hak Soo] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Hyun, Hoon] Chonnam Natl Univ, Sch Med, Dept Biomed Sci, Kwangju 501746, South Korea. RP Choi, HS (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM hchoi@bidmc.harvard.edu; skhanb@postech.ac.kr RI Choi, Hak Soo/C-9954-2011 FU Converging Research Center Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2009-0081871]; Midcareer Researcher Program through an NRF grant - MEST [2012R1A2A2A06045773]; National Institute of Biomedical Imaging and Bioengineering [R01-EB-011523] FX This work was supported by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0081871). This study was also supported by the Midcareer Researcher Program through an NRF grant funded by the MEST (2012R1A2A2A06045773) and a National Institute of Biomedical Imaging and Bioengineering grant (R01-EB-011523). NR 35 TC 3 Z9 3 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 EI 1526-4602 J9 BIOMACROMOLECULES JI Biomacromolecules PD SEP PY 2015 VL 16 IS 9 BP 3054 EP 3061 DI 10.1021/acs.biomac.5b00933 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA CR4WV UT WOS:000361341700052 PM 26258264 ER PT J AU Wang, C Dominici, F Parmigiani, G Zigler, CM AF Wang, Chi Dominici, Francesca Parmigiani, Giovanni Zigler, Corwin Matthew TI Accounting for Uncertainty in Confounder and Effect Modifier Selection When Estimating Average Causal Effects in Generalized Linear Models SO BIOMETRICS LA English DT Article DE Average causal effect; Bayesian adjustment for confounding; Confounder selection; Treatment effect heterogeneity ID PROPENSITY SCORE; VARIABLE SELECTION; ADJUSTMENT UNCERTAINTY; BAYESIAN-ADJUSTMENT; INFERENCE; REGRESSION; BOOTSTRAP; ALGORITHM AB Confounder selection and adjustment are essential elements of assessing the causal effect of an exposure or treatment in observational studies. Building upon work by Wang et al. (2012, Biometrics 68, 661-671) and Lefebvre et al. (2014, Statistics in Medicine 33, 2797-2813), we propose and evaluate a Bayesian method to estimate average causal effects in studies with a large number of potential confounders, relatively few observations, likely interactions between confounders and the exposure of interest, and uncertainty on which confounders and interaction terms should be included. Our method is applicable across all exposures and outcomes that can be handled through generalized linear models. In this general setting, estimation of the average causal effect is different from estimation of the exposure coefficient in the outcome model due to noncollapsibility. We implement a Bayesian bootstrap procedure to integrate over the distribution of potential confounders and to estimate the causal effect. Our method permits estimation of both the overall population causal effect and effects in specified subpopulations, providing clear characterization of heterogeneous exposure effects that may vary considerably across different covariate profiles. Simulation studies demonstrate that the proposed method performs well in small sample size situations with 100-150 observations and 50 covariates. The method is applied to data on 15,060 US Medicare beneficiaries diagnosed with a malignant brain tumor between 2000 and 2009 to evaluate whether surgery reduces hospital readmissions within 30 days of diagnosis. C1 [Wang, Chi] Univ Kentucky, Dept Biostat, Lexington, KY 40506 USA. [Wang, Chi] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. [Dominici, Francesca; Parmigiani, Giovanni; Zigler, Corwin Matthew] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Wang, C (reprint author), Univ Kentucky, Dept Biostat, Lexington, KY 40506 USA. EM chi.wang@uky.edu FU NIH/NCI [P01 CA134294, 5P30 CA006516-46]; HEI [4909]; AHRQ [K18 HS021991]; NIH [R21 ES022585-01, R01 ES019560, R01 GM111339] FX We thank Dr Nils Arvold and Dr Yun Wang for input on the construction and analysis of the brain cancer data. We also thank the Co-Editor, the Associate Editor, and three referees for insightful comments. The work of Drs Dominici and Zigler was supported by NIH/NCI P01 CA134294, and HEI 4909, Dr Dominici was supported by AHRQ K18 HS021991, NIH R21 ES022585-01, NIH R01 ES019560, and NIH R01 GM111339, and Dr Parmigiani was supported by NIH/NCI 5P30 CA006516-46. NR 28 TC 0 Z9 0 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2015 VL 71 IS 3 BP 654 EP 665 DI 10.1111/biom.12315 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CR7JY UT WOS:000361527000010 PM 25899155 ER PT J AU Nakagawa, A Von Alt, K Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Liss, AS AF Nakagawa, Akifumi Von Alt, Kate Lillemoe, Keith D. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Liss, Andrew S. TI A method for fixing and paraffin embedding tissue to retain the natural fluorescence of reporter proteins SO BIOTECHNIQUES LA English DT Article DE FFPE; GFP; natural fluorescence ID MARKER; MOUSE; GFP AB Green fluorescent protein (GFP) and its derivatives are routinely employed as surrogate markers for gene expression and lineage tracing in genetically engineered mice. Tissues from these mice are commonly formalin fixed and paraffin embedded (FFPE) for histological studies. However, this results in inactivation of the natural fluorescence of these proteins, requiring their detection by immunological techniques. Here we present an ethanol fixation protocol that allows for the direct visualization of the natural fluorescence of reporter proteins while maintaining excellent tissue histology. We demonstrate the utility of this method for visualizing green and red fluorescent proteins in a wide range of murine tissues using both cytoplasmic and membrane-localized fluorescent reporter proteins. Tissues fixed by this method also allow for immunohistochemical studies, providing a single method to visualize the natural fluorescence of reporter proteins with subsequent detection of cellular proteins. C1 [Liss, Andrew S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Andrew L Warshaw MD Inst Pancreat Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Liss, AS (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM aliss@mgh.harvard.edu FU Institute for Pancreatic Cancer Research; NIH [P01CA117969] FX We would like to thank Patricia Della Pelle for her advice and technical support. This work was supported in part by the Andrew L Warshaw, MD, Institute for Pancreatic Cancer Research and a grant from the NIH: P01CA117969. This paper is subject to the NIH Public Access Policy. NR 10 TC 1 Z9 1 U1 2 U2 4 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2015 VL 59 IS 3 BP 153 EP 155 DI 10.2144/000114328 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR3RE UT WOS:000361250000010 PM 26345508 ER PT J AU Locascio, JJ Eberly, S Liao, ZX Liu, GQ Hoesing, AN Duong, K Trisini-Lipsanopoulos, A Dhima, K Hung, AY Flaherty, AW Schwarzschild, MA Hayes, MT Wills, AM Sohur, US Mejia, NI Selkoe, DJ Oakes, D Shoulson, I Dong, XJ Marek, K Zheng, B Ivinson, A Hyman, BT Growdon, JH Sudarsky, LR Schlossmacher, MG Ravina, B Scherzer, CR AF Locascio, Joseph J. Eberly, Shirley Liao, Zhixiang Liu, Ganqiang Hoesing, Ashley N. Duong, Karen Trisini-Lipsanopoulos, Ana Dhima, Kaltra Hung, Albert Y. Flaherty, Alice W. Schwarzschild, Michael A. Hayes, Michael T. Wills, Anne-Marie Sohur, U. Shivraj Mejia, Nicte I. Selkoe, Dennis J. Oakes, David Shoulson, Ira Dong, Xianjun Marek, Ken Zheng, Bin Ivinson, Adrian Hyman, Bradley T. Growdon, John H. Sudarsky, Lewis R. Schlossmacher, Michael G. Ravina, Bernard Scherzer, Clemens R. TI Association between alpha-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease SO BRAIN LA English DT Article DE alpha-synuclein; biomarker; gene expression; biobank; mitochondria; cognitive decline ID GENE-EXPRESSION; RNA; BIOMARKERS; DISCOVERY; PROTEIN; RISK; STABILIZATION; PHLEBOTOMY; OPINION; MARKERS AB There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene a-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P50.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. C1 [Locascio, Joseph J.; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Dong, Xianjun; Zheng, Bin; Scherzer, Clemens R.] Harvard Univ, Sch Med, Neurogen Lab, Cambridge, MA 02139 USA. [Locascio, Joseph J.; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Dong, Xianjun; Zheng, Bin; Scherzer, Clemens R.] Harvard Univ, Sch Med, Parkinson Personalized Med Program, Cambridge, MA 02139 USA. [Locascio, Joseph J.; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Dong, Xianjun; Zheng, Bin; Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Locascio, Joseph J.; Hung, Albert Y.; Flaherty, Alice W.; Schwarzschild, Michael A.; Wills, Anne-Marie; Sohur, U. Shivraj; Mejia, Nicte I.; Hyman, Bradley T.; Growdon, John H.; Scherzer, Clemens R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eberly, Shirley; Oakes, David] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Selkoe, Dennis J.; Dong, Xianjun; Zheng, Bin; Ivinson, Adrian; Scherzer, Clemens R.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. [Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Wills, Anne-Marie; Ivinson, Adrian; Hyman, Bradley T.; Scherzer, Clemens R.] Harvard NeuroDiscovery Ctr, Biomarkers Program, Boston, MA 02115 USA. [Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hayes, Michael T.; Selkoe, Dennis J.; Sudarsky, Lewis R.; Scherzer, Clemens R.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Shoulson, Ira] Georgetown Univ, Dept Neurol, Program Regulatory Sci & Med, Washington, DC 20007 USA. [Marek, Ken] Inst Neurodegenerat Disorders, New Haven, CT 06510 USA. [Schlossmacher, Michael G.] Univ Ottawa, Ottawa Hosp Res Inst, Program Neurosci, Ottawa, ON K1H 8M5, Canada. [Ravina, Bernard] Voyager Therapeut, Clin Dev, Cambridge, MA 02142 USA. RP Scherzer, CR (reprint author), Harvard Univ, Sch Med, Neurogen Lab, 65 Landsdowne St,Suite 307A, Cambridge, MA 02139 USA. EM cscherzer@rics.bwh.harvard.edu FU NIH [U01 NS082157, U01 NS082080]; Harvard NeuroDiscovery Center; U.S. Department of Defense [W81XWH-1-0007, W81XWH-13-1-0115, W81XWH-11-1-0150]; Michael J. Fox Foundation; M.E.M.O. Hoffman Foundation; Harvard NeuroDiscovery Center (HNDC); Parkinson's Disease Biomarkers Program (PDBP) of the NINDS [U01 NS082157]; Massachusetts Alzheimer's Disease Research Center (ADRC) of the National Institute on Aging [P50 AG005134]; Department of Defense Neurotoxin Exposure Treatment Parkinson's Research Program [W23RRYX7022N606]; NINDS PD-DOC [NS050095]; Parkinson's Disease Foundation (New York, NY); Cephalon Inc; Lundbeck; Michael J. Fox Foundation for Parkinson's Research; Abbott; Avid; Biogen Idec; Bristol-Myers Squibb; Covance; Elan; GE Healthcare; Genentech; GlaxoSmithKline; Lilly; Merck; Meso Scale Discovery; Pfizer; Roche; UCB FX This study was made possible by NIH grants U01 NS082157 (C.R.S.), U01 NS082080 (C.R.S.) the Harvard NeuroDiscovery Center (to A. I., C.R.S., and B.T.H.), U.S. Department of Defense grants W81XWH-1-0007 (B.R.) and W81XWH-13-1-0115 (C.R.S), and the Michael J. Fox Foundation (C.R.S. and M.G.S.). Additional funding was provided by the M.E.M.O. Hoffman Foundation (C.R.S.) and U.S. Department of Defense grant W81XWH-11-1-0150 (M.A.S.).; The Harvard Biomarker Study is supported by the Harvard NeuroDiscovery Center (HNDC), the Parkinson's Disease Biomarkers Program (PDBP) grant U01 NS082157 of the NINDS, and the Massachusetts Alzheimer's Disease Research Center (ADRC) P50 AG005134 grant of the National Institute on Aging.; The PROBE cohort was funded by Department of Defense Neurotoxin Exposure Treatment Parkinson's Research Program (W23RRYX7022N606), NINDS PD-DOC (NS050095), the Parkinson's Disease Foundation (New York, NY), with initial funding from Cephalon Inc and Lundbeck for the parent PRECEPT clinical trial and follow-up PostCEPT cohort, from which the nested PROBE cohort was derived.; PPMI, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbott, Avid, Biogen Idec, Bristol-Myers Squibb, Covance, Elan, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Merck, Meso Scale Discovery, Pfizer, Roche, UCB. NR 47 TC 10 Z9 10 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD SEP 1 PY 2015 VL 138 BP 2659 EP 2671 DI 10.1093/brain/awv202 PN 9 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR5PS UT WOS:000361396200026 PM 26220939 ER PT J AU Toledo, JB Zetterberg, H van Harten, AC Glodzik, L Martinez-Lage, P Bocchio-Chiavetto, L Rami, L Hansson, O Sperling, R Engelborghs, S Osorio, RS Vanderstichele, H Vandijck, M Hampel, H Teipl, S Moghekar, A Albert, M Hu, WT Argiles, JAM Gorostidi, A Teunissen, CE De Deyn, PP Hyman, BT Molinuevo, JL Frisoni, GB Linazasoro, G de Leon, MJ van der Flier, WM Scheltens, P Blennow, K Shaw, LM Trojanowski, JQ AF Toledo, Jon B. Zetterberg, Henrik van Harten, Argonde C. Glodzik, Lidia Martinez-Lage, Pablo Bocchio-Chiavetto, Luisella Rami, Lorena Hansson, Oskar Sperling, Reisa Engelborghs, Sebastiaan Osorio, Ricardo S. Vanderstichele, Hugo Vandijck, Manu Hampel, Harald Teipl, Stefan Moghekar, Abhay Albert, Marilyn Hu, William T. Argiles, Jose A. Monge Gorostidi, Ana Teunissen, Charlotte E. De Deyn, Peter P. Hyman, Bradley T. Molinuevo, Jose L. Frisoni, Giovanni B. Linazasoro, Gurutz de Leon, Mony J. van der Flier, Wiesje M. Scheltens, Philip Blennow, Kaj Shaw, Leslie M. Trojanowski, John Q. CA Alzheimer's Dis Neuroimaging TI Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects SO BRAIN LA English DT Article DE Alzheimer's disease; dementia; biomarkers; cognitive ageing; imaging ID BETA-AMYLOID 1-42; 2 ANALYTICAL PLATFORMS; ADULT LIFE-SPAN; NEUROPATHOLOGIC ASSESSMENT; ASSOCIATION GUIDELINES; NATIONAL INSTITUTE; CSF BIOMARKERS; TAU PROTEINS; AGING BRAIN; AGE AB In a large multicentre study, Toledo et al. examine core Alzheimer's disease CSF biomarkers in 1233 cognitively normal subjects aged 40-85 years. Alzheimer disease-like changes in A beta 1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both A beta 1-42 and phosphorylated/total tau.In a large multicentre study, Toledo et al. examine core Alzheimer's disease CSF biomarkers in 1233 cognitively normal subjects aged 40-85 years. Alzheimer disease-like changes in A beta 1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both A beta 1-42 and phosphorylated/total tau.In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-beta(1-42). Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or LuminexA (R) measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-beta(1-42) in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-beta amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-beta(1-42) and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE epsilon 4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-beta(1-42) values and APOE epsilon 2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-beta(1-42) levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-beta(1-42), phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology. C1 [Toledo, Jon B.; Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med,Inst Aging, Philadelphia, PA 19104 USA. [Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, Dept Mol Neurosci, London, England. [van Harten, Argonde C.; van der Flier, Wiesje M.; Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. [van Harten, Argonde C.; van der Flier, Wiesje M.; Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Glodzik, Lidia; Osorio, Ricardo S.; de Leon, Mony J.] NYU, Sch Med, Dept Psychiat, Ctr Brain Hlth, New York, NY USA. [Martinez-Lage, Pablo] Fdn CITA Alzheimer Fundazioa, Ctr Res & Adv Therapies, Dept Neurol, Donostia San Sebastian, Spain. [Bocchio-Chiavetto, Luisella; Frisoni, Giovanni B.] IRCCS Ctr San Giovanni di Dio FBF, Brescia, Italy. [Bocchio-Chiavetto, Luisella] eCampus Univ, Fac Psychol, Novedrate, Como, Italy. [Rami, Lorena; Molinuevo, Jose L.] Hosp Clin & Univ, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain. [Hansson, Oskar] Lund Univ, Dept Clin Sci, Lund, Sweden. [Hansson, Oskar] Skane Univ Hosp, Memory Clin, Lund, Sweden. [Sperling, Reisa; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Harvard Aging Brain Study,Dept Neurol,Med Sch, Boston, MA USA. [Engelborghs, Sebastiaan; De Deyn, Peter P.] Hosp Network Antwerp Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium. [Engelborghs, Sebastiaan; De Deyn, Peter P.] Hosp Network Antwerp Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium. [Engelborghs, Sebastiaan; De Deyn, Peter P.] Univ Antwerp, Dept Biomed Sci, Reference Ctr Biol Markers Dementia BIODEM, Lab Neurochem & Behav,Inst Born Bunge, B-2020 Antwerp, Belgium. [Vanderstichele, Hugo] ADx NeuroSci, Ghent, Belgium. [Vandijck, Manu] Fujirebio Europe Nv, Ghent, Belgium. [Hampel, Harald] AXA Res Fund, Paris, France. [Hampel, Harald] Univ Paris 06, Paris, France. [Hampel, Harald] Univ Paris 06, Sorbonne Univ, Inst Memoire & Maladie Alzheimer IM2A, Paris, France. [Hampel, Harald] Hop La Pitie Salpetriere, Dept Neurol, Inst Cerveau & Moelle Epiniere ICM, Paris, France. [Teipl, Stefan] Univ Med Rostock, Dept Psychosomat Med, Rostock, Germany. [Teipl, Stefan] German Ctr Neurodegenerat Dis, DZNE, Rostock, Germany. [Moghekar, Abhay; Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Hu, William T.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Argiles, Jose A. Monge] Univ Gen Hosp Alicante, Dept Neurol, Alicante, Spain. [Gorostidi, Ana] Biodonostia Res Inst, Neurosci Unit, San Sebastian, Spain. [Teunissen, Charlotte E.] VU Univ Med Ctr Amsterdam, Dept Clin Chem, Neurochem Lab, Amsterdam, Netherlands. [Teunissen, Charlotte E.] VU Univ Med Ctr Amsterdam, Dept Clin Chem, Biobank, Amsterdam, Netherlands. [Frisoni, Giovanni B.] Univ Hosp Geneva, Geneva, Switzerland. [Frisoni, Giovanni B.] Univ Geneva, Geneva, Switzerland. [van der Flier, Wiesje M.] VU Univ Med Ctr, Dept Epidemiol Biostat, New York, NY USA. [Blennow, Kaj] Royal Swedish Acad Sci, Torsten Soderberg Professorship Med, Stockholm, Sweden. RP Trojanowski, JQ (reprint author), Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu RI Kowall, Neil/G-6364-2012; Hansson, Oskar/A-7134-2013; Frisoni, Giovanni B/K-1360-2016; OI Kowall, Neil/0000-0002-6624-0213; Hansson, Oskar/0000-0001-8467-7286; Frisoni, Giovanni B/0000-0002-6419-1753; Molinuevo, Jose Luis/0000-0003-0485-6001; de Leon, Mony/0000-0003-2245-4380; Toledo, Jon/0000-0003-4366-9268; Preda, Adrian /0000-0003-3373-2438; Bocchio Chiavetto, Luisella/0000-0002-9801-603X FU NIH [AG022374, AG13616, AG1210]; University of Antwerp Research Fund; Alzheimer Research Foundation (SAO-FRA); central Biobank facility of the Institute Born-Bunge / University Antwerp; Research Foundation Flanders (FWO); Agency for Innovation by Science and Technology (IWT); Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program; Flemish Government; EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF) [115372]; European Research Council; Swedish Research Council; Swedish Brain Foundation; Swedish federal government under the ALF; Miguel Servet program [CP 08/00147]; AXA Research Fund; Fondation Universite Pierre et Marie Curie; 'Fondation pour la Recherche sur Alzheimer', Paris, France; program 'Investissements d'avenir' [ANR-10-IAIHU-06]; ADNI (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Michael J. Fox Foundation for Parkinson's Research; abbvie; Avid Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; GE Healthcare; Genentech; GlaxoSmithKline; Lilly; Lundbeck; Merck; Meso Scale Discovery; Piramal; La Roche Ltd; Pfizer Inc; UCB Pharma SA; [P01 AG032953]; [PO1 AG017586]; [P30 AG010124]; [P50 NS053488]; [K23 AG042856]; [R21 AG043885]; [P50 AG016976] FX J.B.T. is supported by P01 AG032953, PO1 AG017586, P30 AG010124 and P50 NS053488. J.Q.T. is the William Maul Measey-Truman G. Schnabel, Jr., Professor of Geriatric Medicine and Gerontology. H.Z.: The Swedish Research Council, the Knut and Alice Wallenberg Foundation and Swedish State Support for Clinical Research. The NYU CSF studies were supported by the following NIH grants to MdeL (PI): AG022374, AG13616, and AG1210. The Antwerp centre was supported by the University of Antwerp Research Fund; the Alzheimer Research Foundation (SAO-FRA); the central Biobank facility of the Institute Born-Bunge / University Antwerp; the Research Foundation Flanders (FWO); the Agency for Innovation by Science and Technology (IWT); the Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program; the Flemish Government initiated Methusalem excellence grant; the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant no 115372) and this work is part of the BIOMARKAPD project within the EU Joint Programme for Neurodegenerative Disease Research (JPND). W.T.H. is supported by K23 AG042856, R21 AG043885, and P50 AG016976. O.H. is supported by the European Research Council, the Swedish Research Council, the Swedish Brain Foundation, and the Swedish federal government under the ALF agreement. This publication is part of the Consolider-Ingenio 2010 (CSD 2010-00045 PI: Jose L Molinuevo), FIS-Fondo europeo de desarrollo regional, una manera de hacer Europa (PI11/01071 PI: Lorena Rami) and Miguel Servet program (CP 08/00147; PI: Lorena Rami). H.H. is supported by the AXA Research Fund, the Fondation Universite Pierre et Marie Curie and the 'Fondation pour la Recherche sur Alzheimer', Paris, France. The research leading to these results has received funding from the program 'Investissements d'avenir' ANR-10-IAIHU-06. Data collection and sharing for this project was funded ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Supported by the Michael J.; Fox Foundation for Parkinson's Research and funding partners: abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Piramal, La Roche Ltd, Pfizer Inc and UCB Pharma SA. NR 60 TC 16 Z9 16 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD SEP 1 PY 2015 VL 138 BP 2701 EP 2715 DI 10.1093/brain/awv199 PN 9 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR5PS UT WOS:000361396200029 PM 26220940 ER PT J AU Gardner, AJ Iverson, GL Quinn, TN Makdissi, M Levi, CR Shultz, SR Wright, DK Stanwell, P AF Gardner, Andrew J. Iverson, Grant L. Quinn, Tanya N. Makdissi, Michael Levi, Christopher R. Shultz, Sandy R. Wright, David K. Stanwell, Peter TI A preliminary video analysis of concussion in the National Rugby League SO BRAIN INJURY LA English DT Article DE Athletes; brain concussion; epidemiology; injury surveillance ID INCIDENT ANALYSIS; PROFESSIONAL FOOTBALL; INJURY; MATCH; SITUATIONS; NHL AB Primary objective: To conduct the first video analysis of concussion in the Australian National Rugby League (NRL) and describe player and injury characteristics, situational factors and time to return to play. Research design: Descriptive, observational case series. Methods and procedures: Video analysis of 20 medically diagnosed concussions for three consenting clubs during the 2013 NRL season. Main outcome and results: Most concussions (83%) occurred during a high tackle, and all injured ball carriers were hit high. Loss of consciousness was observed in 30% of cases. Common observable signs of injury included clutching of the head, balance problems or wobbly legs and a blank or vacant state. There were no post-concussive seizures. All players with loss of consciousness were removed from play. However, only half of the total sample was removed from play and one athlete who was removed returned to play in the same match. Of the players who were removed from play, the large majority returned the following week. Illegal play accounted for 25% of all concussions. Conclusions: Video analysis may be a useful method to study the incidence, mechanism and management of concussion in sports such as Rugby League. Future studies may include larger numbers to validate this preliminary data and may also investigate other levels of play and age ranges. C1 [Gardner, Andrew J.; Levi, Christopher R.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] MGHfC Sports Concuss Program, 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. [Quinn, Tanya N.] Univ Newcastle, Dept Psychol, Callaghan, NSW 2308, Australia. [Makdissi, Michael] Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. [Makdissi, Michael] Federat Univ, Australian Ctr Res Injury Sport & Its Prevent, Ballarat, Vic, Australia. [Shultz, Sandy R.] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic, Australia. [Wright, David K.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3052, Australia. [Stanwell, Peter] Univ Newcastle, Fac Hlth, Sch Hlth Sci, Ctr Translat Neurosci & Mental Hlth, 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 RI Gardner, Andrew/J-5162-2013; Stanwell, Peter/F-9136-2012; OI Stanwell, Peter/0000-0002-4780-0393 FU New South Wales Sporting Injuries Committee-Sports Research & Injury Prevention Scheme Grant; Brain Foundation, Australia-Brain Injury Award; Hunter Medical Research Institute; Mooney-Reed Charitable Foundation FX Andrew J. Gardner, Peter Stanwell and Christopher R. Levi have been funded to conduct research into concussion in rugby league through a New South Wales Sporting Injuries Committee-Sports Research & Injury Prevention Scheme Grant, and a Brain Foundation, Australia-Brain Injury Award. Andrew J. Gardner acknowledges sport concussion research fellowship funding from Jennie Thomas, Life Governor of the Hunter Medical Research Institute. Grant L. Iverson acknowledges sport concussion research funding from the Mooney-Reed Charitable Foundation. NR 15 TC 4 Z9 4 U1 2 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD SEP PY 2015 VL 29 IS 10 BP 1182 EP 1185 DI 10.3109/02699052.2015.1034179 PG 4 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CR3UK UT WOS:000361258400006 ER PT J AU Suarez, C Puente, J Gallardo, E Mendez-Vidal, MJ Climent, MA Leon, L Olmos, D del Muro, XG Gonzalez-Billalabeitia, E Grande, E Bellmunt, J Mellado, B Maroto, P del Alba, AG AF Suarez, C. Puente, J. Gallardo, E. Mendez-Vidal, M. J. Climent, M. A. Leon, L. Olmos, D. Garcia del Muro, X. Gonzalez-Billalabeitia, E. Grande, E. Bellmunt, J. Mellado, B. Maroto, P. Gonzalez del Alba, A. TI New advances in genitourinary cancer: evidence gathered in 2014 SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Genitourinary cancer; Bladder cancer; Renal cancer; Prostate cancer; Molecular research; Germ cell tumors ID RENAL-CELL CARCINOMA; RESISTANT PROSTATE-CANCER; PHASE-III TRIAL; ADVANCED UROTHELIAL CARCINOMA; INVASIVE BLADDER-CANCER; MITOXANTRONE PLUS PREDNISONE; LONG-TERM SURVIVAL; ANDROGEN RECEPTOR; OPEN-LABEL; DOUBLE-BLIND AB This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed. C1 [Suarez, C.] Univ Autonoma Barcelona, Vall Hebron Univ Hosp, E-08193 Barcelona, Spain. [Suarez, C.] Univ Autonoma Barcelona, Inst Oncol, E-08193 Barcelona, Spain. [Puente, J.] Hosp Clin Univ San Carlos, Dept Med Oncol, Madrid, Spain. [Gallardo, E.] Hosp Univ Parc Tauli, Dept Med Oncol, Barcelona, Spain. [Mendez-Vidal, M. J.] Hosp Univ Reina Sofia, Inst Maimonides Invest Biomed IMIBIC, Dept Med Oncol, Cordoba, Spain. [Climent, M. A.] Fdn Inst Valenciano Oncol, Dept Med Oncol, Valencia, Spain. [Leon, L.] Hosp Clin, Dept Med Oncol, Santiago De Compostela, A Coruna, Spain. [Olmos, D.] Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid, Spain. [Olmos, D.] Hosp Univ Virgen Victoria & Reg Malaga, CNIO IBIMA Genitourinary Canc Res Unit, Madrid, Spain. [Olmos, D.] Ctr Integral Oncol Clara Campal, Madrid, Spain. [Garcia del Muro, X.] Oncol Hosp, Inst Catala, Barcelona, Spain. [Gonzalez-Billalabeitia, E.] Hosp GU Morales Meseguer, Med Oncol & Hematol Dept, Murcia, Spain. [Grande, E.] Ramon & Cajal Univ Hosp, Dept Med Oncol, GI Endocrine & Translat Res Unit, Early Drug Dev Unit IRYCIS, Madrid, Spain. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bladder Canc Ctr,Dana Farber Brigham & Womens Can, Boston, MA 02115 USA. [Mellado, B.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Maroto, P.] Hosp La Santa Creu & St Pau, Dept Med Oncol, Barcelona, Spain. [Gonzalez del Alba, A.] Hosp Univ Son Espases, Dept Med Oncol, Palma De Mallorca 07010, Spain. RP del Alba, AG (reprint author), Hosp Univ Son Espases, Dept Med Oncol, Carretera Valldemosa 79, Palma De Mallorca 07010, Spain. EM aranzazu.gonzalezdelalba@ssib.es FU Astellas FX The authors thank Marta Pulido, MD, PhD, freelance author's editor for assistance in writing of the manuscript and Content Ed Net Communications, Madrid (Spain) for editorial assistance with funding from Astellas. NR 155 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 EI 1573-7233 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD SEP PY 2015 VL 34 IS 3 BP 443 EP 464 DI 10.1007/s10555-015-9577-x PG 22 WC Oncology SC Oncology GA CR7UL UT WOS:000361556900006 PM 26227584 ER PT J AU Khalili, H Gong, J Brenner, H Austin, TR Hutter, CM Baba, Y Baron, JA Berndt, SI Bezieau, S Caan, B Campbell, PT Chang-Claude, J Chanock, SJ Chen, C Hsu, L Jiao, S Conti, DV Duggan, D Fuchs, CS Gala, M Gallinger, S Haile, RW Harrison, TA Hayes, R Hazra, A Henderson, B Haiman, C Hoffmeister, M Hopper, JL Jenkins, MA Kolonel, LN Kury, S LaCroix, A Le Marchand, L Lemire, M Lindor, NM Ma, J Manson, JE Morikawa, T Nan, H Ng, K Newcomb, PA Nishihara, R Potter, JD Qu, CH Schoen, RE Schumacher, FR Seminara, D Taverna, D Thibodeau, S Wactawski-Wende, J White, E Wu, K Zanke, BW Casey, G Hudson, TJ Kraft, P Peters, U Slattery, ML Ogino, S Chan, AT AF Khalili, Hamed Gong, Jian Brenner, Hermann Austin, Thomas R. Hutter, Carolyn M. Baba, Yoshifumi Baron, John A. Berndt, Sonja I. Bezieau, Stephane Caan, Bette Campbell, Peter T. Chang-Claude, Jenny Chanock, Stephen J. Chen, Constance Hsu, Li Jiao, Shuo Conti, David V. Duggan, David Fuchs, Charles S. Gala, Manish Gallinger, Steven Haile, Robert W. Harrison, Tabitha A. Hayes, Richard Hazra, Aditi Henderson, Brian Haiman, Chris Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Kolonel, Laurence N. Kuery, Sebastien LaCroix, Andrea Le Marchand, Loic Lemire, Mathieu Lindor, Noralane M. Ma, Jing Manson, Joann E. Morikawa, Teppei Nan, Hongmei Ng, Kimmie Newcomb, Polly A. Nishihara, Reiko Potter, John D. Qu, Conghui Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Taverna, Darin Thibodeau, Stephen Wactawski-Wende, Jean White, Emily Wu, Kana Zanke, Brent W. Casey, Graham Hudson, Thomas J. Kraft, Peter Peters, Ulrike Slattery, Martha L. Ogino, Shuji Chan, Andrew T. CA GECCO CGFR TI Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer SO CARCINOGENESIS LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; GENOME-WIDE ASSOCIATION; POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; ULCERATIVE-COLITIS; COLON-CANCER; SUSCEPTIBILITY LOCI; MOLECULAR-FEATURES; CROHNS-DISEASE; MAIT CELLS AB We identified the minor allele (T) in SNP rs11676348 to have pleiotropic effect on risk of UC and CRC, particularly in tumors with an inflammatory component. Our findings offer the promise of risk stratification of UC patients for developing CRC.Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11794 CRC cases and 14190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (P (heterogeneity) = 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (P (heterogeneity) = 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (P (heterogeneity) = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC. C1 [Khalili, Hamed; Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gong, Jian; Hsu, Li; Jiao, Shuo; Harrison, Tabitha A.; LaCroix, Andrea; Newcomb, Polly A.; Potter, John D.; Qu, Conghui; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Cosortium DKTK, Heidelberg, Germany. [Austin, Thomas R.] Whitman Coll, Walla Walla, WA 99362 USA. [Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Baba, Yoshifumi] Kumamoto Univ, Dept Surg Gastroenterol, Kumamoto, Japan. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Caan, Bette] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Chen, Constance; Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA USA. [Conti, David V.; Henderson, Brian; Haiman, Chris; Schumacher, Fredrick R.; Casey, Graham] Univ So Calif, Keck Sch Med, Los Angeles, CA USA. [Duggan, David; Taverna, Darin] Syst Imaginat, Computat Biol, Phoenix, AZ USA. [Fuchs, Charles S.; Ng, Kimmie; Nishihara, Reiko; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Hazra, Aditi; Ma, Jing; Nan, Hongmei; Kraft, Peter; Chan, Andrew T.] Indiana Univ, Dept Epidemiol, Sch Publ Hlth, Indianapolis, IN 46204 USA. [Gallinger, Steven] Toronto Gen Hosp, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Haile, Robert W.] Stanford Canc Inst, Palo Alto, CA USA. [Hayes, Richard; Jenkins, Mark A.] NYU, Div Epidemiol, Sch Med, New York, NY USA. [Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Australia. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Epidemiol Program, Ctr Canc, Honolulu, HI 96822 USA. [Lemire, Mathieu; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Serv, Scottsdale, AZ USA. [Manson, Joann E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Nishihara, Reiko; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Potter, John D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Med Ctr, Pittsburgh, PA USA. [Thibodeau, Stephen] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Zanke, Brent W.] Ottawa Hosp, Clin Epidemiol Program, Res Inst, Ottawa, OK USA. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, OK USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM shuji_ogino@dfci.harvard.edu; achan@mgh.harvard.edu RI Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; KURY, Sebastien/0000-0001-5497-0465; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X; Hoffmeister, Michael/0000-0002-8307-3197 FU Crohn's and Colitis Foundation of America (CCFA); American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Institutes of Health [R01 CA60987, UM1 CA167551, R01 CA48998, CA61757, U01 CA074783, CA42182, R01 CA076366, K05 CA154337]; National Cancer Institute, National Institutes of Health [U01 CA122839, R01 CA143237]; National Institutes of Health: Australasian Colorectal Cancer Family Registry [U01/U24 CA097735]; National Institutes of Health: Familial Colorectal Neoplasia Collaborative Group [U01/U24 CA074799]; National Institutes of Health: Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24 CA074800]; National Institutes of Health: Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]; National Institutes of Health: Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; National Institutes of Health: University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Institutes of Health; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research; 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 [U01 HG004446]; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; [R01 CA137178]; [R01 CA050385]; [R01 CA151993]; [P01 CA87969]; [P30 DK043351]; [P50 CA127003]; [UM1 CA 167552]; [UM1 CA186107]; [K24 [DK]098311]; [K07 CA190673]; [K07 CA148894] FX Funded by R01 CA137178, R01 CA050385, R01 CA151993, P01 CA87969, P30 DK043351, P50 CA127003, UM1 CA 167552, UM1 CA186107, K23 DK099681, K24 [DK]098311, K07 CA190673 and K07 CA148894. Senior investigator grant from the Crohn's and Colitis Foundation of America (CCFA) to A.T.C. A career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681 to H.K.).; GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; COLO2&3: National Institutes of Health (R01 CA60987).; CCFR: National Institutes of Health (UM1 CA167551) 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, National Institutes of Health by U01 CA122839 and R01 CA143237 to G.C. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CFR. The following CFR centers contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794) and the University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806).; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 and CA61757 to M.L.S.);; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section. 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.; PLCO: 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. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager,M. et al. (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet., 39, 645-649), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. (2009) Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat. Genet., 41, 986-990, and Petersen, G.M. et al. (2010) A genome-wide association study identifies pancreatic cancer susceptibility locion chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet., 42, 224-228), and the Lung Cancer and Smoking study (Landi,M.T. et al. (2009) A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am. J. Hum. Genet., 85, 679-691). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207v.1p1 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.; PHS: National Institutes of Health (CA42182).; PMH: National Institutes of Health (R01 CA076366 to P.A.N.).; VITAL: National Institutes of Health (K05 CA154337).; WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. NR 50 TC 4 Z9 4 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2015 VL 36 IS 9 BP 999 EP 1007 DI 10.1093/carcin/bgv086 PG 9 WC Oncology SC Oncology GA CR5QA UT WOS:000361397000008 PM 26071399 ER PT J AU Stone, JR Bruneval, P Angelini, A Bartoloni, G Basso, C Batoroeva, L Buja, LM Butany, J d'Amati, G Fallon, JT Gittenberger-de Groot, AC Gouveia, RH Halushka, MK Kelly, KL Kholova, I Leone, O Litovsky, SH Maleszewski, JJ Miller, DV Mitchell, RN Preston, SD Pucci, A Radio, SJ Rodriguez, ER Sheppard, MN Suvarna, SK Tan, CD Thiene, G van der Wal, AC Veinot, JP AF Stone, James R. Bruneval, Patrick Angelini, Annalisa Bartoloni, Giovanni Basso, Cristina Batoroeva, Lubov Buja, L. Maximilian Butany, Jagdish d'Amati, Giulia Fallon, John T. Gittenberger-de Groot, Adriana C. Gouveia, Rosa H. Halushka, Marc K. Kelly, Karen L. Kholova, Ivana Leone, Ornella Litovsky, Silvio H. Maleszewski, Joseph J. Miller, Dylan V. Mitchell, Richard N. Preston, Stephen D. Pucci, Angela Radio, Stanley J. Rodriguez, E. Rene Sheppard, Mary N. Suvarna, S. Kim Tan, Carmela D. Thiene, Gaetano van der Wal, Allard C. Veinot, John P. TI Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases SO CARDIOVASCULAR PATHOLOGY LA English DT Review DE Atherosclerosis; Aortitis; Inflammatory aneurysm; Aorta ID GIANT-CELL ARTERITIS; LARGE-VESSEL VASCULITIS; IGG4-RELATED SYSTEMIC-DISEASE; AMERICAN-HEART-ASSOCIATION; TERM-FOLLOW-UP; ASCENDING AORTA; TAKAYASU ARTERITIS; ATHEROSCLEROTIC LESIONS; NATURAL-HISTORY; LYMPHOPLASMACYTIC AORTITIS AB Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behcet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections. (C) 2015 Elsevier Inc. All rights reserved. C1 [Stone, James R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bruneval, Patrick] Univ Paris 05, Paris, France. [Angelini, Annalisa; Basso, Cristina; Thiene, Gaetano] Univ Padua, Sch Med, Padua, Italy. [Bartoloni, Giovanni] Univ Catania, Catania, Italy. [Batoroeva, Lubov] Russian Acad Med Sci, Irkutsk, Russia. [Buja, L. Maximilian] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Butany, Jagdish] Toronto Gen Hosp, Toronto, ON, Canada. [d'Amati, Giulia] Univ Roma La Sapienza, I-00185 Rome, Italy. [Fallon, John T.] New York Med Coll, Valhalla, NY 10595 USA. [Gittenberger-de Groot, Adriana C.] Leiden Univ, Leiden, Netherlands. [Gouveia, Rosa H.] Hosp Santa Cruz, Carnaxide, Portugal. [Halushka, Marc K.] Johns Hopkins Univ, Baltimore, MD USA. [Kelly, Karen L.] E Carolina Univ, Greenville, NC USA. [Kholova, Ivana] Fimlab Labs, Tampere, Finland. [Leone, Ornella] Univ Bologna, St Orsola Malpighi Hosp, Bologna, Italy. [Litovsky, Silvio H.] Univ Alabama Birmingham, Birmingham, AL USA. [Maleszewski, Joseph J.] Mayo Clin, Rochester, MN USA. [Miller, Dylan V.] Univ Utah, Salt Lake City, UT 84112 USA. [Mitchell, Richard N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Preston, Stephen D.] Papworth Hosp, Papworth Everard, Cambs, England. [Pucci, Angela] Pisa Univ Hosp, Pisa, Italy. [Radio, Stanley J.] Univ Nebraska, Lincoln, NE 68583 USA. [Rodriguez, E. Rene; Tan, Carmela D.] Cleveland Clin, Cleveland, OH 44106 USA. [Sheppard, Mary N.] Univ London, St George Med Sch, London, England. [Suvarna, S. Kim] Sheffield Teaching Hosp, Sheffield, S Yorkshire, England. [van der Wal, Allard C.] Univ Amsterdam, Amsterdam, Netherlands. [Veinot, John P.] Univ Ottawa, Ottawa, ON, Canada. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Simches Bldg Room 8236, Boston, MA 02114 USA. EM jrstone@partners.org; patrick.bruneval@egp.aphp.fr OI leone, ornella/0000-0001-6412-3294; Buja, Louis Maximilian/0000-0001-8386-7029; Halushka, Marc/0000-0002-7112-7389 NR 115 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD SEP-OCT PY 2015 VL 24 IS 5 BP 267 EP 278 DI 10.1016/j.carpath.2015.05.001 PG 12 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA CR2TL UT WOS:000361183400001 PM 26051917 ER PT J AU Song, JW Mitchell, PD Kolasinski, J Grant, PE Galaburda, AM Takahashi, E AF Song, Jae W. Mitchell, Paul D. Kolasinski, James Grant, P. Ellen Galaburda, Albert M. Takahashi, Emi TI Asymmetry of White Matter Pathways in Developing Human Brains SO CEREBRAL CORTEX LA English DT Article DE asymmetry; brain; development; diffusion imaging; human tractography; white matter ID HUMAN FETAL-BRAIN; DIFFUSION TENSOR; DEVELOPMENTAL DYSLEXIA; CEREBRAL ASYMMETRY; CORPUS-CALLOSUM; VISUAL-CORTEX; HUMAN FETUS; IN-UTERO; TRACTOGRAPHY; LATERALIZATION AB Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional anisotropy in the ILF in ages older than 40 GW. These results suggest that morphometric asymmetry in cortical areas precedes the emergence of white matter pathway asymmetry. Future correlative studies will investigate whether such asymmetry is anatomically/genetically driven or associated with functional stimulation. C1 [Song, Jae W.; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Boston Childrens Hosp, Boston, MA 02115 USA. [Song, Jae W.; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Mitchell, Paul D.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Kolasinski, James; Grant, P. Ellen; Takahashi, Emi] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Galaburda, Albert M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Cognit Neurol, Boston, MA 02115 USA. RP Takahashi, E (reprint author), Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Boston Childrens Hosp, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu OI Kolasinski, James/0000-0002-1599-6440 FU Eunice Shriver Kennedy National Institute of Child Health and Development (NICHD) [NIH R01HD078561, R21HD069001]; Ruth L. Kirschstein National Research Service Awards [NIH F32 AR058105]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health [NIH P41RR14075]; NCRR Shared Instrumentation Grant Program [NIH S10RR023401, S10RR019307, S10RR023043]; High-End Instrumentation Grant Program [NIH S10RR016811]; Women's Hospital; Boston Children's Hospital; Harvard Medical School; [NIH MH081896] FX This work was supported the Eunice Shriver Kennedy National Institute of Child Health and Development (NICHD) (NIH R01HD078561, R21HD069001) (E.T.) and the Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (NIH F32 AR058105) (J.W.S.). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, NIH P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program (NIH S10RR023401, S10RR019307, and S10RR023043) and High-End Instrumentation Grant Program (NIH S10RR016811). This study was conducted partly using postmortem human brain specimens from the tissue collection at the Department of Neurobiology at Yale University School of Medicine (supported by grant NIH MH081896), which form a part of the BrainSpan Consortium collection (http://www.brainspan.org). The other brain specimens were provided by Dr Rebecca D. Folkerth, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School. NR 59 TC 6 Z9 6 U1 0 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 2883 EP 2893 DI 10.1093/cercor/bhu084 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000048 PM 24812082 ER PT J AU Sharma, J Sugihara, H Katz, Y Schummers, J Tenenbaum, J Sur, M AF Sharma, Jitendra Sugihara, Hiroki Katz, Yarden Schummers, James Tenenbaum, Joshua Sur, Mriganka TI Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1 SO CEREBRAL CORTEX LA English DT Article DE hazard rate; neural responses; reaction time; top-down influences ID PRIMARY VISUAL-CORTEX; SACCADIC EYE-MOVEMENTS; SELECTIVE ATTENTION; HEMODYNAMIC SIGNALS; NEURAL MECHANISMS; TASK-DIFFICULTY; HAZARD RATE; AREAS V1; DAS 2009; MACAQUE AB The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement-there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. C1 [Sharma, Jitendra; Sugihara, Hiroki; Schummers, James; Sur, Mriganka] MIT, Picower Inst Learning & Memory, Cambridge, MA 01239 USA. [Katz, Yarden; Tenenbaum, Joshua; Sur, Mriganka] MIT, Dept Brain & Cognit Sci, Cambridge, MA 01239 USA. [Sharma, Jitendra] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Schummers, James] Max Planck Florida Inst Neurosci, Jupiter, FL 33458 USA. RP Sur, M (reprint author), MIT, Dept Brain & Cognit Sci, Simons Ctr Social Brain, 43 Vassar St,Room 46-6237, Cambridge, MA 02139 USA. EM msur@mit.edu FU US National Institutes for Health; Simon Foundations FX Supported by grants from the US National Institutes for Health and the Simon Foundations to M.S. NR 83 TC 3 Z9 3 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 2894 EP 2906 DI 10.1093/cercor/bhu086 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000049 PM 24836689 ER PT J AU He, S Chousterman, BG Fenn, A Anzai, A Nairz, M Brandt, M Hilgendorf, I Sun, Y Ye, YX Iwamoto, Y Tricot, B Weissleder, R Macphee, C Libby, P Nahrendorf, M Swirski, FK AF He, Shun Chousterman, Benjamin G. Fenn, Ashley Anzai, Atsushi Nairz, Manfred Brandt, Martin Hilgendorf, Ingo Sun, Yuan Ye, Yu-Xiang Iwamoto, Yoshiko Tricot, Benoit Weissleder, Ralph Macphee, Colin Libby, Peter Nahrendorf, Matthias Swirski, Filip K. TI Lp-PLA(2) Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; inflammation; macrophages; monocytes; myocardial infarction ID CORONARY-HEART-DISEASE; ACTIVATING-FACTOR ACETYLHYDROLASE; PHOSPHOLIPASE A(2); ATHEROSCLEROTIC PLAQUE; MONOCYTE SUBSETS; LIPOPROTEIN; DARAPLADIB; TRIAL; STABILIZATION; INHIBITION AB Background Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a member of the phospholipase A(2) family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Elevated Lp-PLA(2) levels associate with increased risk of cardiovascular events across diverse patient populations, but the mechanisms by which the enzyme elicits its effects remain unclear. This study tested the role of Lp-PLA(2) in healing after MI. Methods and Results In response to MI, Lp-PLA(2) levels markedly increased in the circulation. To test the functional importance of Lp-PLA(2), we generated chimeric mice whose bone marrow-derived leukocytes were Lp-PLA(2)-deficient (bmLp-PLA(2)(-/-)). Compared with wild-type controls, bmLp-PLA(2)(-/-) mice subjected to MI had lower serum levels of inflammatory cytokines tumor necrosis factor-, interleukin (IL)-1, and IL-6, and decreased number of circulating inflammatory myeloid cells. Accordingly, bmLp-PLA(2)(-/-) mice developed smaller and less inflamed infarcts with reduced numbers of infiltrating neutrophils and inflammatory Ly-6C(high) monocytes. During the later, reparative phase, infarcts of bmLp-PLA(2)(-/-) mice contained Ly-6C(low) macrophages with a skewed M2-prone gene expression signature, increased collagen deposition, fewer inflammatory cells, and improved indices of angiogenesis. Consequently, the hearts of bmLp-PLA(2)(-/-) mice healed more efficiently, as determined by improved left ventricle remodeling and ejection fraction. Conclusions Lp-PLA(2) augments the inflammatory response after MI and antagonizes healing by disrupting the balance between inflammation and repair, providing a rationale for focused study of ventricular function and heart failure after targeting this enzyme acutely in MI. C1 [He, Shun; Chousterman, Benjamin G.; Fenn, Ashley; Anzai, Atsushi; Nairz, Manfred; Hilgendorf, Ingo; Sun, Yuan; Ye, Yu-Xiang; Iwamoto, Yoshiko; Tricot, Benoit; Weissleder, Ralph; Nahrendorf, Matthias; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brandt, Martin] GlaxoSmithKline, Biol Sci, Collegeville, PA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Macphee, Colin] GlaxoSmithKline, King Of Prussia, PA USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU GSK; National Institutes of Health [1R01HL095612, R56AI104695] FX This work was supported, in part, by GSK funding (GlaxoSmithKline: Targeting Lp-PLA2 in Inflammatory Cardiovascular Disease) and by National Institutes of Health grants 1R01HL095612 and R56AI104695 (to Dr Swirski). NR 27 TC 0 Z9 0 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2015 VL 8 IS 5 BP 980 EP 987 DI 10.1161/CIRCHEARTFAILURE.115.002334 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR2UL UT WOS:000361186000019 PM 26232205 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI New insights into therapeutic targets in multiple myeloma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Anderson, Kenneth 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA27 DI 10.1158/1557-3265.HEMMAL14-IA27 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200094 ER PT J AU Blackburn, J Molodtsov, A Lobbardi, R Moore, F Langenau, D AF Blackburn, Jessica Molodtsov, Aleksey Lobbardi, Riadh Moore, Finola Langenau, David TI The tyrosine phosphatase PRL3 as a novel drug target in T-cell acute lymphoblastic leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Blackburn, Jessica; Molodtsov, Aleksey; Lobbardi, Riadh; Moore, Finola; Langenau, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 SEP 1 PY 2015 VL 21 SU 17 MA A16 DI 10.1158/1557-3265.HEMMAL14-A16 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200014 ER PT J AU Cottini, F Hideshima, T Richardson, P Anderson, K Tonon, G AF Cottini, Francesca Hideshima, Teru Richardson, Paul Anderson, Kenneth Tonon, Giovanni TI Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. NR 2 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA PR04 DI 10.1158/1557-3265.HEMMAL14-PR04 PG 2 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200109 ER PT J AU Cottini, F Hideshima, T Richardson, P Anderson, K Tonon, G AF Cottini, Francesca Hideshima, Teru Richardson, Paul Anderson, Kenneth Tonon, Giovanni TI Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA B09 DI 10.1158/1557-3265.HEMMAL14-B09 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200047 ER PT J AU Ghobrial, I AF Ghobrial, Irene TI Multiple myeloma as a model of bone metastasis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ghobrial, Irene] 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA07 DI 10.1158/1557-3265.HEMMAL14-IA07 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200079 ER PT J AU Hogdal, L Chyla, B McKeegan, E Leverson, J Potluri, J Humerickhouse, R Mack, M DeAngelo, D Galinsky, I Stone, R Letai, A AF Hogdal, Leah Chyla, Brenda McKeegan, Evelyn Leverson, Joel Potluri, Jalaja Humerickhouse, Rod Mack, Mabry DeAngelo, Daniel Galinsky, Ilene Stone, Richard Letai, Anthony TI Studying BCL-2 dependence using BH3 profiling in a phase 2 clinical trial of ABT-199 in acute myeloid leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hogdal, Leah; DeAngelo, Daniel; Galinsky, Ilene; Stone, Richard; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chyla, Brenda; McKeegan, Evelyn; Leverson, Joel; Potluri, Jalaja; Humerickhouse, Rod] AbbVie Inc, N Chicago, IL USA. [Mack, Mabry] AbbVie Inc, Redwood City, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 SEP 1 PY 2015 VL 21 SU 17 MA B10 DI 10.1158/1557-3265.HEMMAL14-B10 PG 2 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200048 ER PT J AU Karreth, FA Reschke, M Bjoern, C Shipp, M Chiarle, R Pandolfi, PP AF Karreth, Florian A. Reschke, Markus Bjoern, Chapuy Shipp, Margaret Chiarle, Roberto Pandolfi, Pier Paolo TI The BRAF pseudogene is a proto-oncogenic competitive endogenous RNA. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Karreth, Florian A.] Weill Cornell Med Coll, New York, NY USA. [Reschke, Markus; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bjoern, Chapuy; Shipp, Margaret] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiarle, Roberto] Childrens Hosp, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A37 DI 10.1158/1557-3265.HEMMAL14-A37 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200030 ER PT J AU Letai, A Hogdal, L Chonghaile, T Gutierrez, A Roderick, J Kelliher, M Konopleva, M AF Letai, Anthony Hogdal, Leah Chonghaile, Triona Gutierrez, Alejandro Roderick, Justine Kelliher, Michelle Konopleva, Marina TI Using mitochondria to guide leukemia therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Letai, Anthony; Hogdal, Leah; Chonghaile, Triona] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gutierrez, Alejandro] Childrens Hosp, Boston, MA 02115 USA. [Roderick, Justine; Kelliher, Michelle] Univ Massachusetts, Sch Med, Worcester, MA USA. [Konopleva, Marina] Univ Texas MD Anderson Med Ctr, Houston, TX 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA29 DI 10.1158/1557-3265.HEMMAL14-IA29 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200095 ER PT J AU Li, LS Kopp, N Wu, SC Van Der Zwet, J Layer, JV Weigert, O Christie, AL Christodoulou, AN Liu, HY Yoda, A Radimerski, T Weinstock, DM AF Li, Loretta S. Kopp, Nadja Wu, Shuo-Chieh Van Der Zwet, Jordy Layer, Jacob V. Weigert, Oliver Christie, Amanda L. Christodoulou, Alexandra N. Liu, Huiyun Yoda, Akinori Radimerski, Thomas Weinstock, David M. TI Type II JAK2 inhibitor NVP-CHZ868 has potent activity in JAK2-dependent B-cell acute lymphoblastic leukemias (B-ALLs) in vivo. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Li, Loretta S.; Kopp, Nadja; Wu, Shuo-Chieh; Van Der Zwet, Jordy; Layer, Jacob V.; Christie, Amanda L.; Christodoulou, Alexandra N.; Liu, Huiyun; Yoda, Akinori; Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weigert, Oliver] Univ Hosp Grosshadern LMU, Munich, Germany. [Radimerski, Thomas] Novartis Inst Biomed Res, Basel, Switzerland. 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A23 DI 10.1158/1557-3265.HEMMAL14-A23 PG 2 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200019 ER PT J AU Moore, FE Esain, V Lobbardi, R Blackburn, JS North, TE Langenau, DM AF Moore, Finola E. Esain, Virginie Lobbardi, Riadh Blackburn, Jessica S. North, Trista E. Langenau, David M. TI Role for the tumor suppressor phf6 in hematopoiesis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Moore, Finola E.; Lobbardi, Riadh; Blackburn, Jessica S.; Langenau, David M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Esain, Virginie; North, Trista E.] Beth Israel Deaconess, Boston, MA 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A33 DI 10.1158/1557-3265.HEMMAL14-A33 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200027 ER PT J AU Nicholson, B Kodrasov, MP LaRocque, JP Eddins, MJ Kumar, S Chauhan, D Anderson, KC Mattern, MR AF Nicholson, Benjamin Kodrasov, Matthew P. LaRocque, James P. Eddins, Michael J. Kumar, Suresh Chauhan, Dharminder Anderson, Kenneth C. Mattern, Michael R. TI Inhibition of USP7 for the treatment of multiple myeloma and other malignancies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nicholson, Benjamin; Kodrasov, Matthew P.; LaRocque, James P.; Eddins, Michael J.; Kumar, Suresh; Mattern, Michael R.] Progenra Inc, Malvern, PA USA. [Chauhan, Dharminder; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 4 U2 10 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 SEP 1 PY 2015 VL 21 SU 17 MA A21 DI 10.1158/1557-3265.HEMMAL14-A21 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200018 ER PT J AU Shipp, M AF Shipp, Margaret TI Identification of targetable vulnerabilities in lymphoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Shipp, Margaret] 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA38 DI 10.1158/1557-3265.HEMMAL14-IA38 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200101 ER PT J AU Shirai, CL Ley, JN White, B Tibbitts, J Shao, J Ndonwi, M Kim, S Okeyo-Owuor, T Graubert, TA Walter, MJ AF Shirai, Cara Lunn Ley, James N. White, Brian Tibbitts, Justin Shao, Jin Ndonwi, Matthew Kim, Sanghyun Okeyo-Owuor, Theresa Graubert, Timothy A. Walter, Matthew J. TI Mutant U2AF1 alters hematopoiesis and pre-mRNA splicing in transgenic mice. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Shirai, Cara Lunn; Ley, James N.; White, Brian; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Kim, Sanghyun; Okeyo-Owuor, Theresa; Walter, Matthew J.] Washington Univ, St Louis, MO USA. [Graubert, Timothy A.] Dana Farber Harvard Canc Ctr, Boston, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA PR06 DI 10.1158/1557-3265.HEMMAL14-PR06 PG 2 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200110 ER PT J AU Shirai, CL Ley, JN White, B Tibbitts, J Shao, J Ndonwi, M Kim, S Okeyo-Owuor, T Graubert, TA Walter, MJ AF Shirai, Cara Lunn Ley, James N. White, Brian Tibbitts, Justin Shao, Jin Ndonwi, Matthew Kim, Sanghyun Okeyo-Owuor, Theresa Graubert, Timothy A. Walter, Matthew J. TI Mutant U2AF1 alters hematopoiesis and pre-mRNA splicing in transgenic mice. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Shirai, Cara Lunn; Ley, James N.; White, Brian; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Kim, Sanghyun; Okeyo-Owuor, Theresa; Walter, Matthew J.] Washington Univ, St Louis, MO USA. [Graubert, Timothy A.] Dana Farber Harvard Canc Ctr, Boston, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA B41 DI 10.1158/1557-3265.HEMMAL14-B41 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200071 ER PT J AU Stegmaier, K AF Stegmaier, Kimberly TI Integrating chemical and functional genomics for leukemia discovery. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Stegmaier, Kimberly] 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA23 DI 10.1158/1557-3265.HEMMAL14-IA23 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200090 ER PT J AU Weir, M Hellwig, S Gray, NS Smithgall, TE AF Weir, Mark Hellwig, Sabine Gray, Nathanael S. Smithgall, Thomas E. TI Dual inhibition of Flt3 and Fes tyrosine kinases potently blocks proliferation of AML cells expressing an active Flt3 mutant. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Weir, Mark; Hellwig, Sabine; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Microbiol & Mol Genet, Pittsburgh, PA USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Biol Chem & Mol Pharmacol, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A25 DI 10.1158/1557-3265.HEMMAL14-A25 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200021 ER PT J AU Wu, CJ AF Wu, Catherine J. TI The evolutionary landscape of chronic lymphocytic leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Catherine J.] Broad Inst, Boston, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA IA19 DI 10.1158/1557-3265.HEMMAL14-IA19 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200087 ER PT J AU Blumenthal, KG Parker, RA Shenoy, ES Walensky, RP AF Blumenthal, Kimberly G. Parker, Robert A. Shenoy, Erica S. Walensky, Rochelle P. TI Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus aureus Bacteremia and Reported Penicillin Allergy SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE decision analysis; vancomycin; allergy; penicillin; Staphylococcus aureus ID HEMODIALYSIS-DEPENDENT PATIENTS; ADVERSE DRUG-REACTIONS; HOSPITALIZED-PATIENTS; BETA-LACTAMS; SKIN; VANCOMYCIN; INFECTIONS; RESISTANT; HISTORY; CEPHALOSPORINS AB Background. Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection. First-line MSSA therapies (nafcillin, oxacillin, cefazolin) are generally avoided in the 10% of patients reporting penicillin (PCN) allergy, but most of these patients are not truly allergic. We used a decision tree with sensitivity analyses to determine the optimal evaluation and treatment for patients with MSSA bacteremia and reported PCN allergy. Methods. Our model simulates 3 strategies: (1) no allergy evaluation, give vancomycin (Vanc); (2) allergy history-guided treatment: if history excludes anaphylactic features, give cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history-appropriate PCN skin testing: if skin test negative, give cefazolin (ST-Cefaz). Model outcomes included 12-week MSSA cure, recurrence, and death; allergic reactions including major, minor, and potentially iatrogenic; and adverse drug reactions. Results. Vanc results in the fewest patients achieving MSSA cure and the highest rate of recurrence (67.3%/14.8% vs 83.4%/9.3% for Hx-Cefaz and 84.5%/8.9% for ST-Cefaz) as well as the greatest frequency of allergic reactions (3.0% vs 2.4% for Hx-Cefaz and 1.7% for ST-Cefaz) and highest rates of adverse drug reactions (5.2% vs 4.6% for Hx-Cefaz and 4.7% for ST-Cefaz). Even in a "best case for Vanc" scenario, Vanc yields the poorest outcomes. ST-Cefaz is preferred to Hx-Cefaz although sensitive to input variations. Conclusions. Patients with MSSA bacteremia and a reported PCN allergy should have the allergy addressed for optimal treatment. Full allergy evaluation with skin testing seems to be preferred, although more data are needed. C1 [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Parker, Robert A.; Shenoy, Erica S.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Parker, Robert A.; Shenoy, Erica S.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Shenoy, Erica S.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Shenoy, Erica S.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Parker, Robert A.] Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Flr, Boston, MA 02114 USA. EM kblumenthal1@partners.org FU NIH [T32 HL116275] FX This work was supported by the NIH (grant number T32 HL116275 to K. G. B.). NR 66 TC 9 Z9 9 U1 0 U2 5 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 SEP 1 PY 2015 VL 61 IS 5 BP 741 EP 749 DI 10.1093/cid/civ394 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR6PD UT WOS:000361468700011 PM 25991471 ER PT J AU Evans, SR Rubin, D Follmann, D Pennello, G Huskins, WC Powers, JH Schoenfeld, D Chuang-Stein, C Cosgrove, SE Fowler, VG Lautenbach, E Chambers, HF AF Evans, Scott R. Rubin, Daniel Follmann, Dean Pennello, Gene Huskins, W. Charles Powers, John H. Schoenfeld, David Chuang-Stein, Christy Cosgrove, Sara E. Fowler, Vance G., Jr. Lautenbach, Ebbing Chambers, Henry F. TI Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE DOOR; RADAR; antibiotic use strategies ID EQUIVALENCE TRIALS; ANTIMICROBIAL USE; NON-INFERIORITY; SAMPLE-SIZE AB Clinical trials that compare strategies to optimize antibiotic use are of critical importance but are limited by competing risks that distort outcome interpretation, complexities of noninferiority trials, large sample sizes, and inadequate evaluation of benefits and harms at the patient level. The Antibacterial Resistance Leadership Group strives to overcome these challenges through innovative trial design. Response adjusted for duration of antibiotic risk (RADAR) is a novel methodology utilizing a superiority design and a 2-step process: (1) categorizing patients into an overall clinical outcome (based on benefits and harms), and (2) ranking patients with respect to a desirability of outcome ranking (DOOR). DOORs are constructed by assigning higher ranks to patients with (1) better overall clinical outcomes and (2) shorter durations of antibiotic use for similar overall clinical outcomes. DOOR distributions are compared between antibiotic use strategies. The probability that a randomly selected patient will have a better DOOR if assigned to the new strategy is estimated. DOOR/RADAR represents a new paradigm in assessing the risks and benefits of new strategies to optimize antibiotic use. C1 [Evans, Scott R.] Harvard Univ, Boston, MA 02115 USA. [Rubin, Daniel] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Follmann, Dean] NIAID, NIH, Bethesda, MD 20892 USA. [Pennello, Gene] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Huskins, W. Charles] Mayo Clin, Div Pediat Infect Dis, Rochester, MN USA. [Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA. [Powers, John H.] NIH, Leidos Biomed Res, Div Clin Res, Bethesda, MD 20892 USA. [Schoenfeld, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chuang-Stein, Christy] Pfizer Inc, Groton, CT 06340 USA. [Cosgrove, Sara E.] Johns Hopkins Univ, Baltimore, MD USA. [Fowler, Vance G., Jr.] Duke Univ, Durham, NC USA. [Lautenbach, Ebbing] Univ Penn, Philadelphia, PA 19104 USA. [Chambers, Henry F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Evans, SR (reprint author), Harvard Univ, Sch Publ Hlth, CBAR Biostat, FXB 513,651 Huntington Ave, Boston, MA 02115 USA. EM evans@sdac.harvard.edu FU National Institute of Allergy and Infectious Diseases of the NIH [UM1AI104681]; National Cancer Institute, NIH [HHSN261200800001E] FX This work was supported by the National Institute of Allergy and Infectious Diseases of the NIH (award number UM1AI104681) and in part with federal funds from the National Cancer Institute, NIH (contract number HHSN261200800001E). NR 14 TC 16 Z9 16 U1 0 U2 1 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 SEP 1 PY 2015 VL 61 IS 5 BP 800 EP 806 DI 10.1093/cid/civ495 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR6PD UT WOS:000361468700021 PM 26113652 ER PT J AU Sparger, K Deschmann, E Sola-Visner, M AF Sparger, Katherine Deschmann, Emoke Sola-Visner, Martha TI Platelet Transfusions in the Neonatal Intensive Care Unit SO CLINICS IN PERINATOLOGY LA English DT Article DE Platelet transfusions; Neonatal intensive care unit; Thrombocytopenia ID FUNCTION ANALYZER; CORD BLOOD; PRIMARY HEMOSTASIS; PREMATURE-INFANTS; NEWBORN PLATELETS; CONTROLLED-TRIAL; REFERENCE RANGES; BLEEDING TIMES; THROMBOCYTOPENIA; CHILDREN AB There is significant world-wide variability in platelet transfusion thresholds used to transfuse thrombocytopenic neonates. A large multicenter randomized controlled trial comparing 2 different platelet transfusion thresholds in neonates is currently ongoing, and should provide data to guide transfusion practice. However, several studies have found that factors other than the degree of thrombocytopenia determine the bleeding risk. Thus, it will be important to develop better tests to assess primary hemostasis and bleeding risk in neonates. C1 [Sparger, Katherine] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Deschmann, Emoke] Karolinska Univ Hosp, Dept Neonatol, Astrid Lindgren Childrens Hosp, S-17176 Stockholm, Sweden. [Sola-Visner, Martha] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. RP Sola-Visner, M (reprint author), Boston Childrens Hosp, Div Newborn Med, Enders Res Bldg,Room 961,300 Longwood Ave, Boston, MA 02115 USA. EM Martha.Sola-Visner@childrens.harvard.edu FU NHLBI NIH HHS [P01 HL046925, R21 HL087150] NR 43 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-5108 EI 1557-9840 J9 CLIN PERINATOL JI Clin. Perinatol. PD SEP PY 2015 VL 42 IS 3 BP 613 EP + DI 10.1016/j.clp.2015.04.009 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CR2LY UT WOS:000361162700013 PM 26250921 ER PT J AU Kojic, M Milosevic, M Kojic, N Starosolski, Z Ghaghada, K Serda, R Annapragada, A Ferrari, M Ziemys, A AF Kojic, M. Milosevic, M. Kojic, N. Starosolski, Z. Ghaghada, K. Serda, R. Annapragada, A. Ferrari, M. Ziemys, A. TI A multi-scale FE model for convective-diffusive drug transport within tumor and large vascular networks SO COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING LA English DT Article DE Pipe finite element; Coupling fluid and solid; Homogenization; Multiscale; Tumor model; Brain model ID BLOOD-FLOW; NEOPLASTIC TISSUES; MICROVASCULAR ARCHITECTURE; VISCOUS RESISTANCE; SOLID TUMORS; PERMEABILITY; MICROENVIRONMENT; CARCINOMA; FLUID; CAPILLARIES AB Mass transport within an organ occurs through networks of blood vessels and surrounding tissue. This convective-diffusive transport is a very complex process which spans several different scales, from nano-to micro-to macro-scale. The blood vessel network is usually very intricate and irregular with respect to size and geometry, with mass transport being directly coupled to the neighboring tissue. Due to such complexity, development of a comprehensive transport model remains a challenge. The primary focus of this study is on solid tumors which are extremely complex autonomous systems with regard to mass transport. Additionally, tumors develop various biological barriers which hinder effective delivery of drug molecules into cancer tissue. We introduce a multi-scale tumor transport model where larger tumor vessels are modeled by simple 1D finite elements, whereas the capillary bed is replaced by equivalent 3D continuum finite elements. The model couples convective-diffusive transport within capillaries (fluid domain) and tissue (solid domain). These fluid and solid domains are connected by fictitious 1D elements. The proposed tumor model incorporates the imaged inhomogeneous tumor tissue and blood vessel network-from larger vessels to the smallest capillary bed. The tumor model is also applicable to transport within organs, such as the mouse brain, which is presented here as an example. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kojic, M.; Ferrari, M.; Ziemys, A.] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA. [Kojic, M.; Milosevic, M.] Belgrade Metropolitan Univ, Bioengn Res & Dev Ctr BioIRC Kragujevac, Kragujevac 34000, Serbia. [Kojic, M.] Serbian Acad Arts & Sci, Belgrade 11000, Serbia. [Kojic, N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Starosolski, Z.; Ghaghada, K.; Annapragada, A.] Texas Childrens Hosp, Singleton Dept Pediat Radiol, Houston, TX 77030 USA. [Serda, R.] Baylor Coll Med, Houston, TX 77030 USA. RP Kojic, M (reprint author), Houston Methodist Res Inst, Dept Nanomed, 6670 Bertner Ave,R7-117, Houston, TX 77030 USA. EM mkojic42@gmail.com FU State of Texas Emerging Technology Fund; Alliance of NanoHealth (ANH); Ministry of Education and Science of Serbia [OI 174028, III 41007]; City of Kragujevac; Ernest Cockrell Jr. Presidential Distinguished Chair FX This study has been supported from funds of State of Texas Emerging Technology Fund, Alliance of NanoHealth (ANH), and the Ernest Cockrell Jr. Presidential Distinguished Chair (M.F.).; The authors acknowledge support from Ministry of Education and Science of Serbia, grants OI 174028 and III 41007, and City of Kragujevac. NR 53 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0045-7825 EI 1879-2138 J9 COMPUT METHOD APPL M JI Comput. Meth. Appl. Mech. Eng. PD SEP 1 PY 2015 VL 294 BP 100 EP 122 DI 10.1016/j.cma.2015.06.002 PG 23 WC Engineering, Multidisciplinary; Mathematics, Interdisciplinary Applications; Mechanics SC Engineering; Mathematics; Mechanics GA CR6YD UT WOS:000361493600005 ER PT J AU Singbrant, S van Galen, P Lucas, D Challen, G Rossi, DJ Daley, GQ AF Singbrant, Sofie van Galen, Peter Lucas, Daniel Challen, Grant Rossi, Derrick J. Daley, George Q. TI Two new routes to make blood: Hematopoietic specification from pluripotent cell lines versus reprogramming of somatic cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID STEM-CELLS; INDUCTION; PROGENITORS; FIBROBLASTS AB Transplantation of hematopoietic stem cells (HSCs) to treat hematologic disorders is routinely used in the clinic. However, HSC therapy is hindered by the requirements of finding human leukocyte antigen (HLA)-matched donors and attaining sufficient numbers of long-term HSCs in the graft. Therefore, ex vivo expansion of transplantable HSCs remains one of the "holy grails" of hematology. Without the ability to maintain and expand human HSCs in vitro, two complementary approaches involving cellular reprogramming to generate transplantable HSCs have emerged. Reprogrammed HSCs represent a potentially inexhaustible supply of autologous tissue. On March 18th, 2015, Dr. George Q. Daley and Dr. Derrick J. Rossi, two pioneers in the field, presented and discussed their most recent research on these topics in a webinar organized by the International Society for Experimental Hematology (ISEH). Here, we summarize these seminars and discuss the possibilities and challenges in the field of hematopoietic specification. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Singbrant, Sofie] Lund Univ, Lund Stem Cell Ctr, Dept Mol Med, Lund, Sweden. [van Galen, Peter] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [van Galen, Peter] Harvard Univ, Sch Med, Boston, MA USA. [Lucas, Daniel] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA. [Challen, Grant] Washington Univ, Sch Med, Div Dev Regenerat & Stem Cell Biol, St Louis, MO USA. [Challen, Grant] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Rossi, Derrick J.] Harvard Univ, Sch Med, Harvard Stem Cell Inst,Div Hematol & Oncol,Boston, Program Cellular & Mol Med,Dept Stem Cell & Regen, Cambridge, MA 02138 USA. [Daley, George Q.] Harvard Univ, Sch Med, Div Hematol & Oncol,Harvard Stem Cell Inst, Stem Cell Transplantat Program,Boston Childrens H, Cambridge, MA 02138 USA. RP Singbrant, S (reprint author), Lund Univ, Lund Stem Cell Ctr, Dept Mol Med, Lund, Sweden. EM sofie.singbrant@med.lu.se NR 12 TC 4 Z9 4 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 BP 756 EP 759 DI 10.1016/j.exphem.2015.05.007 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XH UT WOS:000361417200002 PM 26143581 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI FANCONI ANEMIA AND BONE MARROW FAILURE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [D'Andrea, Alan D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 1031 BP S40 EP S40 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400031 ER PT J AU Kwan, W Cortes, M Liu, SY Goessling, W North, TE AF Kwan, Wanda Cortes, Mauricio Liu, Sarah Y. Goessling, Wolfram North, Trista E. TI SEROTONIN REGULATES HSC FORMATION VIA GLUCOCORTICOID PRODUCTION FROM THE HYPOTHALAMIC-PITUITARY-INTERRENAL AXIS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Kwan, Wanda; Cortes, Mauricio; Liu, Sarah Y.; North, Trista E.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Goessling, Wolfram] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 2007 BP S46 EP S46 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400042 ER PT J AU Lin, CP AF Lin, Charles P. TI OPTICAL TECHNIQUES FOR CHARACTERIZING THE BONE MARROW MICROENVIRONMENT SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Charles P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 1009 BP S29 EP S29 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400010 ER PT J AU Park, SY Han, EYA Jung, Y Lin, CP Silberstein, LE AF Park, Shin-Young Han, Eun Young Anna Jung, Yookyung Lin, Charles P. Silberstein, Leslie E. TI DECLINED PRESENTATION INFLAMMATORY MODULATION OF HEMATOPOIETIC STROMAL NICHE CELLS BY TNF-alpha LEADS TO RAPID MOBILIZATION OF HEMATOPOIETIC STEM/PROGENITOR CELLS (HSPC) AND NEUTROPHILS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Park, Shin-Young; Han, Eun Young Anna; Silberstein, Leslie E.] Boston Childrens Hosp, Boston, MA USA. [Jung, Yookyung; Lin, Charles P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3059 BP S65 EP S65 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400116 ER PT J AU van Galen, P Ram, O Ryan, RJ Cotton, MJ Donohue, L Drier, Y Sievers, C Gillespie, SM Bernstein, BE AF van Galen, Peter Ram, Oren Ryan, Russel J. Cotton, Matthew J. Donohue, Laura Drier, Yotam Sievers, Cem Gillespie, Shawn M. Bernstein, Bradley E. TI A LOW-INPUT, MULTIPLEXED ASSAY FOR QUANTITATIVE COMPARISON OF CHROMATIN LANDSCAPES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [van Galen, Peter; Ram, Oren; Ryan, Russel J.; Cotton, Matthew J.; Donohue, Laura; Drier, Yotam; Sievers, Cem; Gillespie, Shawn M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [van Galen, Peter; Ram, Oren; Ryan, Russel J.; Cotton, Matthew J.; Donohue, Laura; Drier, Yotam; Sievers, Cem; Gillespie, Shawn M.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [van Galen, Peter; Ram, Oren; Ryan, Russel J.; Cotton, Matthew J.; Donohue, Laura; Drier, Yotam; Sievers, Cem; Gillespie, Shawn M.; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [van Galen, Peter; Ram, Oren; Ryan, Russel J.; Cotton, Matthew J.; Donohue, Laura; Drier, Yotam; Sievers, Cem; Gillespie, Shawn M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. NR 0 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3194 BP S99 EP S99 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400250 ER PT J AU Nicolay, BN Danielian, PS Kottakis, F Lapek, JD Sanidas, I Miles, WO Dehnad, M Tschop, K Gierut, JJ Manning, AL Morris, R Haigis, K Bardeesy, N Lees, JA Haas, W Dyson, NJ AF Nicolay, Brandon N. Danielian, Paul S. Kottakis, Filippos Lapek, John D., Jr. Sanidas, Ioannis Miles, Wayne O. Dehnad, Mantre Tschoep, Katrin Gierut, Jessica J. Manning, Amity L. Morris, Robert Haigis, Kevin Bardeesy, Nabeel Lees, Jacqueline A. Haas, Wilhelm Dyson, Nicholas J. TI Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation SO GENES & DEVELOPMENT LA English DT Article DE pRB; mitochondria; metabolism; proteomics; OXPHOS; C-13-glucose ID RETINOBLASTOMA TUMOR-SUPPRESSOR; CELL LUNG-CANCER; DEFICIENT CELLS; TRANSCRIPTIONAL REPRESSION; MOUSE MODEL; RB MUTANT; PROTEIN; METABOLISM; EXPRESSION; INHIBITION AB The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and proteomic changes in the colon and lungs, where Rb-KO was sufficient or insufficient to induce ectopic proliferation, respectively. As expected, Rb-KO caused similar increases in classic pRb/E2F-regulated transcripts in both tissues, but, unexpectedly, their protein products increased only in the colon, consistent with its increased proliferative index. Thus, these protein changes induced by Rb loss are coupled with proliferation but uncoupled from transcription. The proteomic changes in common between Rb-KO tissues showed a striking decrease in proteins with mitochondrial functions. Accordingly, RB1 inactivation in human cells decreased both mitochondrial mass and oxidative phosphorylation (OXPHOS) function. RBKO cells showed decreased mitochondrial respiratory capacity and the accumulation of hypopolarized mitochondria. Additionally, RB/Rb loss altered mitochondrial pyruvate oxidation from C-13-glucose through the TCA cycle in mouse tissues and cultured cells. Consequently, RBKO cells have an enhanced sensitivity to mitochondria' stress conditions. In summary, proteomic analyses provide a new perspective on Rb/RB1 mutation, highlighting the importance of pRb for mitochondrial function and suggesting vulnerabilities for treatment. C1 [Nicolay, Brandon N.; Kottakis, Filippos; Lapek, John D., Jr.; Sanidas, Ioannis; Miles, Wayne O.; Dehnad, Mantre; Tschoep, Katrin; Gierut, Jessica J.; Manning, Amity L.; Morris, Robert; Haigis, Kevin; Bardeesy, Nabeel; Haas, Wilhelm; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Danielian, Paul S.; Lees, Jacqueline A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Dehnad, Mantre] Univ Med Ctr Utrecht, NL-3584 CX Utrecht, Netherlands. RP Dyson, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU National Institutes of Health [P30-CA14051, 2-P01-CA42063, R01-CA163698, F32-CA165856]; American Cancer Society [PF-13-081-01-TBG] FX We thank Cambridge Isotope Laboratories (Cambridge, MA) for generously supplying the 13C-glucose for all metabolic fate-mapping studies. We thank S. Gygi (Harvard Medical School) for access to the computational platform to perform the proteomics data analysis, T. Jacks (Massachusetts Institute of Technology) for providing the conditional Rb and the RosaCreERT2 alleles, and the Hope Babette Tang Histology Facility at the Koch Institute for technical support. We thank K. Birsoy, J. Coloff, B. Drapkin, I. Harris, L. Gallegos, A. Guarner-Peralta, M. Liesa, S. McBrayer, K. Patra, G. Smolen, and D. Ulanet for discussions and critical reading of the manuscript, and E. Benevolenskaya for sharing data prior to publication. Funding for this work was provided in part by National Institutes of Health P30-CA14051 to the Koch Institute, National Institutes of Health 2-P01-CA42063 to J.A.L., National Institutes of Health R01-CA163698 to N.J.D., National Institutes of Health F32-CA165856 to B.N.N., and American Cancer Society PF-13-081-01-TBG to J.J.G. J.A.L. is a Ludwig scholar, and N.J.D. is a James and Shirley Curvey Massachusetts General Hospital Research Scholar. NR 59 TC 10 Z9 10 U1 0 U2 2 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 SEP 1 PY 2015 VL 29 IS 17 BP 1875 EP 1889 DI 10.1101/gad.264127.115 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA CR5WS UT WOS:000361415700009 PM 26314710 ER PT J AU Cohn, DE Havrilesky, LJ Osann, K Lipscomb, J Hsieh, S Walker, JL Wright, AA Alvarez, RD Karlan, BY Bristow, RE DiSilvestro, PA Wakabayashi, MT Morgan, R Mukamel, DB Wenzel, L AF Cohn, David E. Havrilesky, Laura J. Osann, Kathryn Lipscomb, Joseph Hsieh, Susie Walker, Joan L. Wright, Alexi A. Alvarez, Ronald D. Karlan, Beth Y. Bristow, Robert E. DiSilvestro, Paul A. Wakabayashi, Mark T. Morgan, Robert Mukamel, Dana B. Wenzel, Lari TI Consensus in controversy: The modified Delphi method applied to Gynecologic Oncology practice SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Intraperitoneal (IP); Delphi technique; Opinion ID DECISION-MAKING; OVARIAN-CANCER; BREAST-CANCER AB Objectives. To determine the degree of consensus regarding the probabilities of outcomes associated with IP/IV and IV chemotherapy. Methods. A survey was administered to an expert panel using the Delphi method. Ten ovarian cancer experts were asked to estimate outcomes for patients receiving IP/IV or IV chemotherapy. The clinical estimates were: 1) probability of completing six cycles of chemotherapy, 2) probability of surviving five years, 3) median survival, and 4) probability of ER/hospital visits during treatment Estimates for two patients, one with a low comorbidity index (patient 1) and the other with a moderate index (patient 2), were included. The survey was administered in three rounds, and panelists could revise their subsequent responses based on review of the anonymous opinions of their peers. Results. The ranges were smaller for IV compared with IP/IV therapy. Ranges decreased with each round. Consensus converged around outcomes related to IP/IV chemotherapy for: 1) completion of 6 cycles of therapy (type 1 patient, 62%, type 2 patient, 43%); 2) percentage of patients surviving 5 years (type 1 patient, 66%, type 2 patient, 47%); and 3) median survival (type 1 patient, 83 months, type 2 patient, 58 months). The group required three rounds to achieve consensus on the probabilities of ER/hospital visits (type 1 patient, 24%, type 2 patient, 35%). Conclusions. Initial estimates of survival and adverse events associated with IP/IV chemotherapy differ among experts. The Delphi process works to build consensus and may be a pragmatic tool to inform patients of their expected outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cohn, David E.] Ohio State Univ, Columbus, OH 43210 USA. [Havrilesky, Laura J.] Duke Univ, Sch Med, Durham, NC USA. [Osann, Kathryn; Hsieh, Susie; Bristow, Robert E.; Wenzel, Lari] Univ Calif Irvine, Irvine, CA USA. [Lipscomb, Joseph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Lipscomb, Joseph] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Walker, Joan L.] Univ Oklahoma, Oklahoma City, OK USA. [Wright, Alexi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Alvarez, Ronald D.] Univ Alabama Birmingham, Birmingham, AL USA. [Karlan, Beth Y.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [DiSilvestro, Paul A.] Brown Univ, Women & Infants Hosp, Providence, RI 02912 USA. [Wakabayashi, Mark T.; Morgan, Robert] City Hope Natl Med Ctr, Duarte, CA USA. [Mukamel, Dana B.] Univ Calif Irvine, Sch Med, Orange, CA 92668 USA. RP Cohn, DE (reprint author), 320 West 10th Ave,M210 Starling Loving Hall, Columbus, OH 43210 USA. EM david.cohn@osumc.edu FU NCI NIH HHS [K07 CA166210, P30 CA062203] NR 13 TC 0 Z9 0 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 SEP PY 2015 VL 138 IS 3 BP 712 EP 716 DI 10.1016/j.ygyno.2015.07.014 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CR3YP UT WOS:000361269300037 PM 26177553 ER PT J AU Kishore, SP Kolappa, K Jarvis, JD Park, PH Belt, R Balasubramaniam, T Kiddell-Monroe, R AF Kishore, Sandeep P. Kolappa, Kavitha Jarvis, Jordan D. Park, Paul H. Belt, Rachel Balasubramaniam, Thirukumaran Kiddell-Monroe, Rachel TI Overcoming Obstacles To Enable Access To Medicines For Noncommunicable Diseases In Poor Countries SO HEALTH AFFAIRS LA English DT Article AB The modern access-to-medicines movement grew largely out of the civil-society reaction to the HIV/AIDS pandemic three decades ago. While the movement was successful with regard to HIV/AIDS medications, the increasingly urgent challenge to address access to medicines for noncommunicable diseases has lagged behind-and, in some cases, has been forgotten. In this article we first ask what causes the access gap with respect to lifesaving essential noncommunicable disease medicines and then what can be done to close the gap. Using the example of the push for access to antiretrovirals for HIV/AIDS patients for comparison, we highlight the problems of inadequate global financing and procurement for noncommunicable disease medications, intellectual property barriers and concerns raised by the pharmaceutical industry, and challenges to building stronger civil-society organizations and a patient and humanitarian response from the bottom up to demand treatment. We provide targeted policy recommendations, specific to the public sector, the private sector, and civil society, with the goal of improving access to noncommunicable disease medications globally. C1 [Kishore, Sandeep P.] Yale Univ, New Haven, CT 06520 USA. [Kishore, Sandeep P.; Jarvis, Jordan D.] Young Profess Chron Dis Network, Boston, MA USA. [Kolappa, Kavitha] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Jarvis, Jordan D.] Harvard Global Equ Initiat, Boston, MA USA. [Park, Paul H.] Noncommunicable Dis Partners Hlth Rwanda, Kigali, Rwanda. [Balasubramaniam, Thirukumaran] Knowledge Ecol Int, Zurich, Switzerland. Univ Allied Essential Med, Berkeley, CA USA. RP Kishore, SP (reprint author), Yale Univ, New Haven, CT 06520 USA. EM sunny.kishore@gmail.com FU Open Society Institute FX This work was partially supported by the Open Society Institute. The views of author Rachel Kiddell-Monroe do not represent those of Medecins sans Frontieres. NR 38 TC 3 Z9 3 U1 1 U2 5 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 SEP PY 2015 VL 34 IS 9 BP 1569 EP 1577 DI 10.1377/hlthaff.2015.0375 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CR2FQ UT WOS:000361142100018 PM 26355060 ER PT J AU Manian, FA AF Manian, Farrin A. TI Medical Myths: Unprepared For The End Stages Of End-Stage Kidney Disease SO HEALTH AFFAIRS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. EM fmanian@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2015 VL 34 IS 9 BP 1599 EP 1602 DI 10.1377/HLTHAFF.2014.0992 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CR2FQ UT WOS:000361142100022 PM 26355064 ER PT J AU Kaafarani, HMA Lee, J Masiakos, PT AF Kaafarani, Haytham M. A. Lee, Jarone Masiakos, Peter T. TI Massachusetts Graduated Driver-Licensing Program SO HEALTH AFFAIRS LA English DT Letter C1 [Kaafarani, Haytham M. A.; Lee, Jarone; Masiakos, Peter T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2015 VL 34 IS 9 BP 1609 EP 1609 DI 10.1377/hlthaff.2015.0851 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CR2FQ UT WOS:000361142100028 PM 26355069 ER PT J AU Viana, LM O'Malley, JT Burgess, BJ Jones, DD Oliveira, CACP Santos, F Merchant, SN Liberman, LD Liberman, MC AF Viana, Lucas M. O'Malley, Jennifer T. Burgess, Barbara J. Jones, Dianne D. Oliveira, Carlos A. C. P. Santos, Felipe Merchant, Saumil N. Liberman, Leslie D. Liberman, M. Charles TI Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue SO HEARING RESEARCH LA English DT Article ID INNER HAIR-CELLS; SPIRAL GANGLION NEURONS; GUINEA-PIG COCHLEA; INNERVATION DENSITIES; SYNAPTIC RIBBONS; SERIAL SECTIONS; AFFERENT-FIBERS; USHERS SYNDROME; HENSENS CELLS; CAT COCHLEA AB Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five "normal" ears, aged 54-89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear. (C) 2015 Elsevier B.V. All rights reserved. C1 [Santos, Felipe; Merchant, Saumil N.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Merchant, Saumil N.; Liberman, Leslie D.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [O'Malley, Jennifer T.; Burgess, Barbara J.; Jones, Dianne D.; Santos, Felipe; Merchant, Saumil N.; Liberman, Leslie D.; Liberman, M. Charles] Massachusetts Eye & Ear, Dept Otolaryngol, Boston, MA USA. [Viana, Lucas M.; Oliveira, Carlos A. C. P.] Univ Brasilia, Fac Hlth Sci, Brasilia, DF, Brazil. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu OI Viana, Lucas/0000-0001-5872-4915; Santos, Felipe/0000-0002-3523-665X FU [NIDCD: R01 DC 0188]; [P30 DC 05209]; [U24 DC 011943] FX Research supported by grants from the NIDCD: R01 DC 0188, P30 DC 05209 and U24 DC 011943. NR 52 TC 20 Z9 21 U1 6 U2 15 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 SEP PY 2015 VL 327 BP 78 EP 88 DI 10.1016/j.heares.2015.04.014 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA CR3RX UT WOS:000361251900009 PM 26002688 ER PT J AU Zou, B Mittal, R Grati, M Lu, ZM Shu, YL Tao, Y Feng, Y Xie, DH Kong, WJ Yang, SM Chen, ZY Liu, XZ AF Zou, Bing Mittal, Rahul Grati, M'hamed Lu, Zhongmin Shu, Yilai Tao, Yong Feng, Youg Xie, Dinghua Kong, Weijia Yang, Shiming Chen, Zheng-Yi Liu, Xuezhong TI The application of genome editing in studying hearing loss SO HEARING RESEARCH LA English DT Review ID ZINC-FINGER NUCLEASES; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; CHIMERIC NUCLEASES; DNA RECOGNITION; GENE-REGULATION; CAS9 NUCLEASE; TAL EFFECTORS; III EFFECTORS; STEM-CELLS AB Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss. (C) 2015 Elsevier B.V. All rights reserved. C1 [Zou, Bing; Mittal, Rahul; Grati, M'hamed; Liu, Xuezhong] Univ Miami, Miller Sch Med, Dept Otolaryngol, Miami, FL 33136 USA. [Lu, Zhongmin] Univ Miami, Dept Biol, Miami, FL 33146 USA. [Shu, Yilai; Tao, Yong; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Shu, Yilai; Tao, Yong; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Shu, Yilai] Fudan Univ, Shanghai Med Coll, Eye Ear Nose & Throat Hosp, Dept Otol & Skull Base Surg, Shanghai 200433, Peoples R China. [Tao, Yong; Kong, Weijia] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Otolaryngol, Wuhan 430074, Peoples R China. [Feng, Youg; Liu, Xuezhong] Cent S Univ, Xiangya Hosp, Dept Otolaryngol, Changsha, Hunan, Peoples R China. [Xie, Dinghua; Liu, Xuezhong] Cent S Univ, Xiangya Hosp 2, Dept Otolaryngol Head & Neck Surg, Changsha, Hunan, Peoples R China. [Yang, Shiming; Liu, Xuezhong] Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China. RP Liu, XZ (reprint author), Univ Miami, Miller Sch Med, Dept Otolaryngol, 1601 NW 12th Ave, Miami, FL 33136 USA. EM zheng-yi_chen@meei.harvard.edu; xliu@med.miami.edu FU National Institutes of Health/National Institute on Deafness and Other Communication Disorders [R01 DC05575, R01 DC01246, 2P50DC000422-Sub-Project 6432, R01 DC012115]; NIH [R01 DC006908]; Bertarelli Foundation; David-Shulsky Foundation; Frederick and Ines Yeatts Hair Cell Regeneration grants; University of Miami Provost's Research Award; College of Arts and Sciences Gabelli Fellowship; National Basic Research Program of China (973 program) [2012CB 967904, 2012CB 967900]; National Nature Science Foundation of China [NSFC81300824] FX This work was supported by grants R01 DC05575, R01 DC01246, 2P50DC000422-Sub-Project 6432, and R01 DC012115 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders to Xue Zhong Liu; NIH (R01 DC006908), the Bertarelli Foundation, and the David-Shulsky Foundation, and the Frederick and Ines Yeatts Hair Cell Regeneration grants to Zheng-Yi Chen; the University of Miami Provost's Research Award and College of Arts and Sciences Gabelli Fellowship to Zhongmin Lu; the National Basic Research Program of China (973 program number 2012CB 967904 and 2012CB 967900) to Shiming Yang and Dinghua Xie and the National Nature Science Foundation of China NSFC81300824 to Yilai Shu. We are thankful to Drs. Robert Gerring and Christopher Lisi for the critical reading of the manuscript. NR 82 TC 8 Z9 9 U1 5 U2 20 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 SEP PY 2015 VL 327 BP 102 EP 108 DI 10.1016/j.heares.2015.04.016 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA CR3RX UT WOS:000361251900011 PM 25987504 ER PT J AU Minguez-Alarcon, L Gaskins, AJ Chiu, YH Williams, PL Ehrlich, S Chavarro, JE Petrozza, JC Ford, JB Calafat, AM Hauser, R AF Minguez-Alarcon, Lidia Gaskins, Audrey J. Chiu, Yu-Han Williams, Paige L. Ehrlich, Shelley Chavarro, Jorge E. Petrozza, John C. Ford, Jennifer B. Calafat, Antonia M. Hauser, Russ CA EARTH Study Team TI Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic SO HUMAN REPRODUCTION LA English DT Article DE bisphenol A; IVF outcomes; epidemiology; reproductive health; endocrine disruptor ID ESTROGEN-RECEPTOR-ALPHA; INTRAUTERINE IMPLANTATION; LACTATIONAL EXPOSURE; NEONATAL EXPOSURE; ETHINYL ESTRADIOL; DIETARY EXPOSURE; SEMEN QUALITY; MICE; VARIABILITY; CELLS AB Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. The specific gravity-adjusted geometric mean of BPA was 1.87 A mu g/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (< 37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (a parts per thousand yen37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. C1 [Minguez-Alarcon, Lidia; Ford, Jennifer B.; Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Gaskins, Audrey J.; Chiu, Yu-Han; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gaskins, Audrey J.; Williams, Paige L.; Chavarro, Jorge E.; Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ehrlich, Shelley] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Environm Hlth, Div Biostat & Epidemiol, Cincinnati, OH USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, Jorge E.; Petrozza, John C.; Hauser, Russ] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Petrozza, John C.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Minguez-Alarcon, L (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lminguez@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU NIH from National Institute of Environmental Health Sciences (NIEHS) [R01ES022955, R01ES009718, R01ES000002]; National Institute of Child Health and Human Development (NICHD) [T32DK00770316] FX This work was supported by NIH grants R01ES022955, R01ES009718, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). NR 52 TC 8 Z9 8 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2015 VL 30 IS 9 BP 2120 EP 2128 DI 10.1093/humrep/dev183 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CR3FV UT WOS:000361217300018 PM 26209788 ER PT J AU Chiu, YH Afeiche, MC Gaskins, AJ Williams, PL Petrozza, JC Tanrikut, C Hauser, R Chavarro, JE AF Chiu, Y. H. Afeiche, M. C. Gaskins, A. J. Williams, P. L. Petrozza, J. C. Tanrikut, C. Hauser, R. Chavarro, J. E. TI Reply: Pesticide residues and semen quality SO HUMAN REPRODUCTION LA English DT Letter ID ANTIOXIDANT INTAKE; MEN C1 [Chiu, Y. H.; Gaskins, A. J.; Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Afeiche, M. C.; Hauser, R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, P. L.; Hauser, R.; Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, P. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Petrozza, J. C.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Tanrikut, C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Chavarro, J. E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, J. E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), 665 Huntington Ave, Boston, MA USA. EM jchavarr@hsph.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2015 VL 30 IS 9 BP 2241 EP 2242 DI 10.1093/humrep/dev165 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CR3FV UT WOS:000361217300032 PM 26141708 ER PT J AU Banerji, J AF Banerji, Julian TI Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE asparaginase; diabetes; lipodystrophy; leukemia; lymphoma; immune response; pancreatitis; cystic fibrosis; insulin regulatory substrate-2; Salmonella ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENOME-WIDE ASSOCIATION; TRANSFER-RNA-SYNTHETASE; CORONARY-ARTERY-DISEASE; AMYOTROPHIC-LATERAL-SCLEROSIS; SINGLE NUCLEOTIDE POLYMORPHISM; INSULIN-RECEPTOR SUBSTRATE-2; AMINO-ACID REPEATS; TRANSMEMBRANE CONDUCTANCE REGULATOR; HIGH-DENSITY-LIPOPROTEIN AB The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. C1 Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Boston, MA 02114 USA. RP Banerji, J (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Seventh Floor,185 Cambridge St, Boston, MA 02114 USA. EM jbanerji@molbio.mgh.harvard.edu NR 393 TC 1 Z9 1 U1 2 U2 17 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PD SEP PY 2015 VL 36 IS 3 BP 607 EP 626 DI 10.3892/ijmm.2015.2285 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CR2DH UT WOS:000361134700001 PM 26178806 ER PT J AU Jochum, JR Begley, AE Dew, MA Weiner, DK Karp, JF AF Jochum, John R. Begley, Amy E. Dew, Mary Amanda Weiner, Debra K. Karp, Jordan F. TI Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE fibromyalgia; screening; aging; pain; depression ID COGNITIVE IMPAIRMENT; PAIN; MANAGEMENT; DISORDERS; CRITERIA; CARE; POPULATION; DIAGNOSIS; SEVERITY AB Background: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. Methods: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults >= 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. Results: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95% CI 0.82-0.98], 0.91 [95% CI 0.79-0.97], and 0.94 [95% CI 0.843-0.99] respectively. Conclusions: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation. C1 [Jochum, John R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Begley, Amy E.; Dew, Mary Amanda; Weiner, Debra K.; Karp, Jordan F.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Epidemiol, Sch Med, Pittsburgh, PA 15261 USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Biostat, Sch Med, Pittsburgh, PA 15261 USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Psychol, Sch Med, Pittsburgh, PA 15260 USA. [Dew, Mary Amanda; Weiner, Debra K.; Karp, Jordan F.] Clin & Translat Sci Inst, Pittsburgh, PA USA. [Weiner, Debra K.; Karp, Jordan F.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Karp, JF (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM karpjf@upmc.edu FU M-STREAM program: Medical Student Training and Research Experience in Aging and Mental Health [AG033575, R25 MH071544]; [P30 MH090333]; [UL1 RR024153]; [UL1TR000005] FX Supported in part by AG033575 (Karp) and R25 MH071544 through the M-STREAM program: Medical Student Training and Research Experience in Aging and Mental Health (Jochum). The project also received support by P30 MH090333, UL1 RR024153, and UL1TR000005. The content is solely the responsibility of the authors. NR 36 TC 1 Z9 1 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD SEP PY 2015 VL 27 IS 9 BP 1513 EP 1521 DI 10.1017/S1041610215000666 PG 9 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CR5LS UT WOS:000361384600011 PM 25907254 ER PT J AU Pomerantz, H Hogan, D Eilers, D Swetter, SM Chen, SC Jacob, SE Warshaw, EM Stricklin, G Dellavalle, RP Sidhu-Malik, N Konnikov, N Werth, VP Keri, J Lew, R Weinstock, MA AF Pomerantz, Hyemin Hogan, Daniel Eilers, David Swetter, Susan M. Chen, Suephy C. Jacob, Sharon E. Warshaw, Erin M. Stricklin, George Dellavalle, Robert P. Sidhu-Malik, Navjeet Konnikov, Nellie Werth, Victoria P. Keri, Jonette Lew, Robert Weinstock, Martin A. CA Vet Affairs Keratinocyte Carcinoma TI Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis A Randomized Clinical Trial SO JAMA DERMATOLOGY LA English DT Article ID TRETINOIN CHEMOPREVENTION TRIAL; 0.5-PERCENT FLUOROURACIL; 1-WEEK AB IMPORTANCE Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS Participants applied either topical fluorouracil cream, 5%(n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, rho > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, rho < .001) and for the overall study duration (rho < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (rho < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (rho = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (rho = .05). CONCLUSIONS AND RELEVANCE Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. C1 [Pomerantz, Hyemin; Weinstock, Martin A.] Vet Affairs VA Med Ctr, Ctr Dermatoepidemiol, Providence, RI USA. [Pomerantz, Hyemin; Weinstock, Martin A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Hogan, Daniel] Bay Pines VA Healthcare Syst, Dermatol, Bay Pines, FL USA. [Hogan, Daniel] Nova SE Univ, Coll Osteopath Med, Dept Internal Med Dermatol, Davie, FL USA. [Eilers, David] Edward Hines Jr VA Hosp, Dermatol, Hines, IL USA. [Swetter, Susan M.] VA Palo Alto Hlth Care Syst, Dermatol, Palo Alto, CA USA. [Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Palo Alto, CA 94304 USA. [Chen, Suephy C.] Atlanta VA Med Ctr, Dermatol, Atlanta, GA USA. [Chen, Suephy C.] Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. [Jacob, Sharon E.] VA San Diego Healthcare Syst, Dermatol, San Diego, CA USA. [Warshaw, Erin M.] Minneapolis VA Hlth Care Syst, Dermatol, Minneapolis, MN USA. [Warshaw, Erin M.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Stricklin, George] Tennessee Valley Healthcare Syst, Dermatol, Nashville, TN USA. [Stricklin, George] Vanderbilt Univ, Div Dermatol, Nashville, TN 37235 USA. [Dellavalle, Robert P.] VA Med Ctr, Dermatol, Denver, CO USA. [Sidhu-Malik, Navjeet] Durham VA Med Ctr, Dermatol, Durham, NC USA. [Sidhu-Malik, Navjeet] Duke Univ, Dept Dermatol, Durham, NC USA. [Konnikov, Nellie] Boston VA Med Ctr, Dermatol, Boston, MA USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Dermatol, Philadelphia, PA USA. [Keri, Jonette] Miami VA Hosp, Dermatol, Miami, FL USA. [Keri, Jonette] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Miami, FL 33136 USA. [Lew, Robert] VA Cooperat Studies Coordinating Ctr, Boston, MA USA. [Weinstock, Martin A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. RP Pomerantz, H (reprint author), Providence VA Med Ctr, Ctr Dermatoepidemiol, 830 Chalkstone Ave, Providence, RI 02908 USA. EM hyemin.pomerantz@gmail.com OI Swan, James/0000-0002-9438-6391 FU Office of Research and Development Cooperative Studies Program, US Department of Veterans Affairs FX The study was supported by the Office of Research and Development Cooperative Studies Program, US Department of Veterans Affairs. NR 18 TC 9 Z9 9 U1 0 U2 1 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 SEP PY 2015 VL 151 IS 9 BP 952 EP 960 DI 10.1001/jamadermatol.2015.0502 PG 9 WC Dermatology SC Dermatology GA CR5HG UT WOS:000361371100007 PM 25950503 ER PT J AU Asgari, MM Moffet, HH Ray, GT Quesenberry, CP AF Asgari, Maryam M. Moffet, Howard H. Ray, G. Thomas Quesenberry, Charles P. TI Trends in Basal Cell Carcinoma Incidence and Identification of High-Risk Subgroups, 1998-2012 SO JAMA DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; UNITED-STATES; NEW-MEXICO; MELANOMA; DISPARITIES; POPULATION; BEHAVIORS AB IMPORTANCE The incidence of basal cell carcinomas (BCCs) is increasing globally, but incidence rates in the United States are difficult to quantify because BCCs are not reportable tumors. OBJECTIVE To estimate annual BCC incidence rates by age, sex, and race/ethnicity to identify demographically distinct high-risk subgroups and to assess changes in rates over time. DESIGN, SETTING, AND PARTICIPANTS In this retrospective cohort study (January 1, 1998, through December 31, 2012), we studied 147 093 patients with BCC from Kaiser Permanente Northern California, a large, integrated health care provision system, identified using a previously validated BCC registry. MAIN OUTCOMES AND MEASURES We estimated annual BCC incidence rates by age, sex, and race/ethnicity and assessed changes in rates over time. The BCC incidence rates were standardized to the age, sex, and race/ethnicity distribution of the 2010 US Census population. RESULTS In models adjusting for age, sex, and race, male patients had higher rates than female patients (incidence rate ratio [IRR], 1.65; 95% CI, 1.60-1.70). Persons 65 through 79 years of age and those 80 years and older had higher rates than persons 40 through 64 years of age (IRR, 2.96; 95% CI, 2.86-3.06; and IRR, 5.14; 95% CI, 4.94-5.35, respectively). Whites had higher rates than multiracial persons (IRR, 1.96; 95% CI, 1.80-2.13), Hispanics (IRR, 8.56; 95% CI, 7.79-9.41), Asians (IRR, 33.13; 95% CI, 27.84-39.42), and blacks (IRR, 72.98; 95% CI, 49.21-108.22). CONCLUSIONS AND RELEVANCE We estimate that BCCs occur in approximately 2 million Americans annually. Our findings provide an updated estimate of the incidence of BCCs, highlight the changing epidemiologic findings, and better identify demographically distinct high-risk subgroups. C1 [Asgari, Maryam M.; Moffet, Howard H.; Ray, G. Thomas; Quesenberry, Charles P.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Asgari, Maryam M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Asgari, Maryam M.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Asgari, Maryam M.] Harvard Univ, Sch Med, Boston, MA USA. RP Asgari, MM (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Ste 270, Boston, MA 02114 USA. RI Asgari, Maryam/O-4947-2016 FU National Cancer Institute at the National Institutes of Health [U19 CA79689, R01 CA166672] FX This work was supported by grants U19 CA79689 and R01 CA166672 from the National Cancer Institute at the National Institutes of Health (Dr Asgari). NR 22 TC 9 Z9 9 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 SEP PY 2015 VL 151 IS 9 BP 976 EP 981 DI 10.1001/jamadermatol.2015.1188 PG 6 WC Dermatology SC Dermatology GA CR5HG UT WOS:000361371100012 PM 26039887 ER PT J AU Shen, LQ Kloek, CE Turalba, AV AF Shen, Lucy Q. Kloek, Carolyn E. Turalba, Angela V. TI Assessing the Effect of a Glaucoma Surgical Curriculum in Resident Physicians SO JAMA OPHTHALMOLOGY LA English DT Article ID SURGERY AB IMPORTANCE Subspecialty surgical training is an important part of resident education. We changed the glaucoma rotation in which postgraduate year 4 residents worked with multiple attending physicians with varying teaching styles to a structured surgical curriculum led by 2 dedicated preceptors, and we evaluated the effect on residents' surgical performance prospectively. OBSERVATIONS A curriculum consisting of preoperative training, intraoperative teaching, postoperative feedback, and repetition was implemented for postgraduate year 4 residents between July 2, 2012, and June 30, 2014. In a class of 8 residents per year, the mean (SD) glaucoma surgical volume increased from 8.9 (0.8) cases in the prior year to 13.6 (2.5) in 2013 (mean difference, 4.8 cases; 95% CI, 2.4-7.1; P = .001) and 14.8 (4.2) in 2014 (mean difference, 5.9 cases; 95% CI, 2.1-9.6; P = .007). A self-assessment survey showed improvement in suturing (scores for each section range from 1 [worst] to 5 [best]; mean rating, 3.9 in the prior year vs 4.4 in 2013 [P = .04] and 4.5 in 2014 [P = .02]). A validated survey assessing overall surgical competency revealed improvement in handling adverse events (mean rating, 4.1 in the prior year vs 5.0 for both 2013 and 2014; both P < .001). CONCLUSIONS AND RELEVANCE Despite the small sample size and nonrandomized study design, these data suggest that a structured surgical curriculum has advantages in teaching subspecialty surgery and might be considered by other ophthalmology training programs. C1 [Shen, Lucy Q.; Kloek, Carolyn E.; Turalba, Angela V.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Shen, LQ (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM lucy_shen@meei.harvard.edu FU Harvard Glaucoma Center of Excellence; Glaucoma Service; Residency Committee at Massachusetts Eye and Ear Infirmary FX This study was supported by the Harvard Glaucoma Center of Excellence, the Glaucoma Service, and the Residency Committee at Massachusetts Eye and Ear Infirmary. NR 7 TC 3 Z9 3 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD SEP PY 2015 VL 133 IS 9 BP 1077 EP 1080 DI 10.1001/jamaophthalmol.2015.1846 PG 4 WC Ophthalmology SC Ophthalmology GA CR5JJ UT WOS:000361377100019 PM 26086738 ER PT J AU Leskov, I Rasool, N Cestari, DM AF Leskov, Ilya Rasool, Nailyn Cestari, Dean M. TI Hypometabolic Lateral Recti Due to Bilateral Cranial Nerve VI Palsy SO JAMA OPHTHALMOLOGY LA English DT Editorial Material C1 [Leskov, Ilya; Rasool, Nailyn; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Leskov, I (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ilya_leskov@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD SEP PY 2015 VL 133 IS 9 AR e151490 DI 10.1001/jamaophthalmol.2015.1490 PG 1 WC Ophthalmology SC Ophthalmology GA CR5JJ UT WOS:000361377100004 PM 26356005 ER PT J AU Sonnenberg, A Genta, RM AF Sonnenberg, Amnon Genta, Robert M. TI Epithelial Dysplasia and Cancer in IBD Strictures SO JOURNAL OF CROHNS & COLITIS LA English DT Article DE Colon cancer; dysplasia; epidemiology; histopathology of inflammatory bowel disease; intestinal strictures ID INFLAMMATORY-BOWEL-DISEASE; MALIGNANT COLORECTAL STRICTURES; HELICOBACTER-PYLORI; CROHNS-DISEASE; ESOPHAGEAL EOSINOPHILIA; VIENNA CLASSIFICATION; PATHOLOGY DATABASE; ULCERATIVE-COLITIS; RISK-FACTOR; NEOPLASIA AB Colonic strictures and epithelial dysplasia are both known risk factors for the occurrence of colorectal cancer in inflammatory bowel disease (IBD) patients. The aim of the present work was to study colonic stricture as a risk factor for the occurrence of epithelial dysplasia and colonic adenocarcinoma. In a case-control study among 53568 IBD patients undergoing colonoscopy, we compared the prevalence of strictures among cases with dysplasia or adenocarcinoma and controls without such complications by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). Multivariate logistic regressions were used to assess the joint influence of multiple predictor variables (age, sex, IBD type and stricture) on the occurrence of colonic dysplasia or adenocarcinoma. The prevalence of strictures was 1.06% in ulcerative colitis (UC) and 8.71% in Crohn's disease (CD, OR 11.09, 95% CI 9.72-12.70). The prevalence of dysplasia was 3.22% in UC and 2.08% in CD (OR 0.75, 95% CI 0.65-0.86). The prevalence of dysplasia was similar in IBD patients with and without stricture: 2.82 and 2.41%, respectively. The prevalence of cancer was higher in IBD patients with than without stricture: 0.78 and 0.11%, respectively (OR 6.87, 95% CI 3.30-12.89). In the multivariate analysis, old age, male sex and UC, but not stricture, were all significantly and independently associated with dysplasia. Old age, dysplasia and stricture were significantly and independently associated with cancer. The prevalence of epithelial dysplasia is not generally increased in IBD patients with strictures. C1 [Sonnenberg, Amnon; Genta, Robert M.] Miraca Life Sci, Irving, TX USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 22 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD SEP 1 PY 2015 VL 9 IS 9 BP 769 EP 775 DI 10.1093/ecco-jcc/jjv108 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CR6PY UT WOS:000361470800011 PM 26079724 ER PT J AU Kachooei, AR Rivlin, M Wu, F Faghfouri, A Eberlin, KR Ring, D AF Kachooei, Amir Reza Rivlin, Michael Wu, Fei Faghfouri, Aram Eberlin, Kyle R. Ring, David TI Intraoperative Physical Examination for Diagnosis of Interosseous Ligament Rupture - Cadaveric Study SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Interosseous ligament; interosseous membrane; joystick test; pull-push test; reliability ID FOREARM INSTABILITY; MEMBRANE; RADIUS AB Purpose To study the intraobserver and interobserver reliability of the diagnosis of interosseous ligament (TOL) rupture in a cadaver model. Methods On 12 fresh frozen cadavers, radial heads were cut using an identical incision and osteotomy. After randomization, the soft tissues of the limbs were divided into 4 groups: both IOL and triangular fibrocartilage (TFCC) intact; IOL disruption but TFCC intact; both IOL and TFCC divided; and IOL intact but TFCC divided. All incisions had identical suturing. After standard instruction and demonstration of radius pull-push and radius lateral pull tests, 10 physician evaluators with different levels of experience examined the cadaver limbs in a standardized way (elbow at 90 with the forearm held in both supination and pronation) and were asked to classify them into one of the 4 groups. Next, the same examiners were asked to reexamine the limbs after randomly changing the order of examination. Results The interobserver reliability of agreement for the diagnosis of IOL injury (groups 2 and 3) was fair in both rounds of examination and the intraobserver reliability was moderate. The intra- and interobserver reliabilities of agreement for the 4 groups of injuries among the examiners were fair in both rounds of examination. The sensitivity, specificity, accuracy, positive, and negative predictive Values were all around 70%. The likelihood of a positive test corresponding with the presence of IOL rupture (positive likelihood ratio) was 2.2. The likelihood of a negative test correctly diagnosing an intact IOL was 0.40. Conclusions In cadavers, intraoperative tests had fair reliability and 70% accuracy for the diagnosis of IOL rupture using the push-pull and lateral pull maneuvers. The level of experience did not have any effect on the correct diagnosis of intact versus disrupted IOL. Clinical relevance Although not common, some failure of surgeries for traumatic elbow fracture-dislocations is because of failure in timely diagnosis of IOL disruption. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Kachooei, Amir Reza; Faghfouri, Aram; Eberlin, Kyle R.; Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Kachooei, Amir Reza] Mashhad Univ Med Sci, Orthoped Res Ctr, Mashhad, Iran. [Rivlin, Michael] Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. [Wu, Fei] Wuhan Univ, Renmin Hosp, Dept Orthoped Surg, Wuhan 430072, Peoples R China. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 NR 12 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2015 VL 40 IS 9 BP 1785 EP 1790 DI 10.1016/j.jhsa.2015.06.004 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CR3ZG UT WOS:000361271000008 PM 26231483 ER PT J AU Menendez, ME Chen, NC Mudgal, CS Jupiter, JB Ring, D AF Menendez, Mariano E. Chen, Neal C. Mudgal, Chaitanya S. Jupiter, Jesse B. Ring, David TI Physician Empathy as a Driver of Hand Surgery Patient Satisfaction SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Empathy; communication; patient satisfaction; health literacy; reimbursement ID PRIMARY-CARE PHYSICIANS; SHARED DECISION-MAKING; CARPAL-TUNNEL RELEASE; HEALTH-CARE; EMERGENCY-DEPARTMENT; CONSUMER ASSESSMENT; CENTERED CARE; HOSPITAL-CARE; ITEM BANK; LITERACY AB Purpose To examine the relationship between patient-rated physician empathy and patient satisfaction after a single new hand surgery office visit. Methods Directly after the office visit, 112 consecutive new patients rated their overall satisfaction with the provider and completed the Consultation and Relational Empathy Measure, the Newest Vital Sign health literacy test, a sociodemographic survey, and 3 Patient-Reported Outcomes Measurement Information System-based questionnaires: Pain Interference, Upper-Extremity Function, and Depression. We also measured the waiting time in the office to see the physician, the duration of the visit, and the time from booking until appointment. Multivariable logistic and linear regression models were used to identify factors independently associated with patient satisfaction. Results Patient-rated physician empathy correlated strongly with the degree of overall satisfaction with the provider. After controlling for confounding effects, greater empathy was independently associated with patient satisfaction, and it alone accounted for 65% of the variation in satisfaction scores. Older patient age was also associated with satisfaction. There were no differences between satisfied and dissatisfied patients with regard to waiting time in the office, duration of the appointment, time from booking until appointment, and health literacy. Conclusions Physician empathy was the strongest driver of patient satisfaction in the hand surgery office setting. As patient satisfaction plays a growing role in reimbursement, targeted educational programs to enhance empathic communication skills in hand surgeons merit consideration. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Menendez, Mariano E.; Chen, Neal C.; Mudgal, Chaitanya S.; Jupiter, Jesse B.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 48 TC 7 Z9 7 U1 4 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2015 VL 40 IS 9 BP 1860 EP 1865 DI 10.1016/j.jhsa.2015.06.105 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CR3ZG UT WOS:000361271000019 PM 26231482 ER PT J AU Marjoua, Y Eberlin, KR Mudgal, CS AF Marjoua, Youssra Eberlin, Kyle R. Mudgal, Chaitanya S. TI Multiple Displaced Metacarpal Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID FIXATION; HAND C1 [Marjoua, Youssra; Eberlin, Kyle R.; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 13 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2015 VL 40 IS 9 BP 1869 EP 1870 DI 10.1016/j.jhsa.2015.04.032 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CR3ZG UT WOS:000361271000023 PM 26096220 ER PT J AU Ivers, LC Charles, RC Hilaire, IJ Mayo-Smith, LM Teng, JE Jerome, JG Rychert, J LaRocque, RC Xu, P Kovac, P Ryan, ET Qadri, F Almazor, CP Franke, MF Harris, JB AF Ivers, Louise C. Charles, Richelle C. Hilaire, Isabelle J. Mayo-Smith, Leslie M. Teng, Jessica E. Jerome, J. Gregory Rychert, Jenna LaRocque, Regina C. Xu, Peng Kovac, Pavol Ryan, Edward T. Qadri, Firdausi Almazor, Charles P. Franke, Molly F. Harris, Jason B. TI Immunogenicity of the Bivalent Oral Cholera Vaccine Shanchol in Haitian Adults With HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Cholera vaccine; HIV; Shanchol (BivWC); immunogenicity ID PNEUMOCOCCAL DISEASE; MOZAMBIQUE; CHILDREN; O1 AB We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4(+) T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera. C1 [Ivers, Louise C.; Teng, Jessica E.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Ivers, Louise C.; Franke, Molly F.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Charles, Richelle C.; LaRocque, Regina C.; Ryan, Edward T.; Harris, Jason B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ivers, Louise C.; Hilaire, Isabelle J.; Teng, Jessica E.; Jerome, J. Gregory; Almazor, Charles P.; Franke, Molly F.] Massachusetts Gen Hosp, Partners Hlth, Boston, MA 02114 USA. [Charles, Richelle C.; Mayo-Smith, Leslie M.; Rychert, Jenna; LaRocque, Regina C.; Ryan, Edward T.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Xu, Peng; Kovac, Pavol] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM jbharris@mgh.harvard.edu RI Xu, Peng/K-7036-2012 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [R01 AI099243, R01 AI106878, U01 AI AI058935, R01 AI10355]; NIH [K08 AI089721]; Massachusetts General Hospital FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; R01 AI099243 to J. B. H. and L. C. I.; R01 AI106878 to E. T. R., P. K., and F. Q.; U01 AI AI058935 to E. T. R. and F. Q.; and R01 AI10355); an NIH Career Development Award (K08 AI089721 to R. C. C.); and Massachusetts General Hospital (Massachusetts General Hospital physician scientist development award to R. C. C.). NR 12 TC 1 Z9 1 U1 1 U2 3 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 SEP 1 PY 2015 VL 212 IS 5 BP 779 EP 783 DI 10.1093/infdis/jiv108 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800014 PM 25722294 ER PT J AU Scherrer-Crosbie, M AF Scherrer-Crosbie, Marielle TI Losartan: A new treatment for cardiac cachexia? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID GROWTH-FACTOR-I; ANGIOTENSIN-II; CANCER CACHEXIA; PROSTATE-CANCER; HEART-FAILURE; PATHWAY; RISK C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Blake 254,55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com NR 21 TC 0 Z9 0 U1 2 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2015 VL 86 BP 12 EP 13 DI 10.1016/j.yjmcc.2015.06.018 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CR5YA UT WOS:000361419100003 PM 26141529 ER PT J AU Billmire, DF Rescorla, FJ Ross, JH Schlatter, MG Dicken, BJ Krailo, MD Rodriguez-Galindo, C Olson, TA Cullen, JW Frazier, AL AF Billmire, Deborah F. Rescorla, Frederick J. Ross, Jonathan H. Schlatter, Marc G. Dicken, Bryan J. Krailo, Mark D. Rodriguez-Galindo, Carlos Olson, Thomas A. Cullen, John W. Frazier, A. Lindsay TI Impact of central surgical reviewin a study of malignant germcell tumors SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Malignant germ cell tumors; Surgical quality; Surgical clinical trials ID NATIONAL WILMS-TUMOR; PEDIATRIC-ONCOLOGY-GROUP; CELL TUMORS; OVARY AB Background: Verification of surgical staging has received little attention in clinical oncology trials. Central surgical review was undertaken during a study of malignant pediatric germ cell tumors. Methods: Children's Oncology Group study AGCT0132 included central surgical review during the study. Completeness of submitted data and confirmation of assigned stage were assessed. Review responses were: assigned status confirmed, assignment withheld pending review of additional information requested, or institutional assignment of stage disputed with explanation given. Changes in stage assignment were at the discretion of the enrolling institution. Results: A total of 206 patients underwent central review. Failure to submit required data elements or need for clarification was noted in 40%. Disagreement with stage assignment occurred in 10% with 17/21 discordant patients reassigned to stage recommended by central review. Four ovarian tumor patients not meeting review criteria for Stage I remained in that stratum by institutional decision. Two-year event free survival in Stage I ovarian patients was 25% for discordant patients compared to 57% for those meeting Stage I criteria by central review. Conclusions: Central review of stage assignment improved complete data collection and assignment of correct tumor stage at study entry, and allowed for prompt initiation of chemotherapy in patients determined not to have Stage I disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Billmire, Deborah F.; Rescorla, Frederick J.] Indiana Univ Sch Med, Dept Surg, Riley Hosp Children, Indianapolis, IN 46202 USA. [Ross, Jonathan H.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Div Urol, Cleveland, OH 44106 USA. [Schlatter, Marc G.] Spectrum Hlth, Helen DeVos Childrens Hosp, Grand Rapids, MI USA. [Dicken, Bryan J.] Univ Alberta, Dept Surg, Stollery Childrens Hosp, Edmunton, AB, Canada. [Krailo, Mark D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Olson, Thomas A.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA. [Cullen, John W.] Rocky Mt Hosp Children, Presbyterian St Lukes Med, Denver, CO USA. RP Billmire, DF (reprint author), Indiana Univ, Div Pediat Surg, Dept Surg, Riley Hosp Children, 705 Riley Hosp Dr,Suite 2500, Indianapolis, IN 46202 USA. EM dbillmir@iupui.edu FU NCI NIH HHS [U10 CA098413, U10 CA098543, U10 CA180886, U10 CA180899] NR 12 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2015 VL 50 IS 9 BP 1502 EP 1505 DI 10.1016/j.jpedsurg.2014.12.008 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA CR7AK UT WOS:000361499500012 PM 25783295 ER PT J AU Meng, F Morioka, C AF Meng, Frank Morioka, Craig TI Automating the generation of lexical patterns for processing free text in clinical documents SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE information extraction; natural language processing; text mining ID INFORMATION EXTRACTION; SYSTEM; EXPRESSIONS; NARRATIVES; CRITERIA; RULES AB Objective Many tasks in natural language processing utilize lexical pattern-matching techniques, including information extraction (IE), negation identification, and syntactic parsing. However, it is generally difficult to derive patterns that achieve acceptable levels of recall while also remaining highly precise. Materials and Methods We present a multiple sequence alignment (MSA)-based technique that automatically generates patterns, thereby leveraging language usage to determine the context of words that influence a given target. MSAs capture the commonalities among word sequences and are able to reveal areas of linguistic stability and variation. In this way, MSAs provide a systemic approach to generating lexical patterns that are generalizable, which will both increase recall levels and maintain high levels of precision. Results The MSA-generated patterns exhibited consistent F1-, F.5-, and F2- scores compared to two baseline techniques for IE across four different tasks. Both baseline techniques performed well for some tasks and less well for others, but MSA was found to consistently perform at a high level for all four tasks. Discussion The performance of MSA on the four extraction tasks indicates the method's versatility. The results show that the MSA-based patterns are able to handle the extraction of individual data elements as well as relations between two concepts without the need for large amounts of manual intervention. Conclusion We presented an MSA-based framework for generating lexical patterns that showed consistently high levels of both performance and recall over four different extraction tasks when compared to baseline methods. C1 [Meng, Frank; Morioka, Craig] Univ Calif Los Angeles, Dept Radiol Sci, Med Imaging Informat Grp, Los Angeles, CA 90024 USA. [Meng, Frank] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. [Morioka, Craig] VA Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA USA. RP Meng, F (reprint author), 924 Westwood Blvd,Ste 420, Los Angeles, CA 90024 USA. EM fmeng@mii.ucla.edu FU National Institutes of Health (National Cancer Institute) [R01 CA1575533]; National Institutes of Health (National Institute of Neurological Disorders and Stroke) [R01 NS076534]; National Institutes of Health (National Library of Medicine) [R01 LM011333] FX This work was supported by the following National Institutes of Health grants: R01 CA1575533 (National Cancer Institute), R01 NS076534 (National Institute of Neurological Disorders and Stroke), and R01 LM011333 (National Library of Medicine). NR 38 TC 0 Z9 0 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2015 VL 22 IS 5 BP 980 EP 986 DI 10.1093/jamia/ocv012 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CR4DS UT WOS:000361282600007 PM 25977405 ER PT J AU Yu, S Liao, KP Shaw, SY Gainer, VS Churchill, SE Szolovits, P Murphy, SN Kohane, IS Cai, TX AF Yu, Sheng Liao, Katherine P. Shaw, Stanley Y. Gainer, Vivian S. Churchill, Susanne E. Szolovits, Peter Murphy, Shawn N. Kohane, Isaac S. Cai, Tianxi TI Toward high-throughput phenotyping: unbiased automated feature extraction and selection from knowledge sources SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; RHEUMATOID-ARTHRITIS; HEALTH RECORDS; EMERGE NETWORK; PHENOME-WIDE; RETROSPECTIVE ANALYSIS; ELASTIC-NET; RISK; DISEASE; MORTALITY AB Objective Analysis of narrative (text) data from electronic health records (EHRs) can improve population-scale phenotyping for clinical and genetic research. Currently, selection of text features for phenotyping algorithms is slow and laborious, requiring extensive and iterative involvement by domain experts. This paper introduces a method to develop phenotyping algorithms in an unbiased manner by automatically extracting and selecting informative features, which can be comparable to expert-curated ones in classification accuracy. Materials and methods Comprehensive medical concepts were collected from publicly available knowledge sources in an automated, unbiased fashion. Natural language processing (NLP) revealed the occurrence patterns of these concepts in EHR narrative notes, which enabled selection of informative features for phenotype classification. When combined with additional codified features, a penalized logistic regression model was trained to classify the target phenotype. Results The authors applied our method to develop algorithms to identify patients with rheumatoid arthritis and coronary artery disease cases among those with rheumatoid arthritis from a large multi-institutional EHR. The area under the receiver operating characteristic curves (AUC) for classifying RA and CAD using models trained with automated features were 0.951 and 0.929, respectively, compared to the AUCs of 0.938 and 0.929 by models trained with expert-curated features. Discussion Models trained with NLP text features selected through an unbiased, automated procedure achieved comparable or slightly higher accuracy than those trained with expert-curated features. The majority of the selected model features were interpretable. Conclusion The proposed automated feature extraction method, generating highly accurate phenotyping algorithms with improved efficiency, is a significant step toward high-throughput phenotyping. C1 [Yu, Sheng] Partners Hlth Care Personalized Med, Boston, MA 02139 USA. [Yu, Sheng; Liao, Katherine P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yu, Sheng; Liao, Katherine P.; Kohane, Isaac S.] Harvard Univ, Sch Med, Boston, MA USA. [Shaw, Stanley Y.; Murphy, Shawn N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gainer, Vivian S.; Churchill, Susanne E.; Murphy, Shawn N.] Partners Hlth Care, Res Comp, Charlestown, MA USA. [Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Kohane, Isaac S.] Boston Childrens Hosp, Boston, MA USA. [Cai, Tianxi] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. RP Yu, S (reprint author), Partners Hlth Care Personalized Med, Boston, MA 02139 USA. EM syu7@partners.org OI Szolovits, Peter/0000-0001-8411-6403; Yu, Sheng/0000-0002-6347-0507 FU NIH [U54-H6007963, U54-LM008748, R01-GM079330, AR-060257]; Harold and Duval Bowen Fund; Partners HealthCare FX This work was supported by NIH grants U54-H6007963, U54-LM008748, R01-GM079330, and AR-060257, as well as Harold and Duval Bowen Fund and internal funds from Partners HealthCare. NR 57 TC 9 Z9 9 U1 3 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2015 VL 22 IS 5 BP 993 EP 1000 DI 10.1093/jamia/ocv034 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CR4DS UT WOS:000361282600009 PM 25929596 ER PT J AU Luo, Y Xin, Y Hochberg, E Joshi, R Uzuner, O Szolovits, P AF Luo, Yuan Xin, Yu Hochberg, Ephraim Joshi, Rohit Uzuner, Ozlem Szolovits, Peter TI Subgraph augmented non-negative tensor factorization (SANTF) for modeling clinical narrative text SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE non-negative tensor factorization; unsupervised learning; subgraph mining; natural language processing ID 3-MODE FACTOR-ANALYSIS; MATRIX FACTORIZATION; PATTERN DISCOVERY; MICROARRAY DATA; MUTATIONS; CANCER AB Objective Extracting medical knowledge from electronic medical records requires automated approaches to combat scalability limitations and selection biases. However, existing machine learning approaches are often regarded by clinicians as black boxes. Moreover, training data for these automated approaches at often sparsely annotated at best. The authors target unsupervised learning for modeling clinical narrative text, aiming at improving both accuracy and interpretability. Methods The authors introduce a novel framework named subgraph augmented non-negative tensor factorization (SANTF). In addition to relying on atomic features (e.g., words in clinical narrative text), SANTF automatically mines higher-order features (e.g., relations of lymphoid cells expressing antigens) from clinical narrative text by converting sentences into a graph representation and identifying important subgraphs. The authors compose a tensor using patients, higher-order features, and atomic features as its respective modes. We then apply non-negative tensor factorization to cluster patients, and simultaneously identify latent groups of higher-order features that link to patient clusters, as in clinical guidelines where a panel of immunophenotypic features and laboratory results are used to specify diagnostic criteria. Results and Conclusion SANTF demonstrated over 10% improvement in averaged F-measure on patient clustering compared to widely used non-negative matrix factorization (NMF) and k-means clustering methods. Multiple baselines were established by modeling patient data using patient-by-features matrices with different feature configurations and then performing NMF or k-means to cluster patients. Feature analysis identified latent groups of higher-order features that lead to medical insights. We also found that the latent groups of atomic features help to better correlate the latent groups of higher-order features. C1 [Luo, Yuan; Xin, Yu; Joshi, Rohit; Szolovits, Peter] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Hochberg, Ephraim] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Lymphoma, Cambridge, MA 02138 USA. [Hochberg, Ephraim] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Uzuner, Ozlem] SUNY Albany, Dept Informat Studies, Albany, NY 12222 USA. RP Luo, Y (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. EM yuanluo@mit.edu OI Szolovits, Peter/0000-0001-8411-6403 FU National Library of Medicine [U54LM008748]; Scullen Center for Cancer Data Analysis FX The work described was supported in part by Grant Number U54LM008748 from the National Library of Medicine and by the Scullen Center for Cancer Data Analysis. NR 50 TC 4 Z9 4 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2015 VL 22 IS 5 BP 1009 EP 1019 DI 10.1093/jamia/ocv016 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CR4DS UT WOS:000361282600011 PM 25862765 ER PT J AU Manchikanti, L Benyamin, R Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin Kaye, Alan David Hirsch, Joshua A. TI RE: Efficacy of Cervical Intelaminar Epidural Steroid Injections SO KOREAN JOURNAL OF RADIOLOGY LA English DT Letter DE Cervical; Epidural; Radiculopathy C1 [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Benyamin, Ramsin] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin] Univ Illinois, Dept Surg, Coll Med, Urbana, IL 61701 USA. [Kaye, Alan David] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA 70112 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, NeuroIntervent Spine Serv,Intervent Care, Dept Radiol,Med Sch, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. EM drlm@thepainmd.com NR 4 TC 0 Z9 0 U1 0 U2 2 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD SEP-OCT PY 2015 VL 16 IS 5 BP 1171 EP 1171 DI 10.3348/kjr.2015.16.5.1171 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR7BX UT WOS:000361504000025 PM 26357508 ER PT J AU Jeong, D Kim, J Nam, J Sun, H Lee, YH Lee, TJ Aguiar, RCT Kim, SW AF Jeong, D. Kim, J. Nam, J. Sun, H. Lee, Y-H Lee, T-J Aguiar, R. C. T. Kim, S-W TI MicroRNA-124 links p53 to the NF-kappa B pathway in B-cell lymphomas SO LEUKEMIA LA English DT Article ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; PHOSPHODIESTERASE 4B; CANCER; MYC; EXPRESSION; NETWORK; PATHOGENESIS; VINCRISTINE; DOXORUBICIN; PREDNISONE AB The contribution of microRNAs to lymphoma biology is not fully understood. In particular, it remains untested whether microRNA dysregulation could contribute to the emergence of the aggressive subset of B-cell lymphomas that coexpress MYC and BCL2. Here, we identify microRNA-124 (miR-124) as a negative regulator of MYC and BCL2 expression in B-cell lymphomas. Concordantly, stable or transient ectopic expression of miR-124 suppressed cell proliferation and survival, whereas genetic inhibition of this miRNA enhanced the fitness of these tumors. Mechanistically, the activities of miR-124 towards MYC and BCL2 intersect with both oncogenic and tumor-suppressive pathways. In respect to the former, we show that miR-124 directly targets nuclear factor-kappa B (NF-kappa B) p65, and using genetic approaches, we demonstrate that this interaction accounts for the miR-124-mediated suppression of MYC and BCL2. We also characterized miR-124 promoter region and identified a functional p53 binding site. In agreement with this finding, endogenous or ectopic expression of wild-type, but not mutant, p53 increased miR-124 levels and suppressed p65, MYC and BCL2. Our data unveil an miRNA-dependent regulatory circuitry that links p53 to the NF-kappa B pathway, which when disrupted in B-cell lymphoma may be associated with aberrant coexpression of MYC and BCL2 and poor prognosis. C1 [Jeong, D.; Kim, J.; Nam, J.; Kim, S-W] Pusan Natl Univ, Dept Biol Sci, Pusan 609735, South Korea. [Sun, H.] Pusan Natl Univ, Dept Stat, Pusan 609735, South Korea. [Lee, Y-H] Yonsei Univ, Dept Radiat Oncol, Seoul 120749, South Korea. [Lee, T-J] Yeungnam Univ, Dept Anat, Daegu, South Korea. [Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, San Antonio, TX 78229 USA. [Aguiar, R. C. T.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kim, SW (reprint author), Pusan Natl Univ, Dept Biol Sci, 63 Beon Gil 2, Pusan 609735, South Korea. EM kimsw@pusan.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2013R1A1A2008838]; NCI/NIH [R01-CA138747]; Veterans Administration Merit Award [I01-BX001882] FX We thank Dr Kyung Lib Jang (Pusan National University) for the WT and MUT (R248Q) p53 constructs. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A2008838) to S-WK and RCTA was funded by NCI/NIH R01-CA138747 and Veterans Administration Merit Award (I01-BX001882). NR 28 TC 5 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD SEP PY 2015 VL 29 IS 9 BP 1868 EP 1874 DI 10.1038/leu.2015.101 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA CQ9MA UT WOS:000360937800008 PM 25915824 ER PT J AU Kikuchi, S Suzuki, R Ohguchi, H Yoshida, Y Lu, D Cottini, F Jakubikova, J Bianchi, G Harada, T Gorgun, G Tai, YT Richardson, PG Hideshima, T Anderson, KC AF Kikuchi, S. Suzuki, R. Ohguchi, H. Yoshida, Y. Lu, D. Cottini, F. Jakubikova, J. Bianchi, G. Harada, T. Gorgun, G. Tai, Y-T Richardson, P. G. Hideshima, T. Anderson, K. C. TI Class IIa HDAC inhibition enhances ER stress-mediated cell death in multiple myeloma SO LEUKEMIA LA English DT Article ID UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR XBP-1; HISTONE DEACETYLASES; TRANSLATION INITIATION; ENDOPLASMIC-RETICULUM; OXIDATIVE STRESS; GENE-EXPRESSION; BORTEZOMIB; APOPTOSIS; COMBINATION AB Histone deacetylase (HDAC) inhibitors have been extensively investigated as therapeutic agents in cancer. However, the biological role of class IIa HDACs (HDAC4, 5, 7 and 9) in cancer cells, including multiple myeloma (MM), remains unclear. Recent studies show HDAC4 interacts with activating transcription factor 4 (ATF4) and inhibits activation of endoplasmic reticulum (ER) stress-associated proapoptotic transcription factor C/EBP homologous protein (CHOP). In this study, we hypothesized that HDAC4 knockdown and/or inhibition could enhance apoptosis in MM cells under ER stress condition by upregulating ATF4, followed by CHOP. HDAC4 knockdown showed modest cell growth inhibition; however, it markedly enhanced cytotoxicity induced by either tunicamycin or carfilzomib (CFZ), associated with upregulating ATF4 and CHOP. For pharmacological inhibition of HDAC4, we employed a novel and selective class IIa HDAC inhibitor TMP269, alone and in combination with CFZ. As with HDAC4 knockdown, TMP269 significantly enhanced cytotoxicity induced by CFZ in MM cell lines, upregulating ATF4 and CHOP and inducing apoptosis. Conversely, enhanced cytotoxicity was abrogated by ATF4 knockdown, confirming that ATF4 has a pivotal role mediating cytotoxicity in this setting. These results provide the rationale for novel treatment strategies combining class IIa HDAC inhibitors with ER stressors, including proteasome inhibitors, to improve patient outcome in MM. C1 [Kikuchi, S.; Suzuki, R.; Ohguchi, H.; Yoshida, Y.; Lu, D.; Cottini, F.; Jakubikova, J.; Bianchi, G.; Harada, T.; Gorgun, G.; Tai, Y-T; Richardson, P. G.; Hideshima, T.; Anderson, K. C.] Harvard Univ, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Med Sch, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Med Sch, 450 Brookline Ave,Mayer 557, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU ITO Foundation for the Promotion of Medical Science; National Institutes of Health [RO-1 CA 178264] FX This study was supported by ITO Foundation for the Promotion of Medical Science (to SK) and the National Institutes of Health (RO-1 CA 178264). KCA is an American Cancer Society Clinical Research Professor. NR 43 TC 10 Z9 10 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD SEP PY 2015 VL 29 IS 9 BP 1918 EP 1927 DI 10.1038/leu.2015.83 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CQ9MA UT WOS:000360937800014 PM 25801913 ER PT J AU Dahlberg, A Woo, S Delaney, C Boyle, P Gnirke, A Bock, C Bernstein, BE Meissner, A Gottardo, R Bernstein, ID AF Dahlberg, A. Woo, S. Delaney, C. Boyle, P. Gnirke, A. Bock, C. Bernstein, B. E. Meissner, A. Gottardo, R. Bernstein, I. D. TI Notch-mediated expansion of cord blood progenitors: maintenance of transcriptional and epigenetic fidelity SO LEUKEMIA LA English DT Letter ID LARGE GENE LISTS; BIOINFORMATICS; METHYLATION; PLURIPOTENT; CELLS; CANCER; BEX2; MAPS C1 [Dahlberg, A.; Delaney, C.; Bernstein, I. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Pediat Oncol, Seattle, WA 98104 USA. [Dahlberg, A.; Delaney, C.; Bernstein, I. D.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Woo, S.; Gottardo, R.] Fred Hutchinson Canc Res Ctr, PS Stat Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Boyle, P.; Gnirke, A.; Bock, C.; Bernstein, B. E.; Meissner, A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bernstein, B. E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Bernstein, B. E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bernstein, B. E.] Harvard Univ, Sch Med, Boston, MA USA. RP Dahlberg, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, Pediat Oncol, 1124 Columbia St, Seattle, WA 98104 USA. EM ibernste@fhcrc.org OI Bock, Christoph/0000-0001-6091-3088 FU NCI NIH HHS [K12CA076930, K12 CA076930, T32CA009351, P30 CA015704, T32 CA009351]; NHLBI NIH HHS [U01 HL100395, U01HL100395] NR 13 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD SEP PY 2015 VL 29 IS 9 BP 1948 EP 1951 DI 10.1038/leu.2015.61 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CQ9MA UT WOS:000360937800019 PM 25742749 ER PT J AU Ahlfors, SP Wreh, C AF Ahlfors, Seppo P. Wreh, Christopher, II TI Modeling the effect of dendritic input location on MEG and EEG source dipoles SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Magnetoencephalography; Electroencephalography; Postsynaptic current; Pyramidal cells ID NEOCORTICAL NEURONS; EXTRASTRIATE CORTEX; CEREBRAL-CORTEX; MAGNETOENCEPHALOGRAPHY; POTENTIALS; CURRENTS; SIGNALS; ELECTROENCEPHALOGRAPHY; ORIGINS; CANCELLATION AB The cerebral sources of magneto- and electroencephalography (MEG, EEG) signals can be represented by current dipoles. We used computational modeling of realistically shaped passive-membrane dendritic trees of pyramidal cells from the human cerebral cortex to examine how the spatial distribution of the synaptic inputs affects the current dipole. The magnitude of the total dipole moment vector was found to be proportional to the vertical location of the synaptic input. The dipole moment had opposite directions for inputs above and below a reversal point located near the soma. Inclusion of shunting-type inhibition either suppressed or enhanced the current dipole, depending on whether the excitatory and inhibitory synapses were on the same or opposite side of the reversal point. Relating the properties of the macroscopic current dipoles to dendritic current distributions can help to provide means for interpreting MEG and EEG data in terms of synaptic connection patterns within cortical areas. C1 [Ahlfors, Seppo P.; Wreh, Christopher, II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02135 USA. [Ahlfors, Seppo P.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02135 USA. RP Ahlfors, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02135 USA. EM seppo@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU National Institutes of Health [NS57500, NS037462]; National Center for Research Resources [P41RR14075] FX This work was supported by National Institutes of Health Grants NS57500 and NS037462, and by The National Center for Research Resources (P41RR14075). NR 71 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 EI 1741-0444 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 2015 VL 53 IS 9 BP 879 EP 887 DI 10.1007/s11517-015-1296-5 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA CR6XO UT WOS:000361491900010 PM 25863693 ER PT J AU Stein, BD Pacula, RL Gordon, AJ Burns, RM Leslie, DL Sorbero, MJ Bauhoff, S Mandell, TW Dick, AW AF Stein, Bradley D. Pacula, Rosalie Liccardo Gordon, Adam J. Burns, Rachel M. Leslie, Douglas L. Sorbero, Mark J. Bauhoff, Sebastian Mandell, Todd W. Dick, Andrew W. TI Where Is Buprenorphine Dispensed to Treat Opioid Use Disorders? The Role of Private Offices, Opioid Treatment Programs, and Substance Abuse Treatment Facilities in Urban and Rural Counties SO MILBANK QUARTERLY LA English DT Article DE opioid-related disorders; health policy; substance abuse treatment; buprenorphine ID CLINICAL-TRIALS NETWORK; 1ST 3 YEARS; MAINTENANCE THERAPY; METHADONE-MAINTENANCE; DEPENDENT PATIENTS; AGONIST TREATMENT; OPIATE ADDICTION; UNITED-STATES; NALOXONE; PHYSICIANS AB Context: Opioid use disorders are a significant public health problem. In 2002, the FDA approved buprenorphine as an opioid use disorder treatment when prescribed by waivered physicians who were limited to treating 30 patients at a time. In 2006, federal legislation raised this number to 100 patients. Although federal legislators are considering increasing these limits further and expanding prescribing privileges to nonphysicians, little information is available regarding the impact of such changes on buprenorphine use. We therefore examined the impact of the 2006 legislation- as well as the association between urban and rural waivered physicians, opioid treatment programs, and substance abuse treatment facilities- on buprenorphine distributed per capita over the past decade. Methods: Using 2004- 2011 state- level data on buprenorphine dispensed and county- level data on the number of buprenorphine- waivered physicians and substance abuse treatment facilities using buprenorphine, we estimated a multivariate ordinary least squares regression model with state fixed effects of a state's annual total buprenorphine dispensed per capita as a function of the state's number of buprenorphine providers. Findings: The amount of buprenorphine dispensed has been increasing at a greater rate than the number of buprenorphine providers. The number of physicians waivered to treat 100 patients with buprenorphine in both rural and urban settings was significantly associated with increased amounts of buprenorphine dispensed per capita. There was no significant association in the growth of buprenorphine distributed and the number of physicians with 30- patient waivers. Conclusions: The greater amounts of buprenorphine dispensed are consistent with the potentially greater use of opioid agonists for opioid use disorder treatment, though they also make their misuse more likely. The changes after the 2006 legislation suggest that policies focused on increasing the number of patients that a single waivered physician could safely and effectively treat could bemore effective in increasing buprenorphine use than would alternatives such as opening new substance abuse treatment facilities or raising the overall number of waivered physicians. C1 [Stein, Bradley D.; Pacula, Rosalie Liccardo; Burns, Rachel M.; Sorbero, Mark J.; Bauhoff, Sebastian; Dick, Andrew W.] RAND Corp, Pittsburgh, PA 15213 USA. [Stein, Bradley D.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Leslie, Douglas L.] Penn State Coll Med, Hershey, PA USA. [Mandell, Todd W.] Community Substance Abuse Ctr, Chicopee, MA USA. RP Stein, BD (reprint author), RAND Corp, 4570 Fifth Ave, Pittsburgh, PA 15213 USA. EM stein@rand.org FU National Institute on Drug Abuse of the National Institutes of Health (NIH) [1R01DA032881-01A1] FX The National Institute on Drug Abuse of the National Institutes of Health (NIH) provided support (award 1R01DA032881-01A1) for this study. NR 67 TC 4 Z9 4 U1 8 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-378X EI 1468-0009 J9 MILBANK Q JI Milbank Q. PD SEP PY 2015 VL 93 IS 3 BP 561 EP 583 DI 10.1111/1468-0009.12137 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CR3FQ UT WOS:000361216700011 PM 26350930 ER PT J AU Kabekkodu, SP Chakrabarty, S Shukla, V Varghese, VK Singh, KK Thangaraj, K Satyamoorthy, K AF Kabekkodu, Shama Prasada Chakrabarty, Sanjiban Shukla, Vaibhav Varghese, Vinay Koshy Singh, Keshav K. Thangaraj, Kumarasamy Satyamoorthy, Kapaettu TI Mitochondrial biology: From molecules to diseases SO MITOCHONDRION LA English DT Article DE Mitochondria; Clinical perspective; Mitochondrial biomarker; Mitochondrial database; Signaling and metabolism; Mitochondrial genetics ID TYPE-2 DIABETIC-RETINOPATHY; KEARNS-SAYRE SYNDROME; SODIUM-BUTYRATE; OXIDATIVE-PHOSPHORYLATION; POPULATION-GENETICS; COLORECTAL-CANCER; CERVICAL-CANCER; GENOME DATABASE; CELLS; APOPTOSIS AB As an integral part of the cell, mitochondria play a pivotal role in the regulation of energy metabolism, signaling pathways, cell differentiation, cell proliferation and cell death. Mitochondrion with its own genetic material has characteristics distinct from those of the nuclear counterpart and its dysregulation is associated with a myriad of diseases. The discovery of interplay between the nuclear and mitochondrial genes, and various post-transcriptional modifications associated with their products has added excitement in the field. This has led to a better understanding of the basic mitochondrial function in normal and disease states, and is important for diagnosis and prognosis of a large number of disorders. The Fourth Annual Conference of Society for Mitochondrial Research and Medicine - India (SMRM) was titled "Mitochondrial Biology: from Molecules to Disease". The conference was organized by K. Satyamoorthy and K. Thangaraj at School of Life Sciences, Manipal University, Manipal, India, during 8-9 December, 2014. The aim of the conference was to bring researchers and clinicians to a common platform; create an opportunity for networking between laboratories; and to discuss about the recent development in mitochondrial biology, diagnosis, and therapy. This review summarizes the key outcomes of the conference. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Kabekkodu, Shama Prasada; Chakrabarty, Sanjiban; Shukla, Vaibhav; Varghese, Vinay Koshy; Satyamoorthy, Kapaettu] Manipal Univ, Sch Life Sci, Dept Biotechnol, Manipal 576104, Karnataka, India. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Environm Hlth, Birmingham, AL USA. [Singh, Keshav K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Thangaraj, Kumarasamy] Ctr Cellular & Mol Biol, CSIR, Hyderabad 500007, Andhra Pradesh, India. RP Satyamoorthy, K (reprint author), Manipal Univ, Sch Life Sci, Manipal 576104, Karnataka, India. EM ksatyamoorthy@manipal.edu OI shukla, Vaibhav/0000-0003-4881-9894; Thangaraj, Kumarasamy/0000-0002-0075-0106 NR 50 TC 3 Z9 4 U1 4 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2015 VL 24 BP 93 EP 98 DI 10.1016/j.mito.2015.07.008 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA CR5YD UT WOS:000361419400010 PM 26210788 ER PT J AU Sanchez, JR Reddick, TL Perez, M Centonze, VE Mitra, S Izumi, T McMahan, CA Walter, CA AF Sanchez, Jamila R. Reddick, Traci L. Perez, Marissa Centonze, Victoria E. Mitra, Sankar Izumi, Tadahide McMahan, C. Alex Walter, Christi A. TI Increased human AP endonuclease 1 level confers protection against the paternal age effect in mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Paternal Age; DNA repair; APEX1; Mutagenesis; LacI; Spermatogenesis ID BASE EXCISION-REPAIR; DE-NOVO MUTATIONS; APURINIC APYRIMIDINIC SITES; PROGRAMMED CELL-DEATH; DNA-POLYMERASE-BETA; HETEROZYGOUS MICE; SPERMATOGENIC CELLS; ALTERED EXPRESSION; NUCLEAR EXTRACTS; ABASIC SITES AB Increased paternal age is associated with a greater risk of producing children with genetic disorders originating from de novo germline mutations. Mice mimic the human condition by displaying an age-associated increase in spontaneous mutant frequency in spermatogenic cells. The observed increase in mutant frequency appears to be associated with a decrease in the DNA repair protein, AP endonuclease 1 (APEX1) and Apex1 heterozygous mice display an accelerated paternal age effect as young adults. In this study, we directly tested if APEX1 over-expression in cell lines and transgenic mice could prevent increases in mutagenesis. Cell lines with ectopic expression of APEX1 had increased APEX1 activity and lower spontaneous and induced mutations in the lad reporter gene relative to the control. Spermatogenic cells obtained from mice transgenic for human APEX1 displayed increased APEX1 activity, were protected from the age-dependent increase in spontaneous germline mutagenesis, and exhibited increased apoptosis in the spermatogonial cell population. These results directly indicate that increases in APEXI level confer protection against the murine paternal age effect, thus highlighting the role of APEX1 in preserving reproductive health with increasing age and in protection against genotoxin-induced mutagenesis in somatic cells. (C) 2015 Elsevier B.V. All rights reserved. C1 [Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Sanchez, Jamila R.; Perez, Marissa; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Reddick, Traci L.] Duke Univ, Duke Canc Inst, Durham, NC 27710 USA. [Centonze, Victoria E.] St Jude Childrens Res Hosp, Cell & Tissue Imaging Ctr, Memphis, TN 38105 USA. [Mitra, Sankar] Houston Methodist Res Inst, Dept Radiat Oncol, Houston, TX 77030 USA. [Izumi, Tadahide] Grad Ctr Toxicol, Lexington, KY 40536 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, MC 7762 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU National Institutes of Health [AG024364, AG021163] FX National Institutes of Health grants [AG024364 and AG021163]. NR 55 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP PY 2015 VL 779 BP 124 EP 133 DI 10.1016/j.mrfmmm.2015.06.008 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA CR3RT UT WOS:000361251500013 PM 26201249 ER PT J AU Danovitch, GM Delmonico, FL AF Danovitch, Gabriel M. Delmonico, Francis L. TI A path of hope for organ transplantation in China? SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article ID DONATION AB "aEuro broken vertical bar we declare solemnly that the use of executed prisoner organs has totally stopped in our center and that none of the cases reported in this study were from executed prisoner organs". The content of the study itself reflects the struggle by the authors to rid themselves of the curse of executed prisoner organs at a time when death by neurologic critera ("brain death") has not been ratified by Chinese Law and is thought to be contrary to Chinese cultural values.aEuro broken vertical bar. C1 [Danovitch, Gabriel M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Danovitch, Gabriel M.] Univ Calif Los Angeles, Ronald Reagan Med Ctr, Div Nephrol, Kidney Transplant Program, Los Angeles, CA 90095 USA. [Delmonico, Francis L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Danovitch, GM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM gdanovitch@mednet.ucla.edu NR 9 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 2015 VL 30 IS 9 BP 1413 EP 1414 DI 10.1093/ndt/gfv206 PG 2 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA CR4LL UT WOS:000361303800001 PM 26044833 ER PT J AU Ellingson, BM Bendszus, M Boxerman, J Barboriak, D Erickson, BJ Smits, M Nelson, SJ Gerstner, E Alexander, B Goldmacher, G Wick, W Vogelbaum, M Weller, M Galanis, E Kalpathy-Cramer, J Shankar, L Jacobs, P Pope, WB Yang, DW Chung, C Knopp, MV Cha, S van den Bent, MJ Chang, S Al Yung, WK Cloughesy, TF Wen, PY Gilbert, MR AF Ellingson, Benjamin M. Bendszus, Martin Boxerman, Jerrold Barboriak, Daniel Erickson, Bradley J. Smits, Marion Nelson, Sarah J. Gerstner, Elizabeth Alexander, Brian Goldmacher, Gregory Wick, Wolfgang Vogelbaum, Michael Weller, Michael Galanis, Evanthia Kalpathy-Cramer, Jayashree Shankar, Lalitha Jacobs, Paula Pope, Whitney B. Yang, Dewen Chung, Caroline Knopp, Michael V. Cha, Soonme van den Bent, Martin J. Chang, Susan Al Yung, W. K. Cloughesy, Timothy F. Wen, Patrick Y. Gilbert, Mark R. CA Jumpstarting Brain Tumor Drug Dev TI Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials SO NEURO-ONCOLOGY LA English DT Review DE Brain Tumor Imaging Protocol; clinical trials; glioblastoma; MRI ID NEWLY-DIAGNOSED GLIOBLASTOMA; NUCLEAR MAGNETIC-RESONANCE; RANDOMIZED PHASE-III; HIGH-GRADE GLIOMAS; MP-RAGE; RESPONSE ASSESSMENT; INTEROBSERVER VARIABILITY; GADODIAMIDE INJECTION; ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMAS AB A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems. C1 [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Neuro Oncol Program, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Tumor Imaging Lab, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Pope, Whitney B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Bendszus, Martin] Univ Heidelberg Hosp, Dept Neuroradiol, Heidelberg, Germany. [Boxerman, Jerrold] Brown Univ, Warrne Alpert Med Sch, Dept Diagnost Imaging, Providence, RI 02912 USA. [Barboriak, Daniel] Duke Univ, Sch Med, Dept Neuroradiol, Durham, NC USA. [Erickson, Bradley J.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Smits, Marion] Erasmus MC Univ, Dept Radiol, Rotterdam, Netherlands. [Nelson, Sarah J.; Cha, Soonme] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Gerstner, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Alexander, Brian; Wen, Patrick Y.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Goldmacher, Gregory; Wick, Wolfgang] ICON Med Imaging, Med & Sci Affairs, Warrington, PA USA. [Wick, Wolfgang] Univ Clin Heidelberg, Dept Neurooncol, Natl Ctr Tumor Dis, Heidelberg, Germany. [Vogelbaum, Michael] Cleveland Clin, Dept Neurol Surg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Galanis, Evanthia] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [Shankar, Lalitha; Jacobs, Paula] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Chung, Caroline] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Chung, Caroline] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Knopp, Michael V.] Ohio State Univ, Wright Ctr Innovat Biomed Imaging, Div Imaging Sci, Wexner Med Ctr, Columbus, OH 43210 USA. [van den Bent, Martin J.] Erasmus MC Canc Inst, Dept Neurooncol, Rotterdam, Netherlands. [Cha, Soonme; Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Al Yung, W. K.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Neurooncol, Houston, TX 77030 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Gilbert, Mark R.] NCI, Neurooncol Branch, Bethesda, MD USA. [Ellingson, Benjamin M.; Gerstner, Elizabeth; Wen, Patrick Y.] ABTC, Baltimore, MD USA. [Ellingson, Benjamin M.; Nelson, Sarah J.] Ivy Consortium Early Phase Clin Trials, Garden City, NY USA. [Ellingson, Benjamin M.; Boxerman, Jerrold; Barboriak, Daniel] ACRIN, Philadelphia, PA USA. [Bendszus, Martin; Smits, Marion; Wick, Wolfgang; van den Bent, Martin J.] EORTC, Brussels, Belgium. [Erickson, Bradley J.; Gerstner, Elizabeth] Alliance Clin Trials Oncol, Duarte, CA USA. [Ellingson, Benjamin M.; Barboriak, Daniel; Erickson, Bradley J.; Goldmacher, Gregory; Knopp, Michael V.] RSNA Quantitat Imaging Biomarker Alliance QIBA, Arlington, VA USA. [Ellingson, Benjamin M.; Boxerman, Jerrold; Barboriak, Daniel; Erickson, Bradley J.; Pope, Whitney B.] Amer Soc Neuroradiol ASNR, Oak Brook, IL USA. [Boxerman, Jerrold] Amer Soc Funct Neuroradiol ASFNR, Austin, TX USA. [Vogelbaum, Michael; Gilbert, Mark R.] RTOG, Atlanta, GA USA. RP Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Radiol Sci, 924 Westwood Blvd,Suite 650, Los Angeles, CA 90095 USA. EM bellingson@mednet.ucla.edu RI Gilbert, Mark/J-7494-2016; Smits, Marion/E-4795-2011; OI Gilbert, Mark/0000-0003-2556-9722; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU Roche/Genentech Research Grant; Siemens Healthcare Research Grant; National Brain Tumor Society Research Grant FX Roche/Genentech Research Grant (B.M.E.), Siemens Healthcare Research Grant (B.M.E.), National Brain Tumor Society Research Grant (B.M.E.). NR 62 TC 31 Z9 31 U1 3 U2 11 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 SEP PY 2015 VL 17 IS 9 BP 1188 EP 1198 DI 10.1093/neuonc/nov095 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MH UT WOS:000361306400004 PM 26250565 ER PT J AU Ma, DJ Galanis, E Anderson, SK Schiff, D Kaufmann, TJ Peller, PJ Giannini, C Brown, PD Uhm, JH McGraw, S Jaeckle, KA Flynn, PJ Ligon, KL Buckner, JC Sarkaria, JN AF Ma, Daniel J. Galanis, Evanthia Anderson, S. Keith Schiff, David Kaufmann, Timothy J. Peller, Patrick J. Giannini, Caterina Brown, Paul D. Uhm, Joon H. McGraw, Steven Jaeckle, Kurt A. Flynn, Patrick J. Ligon, Keith L. Buckner, Jan C. Sarkaria, Jann N. TI A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K SO NEURO-ONCOLOGY LA English DT Article DE everolimus; FLT-PET; glioblastoma; mTOR ID PANCREATIC NEUROENDOCRINE TUMORS; TUBEROUS SCLEROSIS COMPLEX; RENAL-CELL CARCINOMA; RADIATION-THERAPY; 3'-DEOXY-3'-F-18-FLUOROTHYMIDINE PET; RAD001 EVEROLIMUS; MTOR INHIBITION; MULTIFORME; COMBINATION; VARIABILITY AB The mammalian target of rapamycin (mTOR) functions within the phosphatidylinositol-3 kinase (PI3K)/Akt pathway as a critical modulator of cell survival. This clinical trial evaluated the combination of the mTOR inhibitor everolimus with conventional temozolomide (TMZ)-based chemoradiotherapy. Newly diagnosed patients with glioblastoma multiforme were eligible for this single arm, phase II study. Everolimus (70 mg/wk) was started 1 week prior to radiation and TMZ, followed by adjuvant TMZ, and continued until disease progression. The primary endpoint was overall survival at 12 months, and secondary endpoints were toxicity and time to progression. Eleven patients were imaged with 3'-deoxy-3'-F-18-fluorothymidine ((FLT)-F-18)-PET/CT before and after the initial 2 doses of everolimus before initiating radiation/TMZ. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis. This study accrued 100 evaluable patients. Fourteen percent of patients had grade 4 hematologic toxicities. Twelve percent had at least one grade 4 nonhematologic toxicity, and there was one treatment-related death. Overall survival at 12 months was 64% and median time to progression was 6.4 months. Of the patients who had (FLT)-F-18-PET data, 4/9 had a partial response after 2 doses of everolimus. Focused exon sequencing demonstrated that (FLT)-F-18-PET responders were less likely to have alterations within the PI3K/Akt/mTOR or tuberous sclerosis complex/neurofibromatosis type 1 pathway compared with nonresponders. Combining everolimus with conventional chemoradiation had moderate toxicity. (FLT)-F-18-PET studies suggested an initial antiproliferative effect in a genetically distinct subset of tumors, but this did not translate into an appreciable survival benefit compared with historical controls treated with conventional therapy. C1 [Ma, Daniel J.; Galanis, Evanthia; Kaufmann, Timothy J.; Peller, Patrick J.; Giannini, Caterina; Brown, Paul D.; Uhm, Joon H.; Buckner, Jan C.; Sarkaria, Jann N.] Mayo Clin, Rochester, MN 55905 USA. [Anderson, S. Keith] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN 55905 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Brown, Paul D.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [McGraw, Steven] Sioux Community Canc Consortium, Sioux Falls, SD USA. [Jaeckle, Kurt A.] Mayo Clin, Jacksonville, FL 32224 USA. [Flynn, Patrick J.] Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. RP Sarkaria, JN (reprint author), Mayo Clin, Dept Radiat Oncol, 200 First St SW, Rochester, MN 55905 USA. EM sarkaria.jann@mayo.edu FU Public Health Service [CA-25224, CA-37404, CA-35103, CA-35267]; CTSA from the National Center for Advancing Translational Sciences (NCATS) [UL1 TR000135]; National Cancer Institute, Department of Health and Human Services [CA-108961, CA-165962]; National Cancer Institute [CA31946]; Alliance for Clinical Trials in Oncology; Alliance Statistics and Data Center [CA33601]; Novartis FX This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35103, CA-35267, CTSA grant no. UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), and Brain SPORE grant no. CA-108961 and CA-165962 from the National Cancer Institute, Department of Health and Human Services. The study was also supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601). This study was also supported by Novartis and presented at the ASCO 2012 Annual Meeting in Chicago, IL. NR 50 TC 17 Z9 17 U1 3 U2 5 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 SEP PY 2015 VL 17 IS 9 BP 1261 EP 1269 DI 10.1093/neuonc/nou328 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MH UT WOS:000361306400011 PM 25526733 ER PT J AU Wen, PY Omuro, A Ahluwalia, MS Fathallah-Shaykh, HM Mohile, N Lager, JJ Laird, AD Tang, JL Jiang, J Egile, C Cloughesy, TF AF Wen, Patrick Y. Omuro, Antonio Ahluwalia, Manmeet S. Fathallah-Shaykh, Hassan M. Mohile, Nimish Lager, Joanne J. Laird, A. Douglas Tang, Jiali Jiang, Jason Egile, Coumaran Cloughesy, Timothy F. TI Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; pharmacodynamics; pharmacokinetics; PI3K; mTOR; temozolomide ID PI3K PATHWAY; GLIOBLASTOMA-MULTIFORME; ADJUVANT TEMOZOLOMIDE; CONFERS RESISTANCE; MALIGNANT GLIOMA; CANCER; RADIATION; TRIAL; CONCOMITANT; KINASE AB This phase I study aimed to evaluate safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of voxtalisib (SAR245409, XL765), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, in combination with temozolomide (TMZ), with or without radiation therapy (RT), in patients with high-grade glioma. Patients received voxtalisib 30-90 mg once daily (q.d.) or 20-50 mg twice daily (b.i.d.), in combination with 200 mg/m(2) TMZ (n = 49), or voxtalisib 20 mg q.d. with 75 mg/m(2) TMZ and RT (n = 5). A standard 3 + 3 dose-escalation design was used to determine the maximum tolerated dose. Patients were evaluated for adverse events (AEs), plasma pharmacokinetics, pharmacodynamic effects in skin biopsies, and tumor response. The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ. The most frequently reported treatment-related AEs were nausea (48%), fatigue (43%), thrombocytopenia (26%), and diarrhea (24%). The most frequently reported treatment-related grade a parts per thousand yen3 AEs were lymphopenia (13%), thrombocytopenia, and decreased platelet count (9% each). Pharmacokinetic parameters were similar to previous studies with voxtalisib monotherapy. Moderate inhibition of PI3K signaling was observed in skin biopsies. Best response was partial response in 4% of evaluable patients, with stable disease observed in 68%. Voxtalisib in combination with TMZ with or without RT in patients with high-grade gliomas demonstrated a favorable safety profile and a moderate level of PI3K/mTOR pathway inhibition. C1 [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Omuro, Antonio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ahluwalia, Manmeet S.] Cleveland Clin, Cleveland, OH 44106 USA. [Fathallah-Shaykh, Hassan M.] Univ Alabama Birmingham, Birmingham, AL USA. [Mohile, Nimish] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Lager, Joanne J.] Sanofi, Cambridge, MA USA. [Laird, A. Douglas] Exelixis Inc, San Francisco, CA USA. [Tang, Jiali] Quintiles, Durham, NC USA. [Jiang, Jason] Sanofi, Bridgewater, NJ USA. [Egile, Coumaran] Sanofi, Vitry Sur Seine, France. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org OI Omuro, Antonio/0000-0003-4299-3664 FU Sanofi; Exelixis FX This study was sponsored by Sanofi and Exelixis. Exelixis was the study sponsor until March 2011, when Sanofi became the sponsor. NR 29 TC 2 Z9 2 U1 2 U2 7 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 SEP PY 2015 VL 17 IS 9 BP 1275 EP 1283 DI 10.1093/neuonc/nov083 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MH UT WOS:000361306400013 PM 26019185 ER PT J AU Mason, DJ Jones, DA Roy, C Sullivan, CG Wood, LJ AF Mason, Diana J. Jones, Dorothy A. Roy, Callista Sullivan, Cheryl G. Wood, Laura J. TI Commonalities of nurse-designed models of health care SO NURSING OUTLOOK LA English DT Article DE Community; Family centered; Health care financing; Health policy; Innovation; Nursing; Patient engagement; Payment; Relationship-based care; Social determinants; Value-based health care ID ALL-INCLUSIVE CARE; AGING IN-PLACE; OLDER-ADULTS; CREATING OPPORTUNITIES; PATIENT ACTIVATION; PARENT EMPOWERMENT; CONTROLLED-TRIAL; YOUNG-CHILDREN; MANAGED CENTER; BIRTH CENTER AB The American Academy of Nursing has identified examples of care-redesign developed by nurses who address the health needs of diverse populations. These models show important clinical and financial outcomes as summarized in the Select Edge Runner Models of Care table included in this article. A study team appointed by the Academy explored the commonalities across these models. Four commonalities emerged: health holistically defined; individual-, family-, and community-centric approaches to care; relationship-based care that enables partnerships and builds patient engagement and activation; and a shift from episodic individual care to continuous group and public health approaches. The policy implications include examining measures of an expanded definition of health, paying for visionary care, and transparency and rewards for community-level engagement. C1 [Mason, Diana J.] CUNY Hunter Coll, Ctr Hlth Media & Policy, Amer Acad Nursing, New York, NY 10021 USA. [Jones, Dorothy A.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Jones, Dorothy A.; Roy, Callista] Massachusetts Gen Hosp, Ctr Nursing Res, Boston, MA 02114 USA. [Sullivan, Cheryl G.] Amer Acad Nursing, Washington, DC USA. [Wood, Laura J.] Boston Childrens Hosp, Boston, MA USA. RP Mason, DJ (reprint author), 455 W 44th St,22, New York, NY 10036 USA. EM djmasonm@gmail.com NR 50 TC 5 Z9 5 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 2015 VL 63 IS 5 BP 540 EP 553 DI 10.1016/j.outlook.2015.04.009 PG 14 WC Nursing SC Nursing GA CR3YH UT WOS:000361268500003 PM 26211847 ER PT J AU Geng, TY Xia, LL Russo, S Kamara, D Cawart, LA AF Geng, Tuoyu Xia, Lili Russo, Sarah Kamara, Davida Cawart, Lauren Ashley TI Prosteatotic genes are associated with unsaturated fat suppression of saturated fat-induced hepatic steatosis in C57BL/6 mice SO NUTRITION RESEARCH LA English DT Article DE Saturated fatty acid; Unsaturated fatty acid; Obese mice; Hepatic steatosis; Hepatic cells ID SKELETAL-MUSCLE CELLS; COA DESATURASE-1 GENE; BILE-ACID METABOLISM; PREGNANE-X-RECEPTOR; INSULIN-RESISTANCE; MEDIATED INDUCTION; NUCLEAR RECEPTORS; PPAR-GAMMA; LXR-ALPHA; LIVER AB Both high sugar and fat diets can induce prosteatotic genes, leading to obesity and obesity-associated diseases, including hepatic steatosis. Unsaturated fat/fatty acid (USFA) reduces high sugar-induced hepatic steatosis by inhibiting the induced prosteatotic genes. In contrast, it is still unclear how USFA ameliorates saturated fat/fatty acid (SFA)-induced hepatic steatosis. As sugar and fat have different transport and metabolic pathways, we hypothesized that USFA suppressed SFA-induced hepatic steatosis via a different set of prosteatotic genes. To test this, we implemented high SFA vs USFA diets and a control diet in C57BL/6 mice for 16 weeks. Severe hepatic steatosis was induced in mice fed the SPA diet. Among a nearly complete set of prosteatotic genes, only the stearoyl-coenzyme a desaturase 1 (Scd1), cluster of differentiation 36 (Cd36), and peroxisome proliferator-activated receptor gamma (Ppar gamma) genes that were differentially expressed in the liver could contribute to SPA-induced steatosis or the alleviative effect of USFA. That is, the SPA diet induced the expression of Cd36 and Ppar gamma but not Scd1, and the USFA diet suppressed Scd1 expression and the induction of Cd36 and Ppar gamma. These findings were mainly recapitulated in cultured hepatocytes. The essential roles of SCD1 and CD36 were confirmed by the observation that the suppression of SCD1 and CD36 with small interfering RNA or drug treatment ameliorated SPA-induced lipid accumulation in hepatocytes. We thus concluded that SCD1, CD36, and PPAR gamma were essential to the suppression of SFA-induced hepatic steatosis by main dietary USFA, which may provide different therapeutic targets for reducing high-fat vs sugar-induced hepatic steatosis. (C) 2015 Elsevier Inc. All rights reserved. C1 [Geng, Tuoyu] Yangzhou Univ, Inst Epigenet & Epigen, Yangzhou 225009, Jiangsu, Peoples R China. [Geng, Tuoyu; Xia, Lili] Yangzhou Univ, Coll Anim Sci & Technol, Yangzhou 225009, Jiangsu, Peoples R China. [Geng, Tuoyu; Russo, Sarah; Cawart, Lauren Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Cawart, Lauren Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Kamara, Davida] Union Hosp Cecil Cty, Elkton, MD 21921 USA. RP Geng, TY (reprint author), Yangzhou Univ, Inst Epigenet & Epigen, 48 Wenhui Rd, Yangzhou 225009, Jiangsu, Peoples R China. EM tygeng@yzu.edu.cn FU Natural Sciences Foundation of China [31472086]; Priority Academic Program Development of Jiangsu Higher Education Institutions; VA Merit Award [1R01HL117233] FX This work was financially supported by the Natural Sciences Foundation of China (31472086) and the Priority Academic Program Development of Jiangsu Higher Education Institutions through awards to TG as well as by a VA Merit Award and 1R01HL117233 awarded to LAC. TG and LAC designed the research and wrote the article; TG, LX, and SBR conducted the research and analyzed the data. DK contributed to writing and editing of the article. NR 52 TC 4 Z9 4 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD SEP PY 2015 VL 35 IS 9 BP 812 EP 822 DI 10.1016/j.nutres.2015.06.012 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR5XE UT WOS:000361416900008 PM 26277244 ER PT J AU Stevens, JR Coffey, MJ Fojtik, M Kurtz, K Stern, TA AF Stevens, Jonathan R. Coffey, M. Justin Fojtik, Megan Kurtz, Kristina Stern, Theodore A. TI The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches SO PSYCHOSOMATICS LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSIVE DISORDER; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; RESTLESS LEGS SYNDROME; MODERATE ALZHEIMERS-DISEASE; CHEMOTHERAPY-INDUCED NAUSEA; MILD COGNITIVE IMPAIRMENT AB Background: Numerous currently available medications that act in the central nervous system can be delivered transdermally. Such medications include cholinesterase inhibitors for dementia, methylphenidate (MPH),for attention-deficit hyperactivity disorder, monoamine oxidase inhibitors (MAOIs) for depression, dopamine agonists for Parkinson disease and restless leg syndrome, and clonidine for attention-deficit hyperactivity disorder and impulse-control disorders. Objective: This article aims to review the literature related to transdermal delivery systems from the perspective of clinical practice and research related to their use in the treatment of psychiatric conditions. Results: Most of the currently available transdermal systems have psychotropic properties or utility in the behavioral health arena and, therefore, are of clinical relevance to consultation-liaison psychiatrists or practitioners of psychosomatic medicine. We discuss their efficacy and safety profiles. We provide a table of these agents and their uses. Conclusions: Transdermal delivery (i.e., patches) for medicines with psycho tropic properties allows mental health providers to customize therapy for patients by altering the duration of therapy, minimizing first-pass metabolism and the potential for drug drug interactions, and decreasing the risk for gastrointestinal irritation. C1 [Stevens, Jonathan R.] Menninger Clin, Outpatient Serv, Houston, TX 77035 USA. [Stevens, Jonathan R.; Coffey, M. Justin] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA. [Coffey, M. Justin] Menninger Clin, Neurostimulat & Clin Informat, Houston, TX 77035 USA. [Fojtik, Megan; Kurtz, Kristina] Henry Ford Hlth Syst, Detroit, MI USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Psychosomat Med Consultat, Boston, MA USA. RP Stevens, JR (reprint author), Menninger Clin, 12301 Main St, Houston, TX 77035 USA. EM jonstevens@menninger.edu NR 133 TC 0 Z9 1 U1 4 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 423 EP 444 PG 22 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500001 PM 26211981 ER PT J AU Freudenreich, O Huffman, JC Sharpe, M Beach, SR Celano, CM Chwastiak, LA Cohen, MA Dickerman, A Fitz-Gerald, MJ Kontos, N Mittal, L Nejad, SH Niazi, S Novak, M Philbrick, K Rasimas, JJ Shim, J Simpson, SA Walker, A Walker, J Wichman, CL Zimbrean, P Sollner, W Stern, TA AF Freudenreich, Oliver Huffman, Jeff C. Sharpe, Michael Beach, Scott R. Celano, Christopher M. Chwastiak, Lydia A. Cohen, Mary Ann Dickerman, Anne Fitz-Gerald, Mary Joe Kontos, Nicholas Mittal, Leena Nejad, Shamim H. Niazi, Shehzad Novak, Marta Philbrick, Kemuel Rasimas, Joseph J. Shim, Jewel Simpson, Scott A. Walker, Audrey Walker, Jane Wichman, Christina L. Zimbrean, Paula Soellner, Wolfgang Stern, Theodore A. TI Updates in Psychosomatic Medicine: 2014 SO PSYCHOSOMATICS LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; QUALITY-OF-LIFE; PSYCHOGENIC NONEPILEPTIC SEIZURES; INTEGRATED COLLABORATIVE CARE; ACUTE CORONARY SYNDROME; SERIOUS MENTAL-ILLNESS; CHRONIC KIDNEY-DISEASE; CLINICAL-TRIAL; LIVER-TRANSPLANTATION; MAJOR DEPRESSION AB Background: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise. Objectives: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014. Methods: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of Psychosomatic Medicine in 15 subspecialties to create a list of important articles. Results: In 2014, subspecialty experts selected 88 articles of interest for practitioners of psychosomatic medicine. For this review, 14 articles were chosen. Conclusions: A group process can he used to whittle clown the vast literature in psychosomatic medicine and compile a list of important articles for individual practitioners. Such an approach is consistent with the idea of physicians as lifelong learners and educators. C1 [Freudenreich, Oliver; Huffman, Jeff C.; Beach, Scott R.; Celano, Christopher M.; Kontos, Nicholas; Nejad, Shamim H.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sharpe, Michael; Walker, Jane] Univ Oxford, Dept Psychiat, Psychol Med Res, Oxford, England. [Chwastiak, Lydia A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cohen, Mary Ann] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Dickerman, Anne] Weill Cornell Med Coll, New York Presbyterian Hosp, Consultat Liaison Serv, Dept Psychiat, New York, NY USA. [Fitz-Gerald, Mary Joe] Louisiana State Univ, Hlth Sci Ctr, Dept Psychiat, Shreveport, LA 71105 USA. [Mittal, Leena] Brigham & Womens Hosp, Dept Psychiat, Div Med Psychiat, Boston, MA 02115 USA. [Mittal, Leena] Brigham & Womens Hosp, Dept Psychiat, Div Womens Mental Hlth, Boston, MA 02115 USA. [Niazi, Shehzad] Mayo Clin, Dept Psychiat & Psychol, Jacksonville, FL 32224 USA. [Novak, Marta] Univ Hlth Network, Dept Psychiat, Toronto, ON, Canada. [Novak, Marta] Univ Toronto, Toronto, ON, Canada. [Novak, Marta] Semmelweis Univ, Inst Behav Sci, H-1085 Budapest, Hungary. [Philbrick, Kemuel] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Rasimas, Joseph J.] HealthPartners Reg Hosp, St Paul, MN USA. [Shim, Jewel] Kaiser Oakland Med Ctr, Dept Psychiat, San Francisco, CA USA. [Shim, Jewel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Simpson, Scott A.] Univ Colorado, Sch Med, Denver Hlth Med Ctr, Denver, CO USA. [Walker, Audrey] Montefiore Med Ctr, Albert Einstein Coll Med, Div Child & Adolescent Psychiat, Bronx, NY 10467 USA. [Wichman, Christina L.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Zimbrean, Paula] Yale New Haven Med Ctr, Dept Psychiat & Surg Transplant, New Haven, CT 06504 USA. [Soellner, Wolfgang] Paracelsus Med Univ, Nuremberg Gen Hosp, Dept Psychosomat Med & Psychotherapy, Nurnberg, Germany. RP Freudenreich, O (reprint author), Erich Lindemann Mental Hlth Ctr, MGH Schizophrenia Program, 25 Staniford St, Boston, MA 02114 USA. EM ofreudenreich@partners.org FU Psychogenics; Forum; Beacon Health Strategies; Optimal Medicine FX Oliver Freudenreich has received grant support from Psychogenics and Forum, has received honoraria from Global Medical Education and the MGH Psychiatry Academy, has received consultant fees from Beacon Health Strategies and Optimal Medicine, and has received royalties from UpToDate. Theodore A. Stern is an employee of the Academy of Psychosomatic Medicine for serving as the editor in chief of Psychosomatics. The other authors had no disclosures. NR 89 TC 0 Z9 0 U1 5 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 445 EP 459 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500002 PM 26032045 ER PT J AU O'Cleirigh, C Magidson, JF Skeer, MR Mayer, KH Safren, SA AF O'Cleirigh, Conall Magidson, Jessica F. Skeer, Margie R. Mayer, Kenneth H. Safren, Steven A. TI Prevalence of Psychiatric and Substance Abuse Symptomatology Among HIV-Infected Gay and Bisexual Men in HIV Primary Care SO PSYCHOSOMATICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOCIAL ANXIETY; TRANSMISSION RISK; SUICIDAL IDEATION; UNITED-STATES; DISORDERS; SEX; WOMEN; HIV/AIDS; PTSD AB Background: The presence of psychiatric symptoms in gay/bisexual men managing HIV are underidentified and undertreated and can interfere with optimal HIV disease management. There is a paucity of prevalence reports of these symptoms in this group, identified in the primary HIV care setting. Few studies have compared prevalence rates based on empirically supported screening tools in relation to diagnoses made in primary care. Objective: The purpose of this study was to identify the prevalence of psychiatric symptoms and substance abuse in HI V-infected gay/bisexual men and to estimate the proportion of those who had been diagnosed within their primary medical care setting. Method: Participants (n = 503) were HIV-infected gayl bisexual men screened for participation in a HIV prevention trial and completed psychosocial assessment. Data were also extracted from patients' electronic medical record. Results: More than 47% of participants met diagnostic screen-in criteria for any anxiety disorder, of whom approximately one-third were identified in primary care. More than 22% screened in for a depressive mood disorder, approximately 50% of whom had been identified in primary care. A quarter of the sample had elevated substance abuse symptoms, 19.4% of whom were identified in primary care. Of those with symptoms of alcohol abuse (19.9%), 9.0% of those were identified in primary care. Conclusion: These results provide some evidence suggesting that mood, anxiety, and substance abuse symptomatology are prevalent among HIV-injected gay/bisexual men and are underidentified in primary care. Increased mental health and substance use screening integrated into HIV primary care treatment settings may help to identify more gay/bisexual men in need of treatment. C1 [O'Cleirigh, Conall; Magidson, Jessica F.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fenway Inst, Boston, MA USA. [Skeer, Margie R.] Tufts Med Sch, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Fenway Inst, Sch Med, Boston, MA 02215 USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq BS-07B, Boston, MA 02114 USA. EM cocleirigh@partners.org FU NIMH, USA [5R01MH068746-05]; HRSA, USA [H97HA01293] FX This study was supported by NIMH, USA Grant no. 5R01MH068746-05 and HRSA, USA Grant no. H97HA01293 awarded to Drs. Kenneth H. Mayer and Steven A. Safren. NR 50 TC 9 Z9 9 U1 6 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 470 EP 478 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500004 PM 25656425 ER PT J AU Nota, SPFT Spit, SA Voskuyl, T Bot, AGJ Hageman, MGJS Ring, D AF Nota, Sjoerd P. F. T. Spit, Silke A. Voskuyl, Timothy Bot, Arjan G. J. Hageman, Michiel G. J. S. Ring, David TI Opioid Use, Satisfaction, and Pain Intensity After Orthopedic Surgery SO PSYCHOSOMATICS LA English DT Article ID TOTAL KNEE ARTHROPLASTY; POSTOPERATIVE PAIN; OPERATIVE TREATMENT; MANAGEMENT; CARE; QUESTIONNAIRE; DEPRESSION; MORPHINE; FRACTURE; RELIEF AB Background: Patients in other countries use fewer opioids than patients in the United States with satisfactory pain relief. Objective: This study tested the null hypothesis that opioid intake after orthopedic surgery does not influence satisfaction with pain management. Methods: A total of 232 orthopedic surgical inpatients' completed measures of pain self-efficacy and symptoms of depression at enrollment and commonly used measures of pain intensity, satisfaction with pain relief and satisfaction with hospital staff attention to pain approximately 14 days after surgery. Inpatient (Third intake per 24-hour period was quantified. Results: At a phone evaluation approximately 2 weeks after discharge from the hospital, patients who were always satisfied with their pain relief in hospital and always satisfied with stuff attention to pain used significantly less opioids on day 1 compared with patients who were not always satisfied There were no differences in satisfaction by type of surgery. The final multivariable model for not always satisfied with pain relief included greater opioid use on day 1 ( odds ratio = 1.2), and preadmission diagnosis of depression (odds ratio = 2.6). Greater opioid use on day I was the only factor associated with less than always satisfied with the staff attention to pain relief ( odds ratio = 1.3). Conclusions: Patients who take more opioids report less satisfaction with pain relief and greater pain intensity. Evidence-based interventions to increase self-efficacy merit additional study for the management of postoperative pain. C1 [Nota, Sjoerd P. F. T.; Spit, Silke A.; Voskuyl, Timothy; Bot, Arjan G. J.; Hageman, Michiel G. J. S.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 28 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 479 EP 485 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500005 PM 25624183 ER PT J AU Goldzweig, G Abramovitch, A Brenner, B Perry, S Peretz, T Baider, L AF Goldzweig, Gil Abramovitch, Amitai Brenner, Baruch Perry, Shlomit Peretz, Tamar Baider, Lea TI Expectations and Level of Satisfaction of Patients and Their Physicians: Concordance and Discrepancies SO PSYCHOSOMATICS LA English DT Article ID CANCER-PATIENTS; INFORMATION; CARE; FAMILY; COMMUNICATION; PERCEPTIONS; INVOLVEMENT; PROGNOSIS; ONCOLOGY; QUALITY AB Background: Identifying discrepancies between patients expectations for support provided by their physicians, and physicians' appraisal of the support they provide to their patients, is a key factor in constructing effective doctor-patient communication. Objective: The current study proposes and explores a paradigm for assessing possible gaps and overlaps between perceptions of patients with cancer and physicians about the "actual" and the "ideal" (desired) emotional and cognitive support oncologists. provide to patients. Methods: Participants included 1027 patients' with cancer and 47 senior oncologists. Patients' and physicians' levels of expectations and satisfaction with the emotional and cognitive support offered by physicians were assessed using a quantitative measure of discrepancy between the actual and the ideal situation. The measure was developed for this study and tested on a random sample of 200 patients and 17 oncologists. Results: The results indicated consistency between physicians' and patients' perceptions of the needs and support that the patients received, Nevertheless, oncologists (lid not feel highly trusted by their patients, oncologists desired less involvement of patients in the treatment plan than the patients expected. Oncologists thought that they actually provided the desired levels of explanation to patients' families, whereas patients thought their flamilies got less explanations than expected. Conclusion: Actual and ideal levels of communication should be described from the points of view of both physicians and patients to better understand the complex picture of patient satisfaction. Oncologists should consider patients' expectations for support vs their own expectations to effectively address patients needs. C1 [Goldzweig, Gil] Acad Coll Tel Aviv Yaffo, Sch Behav Sci, Tel Aviv, Israel. [Abramovitch, Amitai] Harvard Univ, Massachusetts Gen Hosp, Sch Med, OCD & Related Disorders Program, Boston, MA USA. [Brenner, Baruch; Perry, Shlomit] Beilinson Med Ctr, Inst Oncol, Rabin Med Ctr, Petah Tiqwa, Israel. [Peretz, Tamar] Hadassah Univ Hosp, Sharctt Inst Oncol, IL-91120 Jerusalem, Israel. [Baider, Lea] Assuta Med Ctr, Inst Oncol, Tel Aviv, Israel. RP Goldzweig, G (reprint author), Acad Coll Tel Aviv Yaffo, Sch Behav Sci, Tel Aviv, Israel. EM giligold@mta.ac.il FU Israel Cancer Association, Israel [98003570-C] FX Supported by research Grant no. 98003570-C from the Israel Cancer Association, Israel. NR 35 TC 0 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 521 EP 529 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500010 PM 25596021 ER PT J AU Lokko, HN Stern, TA AF Lokko, Hermioni N. Stern, Theodore A. TI Confrontations with Difficult Patients: The Good, the Bad, and the Ugly SO PSYCHOSOMATICS LA English DT Article ID FAMILY PHYSICIANS; ENCOUNTERS; CARE C1 [Lokko, Hermioni N.; Stern, Theodore A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lokko, HN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hlokko@partners.org NR 12 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 556 EP 560 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500014 PM 26117725 ER PT J AU Murugesan, N Utunkaya, T Feener, EP AF Murugesan, Nivetha Utunkaya, Tuna Feener, Edward P. TI Thrombosis and Hemorrhage in Diabetic Retinopathy: A Perspective from an Inflammatory Standpoint SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE thrombosis; hemorrhage; diabetic retinopathy; inflammation ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VASCULAR-PERMEABILITY; PLASMA KALLIKREIN; ACTIVATION; RECEPTOR; PLATELET; DYSFUNCTION; MICROPARTICLES; PATHOGENESIS; LEUKOSTASIS AB Retinal ischemia and hemorrhage are hallmarks of worsening diabetic retinopathy, which can lead to neovascularization, macular edema, and severe vision loss. Although diabetes alters expression of clotting factors and their activities, and increases retinal microthromboses, the effects of thrombotic processes on the pathogenesis of diabetic retinopathy are not fully understood. In addition to the roles of coagulation and fibrinolytic cascades in thrombosis and hemostasis, components in these systems also mediate multiple effects on the vasculature that promote inflammation. Plasma kallikrein, thrombin, and urokinase are increased in diabetic retinopathy, and exert proinflammatory effects that contribute to retinal vascular dysfunction. The accumulation and activation of these and additional coagulation factors in the vitreous due to hemorrhage and chronic retinal injury in the diabetic retina may contribute to worsening of retinal inflammation and capillary dysfunction, which lead to retinal ischemia and edema. Further understanding of the role for specific coagulation factors in diabetic retinopathy may suggest new therapeutic opportunities for this vision-threatening disease. C1 [Murugesan, Nivetha; Feener, Edward P.] Joslin Diabet Ctr, Div Res, Sect Vasc Cell Biol, Boston, MA 02215 USA. [Murugesan, Nivetha; Feener, Edward P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Utunkaya, Tuna] Hacettepe Univ, Sch Med, Ankara, Turkey. RP Feener, EP (reprint author), Joslin Diabet Ctr, Div Res, Sect Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA. EM Edward.Feener@joslin.harvard.edu FU National Institutes of Health (NIH) [EY019029, DK36836, T32EY007145] FX This article was supported by the National Institutes of Health (NIH) Award Numbers EY019029, DK36836, and T32EY007145. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 42 TC 2 Z9 2 U1 0 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 EI 1098-9064 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD SEP PY 2015 VL 41 IS 6 BP 659 EP 664 DI 10.1055/s-0035-1556731 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CR6ZY UT WOS:000361498300014 PM 26305236 ER PT J AU Kim, ND Luster, AD AF Kim, Nancy D. Luster, Andrew D. TI The role of tissue resident cells in neutrophil recruitment SO TRENDS IN IMMUNOLOGY LA English DT Review ID INNATE LYMPHOID-CELLS; GROWTH-STIMULATORY ACTIVITY; BLOOD-BRAIN-BARRIER; MAST-CELLS; IN-VIVO; PULMONARY INFLAMMATION; RHEUMATOID-ARTHRITIS; ENDOTHELIAL-CELLS; IMAGING REVEALS; COCULTURE MODEL AB Neutrophils are first responders of the immune system, rapidly migrating into affected tissues in response to injury or infection. To effectively call in this first line of defense, strategically placed cells within the vasculature and tissue respond to noxious stimuli by sending out coordinated signals that recruit neutrophils. Regulation of organ-specific neutrophil entry occurs at two levels. First, the vasculature supplying the organ provides cues for neutrophil egress out of the bloodstream in a manner dependent upon its unique cellular composition and architectural features. Second, resident immune cells and stromal cells within the organ send coordinated signals that guide neutrophils to their final destination. Here, we review recent findings that highlight the importance of these tissue-specific responses in the regulation of neutrophil recruitment and the initiation and resolution of inflammation. C1 [Kim, Nancy D.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu FU Rheumatology Research Foundation; National Institutes of Health FX N.D.K. was supported by a grant from the Rheumatology Research Foundation and A.D.L. was supported by grants from the National Institutes of Health. NR 77 TC 14 Z9 14 U1 4 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD SEP PY 2015 VL 36 IS 9 BP 547 EP 555 DI 10.1016/j.it.2015.07.007 PG 9 WC Immunology SC Immunology GA CR5TI UT WOS:000361406600007 PM 26297103 ER PT J AU Frias-Lopez, J AF Frias-Lopez, Jorge TI Targeting specific bacteria in the oral microbiome SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material DE oral microbiome; antimicrobial peptide; microbial ecology ID ANTIMICROBIAL PEPTIDES AB A lack of tools that kill selected members of the oral microbiome has hampered the ability to study specific roles of bacteria within bacterial communities. Work by Guo et al. shows the potential of antimicrobial peptides as a tool to assess the role of individual species in the microbial community. C1 Forsyth Inst, Cambridge, MA 02142 USA. RP Frias-Lopez, J (reprint author), Forsyth Inst, 245 First St, Cambridge, MA 02142 USA. EM jfrias@forsyth.org NR 10 TC 2 Z9 2 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 2015 VL 23 IS 9 BP 527 EP 528 DI 10.1016/j.tim.2015.07.004 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA CR5WA UT WOS:000361413900004 PM 26215711 ER PT J AU Asch, DA Rader, DJ Merchant, RM AF Asch, David A. Rader, Daniel J. Merchant, Raina M. TI Mining the social mediome SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material DE communication; health information technology; health services research; social media ID FACEBOOK; HEALTH; DEPRESSION; SCALE; USERS AB The experiences and behaviors revealed in our everyday lives provide as much insight into health and disease as any analysis of our genome could ever produce. These characteristics are not found in the genome, but may be revealed in our online activities, which make up our social mediome. C1 [Asch, David A.; Merchant, Raina M.] Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Asch, David A.; Rader, Daniel J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Rader, Daniel J.] Univ Penn, Dept Med Genet, Philadelphia, PA 19104 USA. [Merchant, Raina M.] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Merchant, RM (reprint author), Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu FU NHLBI NIH HHS [K23 HL109083, R01 HL122457, R01 HL122457-01A1]; PHS HHS [NHLBI K23 109083-01] NR 15 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD SEP PY 2015 VL 21 IS 9 BP 528 EP 529 DI 10.1016/j.molmed.2015.06.004 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CR5TP UT WOS:000361407500002 PM 26341614 ER PT J AU Sheykhkarimli, D Yachie, N Petsalaki, E Cote, A Knapp, J Roth, FP AF Sheykhkarimli, Dayag Yachie, Nozomu Petsalaki, Evangelia Cote, Atina Knapp, Jennifer Roth, Frederick P. TI Towards a platform for global mapping of binary protein interactions under diverse conditions SO YEAST LA English DT Meeting Abstract CT 27th International Conference on Yeast Genetics and Molecular Biology (ICYGMB) CY SEP 06-12, 2015 CL Fondazione Edmund Mach, Levico Terme, ITALY SP Inst Cell Biol Nas Ukraine, Roche, Singer Instruments, Tema Ric, EMBO, Wiley Blackwell, Federat European Microbiol Soc, Assoc Genetica Italiana, Stanford Univ, DSB, Athesina Studiorum Univ, Soc Italiana Microbiologia Generale & Biotecnologie Microbiche, Saccharomyces Genome Database, Fondazione Bruno Kessler, Prov Autonoma Trento HO Fondazione Edmund Mach C1 [Sheykhkarimli, Dayag; Petsalaki, Evangelia; Cote, Atina; Knapp, Jennifer; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Sheykhkarimli, Dayag; Petsalaki, Evangelia; Cote, Atina; Knapp, Jennifer; Roth, Frederick P.] Univ Toronto, Donelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. [Sheykhkarimli, Dayag; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Yachie, Nozomu] Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo, Japan. [Yachie, Nozomu] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan. [Yachie, Nozomu] Japan Sci & Technol Agcy JST, PRESTO, Tokyo, Japan. [Roth, Frederick P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP PY 2015 VL 32 SU 1 MA PS1-13 BP S99 EP S99 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA CR6OF UT WOS:000361466200137 ER PT J AU Rasmussen, DD Kincaid, CL Froehlich, JC AF Rasmussen, Dennis D. Kincaid, Carrie L. Froehlich, Janice C. TI Prazosin plus Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in P Rats with a Protracted History of Extensive Voluntary Alcohol Drinking, Dependence, and Multiple Withdrawals SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Prazosin; Naltrexone; Alcohol; Alcoholism Treatment; Noradrenergic; Opioid ID ALPHA(1)-ADRENERGIC RECEPTOR ANTAGONIST; RANDOMIZED CONTROLLED-TRIAL; ETHANOL-CONSUMPTION; NOREPINEPHRINE; STRESS; BRAIN; INHIBITION; PREFERENCE; ADDICTION; BEHAVIORS AB BackgroundPrazosin (PRZ; an (1)-adrenergic receptor antagonist) and naltrexone (NTX; a nonspecific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively bred for high voluntary alcohol drinking (alcohol-preferring or P), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. As drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence, and repeated withdrawals closely resembling human alcoholism. MethodsMale P rats became alcohol-dependent during 1year of adlibitum 24h/d access to food, water, and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2mg/kg) and NTX (10mg/kg), alone or together, on alcohol drinking during: (i) daily alcohol access with daily drug treatment, (ii) intermittent alcohol access with daily drug treatment, (iii) intermittent alcohol access with occasional drug treatment, and (iv) postdeprivation reinstatement of alcohol access. ResultsThe combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects, or malaise. ConclusionsBoth daily and as-needed treatment with PRZ+NTX are highly effective in suppressing daily, intermittent, and postdeprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence, and repeated relapse, as commonly encountered in clinical practice. C1 [Rasmussen, Dennis D.] VISN 20 Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Rasmussen, Dennis D.; Kincaid, Carrie L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Rasmussen, Dennis D.; Kincaid, Carrie L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Froehlich, Janice C.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst Med Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU VA Puget Sound Health Care System; VA VISN 20 Mental Illness Research, Education and Clinical Center (MIRECC); NIH [R01 AA018604, P20 AA017839, P60 AA007611, R24 AA015512] FX This material is based on work supported in part by resources from the VA Puget Sound Health Care System, the VA VISN 20 Mental Illness Research, Education and Clinical Center (MIRECC), and NIH grants R01 AA018604, P20 AA017839, and P60 AA007611. P rats provided by the Indiana Alcohol Research Resource Center supported by NIH grant R24 AA015512. NR 53 TC 5 Z9 5 U1 2 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 SEP PY 2015 VL 39 IS 9 BP 1832 EP 1841 DI 10.1111/acer.12828 PG 10 WC Substance Abuse SC Substance Abuse GA CQ7ZB UT WOS:000360824300030 PM 26260061 ER PT J AU Solus, JF Goyal, A Duncan, LM Nazarian, RM AF Solus, Jason F. Goyal, Amrita Duncan, Lyn M. Nazarian, Rosalynn M. TI Basaloid Carcinoma of the Breast Mimicking Cutaneous Basaloid Neoplasms SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE basaloid carcinoma of the breast; nipple; basal cell carcinoma; CK17 ID ADENOID CYSTIC CARCINOMA; SQUAMOUS-CELL-CARCINOMA; NIPPLE-AREOLA COMPLEX; ECCRINE SPIRADENOMA; DIAGNOSTIC PITFALL; FEATURES; DIFFERENTIATION; TRICHOBLASTOMA; PREVALENCE; CANCERS AB Basaloid carcinoma of the breast (BCB) is a rare, triple-negative aggressive primary breast tumor that can closely mimic cutaneous basal cell carcinoma (BCC), neuroendocrine tumors, adnexal neoplasms, and other primary breast tumors. Accurate diagnosis of this tumor is critical for appropriate clinical management. We add to the literature 2 female patients with BCB presenting with a nipple mass. Histopathologic findings from both patients showed dermal nests and cords of atypical basaloid cells with epidermal involvement, closely resembling cutaneous BCC. A panel of immunohistochemical stains, including the novel use of CK17, is essential for differentiating BCB from mimickers. BCB is a rare primary breast tumor that follows an aggressive clinical course and closely mimics many basaloid neoplasms, including cutaneous BCC clinicopathologically. Increased awareness of BCB among dermatologists and dermatopathologists is critical for accurate diagnosis and patient care. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit,Pathol Serv, 55 Fruit St,WRN 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org NR 36 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0193-1091 EI 1533-0311 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD SEP PY 2015 VL 37 IS 9 BP e102 EP e106 DI 10.1097/DAD.0000000000000209 PG 5 WC Dermatology SC Dermatology GA CQ9BY UT WOS:000360907100001 PM 25229570 ER PT J AU Hwang, AS Liu, SW Ashburner, JM Auerbach, BJ Atlas, SJ Hong, CS AF Hwang, Andrew S. Liu, Shan W. Ashburner, Jeffrey M. Auerbach, Brandon J. Atlas, Steven J. Hong, Clemens S. TI Outcomes of primary care patients who are frequent and persistent users of the ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID EMERGENCY-DEPARTMENT USE; ACCESS; VISITS C1 [Hwang, Andrew S.; Ashburner, Jeffrey M.; Auerbach, Brandon J.; Atlas, Steven J.; Hong, Clemens S.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Liu, Shan W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hwang, AS (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. EM ahwang1@partners.org NR 11 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 SEP PY 2015 VL 33 IS 9 BP 1320 EP 1322 DI 10.1016/j.ajem.2015.05.042 PG 6 WC Emergency Medicine SC Emergency Medicine GA CQ9GG UT WOS:000360920700056 PM 26092675 ER PT J AU Raslau, FD Augustinack, JC Klein, AP Ulmer, JL Mathews, VP Mark, LP AF Raslau, F. D. Augustinack, J. C. Klein, A. P. Ulmer, J. L. Mathews, V. P. Mark, L. P. TI Memory Part 3: The Role of the Fornix and Clinical Cases SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID FREQUENT MARIJUANA USE; ALZHEIMERS-DISEASE; COLLOID CYST; REMOVAL; HIPPOCAMPUS; DAMAGE C1 [Raslau, F. D.] Univ Kentucky, Dept Radiol, Lexington, KY USA. [Augustinack, J. C.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Augustinack, J. C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Augustinack, J. C.] Harvard Univ, Sch Med, Boston, MA USA. [Klein, A. P.; Ulmer, J. L.; Mathews, V. P.; Mark, L. P.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. RP Mark, LP (reprint author), Froedtert Hosp, Dept Radiol, Neuroradiol Sect, 9200 West Wisconsin Ave, Milwaukee, WI 53226 USA. EM lmark@mcw.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2015 VL 36 IS 9 BP 1604 EP 1608 DI 10.3174/ajnr.A4371 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CR0WO UT WOS:000361044500008 PM 26045575 ER PT J AU Prah, MA Stufflebeam, SM Paulson, ES Kalpathy-Cramer, J Gerstner, ER Batchelor, TT Barboriak, DP Rosen, BR Schmainda, KM AF Prah, M. A. Stufflebeam, S. M. Paulson, E. S. Kalpathy-Cramer, J. Gerstner, E. R. Batchelor, T. T. Barboriak, D. P. Rosen, B. R. Schmainda, K. M. TI Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL BLOOD-VOLUME; HIGH-GRADE GLIOMA; PERFUSION MRI; ADJUVANT TEMOZOLOMIDE; RESPONSE ASSESSMENT; LEAKAGE-CORRECTION; SURVIVAL; HISTOPATHOLOGY; BEVACIZUMAB; PREDICT AB BACKGROUND AND PURPOSE: For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques. MATERIALS AND METHODS: The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naive and pathologically proved glioblastoma multiforme (men = 20; mean age = 55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method. RESULTS: When ordered by the repeatability coefficient, methods using postprocessing leakage correction and Delta R2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor (P = .31), yet inferior in tumor for normalized relative CBV (P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%-20%) than normalized relative CBV estimates (24%-67%). The minimum number of participants needed to detect a change of 10% or 20% is 118-643 or 30-161 for normalized relative CBV and 109-215 or 28-54 for standardized relative CBV. CONCLUSIONS: The Delta R2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and requiring fewer participants to detect a change compared with normalized relative CBV. C1 [Prah, M. A.; Paulson, E. S.; Schmainda, K. M.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Paulson, E. S.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Stufflebeam, S. M.; Kalpathy-Cramer, J.; Gerstner, E. R.; Batchelor, T. T.; Rosen, B. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Barboriak, D. P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Schmainda, KM (reprint author), Med Coll Wisconsin, Dept Radiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM kathleen@mcw.edu OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [RO1 NS060918]; National Institutes of Health/National Cancer Institute [RO1 CA082500, U01 CA176110, U01 CA154601] FX This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke RO1 NS060918, National Institutes of Health/National Cancer Institute RO1 CA082500, National Institutes of Health/National Cancer Institute U01 CA176110 (Medical College of Wisconsin), and National Institutes of Health/National Cancer Institute U01 CA154601 (Massachusetts General Hospital). NR 37 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2015 VL 36 IS 9 BP 1654 EP 1661 DI 10.3174/ajnr.A4374 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CR0WO UT WOS:000361044500017 PM 26066626 ER PT J AU Ducharme, S Price, BH Larvie, M Dougherty, DD Dickerson, BC AF Ducharme, Simon Price, Bruce H. Larvie, Mykol Dougherty, Darin D. Dickerson, Bradford C. TI Clinical Approach to the Differential Diagnosis Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric Disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PRIMARY PROGRESSIVE APHASIA; LOBAR DEGENERATION; BIPOLAR DISORDER; NEUROPSYCHOLOGICAL FUNCTION; HEXANUCLEOTIDE REPEAT; ALZHEIMER-DISEASE; MAJOR DEPRESSION; SOCIAL COGNITION; CONTROLLED-TRIAL; MOOD DISORDERS C1 [Ducharme, Simon] Massachusetts Gen Hosp, Frontotemporal Disorders Unit, Boston, MA 02114 USA. McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. McGill Univ, Dept Psychiat, Montreal, PQ, Canada. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Ducharme, S (reprint author), Massachusetts Gen Hosp, Frontotemporal Disorders Unit, Boston, MA 02114 USA. EM simon.ducharme@mcgill.ca FU Sidney R. Baer, Jr., Foundation; Fonds de Recherche du Quebec-Sante; McGill University Health Centre Research Institute (Frank McGill Travel Fellowship); Cyberonics; Eli Lilly; Medtronic; Roche FX Dr. Ducharme's fellowship was supported by the Sidney R. Baer, Jr., Foundation, the Fonds de Recherche du Quebec-Sante, and the McGill University Health Centre Research Institute (Frank McGill Travel Fellowship).; Dr. Dougherty has received research support from Cyberonics, Eli Lilly, Medtronic, and Roche and honoraria or travel support from Insys, Johnson & Johnson, Medtronic, and Roche. Dr. Dickerson has served as a consultant for Best Doctors, Forum, Isis, Inc., Haymarket Media, and Piramal, has served on a data safety monitoring board for Merck, and receives royalties from Oxford University Press. The other authors report no financial relationships with commercial interests. NR 76 TC 4 Z9 4 U1 3 U2 8 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 SEP PY 2015 VL 172 IS 9 BP 827 EP 837 DI 10.1176/appi.ajp.2015.14101248 PG 11 WC Psychiatry SC Psychiatry GA CR1SA UT WOS:000361103900005 PM 26324301 ER PT J AU Greenberg, T Chase, HW Almeida, JR Stiffler, R Zevallos, CR Aslam, HA Deckersbach, T Weyandt, S Cooper, C Toups, M Carmody, T Kurian, B Peltier, S Adams, P McInnis, MG Oquendo, MA McGrath, PJ Fava, M Weissman, M Parsey, R Trivedi, MH Phillips, ML AF Greenberg, Tsafrir Chase, Henry W. Almeida, Jorge R. Stiffler, Richelle Zevallos, Carlos R. Aslam, Haris A. Deckersbach, Thilo Weyandt, Sarah Cooper, Crystal Toups, Marisa Carmody, Thomas Kurian, Benji Peltier, Scott Adams, Phillip McInnis, Melvin G. Oquendo, Maria A. McGrath, Patrick J. Fava, Maurizio Weissman, Myrna Parsey, Ramin Trivedi, Madhukar H. Phillips, Mary L. TI Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DOPAMINE; RESPONSES; SCALE; ACTIVATION; FRAMEWORK AB Objective: Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. Method: A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Results: Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. Conclusions: The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response. C1 [Greenberg, Tsafrir] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Univ Michigan, Funct MRI Lab, Ann Arbor, MI 48109 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Behav Sci, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. RP Greenberg, T (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. EM greenbergt@upmc.edu RI Parsey, Ramin/J-8254-2014; Greenberg, Tsafrir /Q-7831-2016 FU NIMH NIH HHS [U01 MH092250, R25 MH101076, U01 MH092221, U01MH092221, U01MH092250] NR 34 TC 9 Z9 9 U1 6 U2 10 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 SEP PY 2015 VL 172 IS 9 BP 881 EP 891 DI 10.1176/appi.ajp.2015.14050594 PG 11 WC Psychiatry SC Psychiatry GA CR1SA UT WOS:000361103900011 PM 26183698 ER PT J AU Wortzel, HS AF Wortzel, Hal S. TI Psychiatric Expert Testimony: Emerging Applications SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Wortzel, Hal S.] Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Care Ctr, Neuropsychiat Consultat Serv, Denver, CO 80220 USA. [Wortzel, Hal S.] Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Care Ctr, Psychiat Fellowship Program, Denver, CO USA. RP Wortzel, HS (reprint author), Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Care Ctr, Neuropsychiat Consultat Serv, Denver, CO 80220 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2015 VL 172 IS 9 BP 915 EP 916 DI 10.1176/appi.ajp.2015.15040480 PG 3 WC Psychiatry SC Psychiatry GA CR1SA UT WOS:000361103900022 PM 26324312 ER PT J AU Mackenzie, DC Khan, NA Blehar, D Glazier, S Chang, YC Stowell, CP Noble, VE Liteplo, AS AF Mackenzie, David C. Khan, Noman A. Blehar, David Glazier, Scott Chang, Yuchiao Stowell, Christopher P. Noble, Vicki E. Liteplo, Andrew S. TI Carotid Flow Time Changes With Volume Status in Acute Blood Loss SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID FLUID RESPONSIVENESS; VENTILATED PATIENTS; SEPTIC SHOCK; WAVE-FORM; TRIAL AB Study objective: Noninvasive predictors of volume responsiveness may improve patient care in the emergency department. Doppler measurements of arterial blood flow have been proposed as a predictor of volume responsiveness. We seek to determine the effect of acute blood loss and a passive leg raise maneuver on corrected carotid artery flow time. Methods: In a prospective cohort of blood donors, we obtained a Doppler tracing of blood flow through the carotid artery before and after blood loss. Measurements of carotid flow time, cardiac cycle time, and peak blood velocity were obtained in supine position and after a passive leg raise. Measurements of flow time were corrected for pulse rate. Results: Seventy-nine donors were screened for participation; 70 completed the study. Donors,had a mean blood loss of 452 mL. Mean corrected carotid artery flow time before blood loss was 320 ms (95% confidence interval [Cl] 315 to 325 ms); this decreased after blood loss to 299 ms (95% Cl 294 to 304 ms). A passive leg raise had little effect on mean corrected carotid artery flow time before blood loss (mean increase 4 ms; 95% Cl -1 to 9 ms), but increased mean corrected carotid artery flow time after blood loss (mean increase 23 ms; 95% Cl 18 to 28 ms) to predonation levels. Conclusion: Corrected carotid artery flow time decreased after acute blood loss. In the setting of acute hypovolemia, a passive leg raise restored corrected carotid artery flow time to predonation levels. Further investigation of corrected carotid artery flow time as a predictor of volume responsiveness is warranted. C1 [Mackenzie, David C.] Maine Med Ctr, Dept Emergency Med, Portland, ME 04102 USA. [Mackenzie, David C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Khan, Noman A.; Glazier, Scott; Chang, Yuchiao; Noble, Vicki E.; Liteplo, Andrew S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Stowell, Christopher P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Blehar, David] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. RP Mackenzie, DC (reprint author), Maine Med Ctr, Dept Emergency Med, Portland, ME 04102 USA. EM DMackenzie@mmc.org OI Mackenzie, David/0000-0002-5535-9964 NR 10 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2015 VL 66 IS 3 BP 277 EP 282 DI 10.1016/j.annemergmed.2015.04.014 PG 6 WC Emergency Medicine SC Emergency Medicine GA CR1JW UT WOS:000361082100015 PM 26003002 ER PT J AU Zhou, HY Tapias, LF Gaissert, HA Muniappan, A Wright, CD Wain, JC Donahue, DM Morse, CR Mathisen, DJ Lanuti, M AF Zhou, Haiyu Tapias, Luis F. Gaissert, Henning A. Muniappan, Ashok Wright, Cameron D. Wain, John C. Donahue, Dean M. Morse, Christopher R. Mathisen, Douglas J. Lanuti, Michael TI Lymph Node Assessment and Impact on Survival in Video-Assisted Thoracoscopic Lobectomy or Segmentectomy SO ANNALS OF THORACIC SURGERY LA English DT Article ID CELL LUNG-CANCER; PROGNOSTIC-FACTOR; NUMBER; DISSECTION; LYMPHADENECTOMY; THORACOTOMY; METASTASIS; VALIDATION; RESECTION; RATIO AB Background. The objective of this study was to evaluate the influence of total number of resected lymph nodes, lymph node ratio, and the number of lymph node stations sampled on prognosis in patients with early stage non-small cell lung cancer (NSCLC) treated with video-assisted thoracoscopic surgery (VATS). Methods. Five hundred and fifty patients who underwent VATS lobectomy or segmentectomy for early clinical stage NSCLC were retrospectively analyzed from 2006 to 2012. Disease-free survival (DFS) and overall survival (OS) were compared for cutoff values of total number of resected lymph nodes (RNs) and lymph node stations (LNS) using Kaplan-Meier methods and Cox proportional hazard models. Results. Lobectomy was performed in 493 (90%) patients with a median follow-up of 2.7 years. Median age was 68 (range, 29 to 92 years) and 342 (62%) were female. Pathologic stage I, II, and III was observed in 434 (79%), 80 (14.5%) and 36 (6.5%) patients, respectively. The N0, N1, and N2 pathologic nodal status was observed in 485 (88%), 38 (7%), and 27 (5%) patients, respectively. Nodal upstaging was observed in 11.3% (59 of 550) in the total cohort and 15% (49 of 332) in patients who underwent LNS greater than 3 compared with 5% (10 of 218) in patients with LNS 3 or less (p < 0.01). Multivariate analysis identified LNS greater than 3 as a negative independent predictor for DFS (hazard ratio 2.36, p = 0.003) and OS (hazard ratio 1.77, p = 0.046). Conclusions. Sampling greater than 3 LNS and greater than 10 RNs was associated with an increase in nodal upstaging. Only LNS greater than 3 was found to be an independent predictor of mortality in VATS lobectomy and segmentectomy in clinical early-stage NSCLC. (C) 2015 by The Society of Thoracic Surgeons C1 Guangdong Gen Hosp, Dept Thorac Surg, Guangzhou, Guangdong, Peoples R China. Southern Med Univ, Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA USA. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu FU Division of Thoracic Surgery at the Massachusetts General Hospital FX Financial support for this study was provided by the Division of Thoracic Surgery at the Massachusetts General Hospital. We would like to acknowledge our data manager and research coordinator, Sheila Knoll and Diane Davies, respectively, for their diligence and dedication toward compiling and maintaining the Thoracic Surgery Database. NR 29 TC 7 Z9 8 U1 3 U2 7 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 SEP PY 2015 VL 100 IS 3 BP 910 EP 917 DI 10.1016/j.athoracsur.2015.04.034 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CQ9VF UT WOS:000360962600029 PM 26165483 ER PT J AU O'Brien, SM Jacobs, JP Pasquali, SK Gaynor, JW Karamlou, T Welke, KF Filardo, G Han, JM Kim, S Shahian, DM Jacobs, ML AF O'Brien, Sean M. Jacobs, Jeffrey P. Pasquali, Sara K. Gaynor, J. William Karamlou, Tara Welke, Karl F. Filardo, Giovanni Han, Jane M. Kim, Sunghee Shahian, David M. Jacobs, Marshall L. TI The Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model: Part 1-Statistical Methodology SO ANNALS OF THORACIC SURGERY LA English DT Article ID SURGICAL REGISTRY DATABASE; PREOPERATIVE FACTORS; ADJUSTMENT; EACTS AB Background. This study's objective was to develop a risk model incorporating procedure type and patient factors to be used for case-mix adjustment in the analysis of hospital-specific operative mortality rates after congenital cardiac operations. Methods. Included were patients of all ages undergoing cardiac operations, with or without cardiopulmonary bypass, at centers participating in The Society of Thoracic Surgeons Congenital Heart Surgery Database during January 1, 2010, to December 31, 2013. Excluded were isolated patent ductus arteriosus closures in patients weighing less than or equal to 2.5 kg, centers with more than 10% missing data, and patients with missing data for key variables. Data from the first 3.5 years were used for model development, and data from the last 0.5 year were used for assessing model discrimination and calibration. Potential risk factors were proposed based on expert consensus and selected after empirically comparing a variety of modeling options. Results. The study cohort included 52,224 patients from 86 centers with 1,931 deaths (3.7%). Covariates included in the model were primary procedure, age, weight, and 11 additional patient factors reflecting acuity status and comorbidities. The C statistic in the validation sample was 0.858. Plots of observed-vs-expected mortality rates revealed good calibration overall and within subgroups, except for a slight overestimation of risk in the highest decile of predicted risk. Removing patient preoperative factors from the model reduced the C statistic to 0.831 and affected the performance classification for 12 of 86 hospitals. Conclusions. The risk model is well suited to adjust for case mix in the analysis and reporting of hospital-specific mortality for congenital heart operations. Inclusion of patient factors added useful discriminatory power and reduced bias in the calculation of hospital-specific mortality metrics. (C) 2015 by The Society of Thoracic Surgeons C1 [O'Brien, Sean M.; Kim, Sunghee] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Johns Hopkins All Childrens Heart Inst, Tampa, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Johns Hopkins All Childrens Heart Inst, Orlando, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Florida Hosp Children, Orlando, FL USA. [Pasquali, Sara K.] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Gaynor, J. William] Childrens Hosp Philadelphia, Dept Surg, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [Karamlou, Tara] Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Cardiac Surg, San Francisco, CA 94143 USA. [Welke, Karl F.] Univ Illinois, Coll Med Peoria, Childrens Hosp Illinois, Sect Congenital Cardiovasc Surg, Peoria, IL USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [Han, Jane M.] Soc Thorac Surg, Chicago, IL USA. [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP O'Brien, SM (reprint author), Duke Clin Res Inst, Rm 0311,Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM sean.m.obrien@duke.edu FU NHLBI NIH HHS [R01 HL122261] NR 18 TC 19 Z9 19 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 SEP PY 2015 VL 100 IS 3 BP 1054 EP 1062 DI 10.1016/j.athoracsur.2015.07.014 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CQ9VF UT WOS:000360962600048 PM 26245502 ER PT J AU Jacobs, JP O'Brien, SM Pasquali, SK Gaynor, JW Mayer, JE Karamlou, T Welke, KF Filardo, G Han, JM Kim, S Quintessenza, JA Pizarro, C Tchervenkov, CI Lacour-Gayet, F Mavroudis, C Backer, CL Austin, EH Fraser, CD Tweddell, JS Jonas, RA Edwards, FH Grover, FL Prager, RL Shahian, DM Jacobs, ML AF Jacobs, Jeffrey P. O'Brien, Sean M. Pasquali, Sara K. Gaynor, J. William Mayer, John E., Jr. Karamlou, Tara Welke, Karl F. Filardo, Giovanni Han, Jane M. Kim, Sunghee Quintessenza, James A. Pizarro, Christian Tchervenkov, Christo I. Lacour-Gayet, Francois Mavroudis, Constantine Backer, Carl L. Austin, Erle H., III Fraser, Charles D. Tweddell, James S. Jonas, Richard A. Edwards, Fred H. Grover, Frederick L. Prager, Richard L. Shahian, David M. Jacobs, Marshall L. TI The Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model: Part 2-Clinical Application SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 05-08, 2014 CL Tucson, AZ SP So Thorac Surg Assoc ID EMPIRICALLY BASED TOOL; CARDIAC-SURGERY; OPERATIONS; OUTCOMES; DISEASE AB Background. The empirically derived 2014 Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model incorporates adjustment for procedure type and patient-specific factors. The purpose of this report is to describe this model and its application in the assessment of variation in outcomes across centers. Methods. All index cardiac operations in The Society of Thoracic Surgeons Congenital Heart Surgery Database (January 1, 2010, to December 31, 2013) were eligible for inclusion. Isolated patent ductus arteriosus closures in patients weighing less than or equal to 2.5 kg were excluded, as were centers with more than 10% missing data and patients with missing data for key variables. The model includes the following covariates: primary procedure, age, any prior cardiovascular operation, any noncardiac abnormality, any chromosomal abnormality or syndrome, important preoperative factors (mechanical circulatory support, shock persisting at time of operation, mechanical ventilation, renal failure requiring dialysis or renal dysfunction (or both), and neurological deficit), any other preoperative factor, prematurity (neonates and infants), and weight (neonates and infants). Variation across centers was assessed. Centers for which the 95% confidence interval for the observed-to-expected mortality ratio does not include unity are identified as lower-performing or higher-performing programs with respect to operative mortality. Results. Included were 52,224 operations from 86 centers. Overall discharge mortality was 3.7% (1,931 of 52,224). Discharge mortality by age category was neonates, 10.1% (1,129 of 11,144); infants, 3.0% (564 of 18,554), children, 0.9% (167 of 18,407), and adults, 1.7% (71 of 4,119). For all patients, 12 of 86 centers (14%) were lower-performing programs, 67 (78%) were not outliers, and 7 (8%) were higher-performing programs. Conclusions. The 2014 Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model facilitates description of outcomes (mortality) adjusted for procedural and for patient-level factors. Identification of low-performing and high-performing programs may be useful in facilitating quality improvement efforts. (C) 2015 by The Society of Thoracic Surgeons C1 [Jacobs, Jeffrey P.; Quintessenza, James A.; Mavroudis, Constantine; Jacobs, Marshall L.] Johns Hopkins Childrens Heart Inst, St Petersburg, FL 33701 USA. [Jacobs, Jeffrey P.; Quintessenza, James A.; Mavroudis, Constantine; Jacobs, Marshall L.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. [Jacobs, Jeffrey P.; Quintessenza, James A.; Mavroudis, Constantine; Jacobs, Marshall L.] Florida Hosp Children, Orlando, FL USA. [O'Brien, Sean M.; Kim, Sunghee] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Pasquali, Sara K.] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Gaynor, J. William] Childrens Hosp Philadelphia, Dept Surg, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [Mayer, John E., Jr.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA USA. [Karamlou, Tara] Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Cardiac Surg, San Francisco, CA 94143 USA. [Welke, Karl F.] Univ Illinois, Coll Med, Childrens Hosp Illinois, Sect Congenital Cardiovasc Surg, Peoria, IL 61656 USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [Han, Jane M.] Soc Thorac Surg, Chicago, IL USA. [Pizarro, Christian] Nemours Alfred I duPont Hosp, Wilmington, DE USA. [Tchervenkov, Christo I.] McGill Univ, Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. [Lacour-Gayet, Francois] Royal Brompton Hosp, London SW3 6LY, England. [Backer, Carl L.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Austin, Erle H., III] Univ Louisville, Kosair Childrens Hosp, Louisville, KY 40292 USA. [Fraser, Charles D.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Tweddell, James S.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Jonas, Richard A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Edwards, Fred H.] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Grover, Frederick L.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Prager, Richard L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Jacobs, JP (reprint author), Johns Hopkins Childrens Heart Inst, Cardiac Surg, 601 Fifth St South,Ste 607, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com FU NCATS NIH HHS [UL1 TR000430]; NHLBI NIH HHS [R01 HL122261] NR 16 TC 18 Z9 18 U1 0 U2 2 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 SEP PY 2015 VL 100 IS 3 BP 1063 EP 1070 DI 10.1016/j.athoracsur.2015.07.011 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CQ9VF UT WOS:000360962600049 PM 26245504 ER PT J AU Goldberg, JB Sundt, TM AF Goldberg, Joshua B. Sundt, Thoralf M., III TI More Data Are Needed to Determine an Association Between Transfusions and Coronary Artery Bypass Graft Occlusion SO ANNALS OF THORACIC SURGERY LA English DT Letter ID SAPHENOUS-VEIN; THERAPY C1 [Goldberg, Joshua B.; Sundt, Thoralf M., III] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, Boston, MA 02114 USA. RP Goldberg, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM jgoldberg0@partners.org NR 4 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 SEP PY 2015 VL 100 IS 3 BP 1135 EP 1135 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CQ9VF UT WOS:000360962600080 PM 26354661 ER PT J AU Di Eusanio, M Nienaber, CA Sundt, TM Patel, HJ Trimarchi, S Myrmel, T Eagle, KA AF Di Eusanio, Marco Nienaber, Christoph A. Sundt, Thoralf M. Patel, Himanshu J. Trimarchi, Santi Myrmel, Truls Eagle, Kim A. TI Type A Aortic Dissection: The Controversy of the Root Replacement Reply SO ANNALS OF THORACIC SURGERY LA English DT Letter C1 [Di Eusanio, Marco] G Mazzini Hosp, Cardiovasc Dept, Cardiac Surg Unit, I-64100 Teramo, Italy. [Nienaber, Christoph A.] Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Patel, Himanshu J.] Univ Michigan Hlth Syst, Cardiac Surg, Ann Arbor, MI USA. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Myrmel, Truls] Univ Tromso Hosp, Dept Thorac & Cardiovasc Surg, N-9012 Tromso, Norway. [Eagle, Kim A.] Univ Michigan Hlth Syst, Cardiovasc Ctr, Ann Arbor, MI USA. RP Di Eusanio, M (reprint author), G Mazzini Hosp, Cardiovasc Dept, Cardiac Surg Unit, Piazza Italia, I-64100 Teramo, Italy. EM marco.dieusanio@aslteramo.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2015 VL 100 IS 3 BP 1137 EP 1138 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CQ9VF UT WOS:000360962600083 PM 26354663 ER PT J AU Akca, BI Chang, EW Kling, S Ramier, A Scarcelli, G Marcos, S Yun, SH AF Akca, B. Imran Chang, Ernest W. Kling, Sabine Ramier, Antoine Scarcelli, Giuliano Marcos, Susana Yun, Seok H. TI Observation of sound-induced corneal vibrational modes by optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OCULAR RESPONSE ANALYZER; COLLAGEN CROSS-LINKING; BIOMECHANICAL PROPERTIES; ELASTOGRAPHY; KERATOCONUS; MICROSCOPY; ELASTICITY; OCT AB The mechanical stability of the cornea is critical for maintaining its normal shape and refractive function. Here, we report an observation of the mechanical resonance modes of the cornea excited by sound waves and detected by using phase-sensitive optical coherence tomography. The cornea in bovine eye globes exhibited three resonance modes in a frequency range of 50-400 Hz. The vibration amplitude of the fundamental mode at 80-120 Hz was similar to 8 mu m at a sound pressure level of 100 dB (2 Pa). Vibrography allows the visualization of the radially symmetric profiles of the resonance modes. A dynamic finite-element analysis supports our observation. (C)c 2015 Optical Society of America C1 [Akca, B. Imran; Chang, Ernest W.; Ramier, Antoine; Scarcelli, Giuliano; Yun, Seok H.] Wellman Ctr Photomed, Boston, MA 02140 USA. [Akca, B. Imran; Chang, Ernest W.; Ramier, Antoine; Scarcelli, Giuliano; Yun, Seok H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02140 USA. [Kling, Sabine; Marcos, Susana] CSIC, Inst Opt, E-28006 Madrid, Spain. [Ramier, Antoine] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Scarcelli, Giuliano] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. RP Akca, BI (reprint author), Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02140 USA. RI Akca, Imran/A-2280-2016 FU National Institutes of Health [R01-EY025454, P41-EB015903, UL1-RR025758, R21EY023043, K25EB015885]; National Science Foundation [1264356]; European Research Council [ERC-2011 AdG-294099]; Spanish Government [FIS2011-25637, FIS2014-56643-R, FPI-BES-2009-024560] FX This work was supported by National Institutes of Health (R01-EY025454, P41-EB015903, UL1-RR025758, R21EY023043, K25EB015885), National Science Foundation (1264356), European Research Council (ERC-2011 AdG-294099), and Spanish Government (FIS2011-25637; FIS2014-56643-R and FPI-BES-2009-024560). NR 26 TC 4 Z9 4 U1 0 U2 9 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 SEP 1 PY 2015 VL 6 IS 9 BP 3313 EP 3319 DI 10.1364/BOE.6.003313 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CQ8VR UT WOS:000360888400018 PM 26417503 ER PT J AU Merrick, GS Wallner, KE Galbreath, RW Butler, WM Fiano, R Orio, PF Adamovich, E AF Merrick, Gregory S. Wallner, Kent E. Galbreath, Robert W. Butler, Wayne M. Fiano, Ryan Orio, Peter F., III Adamovich, Edward TI Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with Pd-103? Results of two prospective randomized trials SO BRACHYTHERAPY LA English DT Article DE Brachytherapy; Higher risk; Supplemental external beam radiation therapy; Prospective randomized trial ID BIOCHEMICAL FAILURE; BRACHYTHERAPY; DOSIMETRY; OUTCOMES; GY AB PURPOSE: To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 (Pd-103) brachytherapy for high-risk prostate cancer patients. METHODS AND MATERIALS: Trial 44/20 randomized patients to 44 Gy plus 90 Gy Pd-103 vs. 20 Gy with 115 Gy Pd-103, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy Pd-103 without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D-90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. RESULTS: In 44/20 trial, 13-year BF, prostate cancer specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02 ng/mL. CONCLUSIONS: With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Fiano, Ryan] Wheeling Jesuit Univ, Schiffier Canc Ctr, Dept Radiat Oncol, Wheeling, WV 26003 USA. [Merrick, Gregory S.] Wheeling Hosp, Dept Urol, Wheeling, WV 26003 USA. [Wallner, Kent E.] Puget Sound Hlth Care Syst, Dept Radiat Oncol, Seattle, WA USA. [Galbreath, Robert W.] Ohio Univ Eastern, St Clairsville, OH USA. [Orio, Peter F., III] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. [Adamovich, Edward] Wheeling Hosp, Dept Pathol, Wheeling, WV 26003 USA. RP Merrick, GS (reprint author), Wheeling Hosp, Schiffler Canc Ctr, 1 Med Pk, Wheeling, WV 26003 USA. EM gmerrick@urologicresearchinstitute.org NR 19 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 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2015 VL 14 IS 5 BP 677 EP 685 DI 10.1016/j.brachy.2015.05.001 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CR1JG UT WOS:000361080400013 PM 26051802 ER PT J AU Karabanov, A Ziemann, U Hamada, M George, MS Quartarone, A Classen, J Massimini, M Rothwell, J Siebner, HR AF Karabanov, Anke Ziemann, Ulf Hamada, Masashi George, Mark S. Quartarone, Angelo Classen, Joseph Massimini, Marcello Rothwell, John Siebner, Hartwig Roman TI Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation (vol 8, pg 442, 2015) SO BRAIN STIMULATION LA English DT Correction C1 [Karabanov, Anke; Siebner, Hartwig Roman] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. [Ziemann, Ulf] Univ Tubingen, Dept Neurol & Stroke, Tubingen, Germany. [Ziemann, Ulf] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Hamada, Masashi] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [George, Mark S.] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Quartarone, Angelo] Univ Messina, Dept Neurosci, I-98100 Messina, Italy. [Classen, Joseph] Univ Hosp Leipzig, Dept Neurol, Leipzig, Germany. [Massimini, Marcello] Univ Milan, Dept Clin Sci, I-20122 Milan, Italy. [Rothwell, John] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England. [Siebner, Hartwig Roman] Univ Copenhagen, Bispebjerg Hosp, Dept Neurol, Copenhagen, Denmark. RP Karabanov, A (reprint author), Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM ankenk@drcmr.dk NR 1 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD SEP-OCT PY 2015 VL 8 IS 5 BP 92 EP 92 DI 10.1016/j.brs.2015.06.016 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR0ME UT WOS:000361012000028 ER PT J AU Mir-Moghtadaei, A Caballero, R Fried, P Fox, MD Lee, K Giacobbe, P Daskalakis, ZJ Blumberger, DM Downar, J AF Mir-Moghtadaei, Arsalan Caballero, Ruth Fried, Peter Fox, Michael D. Lee, Katherine Giacobbe, Peter Daskalakis, Zafiris J. Blumberger, Daniel M. Downar, Jonathan TI Concordance Between BeamF3 and MRI-neuronavigated Target Sites for Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex SO BRAIN STIMULATION LA English DT Article DE Neuronavigation; Prefrontal cortex; Transcranial magnetic stimulation; Magnetic resonance imaging; Scalp ID TREATMENT-RESISTANT DEPRESSION; OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; TREATING MAJOR DEPRESSION; THETA-BURST STIMULATION; SHAM-CONTROLLED TRIAL; DOUBLE-BLIND; RANDOMIZED-TRIAL; FUNCTIONAL CONNECTIVITY; WORKING-MEMORY AB Background: The dorsolateral prefrontal cortex (DLPFC) is a common target for repetitive transcranial magnetic stimulation (rTMS) in major depression, but the conventional "5 cm rule" misses DLPFC in >1/3 cases. Another heuristic, BeamF3, locates the F3 EEG site from scalp measurements. MRI-guided neuronavigation is more onerous, but can target a specific DLPFC stereotaxic coordinate directly. The concordance between these two approaches has not previously been assessed. Objective: To quantify the discrepancy in scalp site between BeamF3 versus MRI-guided neuronavigation for left DLPFC. Methods: Using 100 pre-treatment MRIs from subjects undergoing left DLPFC-rTMS, we localized the scalp site at minimum Euclidean distance from a target MNI coordinate (X - 38 Y + 44 Z + 26) derived from our previous work. We performed nasion-inion, tragusetragus, and head-circumference measurements on the same subjects' MRIs, and applied the BeamF3 heuristic. We then compared the distance between BeamF3 and MRI-guided scalp sites. Results: BeamF3-to-MRI-guided discrepancies were <0.65 cm in 50% of subjects, <0.99 cm in 75% of subjects, and <1.36 cm in 95% of subjects. The angle from midline to the scalp site did not differ significantly using MRI-guided versus BeamF3 methods. However, the length of the radial arc from vertex to target site was slightly but significantly longer (mean 0.35 cm) with MRI-guidance versus BeamF3. Conclusions: The BeamF3 heuristic may provide a reasonable approximation to MRI-guided neuronavigation for locating left DLPFC in a majority of subjects. A minor optimization of the heuristic may yield additional concordance. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Mir-Moghtadaei, Arsalan; Lee, Katherine] Univ Toronto, Fac Arts & Sci, Toronto, ON M5S 1A1, Canada. [Caballero, Ruth; Fried, Peter; Fox, Michael D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02215 USA. [Fox, Michael D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fox, Michael D.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Boston, MA USA. [Caballero, Ruth] Univ Politecn Madrid, Bioengn & Telemed Ctr, ETSI Telecomunicac, E-28040 Madrid, Spain. [Daskalakis, Zafiris J.; Blumberger, Daniel M.; Downar, Jonathan] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Giacobbe, Peter; Daskalakis, Zafiris J.; Blumberger, Daniel M.; Downar, Jonathan] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Daskalakis, Zafiris J.; Blumberger, Daniel M.] Ctr Addict & Mental Hlth, Temerty Ctr Therapeut Brain Intervent, Toronto, ON, Canada. [Giacobbe, Peter; Downar, Jonathan] Univ Hlth Network, MRI Guided rTMS Clin, Toronto, ON M5T 2S8, Canada. RP Downar, J (reprint author), Univ Hlth Network, MRI Guided rTMS Clin, 399 Bathurst St 7M-415, Toronto, ON M5T 2S8, Canada. EM jonathan.downar@uhn.ca RI Downar, Jonathan/I-9002-2016 OI Downar, Jonathan/0000-0002-5140-174X FU Canadian Institutes of Health Research [MOP136801]; Brain Canada; Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation; Edgestone Foundation through the Toronto General and Western Hospital Foundation FX The authors acknowledge support for this research from the Canadian Institutes of Health Research (MOP136801), Brain Canada, the Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation, and the Edgestone Foundation through the Toronto General and Western Hospital Foundation. NR 48 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD SEP-OCT PY 2015 VL 8 IS 5 BP 965 EP 973 DI 10.1016/j.brs.2015.05.008 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR0ME UT WOS:000361012000017 PM 26115776 ER PT J AU Karabanov, A Ziemann, U Hamada, M George, MS Quartarone, A Classen, J Massimini, M Rothwell, J Siebner, HR AF Karabanov, Anke Ziemann, Ulf Hamada, Masashi George, Mark S. Quartarone, Angelo Classen, Joseph Massimini, Marcello Rothwell, John Siebner, Hartwig Roman TI Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation SO BRAIN STIMULATION LA English DT Article ID HUMAN MOTOR CORTEX; LONG-TERM POTENTIATION; THETA-BURST STIMULATION; PAIRED ASSOCIATIVE STIMULATION; BIDIRECTIONAL SYNAPTIC PLASTICITY; PARKINSONS-DISEASE PATIENTS; DEPRESSION-LIKE PLASTICITY; LOW-FREQUENCY STIMULATION; FOCAL HAND DYSTONIA; LTP-LIKE PLASTICITY AB Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Karabanov, Anke; Siebner, Hartwig Roman] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. [Ziemann, Ulf] Univ Tubingen, Dept Neurol & Stroke, Hertie Inst Clin Brain Res, Tubingen, Germany. [Hamada, Masashi] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [George, Mark S.] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Quartarone, Angelo] Univ Messina, Dept Neurosci, I-98100 Messina, Italy. [Classen, Joseph] Univ Hosp Leipzig, Dept Neurol, Leipzig, Germany. [Massimini, Marcello] Univ Milan, Dept Clin Sci, I-20122 Milan, Italy. [Rothwell, John] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England. [Siebner, Hartwig Roman] Univ Copenhagen, Bispebjerg Hosp, Dept Neurol, Copenhagen, Denmark. RP Karabanov, A (reprint author), Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM ankenk@drcmr.dk OI Rothwell, John/0000-0003-1367-6467; QUARTARONE, Angelo/0000-0003-1485-6590; Massimini, Marcello/0000-0003-2271-957X FU Swedish Research Council [2011-38769-82837-71] FX AK was supported by the Swedish Research Council (2011-38769-82837-71). NR 162 TC 6 Z9 6 U1 6 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD SEP-OCT PY 2015 VL 8 IS 5 BP 993 EP 1006 DI 10.1016/j.brs.2015.06.017 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR0ME UT WOS:000361012000029 PM 26598772 ER PT J AU Hirsch, J DePalma, G Tsai, TT Sands, LP Leung, JM AF Hirsch, J. DePalma, G. Tsai, T. T. Sands, L. P. Leung, J. M. TI Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE arterial blood pressure; delirium; hypotension ID IMPAIRED CEREBRAL AUTOREGULATION; OBSTRUCTIVE SLEEP-APNEA; RISK-FACTORS; ELDERLY-PATIENTS; HIP FRACTURE; HALOPERIDOL PROPHYLAXIS; PROGNOSTIC-SIGNIFICANCE; COGNITIVE DYSFUNCTION; PREDISPOSING FACTORS; SURGICAL-PATIENTS AB Introduction: Postoperative delirium is common in older patients. Despite its prognostic significance, the pathophysiology is incompletely understood. Although many risk factors have been identified, no reversible factors, particularly ones potentially modifiable by anaesthetic management, have been identified. The goal of this prospective cohort study was to investigate whether intraoperative hypotension was associated with postoperative delirium in older patients undergoing major non-cardiac surgery. Methods: Study subjects were patients >65 years of age, undergoing major non-cardiac surgery, who were enrolled in an ongoing prospective observational study of the pathophysiology of postoperative delirium. Intraoperative blood pressure was measured and predefined criteria were used to define hypotension. Delirium was measured by the Confusion Assessment Method on the first two postoperative days. Data were analysed using t-tests, two-sample proportion tests and ordered logistic regression multivariable models, including correction for multiple comparisons. Results: Data from 594 patients with a mean age of 73.6 years (SD 6.2) were studied. Of these 178 (30%) developed delirium on day 1 and 176 (30%) on day 2. Patients developing delirium were older, more often female, had lower preoperative cognitive scores, and underwent longer operations. Relative hypotension (decreases by 20, 30, or 40%) or absolute hypotension [mean arterial pressure (MAP)<50 mm Hg] were not significantly associated with postoperative delirium, nor was the duration of hypotension (MAP<50 mm Hg). Conversely, intraoperative blood pressure variance was significantly associated with postoperative delirium. Discussion: These results showed that increased blood pressure fluctuation, not absolute or relative hypotension, was predictive of postoperative delirium. C1 [Hirsch, J.; Tsai, T. T.; Leung, J. M.] Univ Calif San Francisco, Dept Anaesthesia & Perioperat Care, San Francisco, CA 94143 USA. [DePalma, G.; Sands, L. P.] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. RP Hirsch, J (reprint author), Univ Calif San Francisco, San Francisco VAMC, San Francisco Anesthesiol Serv, Dept Anaesthesia & Perioperat Care, 4150 Clement St,Mail 129, San Francisco, CA 94121 USA. EM jan.hirsch@ucsf.edu RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU Anesthesia Patient Safety Foundation (Indianapolis, IN, USA); National Institutes of Health of the United States (NIH) [1RO1AG031795-05] FX This work was supported by funding from the Anesthesia Patient Safety Foundation (Indianapolis, IN, USA), and the National Institutes of Health of the United States (NIH 1RO1AG031795-05) (to J.M.L.). NR 71 TC 16 Z9 18 U1 5 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD SEP PY 2015 VL 115 IS 3 BP 418 EP 426 DI 10.1093/bja/aeu458 PG 9 WC Anesthesiology SC Anesthesiology GA CR2WL UT WOS:000361191400015 PM 25616677 ER PT J AU Jin, K Park, S Teo, WW Korangath, P Cho, SS Yoshida, T Gyorffy, B Goswami, CP Nakshatri, H Cruz, LA Zhou, WQ Ji, HK Su, Y Ekram, M Wu, ZS Zhu, T Polyak, K Sukumar, S AF Jin, Kideok Park, Sunju Teo, Wei Wen Korangath, Preethi Cho, Sean Soonweng Yoshida, Takahiro Gyorffy, Balazs Goswami, Chirayu Pankaj Nakshatri, Harikrishna Cruz, Leigh-Ann Zhou, Weiqiang Ji, Hongkai Su, Ying Ekram, Muhammad Wu, Zhengsheng Zhu, Tao Polyak, Kornelia Sukumar, Saraswati TI HOXB7 Is an ER alpha Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance SO CANCER DISCOVERY LA English DT Article ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR MODULATORS; TAMOXIFEN RESISTANCE; TRANSCRIPTION FACTOR; CLINICAL-PRACTICE; BINDING-SITES; EXPRESSION; THERAPY; PHOSPHORYLATION; MECHANISMS AB Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor-alpha (ER alpha) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 chromatin immunoprecipitation analysis followed by validation showed that HOXB7 physically interacts with ER alpha, and that the HOXB7-ER alpha complex enhances transcription of many ER alpha target genes, including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR-HER2 signaling, inhibits transcription of miR-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER target genes, and HER2. Repressing MYC using small-molecule inhibitors reverses these events and causes regression of breast cancer xenografts. The MYC-HOXB7-HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer. SIGNIFICANCE: HOXB7 acts as an ER alpha cofactor regulating a myriad of ER target genes, including HER2, in tamoxifen-resistant breast cancer. HOXB7 expression is controlled by MYC via transcriptional regulation of the HOXB7 repressor miR-196a; consequently, antagonists of MYC cause reversal of selective ER modulator resistance both in vitro and in vivo. (C) 2015 AACR. C1 [Jin, Kideok; Park, Sunju; Teo, Wei Wen; Korangath, Preethi; Cho, Sean Soonweng; Yoshida, Takahiro; Cruz, Leigh-Ann; Sukumar, Saraswati] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD USA. [Gyorffy, Balazs] Semmelweis Univ, MTA TTK Lendulet Canc Biomarker Res Grp, H-1085 Budapest, Hungary. [Yoshida, Takahiro] Semmelweis Univ, Dept Pediat 2, H-1085 Budapest, Hungary. [Goswami, Chirayu Pankaj; Nakshatri, Harikrishna] Indiana Univ, Ctr Computat Biol & Bioinformat, Bloomington, IN USA. [Zhou, Weiqiang; Ji, Hongkai] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Su, Ying; Ekram, Muhammad; Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Zhengsheng; Zhu, Tao] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China. [Wu, Zhengsheng; Zhu, Tao] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. RP Sukumar, S (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1650 Orleans St,CRB 1,Room 143, Baltimore, MD 21231 USA. EM saras@jhmi.edu FU Susan G. Komen Foundation Leadership Grant [SAC110050]; Department of Defense Center of Excellence [W81XWH-04-1-0595]; SKCCC Core Grant [P30 CA006973]; Susan G. Komen Foundation Postdoctoral Fellowship [KG101506]; OTKA [K108655]; Susan G. Komen Foundation [SAC110025]; NIH [R01HG006282] FX This work was supported by Susan G. Komen Foundation Leadership Grant SAC110050 (to S. Sukumar), Department of Defense Center of Excellence W81XWH-04-1-0595 (to S. Sukumar), SKCCC Core Grant P30 CA006973 (to S. Sukumar), Susan G. Komen Foundation Postdoctoral Fellowship KG101506 (to K. Jin), the OTKA K108655 Grant (to B. Gyorffy), Susan G. Komen Foundation Grant SAC110025 (to H. Nakshatri), and NIH R01HG006282 (to H. Nakshatri). NR 68 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 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2015 VL 5 IS 9 BP 944 EP 959 DI 10.1158/2159-8290.CD-15-0090 PG 16 WC Oncology SC Oncology GA CQ8DA UT WOS:000360835200025 PM 26180042 ER PT J AU Tricker, EM Xu, CX Uddin, S Capelletti, M Ercan, D Ogino, A Pratilas, CA Rosen, N Gray, NS Wong, KK Janne, PA AF Tricker, Erin M. Xu, Chunxiao Uddin, Sharmeen Capelletti, Marzia Ercan, Dalia Ogino, Atsuko Pratilas, Christine A. Rosen, Neal Gray, Nathanael S. Wong, Kwok-Kin Jaenne, Pasi A. TI Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR-Mutant Lung Cancer SO CANCER DISCOVERY LA English DT Article ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; GEFITINIB; MUTATION; ACTIVATION; T790M; AMPLIFICATION; MECHANISM; ERLOTINIB; THERAPY AB Irreversible pyrimidine-based EGFR inhibitors, including WZ4002, selectively inhibit both EGFR-activating and EGFR inhibitor-resistant T790M mutations more potently than wild-type EGFR. Although this class of mutant-selective EGFR inhibitors is effective clinically in lung cancer patients harboring EGFR(T790M), prior preclinical studies demonstrate that acquired resistance can occur through genomic alterations that activate ERK1/2 signaling. Here, we find that ERK1/2 reactivation occurs rapidly following WZ4002 treatment. Concomitant inhibition of ERK1/2 by the MEK inhibitor trametinib prevents ERK1/2 reactivation, enhances WZ4002-induced apoptosis, and inhibits the emergence of resistance in WZ4002-sensitive models known to acquire resistance via both T790M-dependent and T790M-independent mechanisms. Resistance to WZ4002 in combination with trametinib eventually emerges due to AKT/mTOR reactivation. These data suggest that initial cotargeting of EGFR and MEK could significantly impede the development of acquired resistance in EGFR-mutant lung cancer. SIGNIFICANCE: Patients with EGFR-mutant lung cancer develop acquired resistance to EGFR and mutant-selective EGFR tyrosine kinase inhibitors. Here, we show that cotargeting EGFR and MEK can prevent the emergence of a broad variety of drug resistance mechanisms in vitro and in vivo and may be a superior therapeutic regimen for these patients. (C) 2015 AACR. C1 [Tricker, Erin M.; Xu, Chunxiao; Capelletti, Marzia; Ercan, Dalia; Ogino, Atsuko; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Tricker, Erin M.; Xu, Chunxiao; Capelletti, Marzia; Ercan, Dalia; Ogino, Atsuko; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Uddin, Sharmeen; Pratilas, Christine A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Uddin, Sharmeen; Pratilas, Christine A.; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10021 USA. [Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM223, Boston, MA 02215 USA. EM Pasi_Janne@dfci.harvard.edu FU NIH [RO1CA114465, R01CA135257, PO1CA154303] FX This study was supported by grants from the NIH RO1CA114465 (to P.A. Janne), R01CA135257 (to P.A. Janne), and PO1CA154303 (to P.A. Janne, N.S. Gray, and K.-K. Wong). NR 39 TC 30 Z9 31 U1 1 U2 12 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 SEP PY 2015 VL 5 IS 9 BP 960 EP 971 DI 10.1158/2159-8290.CD-15-0063 PG 12 WC Oncology SC Oncology GA CQ8DA UT WOS:000360835200026 PM 26036643 ER PT J AU Cottini, F Hideshima, T Suzuki, R Tai, YT Bianchini, G Richardson, PG Anderson, KC Tonon, G AF Cottini, Francesca Hideshima, Teru Suzuki, Rikio Tai, Yu-Tzu Bianchini, Giampaolo Richardson, Paul G. Anderson, Kenneth C. Tonon, Giovanni TI Synthetic Lethal Approaches Exploiting DNA Damage in Aggressive Myeloma SO CANCER DISCOVERY LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; MULTIPLE-MYELOMA; C-MYC; GENOMIC INSTABILITY; REPLICATION STRESS; CANCER-CELLS; CHROMOSOMAL INSTABILITY; EXPRESSION PROFILES; PARP INHIBITORS; MOUSE MODEL AB Ongoing DNA damage is a common feature of epithelial cancers. Here, we show that tumor cells derived from multiple myeloma, a disease of clonal plasma cells, demonstrate DNA-replicative stress, leading to DNA damage. We identified a poor-prognosis subset of multiple myeloma with extensive chromosomal instability and replicative stress, which rely on ATR to compensate for DNA-replicative stress; conversely, silencing of ATR or treatment with a specific ATR inhibitor triggers multiple myeloma cell apoptosis. We show that oncogenes, such as MYC, induce DNA damage in multiple myeloma cells not only by increased replicative stress, but also via increased oxidative stress, and that reactive oxygen species-inducer piperlongumine triggers further DNA damage and apoptosis. Importantly, ATR inhibition combined with piperlongumine triggers synergistic multiple myeloma cytotoxicity. This synthetic lethal approach, enhancing oxidative stress while concomitantly blocking replicative stress response, provides a novel combination targeted therapy to address an unmet medical need in this subset of multiple myeloma. SIGNIFICANCE: Multiple myeloma remains an incurable disease. We have identified a subset of multiple myeloma patients with poor prognosis, whose tumors present chromosomal instability, replicative and oxidative stress, and DNA damage. We define a synthetic lethal approach enhancing oxidative stress while targeting replicative stress response, inducing tumor cell apoptosis in this patient subset. Cancer (C) 2015 AACR. C1 [Cottini, Francesca; Hideshima, Teru; Suzuki, Rikio; Tai, Yu-Tzu; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Cottini, Francesca; Tonon, Giovanni] IRCCS, San Raffaele Sci Inst, Div Expt Oncol, Funct Genom Canc Unit, Milan, Italy. [Bianchini, Giampaolo] Hosp San Raffaele, IRCCS, Dept Med Oncol, I-20132 Milan, Italy. RP Tonon, G (reprint author), Ist Sci San Raffaele, Via Olgettina 60, I-20132 Milan, Italy. EM kenneth_anderson@dfci.harvard.edu; tonon.giovanni@hsr.it FU Associazione Italiana per la Ricerca sul Cancro (AIRC Investigator Grants and Special Program Molecular Clinical Oncology) [9965]; NIH [NIH SPORE P50 100707, P01 78378, R01 50947] FX This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC Investigator Grants and Special Program Molecular Clinical Oncology, 5 per mille no. 9965; to G. Tonon). K.C. Anderson is an American Cancer Society Clinical Research Professor and is supported by the NIH grants NIH SPORE P50 100707, P01 78378, and R01 50947. NR 57 TC 12 Z9 12 U1 1 U2 6 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 SEP PY 2015 VL 5 IS 9 BP 972 EP 987 DI 10.1158/2159-8290.CD-14-0943 PG 16 WC Oncology SC Oncology GA CQ8DA UT WOS:000360835200027 PM 26080835 ER PT J AU Putt, M Hahn, VS Januzzi, JL Sawaya, H Sebag, IA Plana, JC Picard, MH Carver, JR Halpern, EF Kuter, I Passeri, J Cohen, V Banchs, J Martin, RP Gerszten, RE Scherrer-Crosbie, M Ky, B AF Putt, Mary Hahn, Virginia Shalkey Januzzi, James L. Sawaya, Heloisa Sebag, Igal A. Plana, Juan Carlos Picard, Michael H. Carver, Joseph R. Halpern, Elkan F. Kuter, Irene Passeri, Jonathan Cohen, Victor Banchs, Jose Martin, Randolph P. Gerszten, Robert E. Scherrer-Crosbie, Marielle Ky, Bonnie TI Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab SO CLINICAL CHEMISTRY LA English DT Article ID PLACENTAL GROWTH-FACTOR; HIGH-DOSE CHEMOTHERAPY; HEART-FAILURE; ADJUVANT TRASTUZUMAB; PROGNOSTIC VALUE; TROPONIN-I; CARDIAC DYSFUNCTION; OXIDATIVE STRESS; EUROPEAN-SOCIETY; ECHOCARDIOGRAPHY AB BACKGROUND: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS: Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts. (C) 2015 American Association for Clinical Chemistry C1 [Putt, Mary; Hahn, Virginia Shalkey; Carver, Joseph R.; Ky, Bonnie] Univ Penn, Philadelphia, PA 19104 USA. [Januzzi, James L.; Sawaya, Heloisa; Picard, Michael H.; Halpern, Elkan F.; Kuter, Irene; Passeri, Jonathan; Gerszten, Robert E.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Januzzi, James L.; Sawaya, Heloisa; Picard, Michael H.; Halpern, Elkan F.; Kuter, Irene; Passeri, Jonathan; Gerszten, Robert E.; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA. [Sebag, Igal A.; Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Montreal, CA USA. [Sebag, Igal A.; Cohen, Victor] McGill Univ, Montreal, CA USA. [Plana, Juan Carlos] Baylor Coll Med, Houston, TX 77030 USA. [Banchs, Jose] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Martin, Randolph P.] Piedmont Heart Inst, Atlanta, GA USA. RP Ky, B (reprint author), Univ Penn, Sch Med, Smilow Translat Res Ctr, 3400 Civic Ctr Blvd,11-105, Philadelphia, PA 19104 USA. EM bonnie.ky@uphs.upenn.edu OI Picard, Michael/0000-0002-9264-3243 FU Siemens; Thermo Fisher; Singulex; Siemens HealthCare Diagnostics; Abbott Laboratories; Roman Desanctis Distinguished Scholar Award; NHLBI Proteomics Center [HHSN268201000033C]; Susan G. Komen for the Cure Foundation [KG 080818]; Claflin Distinguished Scholar Award; Clinical Innovation Award; Kynett Focus Junior Faculty Investigator Award; NIH/NHLBI [R01 HL118018] FX This study received support from Siemens, Thermo Fisher, and Singulex, as well as assay support provided by Siemens HealthCare Diagnostics and Abbott Laboratories. J. Januzzi, the Roman Desanctis Distinguished Scholar Award; R.E. Gerszten, NHLBI Proteomics Center contract HHSN268201000033C; M. Scherrer-Crosbie, investigator-initiated grant from the Susan G. Komen for the Cure Foundation (KG 080818), Claflin Distinguished Scholar Award, and Clinical Innovation Award; B. Ky, the Kynett Focus Junior Faculty Investigator Award and R01 HL118018 from NIH/NHLBI. NR 35 TC 11 Z9 13 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2015 VL 61 IS 9 BP 1164 EP 1172 DI 10.1373/clinchem.2015.241232 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CR1TD UT WOS:000361107000009 PM 26220066 ER PT J AU Rotrnan, JA Plodkowski, AJ Hayes, SA de Groot, PM Shepard, JAO Munden, RF Ginsberg, MS AF Rotrnan, Jessica A. Plodkowski, Andrew J. Hayes, Sara A. de Groot, Patricia M. Shepard, Jo-Anne O. Munden, Reginald F. Ginsberg, Michelle S. TI Postoperative complications after thoracic surgery for lung cancer SO CLINICAL IMAGING LA English DT Review DE CT; Chest; Lung cancer; Surgery ID POSTPNEUMONECTOMY BRONCHOPLEURAL FISTULA; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY RESECTION; WEDGE RESECTION; CT FINDINGS; ESOPHAGOPLEURAL FISTULA; IMAGING FEATURES; SLEEVE LOBECTOMY; BRONCHIAL STUMP; STAGE IA AB Lung cancer is the leading cause of cancer-related deaths in the United States. Several surgical techniques are currently used as part of the standard of care for early-stage lung cancer. Differentiating normal postoperative changes from complications is essential in the management of these patients. This article will review the various surgical approaches used, ranging from wedge resection to pneumonectomy, and will outline their expected postsurgical changes. Early and late postsurgical complications will be described, some of which are unique to the type of surgery performed. In addition, local tumor recurrence is a form of postoperative complication and must be distinguished from typical postoperative or postradiation change. Knowledge of both common and uncommon postoperative complications is crucial in the follow-up of lung cancer patients. Summary Statement Familiarity with the appearance of postoperative complications in lung cancer patients is vital to distinguish it from the normal postoperative or postradiation appearance in follow-up imaging. (C) 2015 Elsevier Inc. All rights reserved. C1 [Rotrnan, Jessica A.] NY Presbyterian Weill Cornell Med Ctr, Dept Radiol, New York, NY 10065 USA. [Plodkowski, Andrew J.; Hayes, Sara A.; Ginsberg, Michelle S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [de Groot, Patricia M.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Munden, Reginald F.] Houston Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. RP Ginsberg, MS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA. EM rotmanj@mskcc.org; plodkowa@mskcc.org; hayess@mskcc.org; PDeGroot@mdanderson.org; jshepard@partners.org; rfmunden@houstonmethodist.org; ginsberm@mskcc.org OI Plodkowski, Andrew/0000-0002-3772-370X NR 90 TC 0 Z9 0 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2015 VL 39 IS 5 BP 735 EP 749 DI 10.1016/j.clinimag.2015.05.013 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ7IT UT WOS:000360776900002 ER PT J AU Baheti, AD Sewatkar, R Hornick, JL Saboo, SS Jagannathan, JP Ramaiya, NH Tirumani, SH AF Baheti, Akshay D. Sewatkar, Rani Hornick, Jason L. Saboo, Sachin S. Jagannathan, Jyothi P. Ramaiya, Nikhil H. Tirumani, Sree Harsha TI Imaging features of primary and recurrent intrathoracic synovial sarcoma: a single-institute experience SO CLINICAL IMAGING LA English DT Article DE Synovial sarcoma; Intrathoracic; Pleural; Pulmonary ID RETROSPECTIVE ANALYSIS; PROGNOSTIC-FACTORS; PRIMARY PULMONARY; MULTICENTER AB Objective: The objective was to study the imaging features of primary and metastatic intrathoracic synovial sarcoma (ISS). Materials and methods: We reviewed the imaging of 42 patients with ISS (31 pleural, 7 intrapulmonary, 4 mediastinal), with baseline imaging of 19 patients and follow-up imaging in all. Results: Primary tumors (n=19) were well circumscribed (15/19), homogeneous or heterogeneously enhancing, with mean size 9.1 cm (range: 1.8-25 cm). Recurrent/metastatic disease developed in 28/42 patients (67%). Lung was the most common site of metastases (21/28), with most of them predominantly pleural (11/21). On pathology, 30 patients had monophasic tumors, and 6 each had biphasic tumors and poorly differentiated tumors. Conclusion: Intrathoracic SS most commonly presents as a large heterogeneous pleural mass without associated adenopathy. Lung metastases are often pleural based and ipsilateral. (C) 2015 Elsevier Inc. All rights reserved. C1 [Baheti, Akshay D.; Saboo, Sachin S.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Tirumani, Sree Harsha] Harvard Univ, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Baheti, Akshay D.; Sewatkar, Rani; Saboo, Sachin S.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Tirumani, Sree Harsha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Saboo, Sachin S.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Baheti, AD (reprint author), Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM akshaybaheti@gmail.com NR 23 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2015 VL 39 IS 5 BP 803 EP 808 DI 10.1016/j.clinimag.2015.04.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ7IT UT WOS:000360776900013 PM 25963243 ER PT J AU Hassanzadeh, E Chang, CY Huang, AJ Shaqdan, K Mansouri, M Aran, S Abujudeh, HH AF Hassanzadeh, Elmira Chang, Connie Y. Huang, Ambrose J. Shaqdan, Khalid Mansouri, Mohammad Aran, Shima Abujudeh, Hani H. TI CT and MRI manifestations of luxatio erecta humeri and a review of the literature SO CLINICAL IMAGING LA English DT Article DE Luxatio erecta humeri; Inferior shoulder dislocation; MRI; Cr arthrogram; MR arthrogram; CT scan AB Aim: We aimed to study luxatio erecta humeri using advanced imaging modalities. Method: Patients with luxatio erecta humeri and a subsequent magnetic resonance imaging (MRI) and/or computed tomography (CT) scan were included in this study. Results: Among 10 identified cases, we detected 2 rotator cuff, 4 labral, and 2 inferior glenohumeral ligament tears as well as 2 glenohumeral cartilage defects. We observed six comminuted displaced greater tuberosity fractures, four anterior inferior glenoid fractures, and four impaction fractures of humeral head. Conclusion: This study provides detailed radiologic findings associated with luxatio erecta humeri using MRI and CT. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hassanzadeh, Elmira; Chang, Connie Y.; Huang, Ambrose J.; Shaqdan, Khalid; Mansouri, Mohammad; Aran, Shima; Abujudeh, Hani H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ehassanzadeh@partners.org; cychang@partners.org; ajhuang@partners.org; kshaqdan@partners.org; mmansouri1@mgh.harvard.edu; aran.shima@mgh.harvard.edu; Habujudeh@partners.org RI Mansouri, Mohammad/M-4774-2016 OI Mansouri, Mohammad/0000-0002-7472-1287 NR 16 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 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2015 VL 39 IS 5 BP 876 EP 879 DI 10.1016/j.clinimag.2015.04.009 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ7IT UT WOS:000360776900027 PM 25979120 ER PT J AU McNamara, P Minsky, A Pae, V Harris, E Pace-Schott, E Auerbach, S AF McNamara, Patrick Minsky, April Pae, Victoria Harris, Erica Pace-Schott, Edward Auerbach, Sanford TI Aggression in Nightmares and Unpleasant Dreams and in People Reporting Recurrent Nightmares SO DREAMING LA English DT Article DE nightmares; content analysis; sex differences; dreams; aggression ID SLEEP; PSYCHOPATHOLOGY; PREVALENCE; DISORDERS AB We used unique data sets from Dreamboard and Survey Monkey to test the hypothesis that aggression levels would vary significantly with content of recurrent nightmares, nonrecurrent nightmares, and unpleasant dreams. Exactly 475 nightmares and 433 unpleasant dreams were collected from Dreamboard users, while 135 nightmares were collected from individuals who reported having recurrent nightmares via a SurveyMonkey survey. Results demonstrated that physical aggression and anxiety levels were significantly higher for nightmares from individuals who reported recurrent nightmares relative to nightmares from people not reporting recurrent nightmares who in turn reported nightmares, which evidenced higher physical aggression levels relative to unpleasant dreams. Use of personal pronouns, verbs, and social terms were significantly reduced in recurrent nightmares relative to regular nightmares and unpleasant dreams. Aggressors were most often supernatural agents in recurrent nightmares; unfamiliar males in regular nightmares and familiar males in unpleasant dreams. Physical aggression against the dreamer was the most common theme in nightmares while interpersonal conflict was the most common theme in unpleasant dreams. Nightmares associated with awakenings evidenced significantly higher levels of aggression relative to nightmares not associated with awakenings. People with recurrent nightmares were 3 times more likely to report a relative on their maternal side with recurrent nightmares. We conclude that levels of physical aggression within the dream and targeted against the dreamer distinguishes recurrent from nonrecurrent nightmares and unpleasant dreams. C1 [McNamara, Patrick; Auerbach, Sanford] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McNamara, Patrick] Northcent Univ, Grad Sch, Prescott Valley, AZ USA. [Minsky, April] VA New England Hlth Care Syst, Dept Neurol, Boston, MA 02130 USA. [Pae, Victoria] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Harris, Erica] Naval Hlth Res Ctr, Hlth & Behav Sci 163, San Diego, CA USA. [Pace-Schott, Edward] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pace-Schott, Edward] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP McNamara, P (reprint author), VA New England Hlth Care Syst, Dept Neurol, 150 South Huntington Ave,A9-45, Boston, MA 02130 USA. EM mcnamar@bu.edu NR 27 TC 1 Z9 1 U1 3 U2 12 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1053-0797 EI 1573-3351 J9 DREAMING JI Dreaming PD SEP PY 2015 VL 25 IS 3 BP 190 EP 205 DI 10.1037/a0039273 PG 16 WC Psychology, Multidisciplinary SC Psychology GA CR0EW UT WOS:000360992200002 ER PT J AU Kesselheim, AS Campbell, EG Schneeweiss, S Rausch, P Lappin, BM Zhou, EH Seeger, JD Brownstein, JS Woloshin, S Schwartz, LM Toomey, T Dal Pan, GJ Avorn, J AF Kesselheim, Aaron S. Campbell, Eric G. Schneeweiss, Sebastian Rausch, Paula Lappin, Brian M. Zhou, Esther H. Seeger, John D. Brownstein, John S. Woloshin, Steven Schwartz, Lisa M. Toomey, Timothy Dal Pan, Gerald J. Avorn, Jerry TI Methodological Approaches to Evaluate the Impact of FDA Drug Safety Communications (vol 38, pg 565, 2015) SO DRUG SAFETY LA English DT Correction C1 [Kesselheim, Aaron S.; Schneeweiss, Sebastian; Seeger, John D.; Toomey, Timothy; Avorn, Jerry] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Program Regulat Therapeut & Law PORTAL, Boston, MA 02120 USA. [Kesselheim, Aaron S.; Campbell, Eric G.; Schneeweiss, Sebastian; Seeger, John D.; Brownstein, John S.; Toomey, Timothy; Avorn, Jerry] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy Res, Boston, MA 02114 USA. [Rausch, Paula] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Commun, Silver Spring, MD 20993 USA. [Lappin, Brian M.] Food & Drug Adm, Off Commissioner, Off Planning, Silver Spring, MD 20993 USA. [Zhou, Esther H.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Brownstein, John S.] Childrens Hosp, Childrens Hosp Epidemiol Grp, Boston, MA 02115 USA. [Woloshin, Steven; Schwartz, Lisa M.] Dartmouth Inst Hlth Policy & Clin Practice, Ctr Med & Media, Lebanon, NH USA. [Dal Pan, Gerald J.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Kesselheim, AS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Program Regulat Therapeut & Law PORTAL, Suite 3030,1620 Tremont St, Boston, MA 02120 USA. EM akesselheim@partners.org RI Schneeweiss, Sebastian/C-2125-2013 NR 1 TC 0 Z9 0 U1 0 U2 1 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD SEP PY 2015 VL 38 IS 9 BP 845 EP 845 DI 10.1007/s40264-015-0329-1 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA CQ9ME UT WOS:000360938200009 PM 26201399 ER PT J AU Steffel, J Giugliano, RP Braunwald, E Murphy, SA Atar, D Heidbuchel, H Camm, AJ Antman, EM Ruff, CT AF Steffel, J. Giugliano, R. P. Braunwald, E. Murphy, S. A. Atar, D. Heidbuchel, H. Camm, A. J. Antman, E. M. Ruff, C. T. TI Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Edoxaban; Anticoagulation; Amiodarone; Atrial fibrillation ID ORAL THROMBIN INHIBITOR; FACTOR XA INHIBITOR; DABIGATRAN ETEXILATE; CARDIOVASCULAR DRUGS; P-GLYCOPROTEIN AB Background In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. Methods and results At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction < 0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. Conclusions Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE. C1 [Steffel, J.] Univ Heart Ctr Zurich, Dept Cardiol, Zurich, Switzerland. [Giugliano, R. P.; Braunwald, E.; Murphy, S. A.; Antman, E. M.; Ruff, C. T.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Atar, D.] Univ Oslo, Oslo Univ Hosp Ulleval, Dept Cardiol B, Oslo, Norway. [Heidbuchel, H.] Hasselt Univ, Hasselt, Belgium. [Heidbuchel, H.] Jessa Hosp, Ctr Heart, Hasselt, Belgium. [Camm, A. J.] St Georges Univ London, Div Clin Sci, London SW17 0RE, England. RP Ruff, CT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cruff@partners.org FU Daiichi Sankyo Pharma Development FX The ENGAGE AF-TIMI 48 study was supported by Daiichi Sankyo Pharma Development. NR 16 TC 15 Z9 15 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP 1 PY 2015 VL 36 IS 33 BP 2239 EP 2245 DI 10.1093/eurheartj/ehv201 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BR UT WOS:000361205800015 PM 25971288 ER PT J AU Kortman, GAM Mulder, MLM Richters, TJW Shanmugam, NKN Trebicka, E Boekhorst, J Timmerman, HM Roelofs, R Wiegerinck, ET Laarakkers, CM Swinkels, DW Bolhuis, A Cherayil, BJ Tjalsma, H AF Kortman, Guus A. M. Mulder, Michelle L. M. Richters, Thijs J. W. Shanmugam, Nanda K. N. Trebicka, Estela Boekhorst, Jos Timmerman, Harro M. Roelofs, Rian Wiegerinck, Erwin T. Laarakkers, Coby M. Swinkels, Dorine W. Bolhuis, Albert Cherayil, Bobby J. Tjalsma, Harold TI Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Caenorhabditis elegans; gut microbiome; intestinal pathogens; iron supplementation; lipocalin-2 ID GELATINASE-ASSOCIATED LIPOCALIN; CITROBACTER-RODENTIUM INFECTION; INDUCED COLITIS; GUT MICROBIOTA; ULCERATIVE-COLITIS; CONTROLLED-TRIAL; BOWEL-DISEASE; RAT MODEL; MICE; SUPPLEMENTATION AB Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron-and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition. C1 [Kortman, Guus A. M.; Mulder, Michelle L. M.; Richters, Thijs J. W.; Roelofs, Rian; Wiegerinck, Erwin T.; Laarakkers, Coby M.; Swinkels, Dorine W.; Tjalsma, Harold] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Lab Med Translat Metab Lab, NL-6500 HB Nijmegen, Netherlands. [Mulder, Michelle L. M.; Richters, Thijs J. W.; Shanmugam, Nanda K. N.; Trebicka, Estela; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. [Boekhorst, Jos; Timmerman, Harro M.] NIZO Food Res BV, Ede, Netherlands. [Bolhuis, Albert] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. RP Swinkels, DW (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Lab Med TML 830, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM dorine.swinkels@radboudumc.nl RI Kortman, Guus/F-9690-2010; Swinkels, D.W./H-8098-2014 OI Bolhuis, Albert/0000-0001-9307-0515; FU Dutch Digestive Diseases Foundation [WO 10-53, 12-02s, 12-03s]; U.S. National Institutes of Health [R01 AI089700]; Radboud Honours programme; Dutch Cancer foundation (KWF) FX We thank our colleagues and collaborators Anne-Claire Martines, Saskia van Schalkwijk, and Bas Dutilh for useful discussions and/or technical assistance. We are also grateful to Dr. Haining Shi for assistance with scoring of colon histopathology. This work was in part supported by the Dutch Digestive Diseases Foundation (project WO 10-53). B.J.C. was supported by a U.S. National Institutes of Health grant (R01 AI089700). M.L.M.M. and T.J.W.R. were in part supported by scholarships from the Radboud Honours programme, the Dutch Digestive Diseases foundation (12-02s and 12-03s), and the Dutch Cancer foundation (KWF). NR 72 TC 6 Z9 6 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2015 VL 45 IS 9 BP 2553 EP 2567 DI 10.1002/eji.201545642 PG 15 WC Immunology SC Immunology GA CQ9GK UT WOS:000360921200012 PM 26046550 ER PT J AU Degani-Costa, LH Levarge, B Digumarthy, SR Eisman, AS Harris, RS Lewis, GD AF Degani-Costa, Luiza H. Levarge, Barbara Digumarthy, Subba R. Eisman, Aaron S. Harris, R. Scott Lewis, Gregory D. TI Pulmonary vascular response patterns during exercise in interstitial lung disease SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID ARTERIAL-HYPERTENSION; SYSTEMIC-SCLEROSIS; FIBROSIS; PREVALENCE; DIAGNOSIS AB When overt pulmonary hypertension arises in interstitial lung disease (ILD), it contributes to exercise intolerance. We sought to determine the functional significance of abnormal pulmonary arterial pressure (PAP) responses to exercise in ILD. 27 ILD patients and 11 age-matched controls underwent invasive cardiopulmonary exercise testing (iCPET). Mean PAP (mPAP) was indexed to cardiac output (Q'T) during exercise, with a mPAP-Q'T slope >= 3 mmHg.min.L-1 defined as an abnormal pulmonary vascular response. All control subjects had mPAP-Q'T slopes <3 mmHg.min.L-1 (mean +/- SEM 1.5 +/- 0.1 mmHg.min.L-1). 15 ILD patients had mPAP-Q'T slopes >= 3 mmHg.min.L-1 (4.1 +/- 0.2 mmHg.min.L-1) and were labelled as having ILD plus pulmonary vascular dysfunction (PVD). Subjects without pulmonary hypertension and with mPAP-Q'T slopes <3 mmHg.min.L-1 (1.9 +/- 0.2 mmHg.min.L-1) were labelled as ILD minus PVD (n=12). ILD+PVD and ILD-PVD patients did not differ in terms of age, sex, body mass index, pulmonary function testing or degree of exercise oxygen desaturation. Peak oxygen consumption was lower in ILD+PVD than in ILD-PVD (13.0 +/- 0.9 versus 17 +/- 1.1 mL.kg(-1).min(-1), p=0.012) and controls (19.8 +/- 1.7 mL.kg(-1).min(-1), p=0.003). ILD+PVD patients had increased dead space volume (V-D)/tidal volume (V-T) and minute ventilation/carbon dioxide production at the anaerobic threshold. In ILD, mPAP-Q'T slope >= 3 mmHg.min.L-1 is associated with lower peak oxygen consumption, increased V-D/V-T and inefficient ventilation. While noninvasive parameters were unable to predict those with abnormal pulmonary vascular responses to exercise, iCPET-derived mPAP-Q'T slope may aid in identifying physiologically significant, early pulmonary vascular disease in ILD. C1 [Degani-Costa, Luiza H.] Univ Fed Sao Paulo, Div Resp, Paulista Sch Med, Sao Paulo, Brazil. [Degani-Costa, Luiza H.; Levarge, Barbara; Harris, R. Scott; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Digumarthy, Subba R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Imaging & Intervent Div, Boston, MA USA. [Eisman, Aaron S.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Lewis, GD (reprint author), Cardiac Unit Associates, 55 Fruit St, Boston, MA 02114 USA. EM glewis@partners.org FU Hassenfeld Clinical Scholar Award; National Heart, Lung, and Blood Institute grant [R01HL119154] FX This work was supported by the Hassenfeld Clinical Scholar Award (G.D. Lewis) and National Heart, Lung, and Blood Institute grant R01HL119154 (G.D. Lewis). Funding information for this article has been deposited with FundRef. NR 29 TC 7 Z9 7 U1 0 U2 4 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2015 VL 46 IS 3 BP 738 EP 749 DI 10.1183/09031936.00191014 PG 12 WC Respiratory System SC Respiratory System GA CQ6BM UT WOS:000360689400024 PM 25976688 ER PT J AU Willard-Grace, R Dube, K Hessler, D O'Brien, B Earnest, G Gupta, R Shunk, R Grumbach, K AF Willard-Grace, Rachel Dube, Kate Hessler, Danielle O'Brien, Bridget Earnest, Gillian Gupta, Reena Shunk, Rebecca Grumbach, Kevin TI Panel Management, Team Culture, and Worklife Experience SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE burnout; panel management; patient care team; primary health care; team culture ID CENTERED MEDICAL HOME; RANDOMIZED-CONTROLLED-TRIAL; PRIMARY-CARE; INTERNAL-MEDICINE; LOWER BURNOUT; PATIENT-CARE; LOW-INCOME; PHYSICIANS; SATISFACTION; PROGRAM AB Burnout and professional dissatisfaction are threats to the primary care workforce. We investigated the relationship between panel management capability, team culture, cynicism, and perceived "do-ability" of primary care among primary care providers (PCPs) and staff in primary care practices. We surveyed 326 PCPs and 142 staff members in 10 county-administered, 6 university-run, and 3 Veterans Affairs primary care clinics in a large urban area in 2013. Predictor variables included capability for performing panel management and perception of team culture. Outcome variables included 2 work experience measures-the Maslach Burnout Inventory cynicism scale and a 1-item measure of the "do-ability" of primary care this year compared with last year. Generalized Estimation Equation (GEE) models were used to account for clustering at the clinic level. Greater panel management capability and higher team culture were associated with lower cynicism among PCPs and staff and higher reported "do-ability" of primary care among PCPs. Panel management capability and team culture interacted to predict the 2 work experience outcomes. Among PCPs and staff reporting high team culture, there was little association between panel management capability and the outcomes, which were uniformly positive. However, there was a strong relationship between greater panel management capability and improved work experience outcomes for PCPs and staff reporting low team culture. Team-based processes of care such as panel management may be an important strategy to protect against cynicism and dissatisfaction in primary care, particularly in settings that are still working to improve their team culture. C1 [Willard-Grace, Rachel; Dube, Kate; Hessler, Danielle; Grumbach, Kevin] Univ Calif San Francisco, Dept Family & Community Med, Ctr Excellence Primary Care, San Francisco, CA 94114 USA. [O'Brien, Bridget; Earnest, Gillian; Shunk, Rebecca] San Francisco VA Med Ctr, Ctr Excellence Primary Care Educ, San Francisco, CA USA. [O'Brien, Bridget; Gupta, Reena] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94114 USA. [Gupta, Reena] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Family & Community Med, Ctr Excellence Primary Care, San Francisco, CA 94114 USA. RP Willard-Grace, R (reprint author), Univ Calif San Francisco, Dept Family & Community Med, Ctr Excellence Primary Care, 995 Potrero Ave,Ward 83, San Francisco, CA 94114 USA. EM willardr@fcm.ucsf.edu RI Grumbach, Kevin/L-9222-2016; OI Willard-Grace, Rachel/0000-0002-1876-555X FU California Medicaid Waiver Delivery System Reform Incentive Program; University of California, San Francisco Medical Center; San Francisco Department of Public Health; UCSF Medical Center FX This research was supported by funding from the California Medicaid Waiver Delivery System Reform Incentive Program to San Francisco General Hospital and the University of California, San Francisco Medical Center. This research is the result of close partnership with the leadership and staff of 19 primary care clinics across San Francisco. Without the wisdom, expertise, and candid feedback of their clinic leadership, clinicians, and frontline staff, this survey would not have been possible. The study team thanks the San Francisco Department of Public Health and the UCSF Medical Center for their support of this project in conjunction with primary care reforms undertaken for the Centers for Medicare and Medicaid Services Incentive Program for these health systems under the Section 1115 California Medicaid Waiver. We acknowledge the UCSF Clinical & Translational Science Institute and Dr. Christy Boscardin's consultations on preliminary statistical analysis. NR 40 TC 2 Z9 2 U1 0 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD SEP PY 2015 VL 33 IS 3 BP 231 EP 241 DI 10.1037/fsh0000113 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 CR0FA UT WOS:000360992600007 PM 25730504 ER PT J AU Parikh, S Goldstein, A Koenig, MK Scaglia, F Enns, GM Saneto, R Anselm, I Cohen, BH Falk, MJ Greene, C Gropman, AL Haas, R Hirano, M Morgan, P Sims, K Tarnopolsky, M Van Hove, JLK Wolfe, L DiMauro, S AF Parikh, Sumit Goldstein, Amy Koenig, Mary Kay Scaglia, Fernando Enns, Gregory M. Saneto, Russell Anselm, Irina Cohen, Bruce H. Falk, Marni J. Greene, Carol Gropman, Andrea L. Haas, Richard Hirano, Michio Morgan, Phil Sims, Katherine Tarnopolsky, Mark Van Hove, Johan L. K. Wolfe, Lynne DiMauro, Salvatore TI Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society SO GENETICS IN MEDICINE LA English DT Review DE consensus criteria; Delphi method; mitochondrial disease; mitochondrial medicine; Mitochondrial Medicine Society ID KEARNS-SAYRE-SYNDROME; CEREBRAL FOLATE-DEFICIENCY; EXOME SEQUENCING REVEALS; DNA DEPLETION SYNDROME; COMPLEX-I DEFICIENCY; COMPARATIVE GENOMIC HYBRIDIZATION; RESPIRATORY-CHAIN DEFICIENCIES; CLINICAL-PRACTICE PROTOCOL; BRAIN-STEM INVOLVEMENT; RAT-LIVER MITOCHONDRIA AB Purpose: The purpose of this statement is to review the literature regarding mitochondrial disease and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are engaged in diagnosing and treating these patients. Methods: The Writing Group members were appointed by the Mitochondrial Medicine Society. The panel included members with expertise in several different areas. The panel members utilized a comprehensive review of the literature, surveys, and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Results: Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease. Conclusion: The Delphi process enabled the formation of consensus-based recommendations. We hope that these recommendations will help standardize the evaluation, diagnosis, and care of patients with suspected or demonstrated mitochondrial C1 [Parikh, Sumit] Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Dept Neurol, Cleveland, OH 44106 USA. [Goldstein, Amy] Childrens Hosp Pittsburgh, Dept Pediat, Div Child Neurol, Pittsburgh, PA 15213 USA. [Koenig, Mary Kay] Univ Texas Med Sch Houston, Div Child & Adolescent Neurol, Dept Pediat, Houston, TX USA. [Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Scaglia, Fernando] Texas Childrens Hosp, Houston, TX 77030 USA. [Enns, Gregory M.] Stanford Univ, Lucile Packard Childrens Hosp, Div Med Genet, Dept Pediat, Palo Alto, CA 94304 USA. [Saneto, Russell] Univ Washington, Seattle Childrens Hosp, Dept Neurol, Seattle, WA 98195 USA. [Saneto, Russell] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Anselm, Irina] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Cohen, Bruce H.] Childrens Hosp Med Ctr Akron, Dept Pediat, NeuroDev Sci Ctr, Akron, OH USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Greene, Carol] Univ Maryland, Med Ctr, Dept Pediat, Baltimore, MD 21201 USA. [Gropman, Andrea L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gropman, Andrea L.] George Washington Univ Hlth Sci, Washington, DC USA. [Haas, Richard] UCSD Med Ctr, Dept Neurosci & Pediat, La Jolla, CA USA. [Haas, Richard] Rady Childrens Hosp, La Jolla, CA USA. [Hirano, Michio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Morgan, Phil] Seattle Childrens Hosp, Dept Anesthesiol, Seattle, WA USA. [Sims, Katherine] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarnopolsky, Mark] McMaster Univ, Dept Pediat & Med, Hamilton, ON, Canada. [Van Hove, Johan L. K.] Childrens Hosp Colorado, Dept Pediat Clin Genet & Metab, Denver, CO USA. [Wolfe, Lynne] NIH, Bethesda, MD 20892 USA. [DiMauro, Salvatore] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. RP Parikh, S (reprint author), Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Dept Neurol, Cleveland, OH 44106 USA. EM parikhs@ccf.org FU RAPTOR Pharmaceuticals FX G.M.E. has received unrestricted research gift funds from Edison Pharmaceuticals. M.J.F. is a consultant for Mitokyne, research collaborator for Cardero, and a research grant awardee of RAPTOR Pharmaceuticals, and is on the Scientific and Medical Advisory Board for the United Mitochondrial Disease Foundation. A.G. is a consultant for Stealth Peptides. A.L.G. is a consultant for GeneDx. S.P. conducts research for Edison Pharmaceuticals and the North American Mitochondrial Disease Consortium (NAMDC), and is on the Scientific and Medical Advisory Board for the United Mitochondrial Disease Foundation. R.S. conducts research studies for Edison Pharmaceuticals and is part of the NAMDC. F.S. works for a medical college department that owns a Mitochondrial Diagnostic Laboratory and conducts research studies for Edison and Raptor Pharmaceuticals. M.T. is president and CEO of Exerkine, which develops mitochondrial therapies, and receives speaker honoraria from Prevention Genetics and Genzyme. NR 164 TC 23 Z9 24 U1 2 U2 14 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 SEP PY 2015 VL 17 IS 9 BP 689 EP 701 DI 10.1038/gim.2014.177 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CQ8YY UT WOS:000360898500002 PM 25503498 ER PT J AU Morshed, SA Davies, TF AF Morshed, S. A. Davies, T. F. TI Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE Graves' disease; thyroid; TSH-receptor antibodies; TSH; signaling ID HUMAN THYROTROPIN RECEPTOR; SIGNALING CASCADES; CRYSTAL-STRUCTURE; MURINE MODEL; T-CELLS; AUTOIMMUNITY; AUTOANTIBODY; ACTIVATION; EXPRESSION; IMMUNE AB The immunologic processes involved in Graves' disease (GD) have one unique characteristic - the autoantibodies to the TSH receptor (TSHR) which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called "neutral" antibodies and which we now characterize as autoantibodies to the "cleavage" region of the TSHR ectodomain. C1 [Morshed, S. A.; Davies, T. F.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Thyroid Res Unit, New York, NY 10029 USA. RP Morshed, SA (reprint author), Room 2F-26 VA Med Ctr,130 West Kingsbridge Rd, New York, NY 10468 USA. EM syed.morshed@mssm.edu FU NIH [DK069713, DK052464]; VA Merit Award Program FX This work was supported in part by NIH grants DK069713, DK052464 and the VA Merit Award Program. NR 49 TC 8 Z9 8 U1 1 U2 7 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD SEP PY 2015 VL 47 IS 10 BP 727 EP 734 DI 10.1055/s-0035-1559633 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CR2GV UT WOS:000361145500006 PM 26361259 ER PT J AU Branch-Elliman, W Strymish, J Kudesia, V Rosen, AK Gupta, K AF Branch-Elliman, Westyn Strymish, Judith Kudesia, Valmeek Rosen, Amy K. Gupta, Kalpana TI Natural Language Processing for Real-Time Catheter-Associated Urinary Tract Infection Surveillance: Results of a Pilot Implementation Trial SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; CARE-ASSOCIATED INFECTIONS; HEALTH; IDENTIFICATION; PNEUMONIA; HOSPITALS AB BACKGROUND. Incidence of catheter-associated urinary tract infection (CAUTI) is a quality benchmark. To streamline conventional detection methods, an electronic surveillance system augmented with natural language processing (NLP), which gathers data recorded in clinical notes without manual review, was implemented for real-time surveillance. OBJECTIVE. To assess the utility of this algorithm for identifying indwelling urinary catheter days and CAUTI. setting. Large, urban tertiary care Veterans Affairs hospital. METHODS. All patients admitted to the acute care units and the intensive care unit from March 1, 2013, through November 30, 2013, were included. Standard surveillance, which includes electronic and manual data extraction, was compared with the NLP-augmented algorithm. RESULTS. The NLP-augmented algorithm identified 27% more indwelling urinary catheter days in the acute care units and 28% fewer indwelling urinary catheter days in the intensive care unit. The algorithm flagged 24 CAUTI versus 20 CAUTI by standard surveillance methods; the CAUTI identified were overlapping but not the same. The overall positive predictive value was 54.2%, and overall sensitivity was 65% (90.9% in the acute care units but 33% in the intensive care unit). Dissimilarities in the operating characteristics of the algorithm between types of unit were due to differences in documentation practice. Development and implementation of the algorithm required substantial upfront effort of clinicians and programmers to determine current language patterns. CONCLUSIONS. The NLP algorithm was most useful for identifying simple clinical variables. Algorithm operating characteristics were specific to local documentation practices. The algorithm did not perform as well as standard surveillance methods. C1 [Branch-Elliman, Westyn] Eastern Colorado Vet Affairs VA Healthcare Sys, Dept Med, Denver, CO USA. [Branch-Elliman, Westyn] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Strymish, Judith; Kudesia, Valmeek; Gupta, Kalpana] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. [Kudesia, Valmeek] Boston VA Med Ctr, Massachusetts Vet Epidemiol & Informat Ctr, Boston, MA USA. [Rosen, Amy K.; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rosen, Amy K.; Gupta, Kalpana] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. RP Branch-Elliman, W (reprint author), ECHCS, Infect Prevent, 1055 Clermont Ave,Mailstop 111L, Denver, CO 80220 USA. EM westyn.branch-elliman@ucdenver.edu FU Patient Safety Center of Inquiry "Measurement to Advance Patient Safety", Boston, Massachusetts [XVA 68-023] FX Patient Safety Center of Inquiry "Measurement to Advance Patient Safety," grant number XVA 68-023, Boston, Massachusetts. NR 18 TC 0 Z9 0 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2015 VL 36 IS 9 BP 1004 EP 1010 DI 10.1017/ice.2015.122 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CQ9FD UT WOS:000360917200002 PM 26022228 ER PT J AU Young-Xu, Y Kuntz, JL Gerding, DN Neily, J Mills, P Dubberke, ER Olsen, MA Kelly, CP Mahe, C AF Young-Xu, Yinong Kuntz, Jennifer L. Gerding, Dale N. Neily, Julia Mills, Peter Dubberke, Erik R. Olsen, Margaret A. Kelly, Ciaran P. Mahe, Cedric TI Clostridium difficile Infection Among Veterans Health Administration Patients SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID TERM-CARE FACILITY; ASYMPTOMATIC CARRIERS; EPIDEMIOLOGY; DISEASE; SURVEILLANCE; RESIDENTS; BURDEN; SYSTEM AB OBJECTIVE. To report on the prevalence and incidence of Clostridium difficile infection (CDI) from 2009 to 2013 among Veterans Healthcare Administration patients DESIGN. A retrospective descriptive analysis of data extracted from a large electronic medical record (EMR) database SETTING. Data were acquired from VHA healthcare records from 2009 to 2013 that included outpatient clinical visits, long-term care, and hospitalized care as well as pharmacy and laboratory information. RESULTS. In 2009, there were 10,207 CDI episodes, and in 2013, there were 12,143 CDI episodes, an increase of 19.0%. The overall CDI rate increased by 8.4% from 193 episodes per 100,000 patient years in 2009 to 209 episodes per 100,000 patient years in 2013. Of the CDI episodes identified in 2009, 58% were identified during a hospitalization, and 42% were identified in an outpatient setting. In 2013, 44% of the CDI episodes were identified in an outpatient setting. CONCLUSION. This is one of the largest studies that has utilized timely EMR data to describe the current CDI epidemiology at the VHA. Despite an aging population with greater burden of comorbidity than the general US population, our data show that VHACDI rates stabilized between 2011 and 2013 following increases likely attributable to the introduction of the more sensitive nucleic acid amplification tests (NAATs). The findings in this report will help establish an accurate benchmark against which both current and future VA CDI prevention initiatives can be measured. C1 [Young-Xu, Yinong; Neily, Julia; Mills, Peter] Natl Ctr Patient Safety, Dept Vet Affairs, White River Jct, VT USA. [Young-Xu, Yinong; Mills, Peter] Geisel Sch Med Dartmouth, Hanover, NH USA. [Kuntz, Jennifer L.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Dubberke, Erik R.; Olsen, Margaret A.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Olsen, Margaret A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Kelly, Ciaran P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Sch Med, Boston, MA 02215 USA. [Mahe, Cedric] Sanofi Pasteur, Lyon, France. RP Young-Xu, Y (reprint author), VAMC, 10A4E,215 North Main St, White River Jct, VT 05009 USA. EM Yinong.Young-Xu@va.gov FU Sanofi-Pasteur, Lyon, France FX This research was supported by an unrestricted research grant from Sanofi-Pasteur, Lyon, France. NR 24 TC 2 Z9 2 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2015 VL 36 IS 9 BP 1038 EP 1045 DI 10.1017/ice.2015.138 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CQ9FD UT WOS:000360917200007 PM 26047207 ER PT J AU van Driel, B Wang, GX Liao, GX Halibozek, PJ Keszei, M O'Keeffe, MS Bhan, AK Wang, N Terhorst, C AF van Driel, Boaz Wang, Guoxing Liao, Gongxian Halibozek, Peter J. Keszei, Marton O'Keeffe, Michael S. Bhan, Atul K. Wang, Ninghai Terhorst, Cox TI The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Citrobacter rodentium; IL-22; innate; mucosal immunology; Slamf6 ID CD4(+) T-CELLS; ENTERIC BACTERIAL PATHOGENS; HOST-DEFENSE; B-LYMPHOCYTES; INFECTION; IL-22; MICE; SAP; MACROPHAGES; MUCOSAL AB Slamf6 exacerbates colitis caused by a Gram(-) bacterium.The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the T(h)17 response was enhanced inSlamf6(-/-) C57BL/6 mice upon oral infection withCitrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome ofC. rodentium infections inRag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria ofC. rodentium-infectedSlamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those ofRag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower inSlamf6(-/-) Rag(-/-) mice than inRag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 toRag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused byC. rodentium infections inRag(-/-) mice. C1 [van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J.; Keszei, Marton; O'Keeffe, Michael S.; Wang, Ninghai; Terhorst, Cox] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol,Dept Med, Boston, MA 02115 USA. [Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Terhorst, C (reprint author), 3 Blackfan Circle,Room CLS 938, Boston, MA 02115 USA. EM cterhors@bidmc.harvard.edu RI Keszei, Marton/F-3295-2014 OI Keszei, Marton/0000-0002-1158-2179 FU National Institutes of Health [RO1 NIH AI-15066] FX National Institutes of Health (RO1 NIH AI-15066 to C.T.). NR 34 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 EI 1460-2377 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 2015 VL 27 IS 9 BP 447 EP 457 DI 10.1093/intimm/dxv029 PG 11 WC Immunology SC Immunology GA CR3GX UT WOS:000361220800004 PM 25957267 ER PT J AU Hwang, YC Hayashi, T Fujimoto, WY Kahn, SE Leonetti, DL McNeely, MJ Boyko, EJ AF Hwang, Y-C Hayashi, T. Fujimoto, W. Y. Kahn, S. E. Leonetti, D. L. McNeely, M. J. Boyko, E. J. TI Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID JAPANESE-AMERICAN MEN; IMPAIRED GLUCOSE-TOLERANCE; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ALL-CAUSE; PREVALENCE; ASSOCIATION; METAANALYSIS; DEFINITION AB BACKGROUND: A proportion of obese subjects appear metabolically healthy (MHO) but little is known about the natural history of MHO and factors predicting its future conversion to metabolically unhealthy obese (MUO). OBJECTIVES: The aim was to determine prospectively the frequency of conversion of MHO to MUO and the clinical variables that independently predicted this conversion, with a particular focus on the role of body composition. METHODS: We identified 85 Japanese Americans with MHO (56 men, 29 women), aged 34-73 years (mean age 49.8 years) who were followed at 2.5, 5 and 10 years after enrollment with measurements of metabolic characteristics, lifestyle and abdominal and thigh fat areas measured by computed tomography. Obesity was defined using the Asian body mass index criterion of >= 25 kg m(-2). Metabolically healthy was defined as the presence of <= 2 of 5 metabolic syndrome components proposed by the National Cholesterol Education Program Adult Treatment Panel III, while metabolically unhealthy was defined as >= 3 components. RESULTS: Over 10 years of follow-up, 55 MHO individuals (64.7%) converted to MUO. Statistically significant univariate predictors of conversion included dyslipidemia, greater insulin resistance and greater visceral abdominal (VAT) and subcutaneous abdominal fat area (SAT). In multivariate analysis, VAT (odds ratio per 1-s.d. increment (95% confidence interval) 2.04 (1.11-3.72), P = 0.021), high-density lipoprotein (HDL) cholesterol (0.24 (0.11-0.53), P<0.001), fasting plasma insulin (2.45 (1.07-5.62), P = 0.034) and female sex (5.37 (1.14-25.27), P = 0.033) were significantly associated with future conversion to MUO. However, SAT was not an independent predictor for future conversion to MUO. CONCLUSIONS: In this population, MHO was a transient state, with nearly two-thirds developing MUO over 10 years, with higher conversion to MUO independently associated with VAT, female sex, higher fasting insulin level and lower baseline HDL cholesterol level. C1 [Hwang, Y-C; Boyko, E. J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98101 USA. [Hwang, Y-C] Kyung Hee Univ, Sch Med, Kyung Hee Univ Hosp Gangdong, Div Endocrinol & Metab,Dept Med, Seoul, South Korea. [Hayashi, T.] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Fujimoto, W. Y.; Kahn, S. E.; McNeely, M. J.; Boyko, E. J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA 98101 USA. [Leonetti, D. L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eboyko@uw.edu RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU Diabetes Research Center [DK-17047]; Clinical Nutrition Research Unit [DK-35816]; General Clinical Research Center at the University of Washington [RR-00037]; VA Puget Sound Health Care System; King County Japanese American community; National Institutes of Health [DK-31170, HL-49293, DK-017047] FX This work was supported by facilities and services provided by the Diabetes Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound Health Care System provided support for Drs Boyko and Kahn's involvement in this research. We are grateful to the King County Japanese American community for support and cooperation. Funding was through National Institutes of Health grants DK-31170, HL-49293 and DK-017047. The funding entities had no role in the conduct of this study or interpretation of its results. NR 32 TC 15 Z9 15 U1 0 U2 8 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 SEP PY 2015 VL 39 IS 9 BP 1365 EP 1370 DI 10.1038/ijo.2015.75 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CR0BY UT WOS:000360984400005 PM 25920773 ER PT J AU Newman, JC AF Newman, John C. TI Copyright and Bedside Cognitive Testing Why We Need Alternatives to the Mini-Mental State Examination SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. RP Newman, JC (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, 4150 Clement St, San Francisco, CA 94121 USA. EM newman@ucsf.edu RI Newman, John/L-8112-2013 FU NIA NIH HHS [K08AG048354] NR 8 TC 6 Z9 6 U1 1 U2 5 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 SEP PY 2015 VL 175 IS 9 BP 1459 EP 1460 DI 10.1001/jamainternmed.2015.2159 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900010 PM 26053392 ER PT J AU Campbell, EG Vogeli, C Rao, SR Abraham, M Pierson, R Applebaum, S AF Campbell, Eric G. Vogeli, Christine Rao, Sowmya R. Abraham, Melissa Pierson, Roz Applebaum, Sandra TI Industry Relationships Among Academic Institutional Review Board Members Changes From 2005 Through 2014 SO JAMA INTERNAL MEDICINE LA English DT Review ID CONFLICTS-OF-INTEREST; FINANCIAL RELATIONSHIPS; PHYSICIANS; DISCLOSURE; CARE AB IMPORTANCE For the past decade, more attention and concern has been directed toward financial relationships between the life science industry and physicians. Relationships between industry and institutional review board (IRB) members represent an important subclass that has the potential to broadly influence decisions regarding medical research. OBJECTIVES To study the nature, extent, and perceived consequences of industry relationships among IRB members in academic health centers and to compare our results with findings from 2005. DESIGN, SETTING, AND PARTICIPANTS A survey mailed to IRB members from the 115 most research-intensive medical schools and teaching hospitals in the United States from January 16 through May 16, 2014. The survey included questions identical to those used in 2005. Data analysis was conducted from June through October 2014. MAIN OUTCOMES AND MEASURES The frequency of industry relationships among IRB members and the perceived effect of those relationships on IRB-related activities. RESULTS We found no significant change in the percentage of IRB members with an industry relationship from 2005 through 2014 (2005: 37.2%; 95% CI, 32.7%-42.0%; 2014: 32.1%; 95% CI, 28.0%-36.4%; P = .09). However, since 2005, the percentage of members who felt another member did not properly disclose a financial relationship decreased from 10.8% (95% CI, 8.0%-14.4%) to 6.7%(95% CI, 4.7%-9.4%) (P = .04), as did the percentage who felt pressure from their institution or department to approve a protocol (2005: 18.6%; 95% CI, 15.0%-22.9%; 2014: 10.0%; 95% CI, 7.6%-13.0%; P < .001). The percentage of members with a conflict of interest who voted on protocols with which they have a conflict has not changed, although the percentage who said they always disclose relationships increased significantly from 54.9% in 2005 (95% CI, 42.2%-66.9%) to 80.0% in 2014 (95% CI, 65.3%-89.4%) (P = .01). We also found evidence of anti-industry bias in the presentation of protocols to the IRB. CONCLUSIONS AND RELEVANCE The results show significant positive progress in the reporting and management of conflicts of interest among IRB members in academic health centers since 2005 after adjusting for other factors. Additional attention should be focused on deterring IRB members from inappropriately voting on or presenting protocols in a biased manner. C1 [Campbell, Eric G.; Vogeli, Christine; Abraham, Melissa] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Campbell, Eric G.; Vogeli, Christine] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Abraham, Melissa] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Campbell, Eric G.; Vogeli, Christine] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Abraham, Melissa] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford Vet Affairs Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Pierson, Roz; Applebaum, Sandra] Nielsen Co, New York, NY USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Ste 901,Ninth Floor, Boston, MA 02114 USA. EM ecampbell@partners.org FU National Institute of General Medical Sciences, National Institutes of Health [1R01 GM100026-01] FX This study was funded by grant 1R01 GM100026-01 from the National Institute of General Medical Sciences, National Institutes of Health (Dr Campbell). NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2015 VL 175 IS 9 BP 1500 EP 1506 DI 10.1001/jamainternmed.2015.3167 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900019 PM 26168043 ER PT J AU Park, ER Gareen, IF Japuntich, S Lennes, I Hyland, K DeMello, S Sicks, JD Rigotti, NA AF Park, Elyse R. Gareen, Ilana F. Japuntich, Sandra Lennes, Inga Hyland, Kelly DeMello, Sarah Sicks, JoRean D. Rigotti, Nancy A. TI Primary Care Provider-Delivered Smoking Cessation Interventions and Smoking Cessation Among Participants in the National Lung Screening Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID POPULATION-BASED SURVEY; SERVICES TASK-FORCE; COMPUTED-TOMOGRAPHY; HEALTH-CARE; CANCER; PHYSICIANS; SMOKERS; SATISFACTION; PERCEPTIONS; HMOS AB IMPORTANCE The National Lung Screening Trial (NLST) found a reduction in lung cancer mortality among participants screened with low-dose computed tomography vs chest radiography. In February 2015, Medicare announced its decision to cover annual lung screening for patients with a significant smoking history. These guidelines promote smoking cessation treatment as an adjunct to screening, but the frequency and effectiveness of clinician-delivered smoking cessation interventions delivered after lung screening are unknown. OBJECTIVE To determine the association between the reported clinician-delivered 5As (ask, advise, assess, assist [talk about quitting or recommend stop-smoking medications or recommend counseling], and arrange follow-up) after lung screening and smoking behavior changes. DESIGN, SETTING, AND PARTICIPANTS A matched case-control study (caseswere quitters and controls were continued smokers) of 3336 NLST participants who were smokers at enrollment examined participants' rates and patterns of 5A delivery after a lung screen and reported smoking cessation behaviors. MAIN OUTCOMES AND MEASURES Prevalence of the clinician-delivered 5As and associated smoking cessation after lung screening. RESULTS Delivery of the 5As 1 year after screening were as follows: ask, 77.2%; advise, 75.6%; assess, 63.4%; assist, 56.4%; and arrange follow-up, 10.4%. Receipt of ask, advise, and assess was not significantly associated with quitting in multivariate models that adjusted for sociodemographic characteristics, medical history, screening results, nicotine dependence, and motivation to quit. Assist was associated with a 40% increase in the odds of quitting (odds ratio, 1.40; 95% CI, 1.21-1.63), and arrange was associated with a 46% increase in the odds of quitting (odds ratio, 1.46; 95% CI, 1.19-1.79). CONCLUSIONS AND RELEVANCE Assist and arrange follow-up delivered by primary care providers to smokers who were participating in the NLST were associated with increased quitting; less intensive interventions (ask, advise, and assess) were not. However, rates of assist and arrange follow-up were relatively low. Our findings confirm the need for and benefit of clinicians taking more active intervention steps in helping patients who undergo screening to quit smoking. C1 [Park, Elyse R.; Hyland, Kelly; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Park, Elyse R.; Hyland, Kelly] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Gareen, Ilana F.; DeMello, Sarah; Sicks, JoRean D.] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA. [Gareen, Ilana F.] Brown Univ, Dept Epidemiol, Sch Publ Hlth, Providence, RI 02912 USA. [Japuntich, Sandra] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Lennes, Inga] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med,Dept Med, Boston, MA USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM epark@mgh.harvard.edu RI Gareen, Ilana/I-2816-2014 OI Gareen, Ilana/0000-0002-0457-5595 FU American Cancer Society's Mentored Research Scholar Award program [MRSG-005-05-CPPB]; ACRIN-NLST [U01 CA079778, U01 CA080098]; Veterans Affairs Clinical Sciences Research and Development Award program [1IK2CX000918-01A1] FX This project was funded by grant MRSG-005-05-CPPB from the American Cancer Society's Mentored Research Scholar Award program (Dr Park); grants U01 CA079778 and U01 CA080098 from the ACRIN-NLST; and, in part, by grant 1IK2CX000918-01A1 from the Veterans Affairs Clinical Sciences Research and Development Award program (Dr Japuntich). NR 35 TC 18 Z9 18 U1 2 U2 8 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 SEP PY 2015 VL 175 IS 9 BP 1509 EP 1516 DI 10.1001/jamainternmed.2015.2391 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900021 PM 26076313 ER PT J AU Ong, MK AF Ong, Michael K. TI Tobacco Cessation-We Can Do Better SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID SMOKING-CESSATION C1 [Ong, Michael K.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. [Ong, Michael K.] Vet Affairs Greater Los Angeles HealthCare Syst, Los Angeles, CA USA. RP Ong, MK (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, 10940 Wilshire Blvd,Ste 700, Los Angeles, CA 90024 USA. EM michael.ong@ucla.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2015 VL 175 IS 9 BP 1516 EP 1517 DI 10.1001/jamainternmed.2015.2402 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900022 PM 26075733 ER PT J AU Zeliadt, SB Heffner, JL Sayre, G Klein, DE Simons, C Williams, J Reinke, LF Au, DH AF Zeliadt, Steven B. Heffner, Jaimee L. Sayre, George Klein, Deborah E. Simons, Carol Williams, Jennifer Reinke, Lynn F. Au, David H. TI Attitudes and Perceptions About Smoking Cessation in the Context of Lung Cancer Screening SO JAMA INTERNAL MEDICINE LA English DT Article ID SERVICES TASK-FORCE; COMPUTED-TOMOGRAPHY; PULMONARY NODULES; QUALITATIVE RESEARCH; RISK PERCEPTIONS; COGNITIVE-DISSONANCE; TRIAL PARTICIPANTS; FOLLOW-UP; DISCUSSIONS; DEPENDENCE AB IMPORTANCE Broad adoption of lung cancer screeningmay inadvertently lead to negative population health outcomes if it is perceived as a substitute for smoking cessation. OBJECTIVE To understand views on smoking cessation from current smokers in the context of being offered lung cancer screening as a routine service in primary care. DESIGN, SETTING, AND PARTICIPANTS As an ancillary study to the launch of a lung cancer screening program at 7 sites in the Veterans Health Administration, 45 in-depth semi-structured qualitative interviews about health beliefs related to smoking and lung cancer screening were administered from May 29 to September 22, 2014, by telephone to 37 current smokers offered lung cancer screening by their primary care physician. Analysis was conducted from June 15, 2014, to March 29, 2015. MAIN OUTCOMES AND MEASURES Attitudes and perceptions about the importance of smoking cessation in the context of lung cancer screening. RESULTS Lung cancer screening prompted most current smokers to reflect for the first time on what smoking means for their current and future health. However, 17 of 35 (49%) participants described mechanisms whereby screening lowered their motivation for cessation, including the perception that undergoing an imaging test yields the same health benefits as smoking cessation. Other misperceptions include the belief that everyone who participates in screening will benefit; the belief that screening and being able to return for additional screening offers protection from lung cancer; the perception by some individuals that findings from screenings have saved their lives by catching their cancer early when indeterminate findings are identified that can be monitored rather than immediately treated; and a reinforced belief in some individuals that a cancer-free screening test result indicates that they are among the lucky ones who will avoid the harms of smoking. CONCLUSIONS AND RELEVANCE In this qualitative, lung cancer screening prompted many current smokers to reflect on their health and may serve as a potential opportunity to engage patients in discussions about smoking cessation. However, several concerning pathways were identified in which screening, when offered as part of routine care and described as having proven efficacy, may negatively influence smoking cessation. Health care professionals should be aware that the opportunity for early detection of lung cancer may be interpreted as a way of avoiding the harms of smoking. To promote cessation, discussions should focus on the emotional response to screening rather than clinical details (eg, nodule size) and address misperceptions about the value of early detection so that screening does not lower motivation to quit smoking. C1 [Zeliadt, Steven B.; Sayre, George; Simons, Carol; Williams, Jennifer; Reinke, Lynn F.; Au, David H.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA 98108 USA. [Zeliadt, Steven B.; Sayre, George] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Heffner, Jaimee L.] Fred Hutchinson Canc Res Ctr, Tobacco & Hlth Behav Sci Res Grp, Seattle, WA 98104 USA. [Klein, Deborah E.] Swedish Med Ctr, Swedish Med Grp, Seattle, WA USA. [Reinke, Lynn F.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Zeliadt, SB (reprint author), VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, 1660 S Columbian Way, Seattle, WA 98108 USA. EM steven.zeliadt@va.gov FU Centers for Disease Control and Prevention's Health Promotion and Disease Prevention Research Centers Program through a Special Interest Project (Low Dose CT Lung Cancer Screening: Informed Decision Making and Smoking Cessation) [DP9001911-05S2, SIP13-038] FX This study was supported by grant DP9001911-05S2 from the Centers for Disease Control and Prevention's Health Promotion and Disease Prevention Research Centers Program through a Special Interest Project (SIP13-038: Low Dose CT Lung Cancer Screening: Informed Decision Making and Smoking Cessation). This material is the result of work supported by resources from VA Puget Sound Health Care System. NR 39 TC 14 Z9 14 U1 2 U2 6 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 SEP PY 2015 VL 175 IS 9 BP 1530 EP 1537 DI 10.1001/jamainternmed.2015.3558 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900025 PM 26214612 ER PT J AU Cai, JX Campbell, EJ Richter, JM AF Cai, Jennifer X. Campbell, Emily J. Richter, James M. TI Concordance of Outpatient Esophagogastroduodenoscopy of the Upper Gastrointestinal Tract With Evidence-Based Guidelines SO JAMA INTERNAL MEDICINE LA English DT Letter ID BARRETTS-ESOPHAGUS; SURVEILLANCE; PHYSICIANS; ENDOSCOPY C1 [Cai, Jennifer X.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Campbell, Emily J.; Richter, James M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM jrichter@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2015 VL 175 IS 9 BP 1563 EP 1564 DI 10.1001/jamainternmed.2015.3533 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900033 PM 26192987 ER PT J AU He, WJ Jimenez, F Martinez, H Harper, NL Manoharan, MS Carrillo, A Ingale, P Liu, YG Ahuja, SS Clark, RA Rather, CG Ramirez, DA Andrews, CP Jacobs, RL Ahuja, SK AF He, Weijing Jimenez, Fabio Martinez, Hernan Harper, Nathan L. Manoharan, Muthu Saravanan Carrillo, Andrew Ingale, Puraskar Liu, Ya-Guang Ahuja, Seema S. Clark, Robert A. Rather, Cynthia G. Ramirez, Daniel A. Andrews, Charles P. Jacobs, Robert L. Ahuja, Sunil K. TI Cockroach sensitization mitigates allergic rhinoconjunctivitis symptom severity in patients allergic to house dust mites and pollen SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Cockroach sensitization; allergen challenge chamber; allergic rhinoconjunctivitis; T-cell activation; aeroallergens; house dust mite; skin prick test; pollen ID INNATE LYMPHOID-CELLS; CHALLENGE CHAMBER; CD4/CD8 RATIO; HYGIENE HYPOTHESIS; IMMUNE; ACTIVATION; EXPOSURE; RESPONSES; ASTHMA; DISEASE AB Background: Modifiers of symptom severity in patients with allergic rhinoconjunctivitis (AR) are imprecisely characterized. The hygiene hypothesis implicates childhood microbial exposure as a protective factor. Cockroach sensitization (C+) might be a proxy for microbial exposure. Objective: We sought to determine whether C+ assayed by means of skin prick tests influenced AR symptom severity in controlled and natural settings. Methods: Total symptom scores (TSSs) were recorded by 21 participants with house dust mite allergy (M+) in the natural setting and during repeated exposures of 3 hours per day to house dust mite allergen in an allergen challenge chamber (ACC). In M+ participants the peripheral blood and nasal cells were assayed for T-cell activation and transcriptomic profiles (by using RNA sequencing), respectively. Participants allergic to mountain cedar (n = 21), oak (n = 34), and ragweed (n = 23) recorded TSSs during separate out-of-season exposures to these pollens (any pollen sensitization [P+]) in the ACC; a subset recorded TSSs in the pollination seasons. Results: The hierarchy of TSSs (highest to lowest) among M+ participants tracked the following skin prick test sensitization statuses: M+P+C- > M+P+C+ > M+P-C- > M+P-C+. In nasal cells and peripheral blood the immune/inflammatory responses were rapidly resolved in M+P+C+ compared with M+P+C- participants. Among those allergic to pollen, C+ was associated with a lower TSS during pollen challenges and the pollination season. After aggregated analysis of all 4 ACC studies, C+ status was associated with a 2.8-fold greater likelihood of a lower TSS compared with C- status (odds ratio, 2.78; 95% CI, 1.18-6.67; P = .02). Conclusions: C+ status is associated with mitigation of AR symptom severity in adults with AR. C1 [He, Weijing; Jimenez, Fabio; Martinez, Hernan; Harper, Nathan L.; Manoharan, Muthu Saravanan; Carrillo, Andrew; Ingale, Puraskar; Liu, Ya-Guang; Ahuja, Seema S.; Clark, Robert A.; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [He, Weijing; Jimenez, Fabio; Martinez, Hernan; Harper, Nathan L.; Manoharan, Muthu Saravanan; Carrillo, Andrew; Ingale, Puraskar; Liu, Ya-Guang; Ahuja, Seema S.; Clark, Robert A.; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Jimenez, Fabio; Martinez, Hernan; Harper, Nathan L.] Biomed Res Fdn South Texas, San Antonio, TX USA. [Rather, Cynthia G.; Ramirez, Daniel A.; Andrews, Charles P.; Jacobs, Robert L.] Biogen Res Chamber, San Antonio, TX USA. RP Ahuja, SK (reprint author), 7400 Merton Minter Blvd,Room W200, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu OI Ingale, Puraskar/0000-0003-2769-878X FU Doris Duke Distinguished Clinical Scientist Award; Burroughs Wellcome Clinical Scientist in Transitional Research Award; Max and Minnie Tomerlin Voelcker Award; Center for Personalized Medicine at the South Texas Veterans Health Care System [CX00875-01AI] FX S.K.A. received support from the following grants: the Doris Duke Distinguished Clinical Scientist Award, the Burroughs Wellcome Clinical Scientist in Transitional Research Award, the Max and Minnie Tomerlin Voelcker Award, and the Center for Personalized Medicine (CX00875-01AI) at the South Texas Veterans Health Care System. R.L.J., C.P.A., and D.A.R., are co-owners of Biogenics Research Chamber and have not received financial support. C.G.R. is the Executive Director of Chamber Operations. NR 40 TC 5 Z9 5 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2015 VL 136 IS 3 BP 658 EP 666 DI 10.1016/j.jaci.2015.02.041 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA CQ9EA UT WOS:000360913300018 PM 26026342 ER PT J AU Chou, J Massaad, MJ Cangemi, B Bainter, W Platt, C Badran, YR Raphael, BP Kamin, DS Goldsmith, JD Pai, SY Al-Herz, W Geha, RS AF Chou, Janet Massaad, Michel J. Cangemi, Brittney Bainter, Wayne Platt, Craig Badran, Yousef R. Raphael, Bram P. Kamin, Daniel S. Goldsmith, Jeffrey D. Pai, Sung-Yun Al-Herz, Waleed Geha, Raif S. TI A novel mutation in ICOS presenting as hypogammaglobulinemia with susceptibility to opportunistic pathogens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID COMMON VARIABLE IMMUNODEFICIENCY; DEFICIENCY; CELLS; CD4 C1 [Chou, Janet; Massaad, Michel J.; Cangemi, Brittney; Bainter, Wayne; Platt, Craig; Badran, Yousef R.; Geha, Raif S.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Raphael, Bram P.; Kamin, Daniel S.] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Boston, MA USA. [Raphael, Bram P.; Kamin, Daniel S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Goldsmith, Jeffrey D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Goldsmith, Jeffrey D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait. RP Chou, J (reprint author), Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. EM Raif.Geha@childrens.harvard.edu FU NIAID NIH HHS [AI-094017, P01AI-076210] NR 12 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2015 VL 136 IS 3 BP 794 EP + DI 10.1016/j.jaci.2014.12.1940 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA CQ9EA UT WOS:000360913300032 PM 25678089 ER PT J AU Clair, AJ Inneh, IA Iorio, R Berend, KR Della Valle, CJ Healy, WL Pelligrini, VD AF Clair, Andrew James Inneh, Ifeoma A. Iorio, Richard Berend, Keith R. Della Valle, Craig J. Healy, William L. Pelligrini, Vincent D. TI Can Administrative Data Be Used to Analyze Complications Following Total Joint Arthroplasty? SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American Association of Hip and Knee Surgeons (AAHKS) CY NOV 06-09, 2014 CL Dallas, TX DE total knee arthroplasty; total hip arthroplasty; complications; healthcare quality; administrative data ID TOTAL KNEE ARTHROPLASTY; MEDIAL COLLATERAL LIGAMENT; OUTCOMES RESEARCH; TOTAL HIP; DATABASES; INJURY AB We hypothesized that the Centers for Medicare and Medicaid Services Limited Dataset (CMS-LDS) could be used to validate the complications associated with total hip and knee arthroplasty (THA and TKA) endorsed by the Hip and Knee Societies. Using ICD-9 procedure and diagnosis codes, cases were extracted from the first three quarters of the 2009 CMS-LDS to allow all complications within 90-days be captured in the same calendar year. We were unable to validate the Hip and Knee Societies' complications as we could not connect readmissions or outpatient visits to index admissions. In addition, well-known complications were not detected, raising concerns about coding accuracy and stratification. Furthermore, the assignment of outpatient and inpatient codes allows for duplication of complications which may falsely elevate the true incidence. (C) 2015 Elsevier Inc. All rights reserved. C1 [Clair, Andrew James; Inneh, Ifeoma A.; Iorio, Richard] NYU, Langone Med Ctr, Hosp Joint Dis, Dept Orthopaed Surg, New York, NY 10003 USA. [Berend, Keith R.] Joint Implant Surg Inc, New Albany, OH USA. [Della Valle, Craig J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Healy, William L.] Massachusetts Gen Hosp, Newton Wellesley Hosp, Kaplan Joint Ctr, Boston, MA 02114 USA. [Pelligrini, Vincent D.] Med Univ S Carolina, Dept Orthopaed, Charleston, SC 29425 USA. [Pelligrini, Vincent D.] Med Univ Hosp Author, Musculoskeletal Serv Line, Charleston, SC USA. RP Clair, AJ (reprint author), NYU, Langone Med Ctr, Hosp Joint Dis, Dept Orthopaed Surg, 301 East 17th St, New York, NY 10003 USA. OI Iorio, Richard/0000-0001-8083-8687 NR 18 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 SU S BP 17 EP 20 DI 10.1016/j.arth.2015.01.060 PG 4 WC Orthopedics SC Orthopedics GA CQ9HB UT WOS:000360923200005 PM 26187386 ER PT J AU Dwyer, MK Lee, JA McCarthy, JC AF Dwyer, Maureen K. Lee, Jo-Ann McCarthy, Joseph C. TI Cartilage Status at Time of Arthroscopy Predicts Failure in Patients With Hip Dysplasia SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American Association of Hip and Knee Surgeons (AAHKS) CY NOV 06-09, 2014 CL Dallas, TX DE hip arthroscopy; dysplasia; predictors; hip; cartilage ID BERNESE PERIACETABULAR OSTEOTOMY; ACETABULAR DYSPLASIA; PRESERVATION SURGERY; LABRUM; IMPINGEMENT; DISEASE; JOINT AB The purpose of our study was to determine whether chondral damage at the time of arthroscopy predicted conversion to THA in patients with dysplasia. We identified 166 patients with dysplasia who underwent hip arthroscopy. Forty-seven went on to receive THA. The articular cartilage of three regions of the acetabulum and femoral head were assessed for signs of chondral damage (absent, mild, or severe]). A stepwise multivariable logistic regression analysis revealed mild damage on the posterior femoral head (P=0.001) and severe damage on the anterior acetabulum (P=0.007) made a significant contribution to the predictor. The presence of mild posterior femoral head chondral changes was indicative of more global cartilage damage in this series of patients. Our findings show that chondral damage on the posterior femoral head and anterior acetabulum is a strong predictor of ultimate conversion to THA in dysplastic patients. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dwyer, Maureen K.; Lee, Jo-Ann; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Joint Ctr, Newton, MA 02462 USA. [Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Dwyer, MK (reprint author), Newton Wellesley Hosp, Kaplan Joint Ctr, 2000 Washington St,Green Bldg,Ste 361, Newton, MA 02462 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 SU S BP 121 EP 124 DI 10.1016/j.arth.2014.12.034 PG 4 WC Orthopedics SC Orthopedics GA CQ9HB UT WOS:000360923200028 PM 26059500 ER PT J AU Ferraresi, C Parizotto, NA de Sousa, MVP Kaippert, B Huang, YY Koiso, T Bagnato, VS Hamblin, MR AF Ferraresi, Cleber Parizotto, Nivaldo Antonio Pires de Sousa, Marcelo Victor Kaippert, Beatriz Huang, Ying-Ying Koiso, Tomoharu Bagnato, Vanderlei Salvador Hamblin, Michael R. TI Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation SO JOURNAL OF BIOPHOTONICS LA English DT Article DE LLLT; LEDT; muscle performance; muscle recovery; ATP ID BIPHASIC DOSE-RESPONSE; LEVEL LASER THERAPY; SKELETAL-MUSCLE; OXIDATIVE STRESS; PHOTOTHERAPY; MECHANISMS; RADIATION; RATS; IRRADIATION; FATIGUE AB Light-emitting diode therapy (LEDT) applied over the leg, gluteus and lower-back muscles of mice using a LED cluster (630nm and 850nm, 80mW/cm(2), 7.2J/cm(2)) increased muscle performance (repetitive climbing of a ladder carrying a water-filled tube attached to the tail), ATP and mitochondrial metabolism; oxidative stress and proliferative myocyte markers in mice subjected to acute and progressive strength training. Six bi-daily training sessions LEDT-After and LEDT-Before-After regimens more than doubled muscle performance and increased ATP more than tenfold. The effectiveness of LEDT on improving muscle performance and recovery suggest applicability for high performance sports and in training programs. [GRAPHICS] Positioning of the mice and light-emitting diode therapy (LEDT) applied on mouse legs, gluteus and lower-back muscles without contact. C1 [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Postgrad Program Biotechnol, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei Salvador] Univ Sao Paulo, Phys Inst Sao Carlos, Opt Grp, Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Pires de Sousa, Marcelo Victor; Kaippert, Beatriz; Huang, Ying-Ying; Koiso, Tomoharu; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Pires de Sousa, Marcelo Victor] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, BR-05508 Sao Paulo, Brazil. [Kaippert, Beatriz] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Koiso, Tomoharu] Tohoku Univ, Grad Sch Biomed Engn, Sendai, Miyagi 980, Japan. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM mhamblin@partners.org RI Ferraresi, Cleber/B-2458-2014; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; USP, CePOF/J-3608-2015 FU FAPESP [2010/07194-7, 2012/05919-0]; US NIH [R01AI050875] FX Cleber Ferraresi would like to thank FAPESP for his Ph.D. scholarships (numbers 2010/07194-7 and 2012/05919-0). MR Hamblin was supported by US NIH grant R01AI050875. We acknowledge Andrea L. Brissette for administrative assistance and Jenny Zhao for assistance with the core laboratory of histopathology, microscopy and digital imaging of the Wellman Center for Photomedicine, Massachusetts General Hospital. NR 38 TC 12 Z9 12 U1 1 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD SEP PY 2015 VL 8 IS 9 BP 740 EP 754 DI 10.1002/jbio.201400087 PG 15 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA CR1CK UT WOS:000361060200006 PM 25378263 ER PT J AU Wolf, LA Delao, AM Perhats, C Clark, PR Moon, MD Baker, KM Carman, MJ Zavotsky, KE Lenehan, G AF Wolf, Lisa A. Delao, Altair M. Perhats, Cydne Clark, Paul R. Moon, Michael D. Baker, Kathy M. Carman, Margaret J. Zavotsky, Kathleen E. Lenehan, Gail TI EXPLORING THE MANAGEMENT OF DEATH: EMERGENCY NURSES' PERCEPTIONS OF CHALLENGES AND FACILITATORS IN THE PROVISION OF END-OF-LIFE CARE IN THE EMERGENCY DEPARTMENT SO JOURNAL OF EMERGENCY NURSING LA English DT Article DE Mixed methods; End-of-life care; Emergency department; Nursing. ID UNDERGRADUATE NURSING-STUDENTS; EMOTIONAL INTELLIGENCE; SUPPORTIVE BEHAVIORS; DYING PATIENTS; OBSTACLES; ATTITUDES; IMPACT AB Introduction: The importance of end-of-life (EOL) care for dying patients and their families is well described; however, little research has been performed in emergency settings. The purpose of this study was to explore emergency nurses' perceptions of challenges and facilitators in the care of patients at the EOL. Methods: A mixed-methods design using survey data (N = 1,879) and focus group data (N = 17). Data were collected on questions regarding care of the EOL patient in the emergency department, specifically nurses' perceptions of the care of these patients; educational content needs; barriers to safe and effective care; and the availability of resources. Results: High scores on the quantitative survey showed a high mean level of consistently positive attitudes and beliefs toward caring for dying patients and their families and loved ones (131.26 +/- 10.88). Analysis of the focus group transcripts uncovered 9 themes, reflecting concerns around comfort and challenges with EOL care, appropriate training for nurses, and the availability of resources to provide this type of care in the emergency setting. Also noted was dissonance between the nature of emergency care and the nature of EOL care. Discussion: Emergency nurses are comfortable providing EOL care in the emergency setting but note that challenges to providing good care include lack of space, time, and staff. Other challenges involve the mismatch between the goals of emergency care and those of EOL care, as well as the emotional burden of caring for the dying, especially when the appropriate resources are lacking. C1 [Wolf, Lisa A.; Delao, Altair M.; Perhats, Cydne] Emergency Nurses Assoc, Inst Emergency Nursing Res, Des Plaines, IL 60016 USA. [Clark, Paul R.] Norton Healthcare Inst Nursing, Syst Educ, Louisville, KY USA. [Moon, Michael D.] Univ Incarnate Word, San Antonio, TX USA. [Baker, Kathy M.] VCU Hlth Syst, Richmond, VA USA. [Carman, Margaret J.] Duke Univ, Sch Nursing, Durham, NC USA. [Zavotsky, Kathleen E.] Robert Wood Johnson Univ Hosp, Nursing Res Adv Practice & Educ, New Brunswick, NJ USA. [Lenehan, Gail] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wolf, LA (reprint author), Emergency Nurses Assoc, 915 Lee St, Des Plaines, IL 60016 USA. EM lwolf@ena.org OI Clark, Paul/0000-0003-4990-875X NR 27 TC 1 Z9 1 U1 6 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD SEP PY 2015 VL 41 IS 5 BP E23 EP E33 DI 10.1016/j.jen.2015.05.018 PG 11 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA CQ9GA UT WOS:000360919800001 PM 26232873 ER PT J AU Aoki, EM Abdala, R de Oliveira, JX Arita, ES Cortes, ARG AF Aoki, Eduardo Massaharu Abdala-Junior, Reinaldo de Oliveira, Jefferson Xavier Arita, Emiko Saito Gonzalez Cortes, Arthur Rodriguez TI Reliability and Reproducibility of Manual and Automated Volumetric Measurements of Periapical Lesions SO JOURNAL OF ENDODONTICS LA English DT Article DE Cone-beam computed tomography; periapical lesions; region growing; segmentation; volumetric measurements ID BEAM COMPUTED-TOMOGRAPHY; APICAL PERIODONTITIS; BONE DEFECTS; ACCURACY; CT; RADIOGRAPHY; SOFTWARE; IMPLANTS; TEETH; SCANS AB Introduction: The present study aimed to test the reliability and reproducibility of 2 methods: manual and automated segmentation (using a threshold-based region growing algorithm) for measuring the volume of periapical lesions. Methods: A total of 43 cone-beam computed tomographic scans (14 men and 29 women, mean age of 54.6 +/- 8.5 years) were analyzed by 3 observers. Intraobserver reproducibility and inter-observer reliability were assessed using the intraclass correlation coefficient. Parametric correlation between manual and automated volumetric measurements was performed. In addition, the Student t test was also used to compare the mean time required for manual and automated volumetric measurements. Results: Automated segmentation showed slightly higher intraclass correlation coefficient values for all observers. A strong significant correlation was found between manual and automated volumetric measurements performed by the 3 observers. A significant difference in the mean procedure time was also found between both methods (P = .001). Conclusions: Within the limitations of this study, the present results suggest that automated segmentation with a region growing algorithm is faster and slightly more reliable to calculate the volume of periapical lesions. C1 [Aoki, Eduardo Massaharu; Abdala-Junior, Reinaldo; de Oliveira, Jefferson Xavier; Arita, Emiko Saito] Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, Brazil. [Gonzalez Cortes, Arthur Rodriguez] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gonzalez Cortes, Arthur Rodriguez] Harvard Univ, Sch Med, Boston, MA USA. RP Cortes, ARG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr, Room 2103,149 13th St, Charlestown, MA 02129 USA. EM acortes@nmr.mgh.harvard.edu RI Cortes, Arthur/C-8738-2013 OI Cortes, Arthur/0000-0001-6591-7256 FU National Council for Scientific and Technological Development CNPq-Science Without Borders, Brazil [232643/2013-0] FX A postdoctoral scholarship was granted to A.R.G.C by the National Council for Scientific and Technological Development CNPq-Science Without Borders, Brazil (no. 232643/2013-0). NR 23 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 EI 1878-3554 J9 J ENDODONT JI J. Endod. PD SEP PY 2015 VL 41 IS 9 BP 1555 EP 1559 DI 10.1016/j.joen.2015.06.015 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CR1JY UT WOS:000361082300031 PM 26234544 ER PT J AU Yaghmaie, F Esmaeili, S Francis, SA Mostafavi, E AF Yaghmaie, Farhad Esmaeili, Saber Francis, Sanjeev A. Mostafavi, Ehsan TI Q fever endocarditis in Iran: A case report SO JOURNAL OF INFECTION AND PUBLIC HEALTH LA English DT Article DE Q fever; Coxiella burnetii; Endocarditis; Female; Iran ID SEROEPIDEMIOLOGICAL SURVEY; PROVINCE; SHEEP AB In this report, we describe the first chronic case of Q fever endocarditis in a 72-year-old woman in Iran. The patient developed radiation-associated heart disease status post (sip) coronary artery bypass surgery, mitral and aortic valve replacements, and tricuspid valve repair. Endocarditis was also suspected due to a history of heart valve surgery. Blood cultures were negative, but a diagnosis of Q fever endocarditis was confirmed based on serologic titers (IgG phase I 1:32,768). The patient was treated with doxycycline and hydroxychloroquine. (C) 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Limited. All rights reserved. C1 [Yaghmaie, Farhad; Esmaeili, Saber; Mostafavi, Ehsan] Inst Pasteur, Dept Epidemiol, Tehran 1316943551, Iran. [Yaghmaie, Farhad; Esmaeili, Saber; Mostafavi, Ehsan] Res Ctr Emerging & Reemerging Infect Dis, Inst Pasteur, Natl Reference Lab Plague, Tularemia & Q Fever, Hamadan, Iran. [Francis, Sanjeev A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02115 USA. RP Mostafavi, E (reprint author), Inst Pasteur, Dept Epidemiol, 69 Pasteur Ave, Tehran 1316943551, Iran. EM mostafaviehsan@gmail.com RI Mostafavi, Ehsan/A-7627-2011; Esmaeili, Saber/F-2620-2017 OI Mostafavi, Ehsan/0000-0002-1997-517X; Esmaeili, Saber/0000-0003-1920-1737 FU Pasteur Institute of Iran; Center for Disease Control of Iranian Ministry of Health and Medical Education [582] FX We appreciate the financial support of the Pasteur Institute of Iran and Center for Disease Control of Iranian Ministry of Health and Medical Education (Grant No. 582). We would like to express our gratitude to the Massachusetts General Hospital personnel, especially Seth R. Glassman (specializing in infectious disease medicine), for their help in the primary diagnosis and management of this case. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1876-0341 EI 1876-035X J9 J INFECT PUBLIC HEAL JI J. Infect. Public Health PD SEP-OCT PY 2015 VL 8 IS 5 BP 498 EP 501 DI 10.1016/j.jiph.2014.12.004 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CQ8NV UT WOS:000360865900014 PM 25747823 ER PT J AU Lincoln, SE Kobayashi, Y Anderson, MJ Yang, S Desmond, AJ Mills, MA Nilsen, GB Jacobs, KB Monzon, FA Kurian, AW Ford, JM Ellisen, LW AF Lincoln, Stephen E. Kobayashi, Yuya Anderson, Michael J. Yang, Shan Desmond, Andrea J. Mills, Meredith A. Nilsen, Geoffrey B. Jacobs, Kevin B. Monzon, Federico A. Kurian, Allison W. Ford, James M. Ellisen, Leif W. TI A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID DIFFUSE GASTRIC-CANCER; NEXT-GENERATION; COLORECTAL-CANCER; MUTATION CARRIERS; RISK ASSESSMENT; SUSCEPTIBILITY GENE; GERMLINE MUTATIONS; BRCA2 MUTATIONS; FAMILY-HISTORY; MUTYH MUTATION AB Gene panels for hereditary breast and ovarian cancer risk assessment are gaining acceptance, even though the clinical utility of these panels is not yet fully defined. Technical questions remain, however, about the performance and clinical interpretation of gene panels in comparison with traditional tests. We tested 1105 individuals using a 29-gene next-generation sequencing panel and observed 100% analytical concordance with traditional and reference data on >750 comparable variants. These 750 variants included technically challenging classes of sequence and copy number variation that together represent a significant fraction (13.4%) of the pathogenic variants observed. For BRCA1 and BRCA2, we also compared variant interpretations in traditional reports to those produced using only non-proprietary resources and following criteria based on recent (2015) guidelines. We observed 99.8% net report concordance, albeit with a slightly higher variant of uncertain significance rate. In 4.5% of BRCA-negative cases, we uncovered pathogenic variants in other genes, which appear clinically relevant. Previously unseen variants requiring interpretation accumulated rapidly, even after 1000 individuals had been tested. We conclude that next-generation sequencing panel testing can provide results highly comparable to traditional testing and can uncover potentially actionable findings that may be otherwise missed. Challenges remain for the broad adoption of panel tests, some of which will be addressed by the accumulation of large public databases of annotated clinical variants. C1 [Lincoln, Stephen E.; Kobayashi, Yuya; Anderson, Michael J.; Yang, Shan; Nilsen, Geoffrey B.; Jacobs, Kevin B.; Monzon, Federico A.] Invitae, San Francisco, CA 94107 USA. [Desmond, Andrea J.; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mills, Meredith A.; Kurian, Allison W.; Ford, James M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. RP Lincoln, SE (reprint author), Invitae, 458 Brannan St, San Francisco, CA 94107 USA. EM steve.lincoln@invitae.com FU Friends Fighting Breast Cancer; Tracey Davis Memorial Fund; Breast Cancer Research Foundation FX Supported by The Friends Fighting Breast Cancer (L.W.E.), the Tracey Davis Memorial Fund (L.W.E.), and the Breast Cancer Research Foundation (A.W.K. and J.M.F.). NR 96 TC 15 Z9 15 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD SEP PY 2015 VL 17 IS 5 BP 533 EP 544 DI 10.1016/j.jmoldx.2015.04.009 PG 12 WC Pathology SC Pathology GA CQ7JB UT WOS:000360777700009 PM 26207792 ER PT J AU Adams, JM Miyamoto, S AF Adams, Jeffrey M. Miyamoto, Suzanne TI The Influence of Emerging Nursing Strategy and Policy Leaders An Interview With Dr Suzanne Miyamoto SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB This department highlights emerging nursing leaders who have demonstrated great potential in advancing innovation and patient care leadership in practice, policy, research, education, and theory. This interview profiles Suzanne Miyamoto, PhD, RN, Senior Director of Government Affairs and Health Policy at the American Association of Colleges of Nursing. C1 [Adams, Jeffrey M.] Ctr Innovat Care Delivery, Boston, MA USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miyamoto, Suzanne] Amer Assoc Coll Nursing, Govt Affairs & Hlth Policy, Washington, DC USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 432, Boston, MA 02114 USA. EM jadams9@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2015 VL 45 IS 9 BP 420 EP 422 DI 10.1097/NNA.0000000000000226 PG 3 WC Nursing SC Nursing GA CQ8JH UT WOS:000360853200004 ER PT J AU Thompson, DA Marsteller, JA Pronovost, PJ Gurses, A Lubomski, LH Goeschel, CA Gosbee, JW Wahr, J Martinez, EA AF Thompson, David A. Marsteller, Jill A. Pronovost, Peter J. Gurses, Ayse Lubomski, Lisa H. Goeschel, Christine A. Gosbee, John W. Wahr, Joyce Martinez, Elizabeth A. TI Locating Errors Through Networked Surveillance: A Multimethod Approach to Peer Assessment, Hazard Identification, and Prioritization of Patient Safety Efforts in Cardiac Surgery SO JOURNAL OF PATIENT SAFETY LA English DT Article ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE; FAILURES; SCIENCE; QUALITY; HEALTH; IMPACT; FOCUS; RISK AB Objectives The objectives were to develop a scientifically sound and feasible peer-to-peer assessment model that allows health-care organizations to evaluate patient safety in cardiovascular operating rooms and to establish safety priorities for improvement. Methods The locating errors through networked surveillance study was conducted to identify hazards in cardiac surgical care. A multidisciplinary team, composed of organizational sociology, organizational psychology, applied social psychology, clinical medicine, human factors engineering, and health services researchers, conducted the study. We used a transdisciplinary approach, which integrated the theories, concepts, and methods from each discipline, to develop comprehensive research methods. Multiple data collection was involved: focused literature review of cardiac surgery-related adverse events, retrospective analysis of cardiovascular events from a national database in the United Kingdom, and prospective peer assessment at 5 sites, involving survey assessments, structured interviews, direct observations, and contextual inquiries. A nominal group methodology, where one single group acts to problem solve and make decisions was used to review the data and develop a list of the top priority hazards. Results The top 6 priority hazard themes were as follows: safety culture, teamwork and communication, infection prevention, transitions of care, failure to adhere to practices or policies, and operating room layout and equipment. Conclusions We integrated the theories and methods of a diverse group of researchers to identify a broad range of hazards and good clinical practices within the cardiovascular surgical operating room. Our findings were the basis for a plan to prioritize improvements in cardiac surgical care. These study methods allowed for the comprehensive assessment of a high-risk clinical setting that may translate to other clinical settings. C1 [Thompson, David A.; Marsteller, Jill A.; Pronovost, Peter J.; Gurses, Ayse; Lubomski, Lisa H.; Goeschel, Christine A.] Johns Hopkins Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD USA. [Thompson, David A.; Marsteller, Jill A.; Pronovost, Peter J.; Gurses, Ayse; Lubomski, Lisa H.; Goeschel, Christine A.; Martinez, Elizabeth A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21202 USA. [Thompson, David A.; Marsteller, Jill A.; Pronovost, Peter J.; Goeschel, Christine A.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Thompson, David A.; Marsteller, Jill A.; Pronovost, Peter J.; Gurses, Ayse; Goeschel, Christine A.] Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Gosbee, John W.; Wahr, Joyce] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Thompson, DA (reprint author), Johns Hopkins Univ, Sch Med, Armstrong Inst Patient Safety & Qual, 750 E Pratt St,15th Floor, Baltimore, MD 21202 USA. EM dthomps1@jhmi.edu FU National Institutes of Health, RAND; Commonwealth Fund; Michigan Health & Hospital Association Keystone Center for Quality and Patient Safety; Agency for Healthcare Research and Quality; SCA Foundation; Agency for Healthcare Research and Quality (K08) [HS013904-02] FX P.J.P has received grant funding from the National Institutes of Health, RAND, and The Commonwealth Fund; is on the Leigh [speakers] Bureau and received honoraria from various hospitals to speak on quality and patient safety; is a consultant for the Association for Professionals in Infection Control and Epidemiology, Inc.; is a board member for the Cantel Medical and receives book royalties from Penguin Group. L.H.L. received contract funding from Michigan Health & Hospital Association Keystone Center for Quality and Patient Safety and consulted for the Society for Pediatric Anesthesia. C.A.G. received grant funding from Agency for Healthcare Research and Quality and has received honoraria from various nonprofit agencies to speak on quality, health policy, and patient safety. This work was completed as part of the FOCUS initiative. The FOCUS Initiative is a collaborative project of the Society of Cardiovascular Anesthesiologists (SCA), the SCA Foundation, and the Johns Hopkins University Quality and Safety Research group. FOCUS is funded exclusively by the SCA Foundation; the following received support for this research: Drs. Thompson, Marsteller, Lubomski, Goeschel, and Pronovost. Dr. Martinez was supported by the Agency for Healthcare Research and Quality (K08 grant no. HS013904-02). NR 30 TC 0 Z9 0 U1 5 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD SEP PY 2015 VL 11 IS 3 BP 143 EP 151 DI 10.1097/PTS.0000000000000059 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CQ6EX UT WOS:000360698300003 PM 24686159 ER PT J AU Geng, CR Tang, XB Qian, W Guan, FD Johns, J Yu, HY Gong, CH Shu, DY Chen, D AF Geng, Changran Tang, Xiaobin Qian, Wei Guan, Fada Johns, Jesse Yu, Haiyan Gong, Chunhui Shu, Diyun Chen, Da TI Calculations of S values and effective dose for the radioiodine carrier and surrounding individuals based on Chinese hybrid reference phantoms using the Monte Carlo technique SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Article DE Monte Carlo; computational phantoms; radioiodine; S values; effective dose ID COMPUTATIONAL PHANTOMS; ADULT MALE; DOSIMETRY; FEMALE; I-131; FAMILY; SCHEMA; MODEL AB The S values for the thyroid as the radioiodine source organ to other target organs were investigated using Chinese hybrid reference phantoms and the Monte Carlo code MCNP5. Two radioiodine isotopes I-125 and I-131 uniformly distributed in the thyroid were investigated separately. We compared our S values for I-131 in Chinese phantoms with previous studies using other types of phantoms: Oak Ridge National Laboratory (ORNL) stylized phantoms, International Commission on Radiological Protection (ICRP) voxel phantoms, and University of Florida (UF) phantoms. Our results are much closer to the UF phantoms. For each specific target organ, the S value for I-131 is larger than for I-125 in both male and female phantoms. In addition, the S values and effective dose to surrounding face-to-face exposed individuals, including different genders and ages (10- and 15-year-old juniors, and adults) from an adult male radioiodine carrier were also investigated. The target organ S values and effective dose for surrounding individuals obey the inverse square law with the distance between source and target phantoms. The obtained effective dose data in Chinese phantoms are comparable to the results in a previous study using the UF phantoms. The data generated in this study can serve as the reference to make recommendations for radiation protection of the Chinese patients or nuclear workers. C1 [Geng, Changran; Tang, Xiaobin; Qian, Wei; Yu, Haiyan; Gong, Chunhui; Shu, Diyun; Chen, Da] Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 211106, Jiangsu, Peoples R China. [Geng, Changran; Tang, Xiaobin; Yu, Haiyan; Gong, Chunhui; Shu, Diyun; Chen, Da] Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Suzhou 215123, Peoples R China. [Geng, Changran] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Geng, Changran] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Guan, Fada] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Johns, Jesse] Nimbus Innovat LLC, Temple, TX 76501 USA. RP Geng, CR (reprint author), Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 211106, Jiangsu, Peoples R China. EM tangxiaobin@nuaa.edu.cn RI Tang, Xiaobin/I-7601-2014; OI Tang, Xiaobin/0000-0003-3308-0468; GUAN, FADA/0000-0001-8477-7391 FU National Natural Science Foundation of China [11475087]; Jiangsu Innovation Program for Graduate Education [KYLX_0265]; Fundamental Research Funds for the Central Universities [NS2014060]; Priority Academic Program Development of Jiangsu Higher Education Institutions FX This work was supported by National Natural Science Foundation of China (No. 11475087), the funding of Jiangsu Innovation Program for Graduate Education (No. KYLX_0265), the Fundamental Research Funds for the Central Universities (No. NS2014060), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. We thank Dr Choonsik Lee et al for sharing the data for ICRP phantoms. NR 27 TC 0 Z9 0 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD SEP PY 2015 VL 35 IS 3 BP 707 EP 717 DI 10.1088/0952-4746/35/3/707 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CR2FN UT WOS:000361141800018 PM 26344387 ER PT J AU Singh, JA Qu, HY Yazdany, J Chatham, W Dall'era, M Shewchuk, RM AF Singh, Jasvinder A. Qu, Haiyan Yazdany, Jinoos Chatham, Winn Dall'era, Maria Shewchuk, Richard M. TI Barriers to Medication Decision Making in Women with Lupus Nephritis: A Formative Study using Nominal Group Technique SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; MEDICATION DECISION MAKING; MINORITIES; RACE; BARRIERS; CHALLENGES ID ERYTHEMATOSUS PATIENTS; PATIENT PREFERENCES; TREATMENT ADHERENCE; RHEUMATIC-DISEASE; HEALTH-CARE; DISABILITIES; AMERICAN; IDENTIFY; QUALITY; COHORT AB Objective. To assess the perspectives of women with lupus nephritis on barriers to medication decision making. Methods. We used the nominal group technique (NGT), a structured process to elicit ideas from participants, for a formative assessment. Eight NGT meetings were conducted in English and moderated by an expert NGT researcher at 2 medical centers. Participants responded to the question: "What sorts of things make it hard for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized barriers to decisional processes involving medications for treating lupus nephritis. Results. Fifty-one women with lupus nephritis with a mean age of 40.6 +/- 13.3 years and disease duration of 11.8 +/- 8.3 years participated in 8 NGT meetings: 26 African Americans (4 panels), 13 Hispanics (2 panels), and 12 whites (2 panels). Of the participants, 36.5% had obtained at least a college degree and 55.8% needed some help in reading health materials. Of the 248 responses generated (range 19-37 responses/panel), 100 responses (40%) were perceived by patients as having relatively greater importance than other barriers in their own decision-making processes. The most salient perceived barriers, as indicated by percent-weighted votes assigned, were known/anticipated side effects (15.6%), medication expense/ability to afford medications (8.2%), and the fear that the medication could cause other diseases (7.8%). Conclusion. Women with lupus nephritis identified specific barriers to decisions related to medications. Information relevant to known/anticipated medication side effects and medication cost will form the basis of a patient guide for women with systemic lupus erythematosus, currently under development. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Med Serv, Birmingham Vet Affairs VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Chatham, Winn] Univ Alabama Birmingham, Dept Med, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Chatham, Winn] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Qu, Haiyan; Shewchuk, Richard M.] Univ Alabama Birmingham, Dept Hlth Serv Adm, Sch Hlth Profess, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Yazdany, Jinoos; Dall'era, Maria] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Patient-Centered Outcomes Research Institute [CE-1304-6631]; Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19 HS021110]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; National Institute on Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; US National Institutes of Health [K23 AR060259]; Rosalind Russell Medical Research Center for Arthritis FX This material is the result of work supported by the research contract CE-1304-6631 from the Patient-Centered Outcomes Research Institute. J.A. Singh is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA, and research grants from these US agencies: Agency for Health Quality and Research Center for Education and Research on Therapeutics U19 HS021110, National Institute of Arthritis and Musculoskeletal and Skin Diseases P50 AR060772 and U34 AR062891, National Institute on Aging U01 AG018947, and the National Cancer Institute U10 CA149950. J.Yazdany is also supported by the US National Institutes of Health K23 AR060259 and the Rosalind Russell Medical Research Center for Arthritis. NR 33 TC 4 Z9 4 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2015 VL 42 IS 9 BP 1616 EP 1623 DI 10.3899/jrheum.150168 PG 8 WC Rheumatology SC Rheumatology GA CQ6SF UT WOS:000360733600014 PM 26178276 ER PT J AU Raske, ME Dempsey, ME Dillman, JR Dory, CE Garber, M Hayes, LL Iyer, RS Kulkarni, AV Myseros, JS Rice, HE Rigsby, CK Ryan, ME Strouse, PJ Westra, SJ Wootton-Gorges, SL Coley, BD Karmazyn, B AF Raske, Molly E. Dempsey, Molly E. Dillman, Jonathan R. Dory, Christopher E. Garber, Matthew Hayes, Laura L. Iyer, Ramesh S. Kulkarni, Abhaya V. Myseros, John S. Rice, Henry E. Rigsby, Cynthia K. Ryan, Maura E. Strouse, Peter J. Westra, Sjirk J. Wootton-Gorges, Sandra L. Coley, Brian D. Karmazyn, Boaz TI ACR Appropriateness Criteria Vomiting in Infants up to 3 Months of Age SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; vomiting; newborn; infant; diagnostic imaging ID HYPERTROPHIC PYLORIC-STENOSIS; PEDIATRIC GASTROESOPHAGEAL-REFLUX; NORTH-AMERICAN-SOCIETY; INTESTINAL MALROTATION; SONOGRAPHIC DIAGNOSIS; PH PROBE; CHILDREN; ULTRASONOGRAPHY; SCINTIGRAPHY; ROTATION AB Vomiting is a commonly reported symptom in infants less than three months of age. There are a multitude of pathologies to consider, both within and outside the gastrointestinal tract. In addition to conducting a thorough history and physical examination, a clinician formulates a reasonable differential diagnosis by consideration of two main factors: the infant's age and the characterization of the vomit as bilious or nonbilious. In this endeavor, the clinician is able to determine if an imaging study is needed and, if so, the urgency of the request. A review of the appropriate imaging evaluation of vomiting infants in the newborn to three-month-old age group is provided by organizing the discussion around the following three clinical scenarios: bilious vomiting, intermittent nonbilious vomiting since birth, and new-onset bilious vomiting. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Raske, Molly E.] Childrens Hosp & Clin Minnesota, Minneapolis, MN 55404 USA. [Dempsey, Molly E.] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. [Dillman, Jonathan R.; Strouse, Peter J.] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Dory, Christopher E.] Childrens Hosp, San Diego, CA USA. [Garber, Matthew] Div Gen & Hosp Pediat, Columbia, SC USA. [Garber, Matthew] Amer Acad Pediat, Elk Grove Village, IL USA. [Hayes, Laura L.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Iyer, Ramesh S.] Seattle Childrens Hosp, Seattle, WA USA. [Kulkarni, Abhaya V.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kulkarni, Abhaya V.; Myseros, John S.] Amer Assoc Neurol Surg, Rolling Meadows, IL USA. [Kulkarni, Abhaya V.; Myseros, John S.] Congress Neurol Surg, Schaumburg, IL USA. [Myseros, John S.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rice, Henry E.] Duke Univ, Med Ctr, Durham, NC USA. [Rice, Henry E.] Amer Pediat Surg Assoc, Deerfield, IL USA. [Rigsby, Cynthia K.; Ryan, Maura E.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wootton-Gorges, Sandra L.] Univ Calif Davis, Sacramento, CA 95817 USA. [Coley, Brian D.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Karmazyn, Boaz] Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN USA. RP Raske, ME (reprint author), Childrens Hosp & Clin Minnesota, 2525 Chicago Ave, Minneapolis, MN 55404 USA. EM molly.raske@childrensmn.org OI Coley, Brian/0000-0003-0354-4727 NR 44 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2015 VL 12 IS 9 BP 915 EP 922 DI 10.1016/j.jacr.2015.05.023 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ8QU UT WOS:000360874300013 PM 26254159 ER PT J AU Kattapuram, TM Sheth, RA Ganguli, S Mueller, PR Walker, TG AF Kattapuram, Taj M. Sheth, Rahul A. Ganguli, Suvranu Mueller, Peter R. Walker, T. Gregory TI Interventional Radiology Symposium for Medical Students: Raising Awareness, Understanding, and Interest SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID IR C1 [Kattapuram, Taj M.; Sheth, Rahul A.; Ganguli, Suvranu; Mueller, Peter R.; Walker, T. Gregory] Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02114 USA. RP Kattapuram, TM (reprint author), Massachusetts Gen Hosp, Dept Intervent Radiol, Gray 290, Boston, MA 02114 USA. EM tkattapuram@mgh.harvard.edu NR 7 TC 1 Z9 1 U1 2 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 SEP PY 2015 VL 12 IS 9 BP 968 EP 971 DI 10.1016/j.jacr.2015.03.046 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ8QU UT WOS:000360874300025 PM 26123737 ER PT J AU Kattapuram, TM Liu, RW AF Kattapuram, Taj M. Liu, Raymond W. TI Transitioning From Leadership in Training to Leadership in Practice: Advice for Graduating Members-in-Training SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Kattapuram, Taj M.; Liu, Raymond W.] Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02114 USA. RP Kattapuram, TM (reprint author), Massachusetts Gen Hosp, Dept Intervent Radiol, Gray 290, Boston, MA 02114 USA. EM tkattapuram@mgh.harvard.edu NR 5 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2015 VL 12 IS 9 BP 983 EP 984 DI 10.1016/j.jacr.2015.04.023 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ8QU UT WOS:000360874300031 PM 26355208 ER PT J AU Tan, TC Scherrer-Crosbie, M AF Tan, Timothy C. Scherrer-Crosbie, Marielle TI Does Trastuzumab Cause Cardiotoxicity in the Treatment of Patients with Breast Cancer? Reply SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Letter ID EJECTION FRACTION; CARDIAC TOXICITY C1 [Tan, Timothy C.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tan, TC (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2015 VL 28 IS 9 BP 1129 EP 1130 DI 10.1016/j.echo.2015.07.024 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ9LY UT WOS:000360937600016 PM 26354553 ER PT J AU Murugan, VA Kalra, MK Rehani, M Digumarthy, SR AF Murugan, Venkatesh A. Kalra, Mannudeep K. Rehani, Madan Digumarthy, Subba R. TI Lung Cancer Screening Computed Tomography Radiation and Protocols SO JOURNAL OF THORACIC IMAGING LA English DT Review DE lung cancer screening protocols; low-dose computed tomography; CT radiation dose ID STATISTICAL ITERATIVE RECONSTRUCTION; FILTERED BACK-PROJECTION; LOW-DOSE CT; TUBE CURRENT MODULATION; CHEST CT; IMAGE-QUALITY; COST-EFFECTIVENESS; ABDOMINAL CT; SPIRAL CT; REDUCTION AB Recent studies have supported the use of low-dose computed tomography (LDCT) of the chest as a screening tool for lung cancer. Several professional organizations have now included LDCT screening in high-risk populations in their guidelines. The United States Preventive Services Task Force has added LDCT to its lung cancer-screening guidelines as of December 2013. Recently, the Centers for Medicare and Medicaid Services acknowledged that the evidence for LDCT lung cancer screening is adequate, provided that eligibility criteria are met. As widespread use of LDCT is anticipated, the radiation dose associated with LDCT needs to be optimized. The American College of Radiology-Society of Thoracic Radiology collaboration and the National Comprehensive Cancer Care Network recently provided some guidelines for LDCT utilization for lung cancer screening. There are several scanning and image reconstruction techniques that can be used for reducing radiation dose in LDCT lung cancer screening. This review article presents protocols and guidelines for use of LDCT in lung cancer screening and describes our early experience in implementing LDCT at our institution. C1 [Murugan, Venkatesh A.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Murugan, Venkatesh A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Murugan, VA (reprint author), Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. EM varumuganmurugan@mgh.harvard.edu NR 59 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD SEP PY 2015 VL 30 IS 5 BP 283 EP 289 DI 10.1097/RTI.0000000000000150 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ9WP UT WOS:000360966200001 PM 25856411 ER PT J AU Kulvatunyou, N Pandit, V Moutamn, S Inaba, K Chouliaras, K DeMoya, M Naraghi, L Kalb, B Arif, H Sravanthi, R Joseph, B Gries, L Tang, AL Rhee, P AF Kulvatunyou, Narong Pandit, Viraj Moutamn, Sadoun Inaba, Kenji Chouliaras, Konstantinos DeMoya, Marc Naraghi, Leily Kalb, Bobby Arif, Hina Sravanthi, Reddy Joseph, Bellal Gries, Lynn Tang, Andrew L. Rhee, Peter TI A multi-institution prospective observational study of small bowel obstruction: Clinical and computerized tomography predictors of which patients may require early surgery SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Small bowel obstruction; adhesion; predictors; CT scan ID SOLUBLE CONTRAST AGENT; CT; NEED; INTERVENTION; METAANALYSIS; OPERATION; ISCHEMIA; CRITERIA; MODEL AB BACKGROUND: For patients with adhesive small bowel obstruction (ASBO), early surgery after a failed trial of nonoperative treatment can improve outcome. However, deciding which patients require early surgery is difficult, given the lack of specific clinical or radiographic signs. The study goals were to identify clinical and computed tomography (CT) predictors of which patients may need early surgery and to evaluate the utility of the common CT findings. METHODS: This was a multi-institution prospective observational study for patients who were admitted with ASBO. Patients were excluded if their SBO were not managed conservative initially; were within 30 days postoperatively; were caused by external hernias, small bowel tumor, or intussusception; and were related to Crohn's disease. Clinical and laboratory variables were collected prospectively. CT findings were interpreted by a blinded designated radiologist. To identify significant predictors, we performed a multivariable regression analysis. RESULTS: During 22 months, we enrolled 200 patients with ASBO. Patients' mean (SD) age was 60 (18) years; 50% were male. Fifty-two patients (26%) underwent surgery. Of those who underwent surgery, the median duration of nonoperative treatment was 1.5 days (interquartile range, 1-2.5 days). In the regression model, we identified no flatus (odds ratio [OR], 3.28; 95% confidence interval [CI], 1.51-7.12; p = 0.003), presence of free fluid on CT (OR, 2.59; 95% CI, 1.13-5.90; p = 0.023), and high-grade obstruction by CT (OR, 2.44; 95% CI, 1.10-5.43; p = 0.028) to be significant predictors for ASBO patients who may need early surgery. CONCLUSION: In this study, we prospectively derived one clinical and two CT predictors which ASBO patients may benefit from an early surgical intervention. However, a future study to validate these predictors is needed. (J Trauma Acute Care Surg. 2015;79: 393-398. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Kulvatunyou, Narong; Pandit, Viraj; Moutamn, Sadoun; Gries, Lynn; Tang, Andrew L.; Rhee, Peter] Univ Arizona, Dept Surg, Div Acute Care Surg, Tucson, AZ 85727 USA. [Kalb, Bobby; Arif, Hina] Univ Arizona, Dept Radiol, Tucson, AZ 85727 USA. [Inaba, Kenji; Chouliaras, Konstantinos] Univ So Calif, Dept Surg, Div Acute Care Surg, Los Angeles, CA USA. [Sravanthi, Reddy] Univ So Calif, Dept Radiol, Los Angeles, CA USA. [DeMoya, Marc; Naraghi, Leily] Massachusetts Gen Hosp, Dept Surg, Div Acute Care Surg, Boston, MA 02114 USA. RP Kulvatunyou, N (reprint author), Univ Arizona, Dept Surg, Div Acute Care Surg, 1501 N Campbell Ave,Rm 5411,POB 245063, Tucson, AZ 85727 USA. EM nkulvatunyou@surgery.arizona.edu NR 20 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2015 VL 79 IS 3 BP 393 EP 398 DI 10.1097/TA.0000000000000759 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CQ4JV UT WOS:000360571900012 PM 26307871 ER PT J AU Cauley, CE Panizales, MT Reznor, G Haynes, AB Havens, JM Kelley, E Mosenthal, AC Cooper, Z AF Cauley, Christy E. Panizales, Maria T. Reznor, Gally Haynes, Alex B. Havens, Joaquim M. Kelley, Edward Mosenthal, Anne C. Cooper, Zara TI Outcomes after emergency abdominal surgery in patients with advanced cancer: Opportunities to reduce complications and improve palliative care SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Advanced cancer; emergency surgery; palliative care ID QUALITY-OF-LIFE; SURGICAL QUALITY; POSTOPERATIVE COMPLICATIONS; TREATMENT PREFERENCES; AMERICAN-COLLEGE; MENTAL-HEALTH; DEATH; END; MORTALITY; DISCUSSIONS AB BACKGROUND: There is increasing emphasis on the appropriateness and quality of acute surgical care for patients with serious illness and at the end of life. However, there is a lack of evidence regarding outcomes after emergent major abdominal surgery among patients with advanced cancer to guide treatment decisions. This analysis sought to characterize adverse outcomes (mortality, complications, institutional discharge) and to identify factors independently associated with 30-day mortality among patients with disseminated cancer who undergo emergent abdominal surgery for intestinal obstruction or perforation. METHODS: This is a retrospective cohort study of 875 disseminated cancer patients undergoing emergency surgery for perforation (n = 499) or obstruction (n = 376) at hospitals participating in the American College of Surgeons' National Surgical Quality Improvement Program from 2005 to 2012. Predictors of 30-day mortality were identified using multivariate logistic regression. RESULTS: Among patients who underwent surgery for perforation, 30-day mortality was 34%, 67% had complications, and 52% were discharged to an institution. Renal failure, septic shock, ascites, dyspnea at rest, and dependent functional status were independent preoperative predictors of death at 30 days. When complications were considered, postoperative respiratory complications and age (75-84 years) were also predictors of mortality. Patients who had surgery for obstruction had a 30-day mortality rate of 18% (n = 68), 41% had complications, and 60% were discharged to an institution. Dependent functional status and ascites were independent predictors of death at 30 days. In addition to these predictors, postoperative predictors of mortality included respiratory and cardiac complications. Few patients (4%) had do-not-resuscitate orders before surgery. CONCLUSION: Emergency abdominal operations in patients with disseminated cancer are highly morbid, and many patients die soon after surgery. High rates of complications and low rates of preexisting do-not-resuscitate orders highlight the need for targeted interventions to reduce complications and integrate palliative approaches into the care of these patients. (J Trauma Acute Care Surg. 2015;79: 399-406. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Cauley, Christy E.; Haynes, Alex B.; Cooper, Zara] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA. [Reznor, Gally; Havens, Joaquim M.; Kelley, Edward; Cooper, Zara] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Reznor, Gally; Havens, Joaquim M.; Cooper, Zara] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Cauley, Christy E.; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Haynes, Alex B.] Codman Ctr Clin Effectiveness Surg, Boston, MA USA. [Panizales, Maria T.] Partners Healthcare Int, Boston, MA USA. [Mosenthal, Anne C.] Rutgers State Univ, Dept Surg, Newark, NJ 07102 USA. RP Cauley, CE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM zcooper@partners.org FU National Cancer Institute at the National Institutes of Health [R25CA092203] FX C.E.C. is currently receiving a grant (R25CA092203) from the National Cancer Institute at the National Institutes of Health. NR 37 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2015 VL 79 IS 3 BP 399 EP 406 DI 10.1097/TA.0000000000000764 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CQ4JV UT WOS:000360571900013 PM 26307872 ER PT J AU Deipolyi, AR Al-Ansari, S Khademhosseini, A Oklu, R AF Deipolyi, Amy R. Al-Ansari, Shehab Khademhosseini, Ali Oklu, Rahmi TI Occlusion of the Internal Iliac Artery Is Associated with Smaller Prostate and Decreased Urinary Tract Symptoms SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID EMBOLIZATION; HYPERPLASIA; VOLUME; PREVALENCE; PROJECT; LUTS; CT AB Purpose: To characterize the relationship of proximal internal iliac artery (HA) occlusion or embolization on prostate volume (PV) and the presence of lower urinary tract symptoms (LUTS) or benign prostatic hyperplasia (BPH). Materials and Methods: The study included 2 parts: Part 1 comprised 99 men >= 50 years old who underwent abdominopelvic computed tomography angiography for lower extremity claudication assessed in a retrospective cohort design; Part 2 comprised 18 patients who underwent iatrogenic IIA embolization during endovascular aneurysm repair assessed by a within-subjects approach. Prostate volume and IIA origin diameter were measured; IIA occlusion was noted. Chart review documented body mass index, LUTS, impotence, and buttock claudication. Results: Of 99 men in Part 1, 60 had no IIA occlusion, and 39 had IIA occlusion (17 unilateral, 22 bilateral). Prostate volume differed significantly between groups (no IIA occlusion, 27.3 mL; unilateral HA occlusion, 20.7 mL; bilateral IIA occlusion, 17.1 mL; P = .001). Men without IIA occlusion had more LUTS (27%) than men with IIA occlusion (10%; P = .04). The number of men with complaints of impotence or buttock claudication was similar in both groups (40% vs 46%; P > .05). Multiple regression showed that age and IIA occlusion were independent predictors of PV (P < 0.05), whereas body mass index was not (P > .05), and that HA occlusion was the only independent predictor of LUTS/BPH (P < .05). Among the 18 men in Part 2, PV declined by 29% after ernbolization (P = .00001); 6 men had improvement or resolution of LUTS. Conclusion: Proximal IIA occlusion is associated with nearly one-third reduction in PV and decreased findings of LUTS/BPH. C1 [Deipolyi, Amy R.; Al-Ansari, Shehab; Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, Boston, MA 02114 USA. [Khademhosseini, Ali; Oklu, Rahmi] Harvard Univ, Sch Med, Brigham & Womens Hosp, Biomat Innovat Res Ctr,Dept Med, Cambridge, MA 02138 USA. [Khademhosseini, Ali] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Khademhosseini, Ali] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu OI Khademhosseini, Ali/0000-0001-6322-8852; Deipolyi, Amy/0000-0003-3144-386X NR 21 TC 2 Z9 2 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 SEP PY 2015 VL 26 IS 9 BP 1305 EP 1310 DI 10.1016/j.jvir.2015.04.019 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CR1KV UT WOS:000361084600009 PM 26065926 ER PT J AU Andrabi, Y Saadeh, TS Uppot, RN Arellano, RS Sahani, DV AF Andrabi, Yasir Saadeh, Thomas S. Uppot, Raul N. Arellano, Ronald S. Sahani, Dushyant V. TI Impact of Dose-Modified Protocols on Radiation Doses in Patients Undergoing CT Examinations following Image-Guided Catheter Placement SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID STATISTICAL ITERATIVE RECONSTRUCTION; FILTERED BACK-PROJECTION; PERCUTANEOUS DRAINAGE; ABSCESS DRAINAGE; PELVIC ABSCESSES; MULTIDETECTOR CT; TUBE CURRENT; EXPOSURE; QUALITY; ALGORITHMS AB Purpose: To investigate the impact of dose-modified'(DM) scan protocols on decreasing radiation exposure from computed tomography (CT) scans obtained following image-guided catheter procedures. Materials and Methods: In this retrospective analysis, between December 2012 and June 2014, 192 patients (mean age, 60.7 y; 102 men) who underwent abdomen/pelvis CT examinations for catheter placement follow-up were included. The standard-dose (SD) baseline CT parameters included tube potential of 120 kVp, tube current of 75-550 mA, and noise index (NI) of 18-22. Weight-based scan parameters applied for follow-up CT were based on two reconstruction algorithms: filtered back projection (FBP; 120 kVp, 75-350 mA, NI = 30) and iterative reconstruction technique (IRT; 100/120 kVp, 75-250/350 mA, NI = 35). Two readers reviewed image quality (IQ) of follow-up and baseline CT examinations for 22 randomly sampled patients. Radiation doses were retrieved by dose monitoring software. Results: Compared with baseline, DM follow-up CT protocols enabled substantial (62.4%) dose reductions (mean CT dose indexes: 4.1 mGy at follow-up, 10.9 mGy at baseline; P<.0001). Doses were significantly lower for IRT follow-up CT examinations compared with FBP (mean CT dose indexes: IRT, 3.6 mGy; FBP, 4.6 mGy; P<.05). In 47 patients with more than one follow-up CT examination (mean, 3.1 examinations per patient; range, 2-6), the observed cumulative radiation dose (CRD) was 42.1% lower than the expected CRD (observed, 1,437.9 mGy.cm; expected, 2,483.6 mGy.cm; P<.0001). Subjective IQ scores were acceptable for follow-up CT examinations (follow-up, 3.6; baseline, 4; P<.05). Conclusions: DM CT eXaminations enable substantial dose reduction (62.4%) for each follow-up examination compared with SD baseline scans, without any IQ concerns. Use of IRT decreases dose by an additional 22%. The CRD is lowered by 42% in patients undergoing multiple DM follow-up CT examinations. C1 [Andrabi, Yasir; Saadeh, Thomas S.; Uppot, Raul N.; Arellano, Ronald S.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 32 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2015 VL 26 IS 9 BP 1339 EP 1346 DI 10.1016/j.jvir.2015.05.029 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CR1KV UT WOS:000361084600016 PM 26190187 ER PT J AU Seay, K Khajoueinejad, N Zheng, JH Kiser, P Ochsenbauer, C Kappes, JC Herold, B Goldstein, H AF Seay, Kieran Khajoueinejad, Nazanin Zheng, Jian Hua Kiser, Patrick Ochsenbauer, Christina Kappes, John C. Herold, Betsy Goldstein, Harris TI The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TENOFOVIR DISOPROXIL FUMARATE; FEMALE GENITAL-TRACT; SUB-SAHARAN AFRICA; HUMANIZED BLT MICE; TYPE-2 INFECTION; DENDRITIC CELLS; NEUTRALIZING ANTIBODIES; PREEXPOSURE PROPHYLAXIS; MUCOSAL TRANSMISSION AB Epidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4(+) T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4(+) T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2(env)-NLuc, which expresses an env gene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV-Du151.2(env)-NLuc intravaginal challenge was increased similar to 4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4(+) T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2-coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract. IMPORTANCE Multiple epidemiological studies have reported that genital herpes simplex virus 2 (HSV-2) infection increases the risk of HIV-1 sexual acquisition by severalfold. Understanding the underlying mechanisms by which HSV-2 facilitates HIV-1 infection and optimizing the efficacy of therapies to inhibit HIV-1 infection during HSV-2 coinfection should contribute to reducing HIV-1 transmission. Using our novel transgenic hCD4/R5/cT1 mouse model infectible with HIV-1, we demonstrated that HSV-2 infection enhances vaginal transmission and dissemination of HIV-1 infection while stimulating recruitment and activation of CD4(+) T cells and dendritic cells in the lower genital tract. HIV acquisition by hCD4/R5/cT1 mice vaginally coinfected with HSV-2 could be completely prevented in almost half the mice by preexposure prophylaxis (PrEP) with a novel gel containing tenofovir disoproxil fumarate (TDF), the tenofovir prodrug, but not with the tenofovir microbicide gel utilized in CAPRISA-004, VOICE, and FACTS-001 clinical trials. The hCD4/R5/cT1 mice represent a new preclinical mouse model to evaluate vaginal HIV-1 acquisition. C1 [Seay, Kieran; Khajoueinejad, Nazanin; Herold, Betsy; Goldstein, Harris] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Khajoueinejad, Nazanin; Zheng, Jian Hua; Herold, Betsy; Goldstein, Harris] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Kiser, Patrick] Northwestern Univ, Dept Biomed Engn, McCormick Sch Engn, Evanston, IL 60208 USA. [Ochsenbauer, Christina; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Goldstein, H (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM harris.goldstein@einstein.yu.edu RI Kiser, Patrick/C-2843-2014 OI Kiser, Patrick/0000-0002-3868-7122 FU National Institute of Drug Abuse at the National Institutes of Health [DA033788]; Einstein-Montefiore Center for AIDS Research [P30-AI51519]; University of Alabama at Birmingham Center for AIDS Research [P30-AI277670]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [AI065309, T32-AI007501]; NIH Center for HIV-1/AIDS Vaccine Immunology (CHAVI) [UO1-AI067854]; Charles Michael Chair in Autoimmune Diseases; VHA Merit Review Award FX This work was supported by the National Institute of Drug Abuse at the National Institutes of Health (DA033788), the Einstein-Montefiore Center for AIDS Research (P30-AI51519), the University of Alabama at Birmingham Center for AIDS Research (P30-AI277670), the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (AI065309 and T32-AI007501 to K.S.), NIH Center for HIV-1/AIDS Vaccine Immunology (CHAVI) (UO1-AI067854 to J.C.K. and C.O.), the Charles Michael Chair in Autoimmune Diseases (to H.G.), and a VHA Merit Review Award (to J.C.K.). NR 63 TC 5 Z9 5 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2015 VL 89 IS 18 BP 9559 EP 9570 DI 10.1128/JVI.01326-15 PG 12 WC Virology SC Virology GA CQ6HE UT WOS:000360704400036 PM 26157126 ER PT J AU Toyoda, M Ogata, Y Mahiti, M Maeda, Y Kuang, XMT Miura, T Jessen, H Walker, BD Brockman, MA Brumme, ZL Ueno, T AF Toyoda, Mako Ogata, Yoko Mahiti, Macdonald Maeda, Yosuke Kuang, Xiaomei T. Miura, Toshiyuki Jessen, Heiko Walker, Bruce D. Brockman, Mark A. Brumme, Zabrina L. Ueno, Takamasa TI Differential Ability of Primary HIV-1 Nef Isolates To Downregulate HIV-1 Entry Receptors SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-LEUKOCYTE ANTIGEN; TYPE-1 NEF; INDUCED CD4; T-CELLS; ELITE CONTROLLERS; DYNAMIC-RANGE; INFECTION; RESISTANCE; PROTEIN AB HIV-1 Nef downregulates the viral entry receptor CD4 as well as the coreceptors CCR5 and CXCR4 from the surface of HIV-infected cells, and this leads to promotion of viral replication through superinfection resistance and other mechanisms. Nef sequence motifs that modulate these functions have been identified via in vitro mutagenesis with laboratory HIV-1 strains. However, it remains unclear whether the same motifs contribute to Nef activity in patient-derived sequences and whether these motifs may differ in Nef sequences isolated at different infection stages and/or from patients with different disease phenotypes. Here, nef clones from 45 elite controllers (EC), 46 chronic progressors (CP), and 43 acute progressors (AP) were examined for their CD4, CCR5, and CXCR4 downregulation functions. Nef clones from EC exhibited statistically significantly impaired CD4 and CCR5 downregulation ability and modestly impaired CXCR4 downregulation activity compared to those from CP and AP. Nef's ability to downregulate CD4 and CCR5 correlated positively in all cohorts, suggesting that they are functionally linked in vivo. Moreover, impairments in Nef's receptor downregulation functions increased the susceptibility of Nef-expressing cells to HIV-1 infection. Mutagenesis studies on three functionally impaired EC Nef clones revealed that multiple residues, including those at novel sites, were involved in the alteration of Nef functions and steady-state protein levels. Specifically, polymorphisms at highly conserved tryptophan residues (e.g., Trp-57 and Trp-183) and immune escape-associated sites were responsible for reduced Nef functions in these clones. Our results suggest that the functional modulation of primary Nef sequences is mediated by complex polymorphism networks. IMPORTANCE HIV-1 Nef, a key factor for viral pathogenesis, downregulates functionally important molecules from the surface of infected cells, including the viral entry receptor CD4 and coreceptors CCR5 and CXCR4. This activity enhances viral replication by protecting infected cells from cytotoxicity associated with superinfection and may also serve as an immune evasion strategy. However, how these activities are maintained under selective pressure in vivo remains elusive. We addressed this question by analyzing functions of primary Nef clones isolated from patients at various infection stages and with different disease phenotypes, including elite controllers, who spontaneously control HIV-1 viremia to undetectable levels. The results indicated that downregulation of HIV-1 entry receptors, particularly CCR5, is impaired in Nef clones from elite controllers. These functional impairments were driven by rare Nef polymorphisms and adaptations associated with cellular immune responses, underscoring the complex molecular pathways responsible for maintaining and attenuating viral protein function in vivo. C1 [Toyoda, Mako; Ogata, Yoko; Mahiti, Macdonald; Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. [Maeda, Yosuke] Kumamoto Univ, Fac Life Sci, Dept Microbiol, Kumamoto, Japan. [Kuang, Xiaomei T.; Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Miura, Toshiyuki] Univ Tokyo, Tokyo, Japan. [Jessen, Heiko] Jessen Praxis, Berlin, Germany. [Walker, Bruce D.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Brockman, Mark A.; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Ueno, Takamasa] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan. RP Ueno, T (reprint author), Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. EM uenotaka@kumamoto-u.ac.jp RI Ueno, Takamasa/F-5788-2013; OI Ueno, Takamasa/0000-0003-4852-4236; Brockman, Mark/0000-0001-6432-1426 FU Bill and Melinda Gates Foundation; Schwartz Foundation; Harvard University Center for AIDS Research; Ministry of Education, Science, Sports, and Culture of Japan; Japan Agency for Medical Research and Development, AMED (Research Program on HIV/AIDS); Otsuka Toshimi Scholarship Foundation; Canadian Association for HIV Research; Bristol-Myers Squibb Canada; ViiV Healthcare; Canadian Institutes for Health Research; Michael Smith Foundation for Health Research FX We thank Philip Mwimanzi, Hirohito Ootsuka, Michiyo Tokunaga, and Hua Qian for their technical contributions to the initial stage of this study and Martin Markowitz for access to clinical specimens. We also acknowledge and thank the International HIV Controllers Study group, funded by the Bill and Melinda Gates Foundation, the Schwartz Foundation, and the Harvard University Center for AIDS Research.; This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan and by a grant from the Japan Agency for Medical Research and Development, AMED (Research Program on HIV/AIDS) (to T.U.). M.M. is supported by the Otsuka Toshimi Scholarship Foundation. X.T.K. was supported by a Master's scholarship from the Canadian Association for HIV Research in partnership with Bristol-Myers Squibb Canada and ViiV Healthcare. M.A.B. holds a Canada Research Chair in Viral Pathogenesis and Immunity from the Canada Research Chairs Program. Z.L.B. is the recipient of a New Investigator Award from the Canadian Institutes for Health Research and a Scholar Award from the Michael Smith Foundation for Health Research. NR 54 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2015 VL 89 IS 18 BP 9639 EP 9652 DI 10.1128/JVI.01548-15 PG 14 WC Virology SC Virology GA CQ6HE UT WOS:000360704400043 PM 26178998 ER PT J AU Panzer, SE Laskowski, J Renner, B Kulik, L Ljubanovic, D Huber, KM Zhong, WX Pickering, MC Holers, VM Thurman, JM AF Panzer, Sarah E. Laskowski, Jennifer Renner, Brandon Kulik, Liudmila Ljubanovic, Danica Huber, Kendra M. Zhong, Weixiong Pickering, Matthew C. Holers, V. Michael Thurman, Joshua M. TI IgM exacerbates glomerular disease progression in complement-induced glomerulopathy SO KIDNEY INTERNATIONAL LA English DT Article DE complement; glomerulonephritis; immunology ID NEPHROTIC SYNDROME; MESANGIAL HYPERCELLULARITY; REPERFUSION INJURY; NATURAL ANTIBODY; CELL; MICE; DEFICIENT; GLOMERULONEPHRITIS; ACTIVATION; DEPOSITION AB Although glomerular immunoglobulin M (IgM) deposition occurs in a variety of glomerular diseases, the mechanism of deposition and its clinical significance remain controversial. Some have theorized IgM becomes passively trapped in areas of glomerulosclerosis. However, recent studies found that IgM specifically binds damaged glomeruli. Therefore, we tested whether natural IgM binds to neo-epitopes exposed after insults to the glomerulus and exacerbates disease in mice deficient in the complement regulatory protein factor H; a model of non-sclerotic and nonimmune-complex glomerular disease. Immunofluorescence microscopy demonstrated mesangial and capillary loop deposition of IgM, whereas ultrastructural analysis found IgM deposition on endothelial cells and subendothelial areas. Factor H-deficient mice lacking B cells were protected from renal damage, as evidenced by milder histologic lesions on light and electron microscopy. IgM, but not IgG, from wild-type mice bound to cultured murine mesangial cells. Furthermore, injection of purified IgM into mice lacking B cells bound within the glomeruli and induced proteinuria. A monoclonal natural IgM-recognizing phospholipids also bound to glomeruli in vivo and induced albuminuria. Thus, our results indicate specific IgM antibodies bind to glomerular epitopes and that IgM contributes to the progression of glomerular damage in this mouse model of non-sclerotic glomerular disease. C1 [Panzer, Sarah E.] Univ Wisconsin, Div Nephrol, Dept Med, Madison, WI 53705 USA. [Laskowski, Jennifer; Renner, Brandon; Kulik, Liudmila; Huber, Kendra M.; Holers, V. Michael; Thurman, Joshua M.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Ljubanovic, Danica] Univ Hosp Dubrava, Dept Pathol, Zagreb, Croatia. [Zhong, Weixiong] Univ Wisconsin, Dept Pathol, Madison, WI 53705 USA. [Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Serv, Madison, WI USA. [Pickering, Matthew C.] Univ London Imperial Coll Sci Technol & Med, Ctr Complement & Inflammat Res, London, England. RP Panzer, SE (reprint author), Univ Wisconsin, Div Nephrol, Dept Med, 1685 Highland Ave,Suite 5000, Madison, WI 53705 USA. EM sepanzer@medicine.wisc.edu FU KIDNEEDS Foundation; National Institutes of Health [F32DK096711-01, R01 DK076690] FX ZThis work was supported in part by the KIDNEEDS Foundation (JMT) and National Institutes of Health grants F32DK096711-01 (SEP) and R01 DK076690 (JMT). NR 34 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2015 VL 88 IS 3 BP 528 EP 537 DI 10.1038/ki.2015.120 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CR1JA UT WOS:000361079800017 PM 25945405 ER PT J AU Freeman, MC Kolappa, K de Almeida, JMC Kleinman, A Makhashvili, N Phakathi, S Saraceno, B Thornicroft, G AF Freeman, Melvyn Colin Kolappa, Kavitha de Almeida, Jose Miguel Caldas Kleinman, Arthur Makhashvili, Nino Phakathi, Sifiso Saraceno, Benedetto Thornicroft, Graham TI Reversing hard won victories in the name of human rights: a critique of the General Comment on Article 12 of the UN Convention on the Rights of Persons with Disabilities SO LANCET PSYCHIATRY LA English DT Editorial Material ID MENTAL-HEALTH LAW AB The UN Convention on the Rights of Persons with Disabilities (CRPD) is a major milestone in safeguarding the rights of persons with disabilities. However, the General Comment on Article 12 of the CRPD threatens to undermine critical rights for persons with mental disabilities, including the enjoyment of the highest attainable standard of health, access to justice, the right to liberty, and the right to life. Stigma and discrimination might also increase. Much hinges on the Committee on the Rights of Persons with Disabilities' view that all persons have legal capacity at all times irrespective of mental status, and hence involuntary admission and treatment, substitute decision-making, and diversion from the criminal justice system are deemed indefensible. The General Comment requires urgent consideration with the full participation of practitioners and a broad range of user and family groups. C1 [Freeman, Melvyn Colin; Phakathi, Sifiso] Natl Dept Hlth, ZA-0001 Pretoria, South Africa. [Freeman, Melvyn Colin] Univ Witwatersrand, Johannesburg, South Africa. [Kolappa, Kavitha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [de Almeida, Jose Miguel Caldas; Saraceno, Benedetto] Univ Nova Lisboa, Fac Ciencias Med, P-1200 Lisbon, Portugal. [Kleinman, Arthur] Harvard Univ, Sch Med, Boston, MA USA. [Makhashvili, Nino] Ilia State Univ, Tbilisi, Rep of Georgia. [Thornicroft, Graham] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Global Mental Hlth, London WC2R 2LS, England. RP Freeman, MC (reprint author), Natl Dept Hlth, Private Bag X828, ZA-0001 Pretoria, South Africa. EM Freemm@health.gov.za RI Thornicroft, Graham/B-4027-2010; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013 OI Thornicroft, Graham/0000-0003-0662-0879; NR 15 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD SEP PY 2015 VL 2 IS 9 BP 844 EP 850 DI 10.1016/S2215-0366(15)00218-7 PG 7 WC Psychiatry SC Psychiatry GA CQ9WY UT WOS:000360967200034 PM 26236004 ER PT J AU Abbatiello, SE Schilling, B Mani, DR Zimmerman, LJ Hall, SC Maclean, B Albertolle, M Allen, S Burgess, M Cusack, MP Gosh, M Hedrick, V Held, JM Inerowicz, HD Jackson, A Keshishian, H Kinsinger, CR Lyssand, J Makowski, L Mesri, M Rodriguez, H Rudnick, P Sadowski, P Sedransk, N Shaddox, K Skates, SJ Kuhn, E Smith, D Whiteaker, JR Whitwell, C Zhang, S Borchers, CH Fisher, SJ Gibson, BW Liebler, DC MacCoss, MJ Neubert, TA Paulovich, AG Regnier, FE Tempst, P Carr, SA AF Abbatiello, Susan E. Schilling, Birgit Mani, D. R. Zimmerman, Lisa J. Hall, Steven C. Maclean, Brendan Albertolle, Matthew Allen, Simon Burgess, Michael Cusack, Michael P. Gosh, Mousumi Hedrick, Victoria Held, Jason M. Inerowicz, H. Dorota Jackson, Angela Keshishian, Hasmik Kinsinger, Christopher R. Lyssand, John Makowski, Lee Mesri, Mehdi Rodriguez, Henry Rudnick, Paul Sadowski, Pawel Sedransk, Nell Shaddox, Kent Skates, Stephen J. Kuhn, Eric Smith, Derek Whiteaker, Jeffery R. Whitwell, Corbin Zhang, Shucha Borchers, Christoph H. Fisher, Susan J. Gibson, Bradford W. Liebler, Daniel C. MacCoss, Michael J. Neubert, Thomas A. Paulovich, Amanda G. Regnier, Fred E. Tempst, Paul Carr, Steven A. TI Large-Scale Interlaboratory Study to Develop, Analytically Validate and Apply Highly Multiplexed, Quantitative Peptide Assays to Measure Cancer-Relevant Proteins in Plasma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MONITORING MASS-SPECTROMETRY; LOW-ABUNDANCE PROTEINS; ABSOLUTE QUANTIFICATION; BIOMARKER DISCOVERY; TARGETED PROTEOMICS; ISOTOPE-DILUTION; STANDARDS; MS; PROTEOLYSIS; PERFORMANCE AB There is an increasing need in biology and clinical medicine to robustly and reliably measure tens to hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility, and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here, we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and seven control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data, we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to sub-nanogram/ml sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and interlaboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy-isotope-labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an interlaboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality control measures, enables sensitive, specific, reproducible, and quantitative measurements of proteins and peptides in complex biological matrices such as plasma. C1 [Abbatiello, Susan E.; Mani, D. R.; Burgess, Michael; Keshishian, Hasmik; Kuhn, Eric; Carr, Steven A.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Schilling, Birgit; Cusack, Michael P.; Held, Jason M.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. [Zimmerman, Lisa J.; Shaddox, Kent; Whitwell, Corbin; Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Zimmerman, Lisa J.; Shaddox, Kent; Whitwell, Corbin; Liebler, Daniel C.] Vanderbilt Ingram Canc Ctr, Jim Ayers Inst Precancer Detect & Diag, Nashville, TN 37232 USA. [Hall, Steven C.; Albertolle, Matthew; Allen, Simon; Fisher, Susan J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Maclean, Brendan; MacCoss, Michael J.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Gosh, Mousumi; Tempst, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Hedrick, Victoria; Inerowicz, H. Dorota; Regnier, Fred E.] Purdue Univ, W Lafayette, IN 47907 USA. [Jackson, Angela; Smith, Derek; Borchers, Christoph H.] Univ Victoria, Genome BC Prote Ctr, Victoria, BC V8Z 7X8, Canada. [Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Neubert, Thomas A.] NCI, NIH, Bethesda, MD 20892 USA. [Lyssand, John; Sadowski, Pawel; Neubert, Thomas A.] NYU, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Rudnick, Paul] NIST, Gaithersburg, MD 20899 USA. [Sedransk, Nell] Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. [Skates, Stephen J.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Whiteaker, Jeffery R.; Zhang, Shucha; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Carr, SA (reprint author), Broad Inst & Harvard, Cambridge, MA 02142 USA. EM scarr@broad.mit.edu OI Tempst, Paul/0000-0002-6680-3987; Held, Jason/0000-0001-8024-2736 FU National Cancer Institute, NCI Clinical Proteomic Technologies for Cancer initiative [U24 CA126476, U24 126477, U24 126480, U24 CA126485, U24 126479]; NCI [U24CA160034]; Vanderbilt University Center via NCI [U24CA159988]; National Institute of Standards and Technology [70NANB9H9001]; NCRR Shared Instrumentation program [S10 RR027953, S10 RR024604]; National Institute of Statistical Sciences; Canary Foundation FX This work was supported by grants from the National Cancer Institute (U24 CA126476, U24 126477, U24 126480, U24 CA126485, and U24 126479), part of NCI Clinical Proteomic Technologies for Cancer (http://proteomics.cancer.gov) initiative. A component of this initiative is the Clinical Proteomic Technology Assessment for Cancer (CPTAC) Network and teams, which include the Broad Institute of MIT and Harvard (with the Fred Hutchinson Cancer Research Center, Massachusetts General Hospital, the University of North Carolina at Chapel Hill, the University of Victoria, and the Plasma Proteome Institute), Memorial Sloan-Kettering Cancer Center (with the Skirball Institute at New York University), Purdue University (with Monarch Life Sciences, Indiana University, Indiana University-Purdue University Indianapolis, and the Hoosier Oncology Group), University of California, San Francisco (with the Buck Institute for Research on Aging, Lawrence Berkeley National Laboratory, and the University of Texas M.D. Anderson Cancer Center), and Vanderbilt University School of Medicine (with the University of Texas M.D. Anderson Cancer Center, the University of Washington, and the University of Arizona). The Broad Institute and Fred Hutchinson Cancer Research Center also acknowledge CPTAC phase 2 support from NCI U24CA160034, as does the Vanderbilt University Center via NCI U24CA159988. The UCSF CPTAC team gratefully acknowledges the support of the Canary Foundation for providing funds to purchase a 4000 QTRAP mass spectrometer. The Vanderbilt CPTAC team was additionally supported by Cooperative Agreement No. 70NANB9H9001 from the National Institute of Standards and Technology. B.W.G. and T.A.N. acknowledge support from the NCRR Shared Instrumentation program for instrumentation (grants S10 RR027953 and S10 RR024604, respectively). The NCI CPTAC also supported the work by the National Institute of Statistical Sciences. NR 59 TC 42 Z9 42 U1 8 U2 35 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2015 VL 14 IS 9 BP 2357 EP 2374 DI 10.1074/mcp.M114.047050 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ7YO UT WOS:000360823000006 PM 25693799 ER PT J AU Keshishian, H Burgess, MW Gillette, MA Mertins, P Clauser, KR Mani, DR Kuhn, EW Farrell, LA Gerszten, RE Carr, SA AF Keshishian, Hasmik Burgess, Michael W. Gillette, Michael A. Mertins, Philipp Clauser, Karl R. Mani, D. R. Kuhn, Eric W. Farrell, Laurie A. Gerszten, Robert E. Carr, Steven A. TI Multiplexed, Quantitative Workflow for Sensitive Biomarker Discovery in Plasma Yields Novel Candidates for Early Myocardial Injury SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID ACUTE CORONARY SYNDROMES; MASS-SPECTROMETRY; LTQ ORBITRAP; LABEL-FREE; PROTEOME; PROTEINS; QUANTIFICATION; CHROMATOGRAPHY; STRATEGY; DISEASE AB We have developed a novel plasma protein analysis platform with optimized sample preparation, chromatography, and MS analysis protocols. The workflow, which utilizes chemical isobaric mass tag labeling for relative quantification of plasma proteins, achieves far greater depth of proteome detection and quantification while simultaneously having increased sample throughput than prior methods. We applied the new workflow to a time series of plasma samples from patients undergoing a therapeutic, "planned" myocardial infarction for hypertrophic cardiomyopathy, a unique human model in which each person serves as their own biologic control. Over 5300 proteins were confidently identified in our experiments with an average of 4600 proteins identified per sample (with two or more distinct peptides identified per protein) using iTRAQ four-plex labeling. Nearly 3400 proteins were quantified in common across all 16 patient samples. Compared with a previously published label-free approach, the new method quantified almost fivefold more proteins/sample and provided a six-to nine-fold increase in sample analysis throughput. Moreover, this study provides the largest high-confidence plasma proteome dataset available to date. The reliability of relative quantification was also greatly improved relative to the label-free approach, with measured iTRAQ ratios and temporal trends correlating well with results from a 23-plex immunoMRM (iMRM) assay containing a subset of the candidate proteins applied to the same patient samples. The functional importance of improved detection and quantification was reflected in a markedly expanded list of significantly regulated proteins that provided many new candidate biomarker proteins. Preliminary evaluation of plasma sample labeling with TMT six-plex and ten-plex reagents suggests that even further increases in multi-plexing of plasma analysis are practically achievable without significant losses in depth of detection relative to iTRAQ four-plex. These results obtained with our novel platform provide clear demonstration of the value of using isobaric mass tag reagents in plasma-based biomarker discovery experiments. C1 [Keshishian, Hasmik; Burgess, Michael W.; Gillette, Michael A.; Mertins, Philipp; Clauser, Karl R.; Mani, D. R.; Kuhn, Eric W.; Gerszten, Robert E.; Carr, Steven A.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Gillette, Michael A.; Farrell, Laurie A.; Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keshishian, H (reprint author), Broad Inst & Harvard, Prote, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM hasmik@broadinstitute.org; scarr@broad.mit.edu FU National Institutes of Health [HHSN268201000033C]; NHLBI [R01HL096738]; NCI Clinical Proteomics Tumor Analysis Consortium initiative [U24CA160034]; NCI Early Detection Research Network program [5U01CA152990-05] FX This work was supported in part by grants from National Institutes of Health: HHSN268201000033C and R01HL096738 from NHLBI (to REG and SAC) and Grants U24CA160034 from NCI Clinical Proteomics Tumor Analysis Consortium initiative and 5U01CA152990-05 from the NCI Early Detection Research Network program (to SAC). NR 37 TC 25 Z9 25 U1 8 U2 31 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2015 VL 14 IS 9 BP 2375 EP 2393 DI 10.1074/mcp.M114.046813 PG 19 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ7YO UT WOS:000360823000007 PM 25724909 ER PT J AU Zhang, X AF Zhang, Xi TI Less is More: Membrane Protein Digestion Beyond Urea-Trypsin Solution for Next-level Proteomics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Review ID EXCHANGE-MASS-SPECTROMETRY; CYTOCHROME-C-OXIDASE; BETA(2) ADRENERGIC-RECEPTOR; ALKYL GLYCOSIDE DETERGENTS; POROUS POLYMER MONOLITH; X-RAY-STRUCTURE; SHOTGUN PROTEOMICS; CRYSTAL-STRUCTURE; COUPLED RECEPTOR; SACCHAROMYCES-CEREVISIAE AB The goal of next-level bottom-up membrane proteomics is protein function investigation, via high-coverage high-throughput peptide-centric quantitation of expression, modifications and dynamic structures at systems scale. Yet efficient digestion of mammalian membrane proteins presents a daunting barrier, and prevalent day-long urea-trypsin in-solution digestion proved insufficient to reach this goal. Many efforts contributed incremental advances over past years, but involved protein denaturation that disconnected measurement from functional states. Beyond denaturation, the recent discovery of structure/proteomics omni-compatible detergent n-dodecyl-beta-D-maltopyranoside, combined with pepsin and PNGase F columns, enabled breakthroughs in membrane protein digestion: a 2010 DDM-low-TCEP (DLT) method for H/D-exchange (HDX) using human G protein-coupled receptor, and a 2015 flow/detergent-facilitated protease and de-PTM digestions (FDD) for integrative deep sequencing and quantitation using full-length human ion channel complex. Distinguishing protein solubilization from denaturation, protease digestion reliability from theoretical specificity, and reduction from alkylation, these methods shifted day(s)-long paradigms into minutes, and afforded fully automatable (HDX)-protein-peptide-(tandem mass tag)-HPLC pipelines to instantly measure functional proteins at deep coverage, high peptide reproducibility, low artifacts and minimal leakage. Promoting-not destroying-structures and activities harnessed membrane proteins for the next-level streamlined functional proteomics. This review analyzes recent advances in membrane protein digestion methods and highlights critical discoveries for future proteomics. C1 [Zhang, Xi] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zhang, Xi] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. RP Zhang, X (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 32 Fruit St, Boston, MA 02114 USA. EM xi.zhang.edu@gmail.com OI Zhang, Xi/0000-0003-2755-7901 FU National Institute of General Medical Sciences [GM 58448] FX This work was supported in part by the National Institute of General Medical Sciences (GM 58448, K.W.M.). NR 83 TC 5 Z9 5 U1 9 U2 40 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2015 VL 14 IS 9 BP 2441 EP 2453 DI 10.1074/mcp.R114.042572 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ7YO UT WOS:000360823000012 PM 26081834 ER PT J AU Wang, SJ Huttmann, G Zhang, ZX Vogel, A Birngruber, R Tangutoori, S Hasan, T Rahmanzadeh, R AF Wang, Sijia Huettmann, Gereon Zhang, Zhenxi Vogel, Alfred Birngruber, Reginald Tangutoori, Shifalika Hasan, Tayyaba Rahmanzadeh, Ramtin TI Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67 SO MOLECULAR PHARMACEUTICS LA English DT Article DE liposome; nuclear localization sequence (NLS); nanotechnology; endosomal entrapment; photodynamic therapy ID ASSISTED LASER INACTIVATION; INTRACELLULAR DELIVERY; PHOTODYNAMIC THERAPY; SINGLET-OXYGEN; CELL-PROLIFERATION; CANCER-THERAPY; OVARIAN-CANCER; IN-VITRO; BPD-MA; TRANSLOCATION AB The selective inhibition of intracellular and nuclear molecules such as Ki-67 holds great promise for the treatment of cancer and other diseases. However, the choice of the target protein and the intracellular delivery of the functional agent remain crucial challenges. Main hurdles are (a) an effective delivery into cells, (b) endosomal escape of the delivered agents, and (c) an effective, externally triggered destruction of cells. Here we show a light-controlled two-step approach for selective cellular delivery and cell elimination of proliferating cells. Three different cell-penetrating nano constructs, including liposomes, conjugates with the nuclear localization sequence (NLS), and conjugates with the cell penetrating peptide Pep-1, delivered the light activatable antibody conjugate TuBB-9-FITC, which targets the proliferation associated protein Ki-67. HeLa cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and the antibody constructs. In the first optically controlled step, activation of BPD at 690 nm triggered a controlled endosomal escape of the TuBB-9-FITC constructs. In more than 75% of Ki-67 positive, irradiated cells TuBB-9-FITC antibodies relocated within 24 h from cytoplasmic organelles to the cell nucleus and bound to Ki-67. After a second light irradiation at 490 nm, which activated FITC, cell viability decreased to approximately 13%. Our study shows an effective targeting strategy, which uses light-controlled endosomal escape and the light inactivation of Ki-67 for cell elimination. The fact that liposomal or peptide-assisted delivery give similar results leads to the additional conclusion that an effective mechanism for endosomal escape leaves greater variability for the choice of the delivery agent. C1 [Wang, Sijia; Zhang, Zhenxi] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Biomed Analyt Technol & Instrumentat, Key Lab Biomed Informat Engn,Minist Educ, Xran 710049, Peoples R China. [Wang, Sijia; Huettmann, Gereon; Vogel, Alfred; Birngruber, Reginald; Rahmanzadeh, Ramtin] Univ Lubeck, Inst Biomed Opt, D-23562 Lubeck, Germany. [Tangutoori, Shifalika; Hasan, Tayyaba] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rahmanzadeh, R (reprint author), Univ Lubeck, Inst Biomed Opt, Peter Monnik Weg 4, D-23562 Lubeck, Germany. EM rahmanzadeh@bmo.uni-luebeck.de RI Vogel, Alfred/D-9852-2011; Rahmanzadeh, Ramtin/L-7941-2016; Birngruber, Reginald/Q-2342-2016; Huttmann, Gereon/A-9072-2012 FU German Research Foundation (DFG) [Ra1771/3-1]; National Natural Science Foundation of China [61120106013] FX This work was supported by the German Research Foundation (DFG, Grant No. Ra1771/3-1) and The National Natural Science Foundation of China (No. 61120106013). NR 43 TC 4 Z9 4 U1 7 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP PY 2015 VL 12 IS 9 BP 3272 EP 3281 DI 10.1021/acs.molpharmaceut.5b00260 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CR1LR UT WOS:000361086800017 PM 26226545 ER PT J AU Guda, S Brendel, C Renella, R Du, P Bauer, DE Canver, MC Grenier, JK Grimson, AW Kamran, SC Thornton, J de Boer, H Root, DE Milsom, MD Orkin, SH Gregory, RI Williams, DA AF Guda, Swaroopa Brendel, Christian Renella, Raffaele Du, Peng Bauer, Daniel E. Canver, Matthew C. Grenier, Jennifer K. Grimson, Andrew W. Kamran, Sophia C. Thornton, James de Boer, Helen Root, David E. Milsom, Michael D. Orkin, Stuart H. Gregory, Richard I. Williams, David A. TI miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction SO MOLECULAR THERAPY LA English DT Article ID LYMPHOID DEVELOPMENT; MICRORNA BIOGENESIS; GENE-EXPRESSION; GAMMA-GLOBIN; RNAI; CELLS; TOXICITY; VECTORS; DICER; MICE AB RNA interference (RNAi) technology using short hairpin RNAs (shRNAs) expressed via RNA polymerase (pol) III promoters has been widely exploited to modulate gene expression in a variety of mammalian cell types. For certain applications, such as lineage-specific knockdown, embedding targeting sequences into pol II-driven microRNA (miRNA) architecture is required. Here, using the potential therapeutic target BCL11A, we demonstrate that pol III-driven shRNAs lead to significantly increased knockdown but also increased cytotoxcity in comparison to pol II-driven miRNA adapted shRNAs (shRNA(miR)) in multiple hematopoietic cell lines. We show that the two expression systems yield mature guide strand sequences that differ by a 4 bp shift. This results in alternate seed sequences and consequently influences the efficacy of target gene knockdown. Incorporating a corresponding 4 bp shift into the guide strand of shRNA(miR)s resulted in improved knockdown efficiency of BCL11A. This was associated with a significant de-repression of the hemoglobin target of BCL11A, human gamma-globin or the murine homolog Hbb-y. Our results suggest the requirement for optimization of shRNA sequences upon incorporation into a miRNA backbone. These findings have important implications in future design of shRNA(miR)s for RNAi-based therapy in hemoglobinopathies and other diseases requiring lineage-specific expression of gene silencing sequences. C1 [Guda, Swaroopa; Brendel, Christian; Renella, Raffaele; Du, Peng; Bauer, Daniel E.; Thornton, James; de Boer, Helen; Orkin, Stuart H.; Gregory, Richard I.; Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Guda, Swaroopa; Brendel, Christian; Renella, Raffaele; Bauer, Daniel E.; Canver, Matthew C.; Kamran, Sophia C.; Orkin, Stuart H.; Williams, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Renella, Raffaele; Bauer, Daniel E.; Orkin, Stuart H.; Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Du, Peng; Thornton, James; Gregory, Richard I.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Stem Cell Program,Boston Childrens Hosp,Harvard S, Boston, MA 02115 USA. [Grenier, Jennifer K.; Root, David E.] Broad Inst Harvard & MIT, Genet Perturbat Platform, Cambridge, MA USA. [Grimson, Andrew W.] Cornell Univ, Dept Mol Biol & Genet, Coll Arts & Sci, Ithaca, NY USA. [Kamran, Sophia C.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Milsom, Michael D.] German Canc Res Ctr, Div Stem Cells & Canc, Heidelberg Inst Stem Cell Technol & Expt Med, Heidelberg, Germany. RP Williams, DA (reprint author), Boston Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu OI Kamran, Sophia/0000-0001-9283-6515 FU Howard Hughes Medical Institute; NHLBI NIH HHS [U01 HL117720, U01HL117720-01]; NIDDK NIH HHS [F30 DK103359, F30DK103359-01A1, K08 DK093705] NR 47 TC 19 Z9 18 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD SEP PY 2015 VL 23 IS 9 BP 1465 EP 1474 DI 10.1038/mt.2015.113 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CR1PF UT WOS:000361096600009 PM 26080908 ER PT J AU Procopio, MG Laszlo, C Al Labban, D Kim, DE Bordignon, P Jo, SH Goruppi, S Menietti, E Ostano, P Ala, U Provero, P Hoetzenecker, W Neel, V Kilarski, WW Swartz, MA Brisken, C Lefort, K Dotto, GP AF Procopio, Maria-Giuseppina Laszlo, Csaba Al Labban, Dania Kim, Dong Eun Bordignon, Pino Jo, Seung-Hee Goruppi, Sandro Menietti, Elena Ostano, Paola Ala, Ugo Provero, Paolo Hoetzenecker, Wolfram Neel, Victor Kilarski, Witold W. Swartz, Melody A. Brisken, Cathrin Lefort, Karine Dotto, G. Paolo TI Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation SO NATURE CELL BIOLOGY LA English DT Article ID CARCINOMA-ASSOCIATED FIBROBLASTS; MULTIFOCAL EPITHELIAL TUMORS; SQUAMOUS-CELL CARCINOMAS; TRANSCRIPTION COMPLEX; FIELD CANCERIZATION; SECRETORY PHENOTYPE; SENESCENT CELLS; LUNG-CANCER; NOTCH; MICROENVIRONMENT AB Stromal fibroblast senescence has been linked to ageing-associated cancer risk. However, density and proliferation of cancer-associated fibroblasts (CAFs) are frequently increased. Loss or downmodulation of the Notch effector CSL (also known as RBP-J kappa) in dermal fibroblasts is sufficient for CAF activation and ensuing keratinocyte-derived tumours. We report that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as a direct repressor of multiple senescence-and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is downmodulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas, whereas p53 expression and function are downmodulated only in the latter, with paracrine FGF signalling as the probable culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effectors and promotes stromal and cancer cell expansion. The findings support a CAF activation-stromal co-evolution model under convergent CSL-p53 control. C1 [Procopio, Maria-Giuseppina; Laszlo, Csaba; Al Labban, Dania; Kim, Dong Eun; Bordignon, Pino; Menietti, Elena; Lefort, Karine; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Jo, Seung-Hee; Goruppi, Sandro; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Ostano, Paola] Edo & Elvo Tempia Valenta Fdn, Canc Genom Lab, I-13900 Biella, Italy. [Ala, Ugo; Provero, Paolo] Univ Turin, Dept Mol Biotechnol & Life Sci, I-10126 Turin, Italy. [Hoetzenecker, Wolfram] Univ Zurich, Dept Dermatol, CH-8091 Zurich, Switzerland. [Neel, Victor] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kilarski, Witold W.; Swartz, Melody A.] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland. [Brisken, Cathrin] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland. [Lefort, Karine] Univ Hosp CHUV, Sect Dermatol, Dept Med, CH-1011 Lausanne, Switzerland. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. EM Paolo.Dotta@unil.ch RI Swartz, Melody/F-9563-2011; Ala, Ugo/K-2029-2016; Kilarski, Witold/G-8673-2012 OI Ala, Ugo/0000-0001-5408-6397; Kilarski, Witold/0000-0003-0734-4749 FU Swiss National Science Foundation [310030_156191/1]; National Institutes of Health [R01AR039190, R01AR064786]; European Research Council [26075083]; OncoSuisse [OCS-2922-02-2012, KFS-3301-08-2013]; Lauretana S.P.A. FX We thank R. Bernards, R. Agami, W. Raffoul, J. P. Rival, J. M. Joseph, U. Just, F. Martinon and T. Petrova for vectors or cells, F. De Sousa e Melo and B. Hu for early contributions, K. Harshman for RNA-Seq and ChIP-Seq analysis and C. Pasche and T. Proust for technical help. The work was supported by grants from the Swiss National Science Foundation (310030_156191/1), National Institutes of Health (R01AR039190; R01AR064786; the content not necessarily representing the offcial views of NIH), European Research Council (26075083) and OncoSuisse (OCS-2922-02-2012 and KFS-3301-08-2013). P. Ostano was supported by a grant from Lauretana S.P.A. NR 68 TC 23 Z9 23 U1 3 U2 26 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 SEP PY 2015 VL 17 IS 9 BP 1193 EP + DI 10.1038/ncb3228 PG 15 WC Cell Biology SC Cell Biology GA CR1VQ UT WOS:000361113700013 PM 26302407 ER PT J AU Geva-Zatorsky, N Alvarez, D Hudak, JE Reading, NC Erturk-Hasdemir, D Dasgupta, S von Andrian, UH Kasper, DL AF Geva-Zatorsky, Naama Alvarez, David Hudak, Jason E. Reading, Nicola C. Erturk-Hasdemir, Deniz Dasgupta, Suryasarathi von Andrian, Ulrich H. Kasper, Dennis L. TI In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria SO NATURE MEDICINE LA English DT Article ID BACTEROIDES-FRAGILIS; IMMUNE-SYSTEM; DENDRITIC CELLS; T-CELLS; POLYSACCHARIDE; DISEASE; MACROPHAGES; HOMEOSTASIS; INDUCTION; DIVERSITY AB The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal click chemistry to label various commensal anaerobes, including Bacteroides fragilis, a common and immunologically important commensal. We studied the dissemination of B. fragilis after acute peritonitis and characterized the interactions of the intact microbe and its polysaccharide components in myeloid and B cell lineages. We were able to assess the distribution and colonization of labeled B. fragilis along the intestine, as well as niche competition after coadministration of multiple species of the microbiota. We also fluorescently labeled nine additional commensals (eight anaerobic and one microaerophilic) from three phyla common in the gut-Bacteroidetes, Firmicutes and Proteobacteria-as well as one aerobic pathogen (Staphylococcus aureus). This strategy permits visualization of the anaerobic microbial niche by various methods, including intravital two-photon microscopy and non-invasive whole-body imaging, and can be used to study microbial colonization and host-microbe interactions in real time. C1 [Geva-Zatorsky, Naama; Alvarez, David; Hudak, Jason E.; Reading, Nicola C.; Erturk-Hasdemir, Deniz; Dasgupta, Suryasarathi; von Andrian, Ulrich H.; Kasper, Dennis L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02163 USA. [von Andrian, Ulrich H.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. RP Kasper, DL (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02163 USA. EM dennis_kasper@hms.harvard.edu FU Neurobiology Imaging Facility; Neural Imaging Center as part of NINDS P30 Core Center grant [NS072030]; NIH [1 S10 OD016401]; BCH/PCMM; US National Institutes of Health [PO1 AI1112521, RO1 AI111595, 5T32 HL066987]; Ragon Institute at MGH; EMBO Long-Term Fellowship [ALTF 251-2011]; Human Frontiers Science Program [LT000079/2012]; UNESCO L'Oreal National and International Women in Science Award; Fulbright Award; Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science; Cancer Research Institute Irvington Fellowship Program; departmental Kirschstein-NRSA training grant; Ragon Institute at MIT; Ragon Institute at Harvard; [U19AI095261] FX We thank the Neurobiology Imaging Facility for consultation and instrument availability that supported this work. This facility is supported in part by the Neural Imaging Center as part of NINDS P30 Core Center grant NS072030. We also thank N. Barteneva of the Flow and Imaging Cytometry Resource for help in whole-body imaging on the IVIS Spectrum (funded by grants NIH 1 S10 OD016401 and BCH/PCMM); J. Czupryna and M. Guerra from PerkinElmer for consultation and expert advice; C. Araneo (Division of Immunology Flow Cytometry Core Facility, HMS) and L. Comstock for helpful discussions, comments and reagents; and members of the Kasper and von Andrian labs for helpful discussions.; This work was also partly supported by the US National Institutes of Health (grants PO1 AI1112521, RO1 AI111595 (to U.H.v.A.) and 5T32 HL066987 (to D.A.)). Additional support to U.H.v.A. was provided by U19AI095261 and the Ragon Institute at MGH, MIT and Harvard. N.G.-Z. was supported by an EMBO Long-Term Fellowship (ALTF 251-2011), the Human Frontiers Science Program (LT000079/2012), a UNESCO L'Oreal National and International Women in Science Award, a Fulbright Award and the Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science. J.E.H. was supported by the Cancer Research Institute Irvington Fellowship Program. N.C.R. was supported by a departmental Kirschstein-NRSA training grant. NR 37 TC 20 Z9 20 U1 5 U2 43 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD SEP PY 2015 VL 21 IS 9 BP 1091 EP + DI 10.1038/nm.3929 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CQ9US UT WOS:000360961300024 PM 26280120 ER PT J AU Yan, G Tsekenis, G Barzel, B Slotine, JJ Liu, YY Barabasi, AL AF Yan, Gang Tsekenis, Georgios Barzel, Baruch Slotine, Jean-Jacques Liu, Yang-Yu Barabasi, Albert-Laszlo TI Spectrum of controlling and observing complex networks SO NATURE PHYSICS LA English DT Article ID DYNAMICS; CONTROLLABILITY; STABILITY; SYSTEMS; ORGANIZATION AB Recent studies have made important advances in identifying sensor or driver nodes, through which we can observe or control a complex system. But the observational uncertainty induced by measurement noise and the energy required for control continue to be significant challenges in practical applications. Here we show that the variability of control energy and observational uncertainty for different directions of the state space depend strongly on the number of driver nodes. In particular, we find that if all nodes are directly driven, control is energetically feasible, as the maximum energy increases sublinearly with the system size. If, however, we aim to control a system through a single node, control in some directions is energetically prohibitive, increasing exponentially with the system size. For the cases in between, the maximum energy decays exponentially when the number of driver nodes increases. We validate our findings in several model and real networks, arriving at a series of fundamental laws to describe the control energy that together deepen our understanding of complex systems. C1 [Yan, Gang; Tsekenis, Georgios; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Yan, Gang; Tsekenis, Georgios; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barzel, Baruch] Bar Ilan Univ, Dept Math, IL-52900 Ramat Gan, Israel. [Slotine, Jean-Jacques] MIT, Dept Engn Mech, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Liu, Yang-Yu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu RI Yan, Gang/B-9020-2009; Liu, Yang-Yu/G-8885-2011 OI Yan, Gang/0000-0001-6196-2615; Liu, Yang-Yu/0000-0003-2728-4907 FU Army Research Laboratories (ARL) Network Science (NS) Collaborative Technology Alliance (CTA) [ARL NS-CTA W911NF-09-2-0053]; DARPA Social Media in Strategic Communications project [W911NF-12-C-002]; John Templeton Foundation: Mathematical and Physical Sciences [PFI-777]; European Commission [FP7 317532 (MULTIPLEX), 641191 (CIMPLEX)] FX We thank E. Guney, C. Song, J. Gao, M. T. Angulo, S. P. Cornelius, B. Coutinho and A. Li for discussions. This work was supported by Army Research Laboratories (ARL) Network Science (NS) Collaborative Technology Alliance (CTA) grant ARL NS-CTA W911NF-09-2-0053; DARPA Social Media in Strategic Communications project under agreement number W911NF-12-C-002; the John Templeton Foundation: Mathematical and Physical Sciences grant number PFI-777; European Commission grant numbers FP7 317532 (MULTIPLEX) and 641191 (CIMPLEX). NR 54 TC 22 Z9 23 U1 10 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 EI 1745-2481 J9 NAT PHYS JI Nat. Phys. PD SEP PY 2015 VL 11 IS 9 BP 779 EP 786 DI 10.1038/NPHYS3422 PG 8 WC Physics, Multidisciplinary SC Physics GA CQ6IY UT WOS:000360709200024 ER PT J AU Preusser, M Lim, M Hafler, DA Reardon, DA Sampson, JH AF Preusser, Matthias Lim, Michael Hafler, David A. Reardon, David A. Sampson, John H. TI Prospects of immune checkpoint modulators in the treatment of glioblastoma SO NATURE REVIEWS NEUROLOGY LA English DT Review ID CELL LUNG-CANCER; NEWLY-DIAGNOSED GLIOBLASTOMA; TUMOR-INFILTRATING LYMPHOCYTES; RESPONSE ASSESSMENT CRITERIA; PRIMARY BRAIN-TUMORS; LIGAND 1 PD-L1; ADVANCED MELANOMA; NIVOLUMAB ANTI-PD-1; ANTITUMOR IMMUNITY; CTLA-4 BLOCKADE AB Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment-maximal safe resection and combination of radiotherapy with temozolomide chemotherapy-the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies. C1 [Preusser, Matthias] Med Univ Vienna, Dept Med 1, A-1090 Vienna, Austria. [Preusser, Matthias] Med Univ Vienna, Ctr Comprehens Canc, CNS Tumours Unit, A-1090 Vienna, Austria. [Lim, Michael] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Hafler, David A.] Yale Univ, Dept Neurol, Sch Med, Yale New Haven Hosp, New Haven, CT 06520 USA. [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Sampson, John H.] Duke Univ, Sch Med, Div Neurosurg, Durham, NC 27705 USA. RP Sampson, JH (reprint author), Duke Univ, Sch Med, Div Neurosurg, 220 Sands Bldg,Res Dr, Durham, NC 27705 USA. EM john.sampson@duke.edu OI Preusser, Matthias/0000-0003-3541-2315 FU National Multiple Sclerosis Society Collaborative Research Centre Award [CA1061-A18]; NIH grants [P01 AI045757, U19 AI046130, U19 AI070352, P01 AI039671, R01-CA177476-02, R01-NS086943-01, P50-CA190991-01, 2R25-NS065731-06]; Nancy Taylor Foundation for Chronic Diseases; Penates Foundation; Accelerate Brain Cancer Cure; Pediatric Brain Tumor Foundation; Bristol-Myers Squibb FX M. Daniels from inScience Communications in Philadelphia, PA, USA, provided editorial support for writing this article, comprising compilation of tables, management of the reference database, and editing of the manuscript text before submission. The editorial support was funded by Bristol-Myers Squibb. D.A.H. has received the National Multiple Sclerosis Society Collaborative Research Centre Award CA1061-A-18, NIH grants P01 AI045757, U19 AI046130, U19 AI070352, and P01 AI039671, and research support from the Nancy Taylor Foundation for Chronic Diseases and the Penates Foundation. J.H.S. has received the NIH grants R01-CA177476-02, R01-NS086943-01, P50-CA190991-01, and 2R25-NS065731-06, and research support from the Accelerate Brain Cancer Cure and Pediatric Brain Tumor Foundation. NR 112 TC 29 Z9 29 U1 11 U2 33 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 SEP PY 2015 VL 11 IS 9 BP 504 EP 514 DI 10.1038/nrneurol.2015.139 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CQ9WZ UT WOS:000360967300005 PM 26260659 ER PT J AU Wu, H Zhang, Y AF Wu, Hao Zhang, Yi TI Charting oxidized methylcytosines at base resolution SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; DNA METHYLATION PATTERNS; GENOME-WIDE ANALYSIS; TET PROTEINS; MAMMALIAN DEVELOPMENT; GENE BODIES; 5-HYDROXYMETHYLCYTOSINE; 5-FORMYLCYTOSINE; DEMETHYLATION; 5-CARBOXYLCYTOSINE AB DNA cytosine methylation is a key epigenetic mark that is required for normal mammalian development. Iterative oxidation of 5-methylcytosine (5mC) by the TET family of DNA dioxygenases generates three oxidized nucleotides: 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Recent advances in genomic mapping techniques have suggested that these oxidized cytosines not only function in the process of active reversal of 5mC but also may possess unique regulatory functions in the mammalian genome. C1 [Wu, Hao; Zhang, Yi] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Wu, Hao; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wu, Hao; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Zhang, Y (reprint author), Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu FU US National Institutes of Health [GM68804, U01DK089565]; Jane Coffin Childs Memorial Fund for Medical Research; US National Human Genome Research Institute [K99HG007982]; Investigator of the Howard Hughes Medical Institute FX We thank L.M. Tuesta for critical reading of the manuscript. This work was supported by US National Institutes of Health grants GM68804 and U01DK089565 (to Y.Z.). H.W. was supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research and is currently supported by the US National Human Genome Research Institute (K99HG007982). Y.Z. is supported as an Investigator of the Howard Hughes Medical Institute. NR 57 TC 6 Z9 6 U1 1 U2 7 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 SEP PY 2015 VL 22 IS 9 BP 1 EP 6 DI 10.1038/nsmb.3071 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CQ9KK UT WOS:000360933200007 PM 26333715 ER PT J AU Park, E Kim, N Ficarro, SB Zhang, Y Lee, BI Cho, A Kim, K Park, AKJ Park, WY Murray, B Meyerson, M Beroukhim, R Marto, JA Cho, J Eck, MJ AF Park, Eunyoung Kim, Nayoung Ficarro, Scott B. Zhang, Yi Lee, Byung Il Cho, Ahye Kim, Kihong Park, Angela K. J. Park, Woong-Yang Murray, Bradley Meyerson, Matthew Beroukhim, Rameen Marto, Jarrod A. Cho, Jeonghee Eck, Michael J. TI Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; LUNG-CANCER; NEGATIVE REGULATOR; TARGETED THERAPIES; TUMOR-SUPPRESSOR; GENOMIC ANALYSIS; KINASE DOMAIN; GLIOBLASTOMA; MUTANTS; PROTEIN AB Mig6 is a feedback inhibitor that directly binds, inhibits and drives internalization of ErbB-family receptors. Mig6 selectively targets activated receptors. Here we found that the epidermal growth factor receptor (EGFR) phosphorylates Mig6 on Y394 and that this phosphorylation is primed by prior phosphorylation of an adjacent residue, Y395, by Src. Crystal structures of human EGFR-Mig6 complexes reveal the structural basis for enhanced phosphorylation of primed Mig6 and show how Mig6 rearranges after phosphorylation by EGFR to effectively irreversibly inhibit the same receptor that catalyzed its phosphorylation. This dual phosphorylation site allows Mig6 to inactivate EGFR in a manner that requires activation of the target receptor and that can be modulated by Src. Loss of Mig6 is a driving event in human cancer; analysis of 1,057 gliomas reveals frequent focal deletions of ERRFI1, the gene that encodes Mig6, in EGFR-amplified glioblastomas. C1 [Park, Eunyoung; Ficarro, Scott B.; Zhang, Yi; Lee, Byung Il; Beroukhim, Rameen; Marto, Jarrod A.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Park, Eunyoung; Marto, Jarrod A.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, Nayoung; Cho, Ahye; Park, Angela K. J.; Park, Woong-Yang; Cho, Jeonghee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Genome Inst, Seoul, South Korea. [Kim, Nayoung; Cho, Ahye; Kim, Kihong; Park, Angela K. J.; Park, Woong-Yang; Cho, Jeonghee] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Seoul, South Korea. [Ficarro, Scott B.; Zhang, Yi; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Lee, Byung Il] Natl Canc Ctr, Res Inst, Div Convergence Technol, Biomol Funct Res Branch, Goyang, South Korea. [Murray, Bradley; Meyerson, Matthew; Beroukhim, Rameen] Broad Inst Harvard & MIT, Cambridge, MA USA. [Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jeong.cho@skku.edu; eck@crystal.harvard.edu FU US National Institutes of Health (NIH); NIH [CA116020, CA154303, CA156021, CA178860]; Samsung Medical Center; Basic Science Research Program of the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning [2013065771] FX We thank L. Cantley and M. Begley for helpful discussions and sharing unpublished data, and R. McNally for critical reading of the manuscript. We thank P. Cole, D. Leahy and Z. Wang for helpful discussions and for testing the effect of phospho-Mig6 species on the activity of transmembrane EGFR (Supplementary Fig. 4e). We thank P. Janne (Dana-Farber Cancer Institute) for providing cells. We thank beamline personnel at the Northeast Collaborative Access Team at the Advanced Photon Source, Argonne National Laboratory (NE-CAT) for assistance with data collection and processing. NE-CAT is supported by grants from the US National Institutes of Health (NIH). This work was supported in part by NIH grants CA116020 (M.J.E. and M.M.), CA154303 (M.J.E. and M.M.), CA156021 (J.A.M.) and CA178860 (J.A.M.). This work was also supported in part by grants from Samsung Medical Center (J.C.) and the Basic Science Research Program of the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning (grant 2013065771; J.C.). NR 59 TC 9 Z9 9 U1 3 U2 6 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 SEP PY 2015 VL 22 IS 9 BP 703 EP U84 DI 10.1038/nsmb.3074 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CQ9KK UT WOS:000360933200013 PM 26280531 ER PT J AU Gadd, MA AF Gadd, Michele A. TI Changing Beliefs and Practices in Women With Breast Cancer in China SO ONCOLOGIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Gadd, MA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Gillette Ctr Womens Canc, 55 Fruit St, Boston, MA 02114 USA. EM MGadd@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2015 VL 20 IS 9 BP 979 EP 980 DI 10.1634/theoncologist.2015-0249 PG 2 WC Oncology SC Oncology GA CQ9ZB UT WOS:000360975000004 PM 26253558 ER PT J AU Seah, DS Scott, S Guo, H Najita, J Lederman, R Frank, E Sohl, J Stadler, Z Silverman, S Peppercorn, J Winer, E Come, S Lin, NU AF Seah, Davinia S. Scott, Sarah Guo, Hao Najita, Julie Lederman, Ruth Frank, Elizabeth Sohl, Jessica Stadler, Zsofia Silverman, Stuart Peppercorn, Jeffrey Winer, Eric Come, Steve Lin, Nancy U. TI Variation in the Attitudes of Medical Oncologists Toward Research Biopsies in Patients With Metastatic Breast Cancer SO ONCOLOGIST LA English DT Article DE Research biopsies; Physicians; Attitudes; Metastatic breast cancer ID CLINICAL-TRIALS; FEASIBILITY; EXPERIENCE; MUTATIONS; OUTCOMES; SAFETY; RISKS; HELP AB Background. Tissue from research biopsies provides access to insights into tumor biology. We aimed to determine medical oncologists' (MOs') attitudes toward research biopsies in patients with metastatic breast cancer (MBC). Materials and Methods. A total of 309 breast MOs from National Cancer Institute (NCI)-designated cancer centers were invited to complete a self-administered survey about their attitudes toward approaching patients for research purpose-only biopsies (RPOBs), performed as a standalone procedure, or additional biopsies, performed with a clinically indicated biopsy. The MOs were asked to predict what proportion of their MBC patients would consider undergoing research biopsies. Results. Of the 309 MOs, 221 (72%) responded. Of these 221 MOs, 30 were ineligible, leaving 191 eligible responders. Nearly all the MOs reported they were comfortable approaching patients regarding research biopsies of blood or skin. One fifth of MOs were uncomfortable approaching patients for RPOBs of the breast. One half of MOs were uncomfortable approaching patients for RPOBs of the liver. A significant variation was found in the perceptions by MOs of their patients' willingness to undergo research biopsies. The factors associated with increased comfort in approaching patients for research biopsies included fewer years in practice, caring for patients who had undergone recent research biopsies, and the predicted willingness of patients to consent to biopsies. The risk of a biopsy and biopsy-related pain were the most common reasons for reluctance to refer patients for research biopsies. Conclusion. Significant variation exists, even at NCI centers, in the comfort level of MOs in approaching MBC patients for research biopsies. MOs' attitudes toward research biopsies might be a modifiable factor in increasing tissue collection for research. C1 [Seah, Davinia S.; Guo, Hao; Najita, Julie; Lederman, Ruth; Frank, Elizabeth; Sohl, Jessica; Winer, Eric; Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Scott, Sarah; Come, Steve] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stadler, Zsofia] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Silverman, Stuart] Brigham & Womens Hosp, Boston, MA 02115 USA. [Peppercorn, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 FU Metastatic Research Fund; Susan G. Komen For the Cure fund; Friends of Dana-Farber Cancer Institute FX The study was funded by the Metastatic Research Fund (an anonymous donor to Eric Winer and Nancy U. Lin), the Susan G. Komen For the Cure fund, and the Friends of Dana-Farber Cancer Institute. These results were presented at the 36th Annual San Antonio Breast Cancer Symposium as a poster presentation, San Antonio, Texas, December 10-14, 2013. NR 19 TC 2 Z9 2 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2015 VL 20 IS 9 BP 992 EP 1000 DI 10.1634/theoncologist.2015-0112 PG 9 WC Oncology SC Oncology GA CQ9ZB UT WOS:000360975000008 PM 26240134 ER PT J AU Goyal, L Govindan, A Sheth, RA Nardi, V Blaszkowsky, LS Faris, JE Clark, JW Ryan, DP Kwak, EL Allen, JN Murphy, JE Saha, SK Hong, TS Wo, JY Ferrone, CR Tanabe, KK Chong, DQ Deshpande, V Borger, DR Iafrate, AJ Bardeesy, N Zheng, H Zhu, AX AF Goyal, Lipika Govindan, Aparna Sheth, Rahul A. Nardi, Valentina Blaszkowsky, Lawrence S. Faris, Jason E. Clark, Jeffrey W. Ryan, David P. Kwak, Eunice L. Allen, Jill N. Murphy, Janet E. Saha, Supriya K. Hong, Theodore S. Wo, Jennifer Y. Ferrone, Cristina R. Tanabe, Kenneth K. Chong, Dawn Q. Deshpande, Vikram Borger, Darrell R. Iafrate, A. John Bardeesy, Nabeel Zheng, Hui Zhu, Andrew X. TI Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma SO ONCOLOGIST LA English DT Article DE Cholangiocarcinoma; Isocitrate dehydrogenase; Prognosis; Metastatic; Phenotype ID PRIMARY SCLEROSING CHOLANGITIS; ACUTE MYELOID-LEUKEMIA; BILIARY-TRACT CANCER; ONCOMETABOLITE 2-HYDROXYGLUTARATE; MUTATIONS; LEWIS; DIFFERENTIATION; CA19-9; CHEMOTHERAPY; BIOMARKER AB Background. Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. Methods. Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. Results. Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. Conclusion. The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. C1 [Goyal, Lipika; Govindan, Aparna; Sheth, Rahul A.; Nardi, Valentina; Blaszkowsky, Lawrence S.; Faris, Jason E.; Clark, Jeffrey W.; Ryan, David P.; Kwak, Eunice L.; Allen, Jill N.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Chong, Dawn Q.; Deshpande, Vikram; Borger, Darrell R.; Iafrate, A. John; Bardeesy, Nabeel; Zheng, Hui; Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org FU Agios; Novartis FX Jason E. Faris: N-of-One, Merrimack Pharmaceuticals (C/A), Agios (RF); David P. Ryan: Uptodate, McGraw Hill (H); Eunice L. Kwak: Amgen (C/A); Theodore S. Hong: Eisai (C/A), Novartis (RF); A. John Iafrate: ArcherDx (IP, OI). The other authors indicated no financial relationships. NR 40 TC 7 Z9 7 U1 2 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2015 VL 20 IS 9 BP 1019 EP 1027 DI 10.1634/theoncologist.2015-0210 PG 9 WC Oncology SC Oncology GA CQ9ZB UT WOS:000360975000011 PM 26245674 ER PT J AU Diver, EJ Foster, R Rueda, BR Growdon, WB AF Diver, Elisabeth J. Foster, Rosemary Rueda, Bo R. Growdon, Whitfield B. TI The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer SO ONCOLOGIST LA English DT Article DE Endometrial cancer; HER2; Uterine serous carcinoma; Resistance ID METASTATIC BREAST-CANCER; EPIDERMAL-GROWTH-FACTOR; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; SURGICALLY STAGED PATIENTS; FACTOR-RECEPTOR; SEROUS CARCINOMA; TRASTUZUMAB RESISTANCE; TYROSINE KINASE; ADJUVANT TRASTUZUMAB AB Endometrial cancer is the mostcommon gynecologic cancer in the United States, diagnosed in more than 50,000 women annually. While the majority ofwomenpresent with low-grade tumors that are cured with surgery and adjuvant radiotherapy, a significant subset of women experience recurrence and do not survive their disease. A disproportionate number of the more than 8,000 annual deaths attributed to endometrial cancer are due to high-grade uterine cancers, highlighting the need for new therapies that target molecular alterations specific to this subset of tumors. Numerous correlative scientific investigations have demonstrated that the HER2 (ERBB2) gene is amplified in 17%-33% of carcinosarcoma, uterine serous carcinoma, and a subset of high-grade endometrioid endometrial tumors. In breast cancer, this potent signature has directed women to anti-HER2-targeted therapies such as trastuzumab and lapatinib. In contrast to breast cancer, therapy with trastuzumab alone revealed no responses in women with recurrent HER2 overexpressing endometrial cancer, suggesting that these tumors may possess acquired or innate trastuzumab resistance mechanisms. This review explores the literature surrounding HER2 expression in endometrial cancer, focusing on trastuzumab and other anti-HER2 therapy and resistance mechanisms characterized in breast cancer but germane to endometrial tumors. Understanding resistance pathwayswill suggest combination therapies that target both HER2 and key oncogenic escape pathways in endometrial cancer. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM wgrowdon@partners.org NR 151 TC 5 Z9 5 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2015 VL 20 IS 9 BP 1058 EP 1068 DI 10.1634/theoncologist.2015-0149 PG 11 WC Oncology SC Oncology GA CQ9ZB UT WOS:000360975000016 PM 26099744 ER PT J AU Nishino, M Boswell, EN Hatabu, H Ghobrial, IM Ramaiya, NH AF Nishino, Mizuki Boswell, Erica N. Hatabu, Hiroto Ghobrial, Irene M. Ramaiya, Nikhil H. TI Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenstrom Macroglobulinemia as a Paradigm SO ONCOLOGIST LA English DT Article DE Mammalian target of rapamycin inhibitor; mTOR; Pneumonitis; Drug toxicity; Computed tomography; Waldenstrom macroglobulinemia ID RENAL-CELL CARCINOMA; HIGH-RESOLUTION CT; IDIOPATHIC INTERSTITIAL PNEUMONIAS; INDUCED LUNG-DISEASE; PHASE-II TRIAL; MULTIPLE-MYELOMA; TEMSIROLIMUS; RITUXIMAB; EVEROLIMUS; LYMPHOMA AB Background. This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenstrom macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. Materials and Methods. A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenstrom macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results. Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p<.001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients. Conclusion. Drug-related pneumonitis was noted on CT in 58% of Waldenstrom macroglobulinemia patients treated with mTOR inhibitor therapy. Mostcommon findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns. C1 [Nishino, Mizuki; Hatabu, Hiroto; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Boswell, Erica N.; Ghobrial, Irene M.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU National Cancer Institute [1K23CA157631] FX M.N. was supported by National Cancer Institute Grant 1K23CA157631. NR 28 TC 6 Z9 6 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD SEP PY 2015 VL 20 IS 9 BP 1077 EP 1083 DI 10.1634/theoncologist.2015-0033 PG 7 WC Oncology SC Oncology GA CQ9ZB UT WOS:000360975000018 PM 26205737 ER PT J AU Zhou, J Zhang, XF Wang, YH Guan, YH AF Zhou, Jing Zhang, Xiaofeng Wang, Yuhua Guan, Yinghui TI PU.1 affects proliferation of the human acute myeloid leukemia U937 cell line by directly regulating MEIS1 SO ONCOLOGY LETTERS LA English DT Article DE PU.1; MEIS1; leukemia; transcription ID TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; PROGENITORS; EXPRESSION; DIFFERENTIATION; COMMITMENT; MUTATIONS; TARGETS; ALPHA; HOXA9 AB The transcription factor PU.1 is a member of the ETS family, which is expressed in a wide variety of hematopoietic lineages. Accumulating evidence has indicated that PU.1 plays a key role in hematopoiesis, and reduced expression of PU.1 leads to the pathogenesis of human myeloid leukemia. As a multi-functional factor, PU.1 is also required for mixed lineage leukemia (MLL) stem cell potential and the development of MLL. However, the function of PU.1 in human non-MLL leukemia and its molecular mechanism remains poorly understood. In the present study, PU.1 siRNA was demonstrated to efficiently inhibit the transcription level of oncogene MEIS1 in the human acute myeloid non-MLL leukemia U937 cell line. In addition, PU.1, as a positive regulator of MEIS1, performed a crucial role in maintaining cell proliferation. Using electrophoretic mobility shift assay, chromatin immunoprecipitation analysis and luciferase reporter assay, previously unexplored evidence that PU.1 activated the MEIS1 promoter through a conserved binding motif in vitro and in vivo was further defined. Overall, the present study provides insight into the molecular mechanism of the contribution of PU.1 to the pathogenesis of non-MLL U937 cells, which is mediated by direct regulation of MEIS1 transcription. The present data reveal the possibility of developing an alternative therapy for non-MLL leukemia by targeting PU.1-mediated MEIS1 gene activation. C1 [Zhou, Jing] Chinese Acad Sci, Beijing Inst Genom, Lab Genome Variat & Precis Biomed, Beijing 100101, Peoples R China. [Zhou, Jing; Wang, Yuhua] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. [Zhang, Xiaofeng] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA. [Wang, Yuhua] Shanghai Jiao Tong Univ, Sch Med, Coll Stomatol, Shanghai Key Lab Stomatol,Dept Prosthodont,People, Shanghai 200011, Peoples R China. [Guan, Yinghui] Jilin Univ, Resp Dept, Branch 2, Hosp 1, Changchun 130021, Jilin, Peoples R China. RP Zhou, J (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM Jzhou@forsyth.org; gyinghui@sina.com RI Zhou, jing/B-4718-2016 FU National Natural Science Foundation of China [81100381] FX This study was supported by the National Natural Science Foundation of China (grant no., 81100381). NR 29 TC 1 Z9 1 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD SEP PY 2015 VL 10 IS 3 BP 1912 EP 1918 DI 10.3892/ol.2015.3404 PG 7 WC Oncology SC Oncology GA CQ9GZ UT WOS:000360923000120 ER PT J AU Lippok, N Villiger, M Bouma, BE AF Lippok, Norman Villiger, Martin Bouma, Brett E. TI Degree of polarization (uniformity) and depolarization index: unambiguous depolarization contrast for optical coherence tomography SO OPTICS LETTERS LA English DT Article ID MUELLER MATRIX; SYSTEM AB The degree of polarization (uniformity) has attracted increased interest as a functional contrast in optical coherence tomography (OCT). However, its computation from a single polarization state suggests an ambiguity that is strongly dependent on a sample's orientation. We here propose an improved metric to present depolarization with respect to the optical system rather than the propagating field. Using numerical simulations and optical frequency domain imaging, we evaluate the conventional DOP(U) for different polarization states and compare its performance with the unambiguous depolarization index. (C) 2015 Optical Society of America C1 [Lippok, Norman; Villiger, Martin; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lippok, Norman; Villiger, Martin; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Bouma, Brett E.] Harvard Massachusetts Inst Technol, Program Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Lippok, N (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM nlippok@mgh.harvard.edu FU National Institute of Health [P41 EB015903]; Terumo Corporation FX National Institute of Health (P41 EB015903); Terumo Corporation. NR 15 TC 4 Z9 4 U1 5 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD SEP 1 PY 2015 VL 40 IS 17 BP 3954 EP 3957 DI 10.1364/OL.40.003954 PG 4 WC Optics SC Optics GA CQ7UM UT WOS:000360810200009 PM 26368685 ER PT J AU Beach, MC Roter, DL Saha, S Korthuis, PT Eggly, S Cohn, J Sharp, V Moore, RD Wilson, IB AF Beach, Mary Catherine Roter, Debra L. Saha, Somnath Korthuis, P. Todd Eggly, Susan Cohn, Jonathan Sharp, Victoria Moore, Richard D. Wilson, Ira B. TI Impact of a brief patient and provider intervention to improve the quality of communication about medication adherence among HIV patients SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Communication skills training; HIV/AIDS; Medication adherence ID ANTIRETROVIRAL THERAPY; CARE; SATISFACTION; PHYSICIANS; OUTCOMES; INFECTION; HIV/AIDS; DIALOGUE; RECALL AB Introduction: Medication adherence is essential in HIV care, yet provider communication about adherence is often suboptimal. We designed this study to improve patient-provider communication about HIV medication adherence. Methods: We randomized 26 providers at three HIV care sites to receive or not receive a one-hour communication skills training based on motivational interviewing principles applied to medication adherence. Prior to routine office visits, non-adherent patients of providers who received the training were coached to discuss adherence with their providers. Patients of providers who did not receive the training providers were not coached. We audio-recorded and coded patient-provider interactions using the roter interaction analysis system (RIAS). Results: There was more dialogue about therapeutic regimen in visits with intervention patients and providers (167 vs 128, respectively, p=.004), with the majority of statements coming from providers. These visits also included more brainstorming solutions to nonadherence (41% vs. 22%, p=0.026). Intervention compared with control visit providers engaged in more positive talk (44 vs. 38 statements, p=0.039), emotional talk (26 vs. 18 statements, p<0.001), and probing of patient opinion (3 vs. 2 statements, p=0.009). Conclusion: A brief provider training combined with patient coaching sessions, improved provider communication behaviors and increased dialogue regarding medication adherence. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Beach, Mary Catherine] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD 21287 USA. [Beach, Mary Catherine; Roter, Debra L.; Moore, Richard D.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Beach, Mary Catherine; Roter, Debra L.; Moore, Richard D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21287 USA. [Beach, Mary Catherine] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Saha, Somnath; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Eggly, Susan; Cohn, Jonathan] Wayne State Univ, Dept Med, Detroit, MI 48202 USA. [Wilson, Ira B.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Gen Internal Med, 2024 East Monument St, Baltimore, MD 21287 USA. EM mcbeach@jhmi.edu RI Wilson, Ira/F-9190-2016; OI Wilson, Ira/0000-0002-0246-738X; Eggly, Susan/0000-0002-8137-6098 FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08HS013903-05]; National Institute of Drug Abuse [K23 DA019809]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Korthuis. was supported by the National Institute of Drug Abuse (K23 DA019809), Dr. Saha was supported by the Department of Veterans Affairs, Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. None of the funders had a role in the design and conduct of this analysis, nor was it subject to their final approval. None of the authors have any relevant financial conflicts of interest. NR 33 TC 7 Z9 7 U1 3 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2015 VL 98 IS 9 BP 1078 EP 1083 DI 10.1016/j.pec.2015.05.011 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA CQ8PH UT WOS:000360870200006 PM 26021185 ER PT J AU Kolappa, K Kern, DE AF Kolappa, Kavitha Kern, David E. TI One good hand SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Narrative medicine; Patient-centered care; Medical education; Physician-patient relations; Patient compliance; Empathy; Holistic health; Cost-effectiveness; Healthcare delivery; Career choice C1 [Kolappa, Kavitha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kern, David E.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21218 USA. RP Kern, DE (reprint author), Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, MFL Ctr Tower,Suite 2300,5200 Eastern Ave, Baltimore, MD 21224 USA. EM dkernl@jhmi.edu OI Kolappa, Kavitha/0000-0002-5464-4683 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2015 VL 98 IS 9 BP 1164 EP 1166 DI 10.1016/j.pec.2015.06.010 PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA CQ8PH UT WOS:000360870200019 PM 26138157 ER PT J AU Kim, GE Seidler, E Kimball, AB AF Kim, Grace E. Seidler, Elizabeth Kimball, Alexa Boer TI Effect of Age at Diagnosis on Chronic Quality of Life and Long-Term Outcomes of Individuals with Psoriasis SO PEDIATRIC DERMATOLOGY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; INDEX; CONSEQUENCES; ADOLESCENTS; MECHANISMS; CHILDREN AB Psoriasis is a skin disorder that frequently begins in the pediatric and young adult population but imposes physical and psychosocial burdens over a lifetime. The objective of this retrospective cohort study was to evaluate the effect of age at diagnosis on the lifetime outcomes of psoriasis patients. Individuals with psoriasis (N=114) completed a questionnaire regarding disabilities, relationships, education, finances, and medical outcomes. Responses were compared among quartiles of age at diagnosis and regression analyses were performed. Those diagnosed at a younger age were more likely to have a greater lifetime Dermatology Life Quality Index (LT DLQI) (p<0.001), have felt depressed (p=0.003), believe that psoriasis had caused their depression (p<0.001), experience lifetime sleep problems (p=0.004), use recreational drugs (p<0.001), hide their psoriasis over their lifetime (p<0.001), and experience more severe lifetime discrimination in social settings (p=0.002). Early onset psoriasis is associated with depression, social discrimination, and greater LT DLQI. C1 [Kim, Grace E.; Kimball, Alexa Boer] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Seidler, Elizabeth] Emory Univ, Sch Med, Atlanta, GA USA. [Kimball, Alexa Boer] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin, Boston, MA 02114 USA. RP Kimball, AB (reprint author), 50 Staniford St,240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship FX This study was supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. The funder was not involved in any aspect of the study. NR 26 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2015 VL 32 IS 5 BP 656 EP 662 DI 10.1111/pde.12416 PG 7 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA CR2TR UT WOS:000361184000026 PM 25556559 ER PT J AU Sheldon, LK Blonquist, TM Hilaire, DM Hong, FX Berry, DL AF Sheldon, Lisa Kennedy Blonquist, Traci M. Hilaire, Dany M. Hong, Fangxin Berry, Donna L. TI Patient cues and symptoms of psychosocial distress: what predicts assessment and treatment of distress by oncology clinicians? SO PSYCHO-ONCOLOGY LA English DT Article DE distress; cancer; symptoms; communication; psychosocial factors; oncology ID CANCER-PATIENTS; RANDOMIZED-TRIAL; DEPRESSION; ANXIETY; CARE AB Objective: Psychosocial concerns arise after a cancer diagnosis and during treatment requiring oncology clinicians to initiate discussions to identify distress. This study examined patient-clinician communication about psychosocial concerns and predictors of assessment and treatment/referral for distress. Methods: Secondary analysis of existing dataset coded to explore patient-clinician communication during ambulatory visits in two comprehensive cancer centers was carried out. Sample included adult patients with various cancers and stages. Dataset included audio-recordings and symptom/QOL reports 4-6weeks after starting treatment from all distressed patients (n=66) in parent study and random sample of nondistressed patients (n=23). Distressed patients had moderate-to-severe depression (Patient Health Questionnaire-9 scores 10) and/or poor emotional functioning (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire emotional function scores <50). Audio-recordings were coded to describe patient-clinician communication about psychosocial concerns using the coding scheme from the parent study plus Medical Interview Aural Rating System. Results: The remaining patients gave 222 cues of psychosocial concerns: 183 from 46 distressed patients and 39 from nine nondistressed patients. Distressed patients were younger, were female, had higher symptom burden, and/or gave more cues. Significantly, more distressed patients had at least one cue/visit. Clinicians initiated 62% of discussions overall with no statistical difference between distressed and nondistressed groups. More explicit cues and more than four cues predicted treatment/referral for distress. Conclusions: Distressed patients were younger, were female, had higher symptom burden, and/or gave more verbal cues. Clinicians responded to explicit and more frequent cues by providing treatment and/or referrals for distress. Further exploration is needed regarding clinician factors related to assessment of psychosocial concerns. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Sheldon, Lisa Kennedy; Hilaire, Dany M.] Univ Massachusetts, Boston, MA 02125 USA. [Blonquist, Traci M.; Hong, Fangxin; Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berry, Donna L.] Harvard Univ, Sch Med, Boston, MA USA. RP Sheldon, LK (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, 100 Morrissey Blvd, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 FU Oncology Nursing Society Foundation; National Institute of Nursing Research [2R01 NR008726] FX This research was supported by a grant from the Oncology Nursing Society Foundation. The parent study was supported by the National Institute of Nursing Research (2R01 NR008726). This study was reviewed as exempt by the Institutional Review Board of the University of Massachusetts Boston. NR 33 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2015 VL 24 IS 9 BP 1020 EP 1027 DI 10.1002/pon.3689 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CR0FD UT WOS:000360992900005 PM 25288344 ER PT J AU Meyer, F Fletcher, K Prigerson, HG Braun, IM Maciejewski, PK AF Meyer, Fremonta Fletcher, Kalen Prigerson, Holly G. Braun, Ilana M. Maciejewski, Paul K. TI Advanced cancer as a risk for major depressive episodes SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; depression; etiology; epidemiology ID NATIONAL COMORBIDITY SURVEY; STRESSFUL LIFE EVENTS; REPLICATION NCS-R; QUALITY-OF-LIFE; BREAST-CANCER; MENTAL-DISORDERS; PALLIATIVE CARE; DISTRESS; WOMEN; PREVALENCE AB Objective Major depression adversely affects health communication, quality of life, and survival in patients with advanced cancer. Prior research provides limited insight into how patients with advanced cancer differ from the general population in risk for developing a major depressive episode (MDE). This study aims to determine whether advanced cancer poses distinct risks for initial and recurrent MDEs. Methods Advanced cancer patients (N=628) from Coping with Cancer were compared with propensity-weighted general population controls (N=9282) from the National Comorbidity Survey Replication. Results Patients with advanced cancer were more likely than comparisons to have an initial MDE [OR=27.3, 95% CI=(14.8-50.4); p<0.001] but no more likely than comparisons to have a recurrent MDE [OR=1.5, 95% CI=(0.9-2.6); p=0.160]. Nearly two thirds (64.4%) of current MDEs in patients were initial onset; the vast majority (91.8%) of current MDEs in comparisons were recurrent. Conclusions Advanced cancer increases risk of an initial MDE but appears not to enhance risk of a recurrent MDE. This suggests the importance of screening widely for depression in patients with advanced cancer as opposed to targeting screening to presumably high-risk subgroups of those with psychiatric histories. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Meyer, Fremonta; Braun, Ilana M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Meyer, Fremonta; Braun, Ilana M.] Harvard Univ, Sch Med, Boston, MA USA. [Meyer, Fremonta; Braun, Ilana M.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Fletcher, Kalen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Prigerson, Holly G.; Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Med, Ctr Res End Life Care, New York, NY 10065 USA. [Prigerson, Holly G.; Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA. RP Maciejewski, PK (reprint author), Weill Cornell Med Coll, Dept Med, Ctr Res End Life Care, 525 East 68th St,Box 141, New York, NY 10065 USA. EM pam2056@med.cornell.edu FU National Institute of Mental Health [MH63892, MH60220]; National Cancer Institute [CA106370] FX This research was supported by the National Institute of Mental Health (MH63892, Prigerson) and the National Cancer Institute (CA106370, Prigerson). The National Comorbidity Survey Replication was sponsored by the National Institute of Mental Health (MH60220). NR 39 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2015 VL 24 IS 9 BP 1080 EP 1087 DI 10.1002/pon.3722 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CR0FD UT WOS:000360992900013 PM 25389107 ER PT J AU Sporn, NJ Smith, KB Pirl, WF Lennes, IT Hyland, KA Park, ER AF Sporn, Nora J. Smith, Kelly B. Pirl, William F. Lennes, Inga T. Hyland, Kelly A. Park, Elyse R. TI Sexual health communication between cancer survivors and providers: how frequently does it occur and which providers are preferred? SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; survivorship care; survivorship clinic; sexual health; patient-provider communication ID PRIMARY-CARE PHYSICIANS; QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; GYNECOLOGIC CANCER; TESTICULAR CANCER; FOLLOW-UP; INTIMACY; NEEDS; ONCOLOGISTS; DEPRESSION AB BackgroundSexual health concerns in cancer survivors are often unaddressed by providers. Study objectives were to assess cancer survivors' reported rates of communication with oncology providers about sexual health, preference for such communication with their oncology or primary care providers (PCPs), and factors associated with these communication rates and preferences. MethodsSixty-six patients attending a cancer survivorship clinic were asked how often their oncologist addressed and initiated discussion about sexual functioning and whether they wanted their oncologist or PCP to ask about their sexual health. We also assessed whether various sociodemographic characteristics and levels of depression, anxiety, and sexual satisfaction were associated with survivors' sexual health communication rates and preferences. Results41% of patients wanted their oncologist to ask about sexual health and 58% of patients wanted their PCP to ask about sexual health. Over 90% of patients reported that their oncologist infrequently addressed sexual health concerns and that their oncologist was unlikely to initiate such discussions. Education level influenced whether patients wanted their oncologist to ask about sexual health. Age, education level, and insurance type influenced whether patients wanted their PCP to ask about sexual health. Levels of depression, anxiety, and sexual satisfaction were not associated with communication rates or preferences. ConclusionsPatients attending a survivorship clinic reported infrequent communication about sexual health with their oncology providers, despite wanting their providers to ask about sexual health concerns. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Sporn, Nora J.] Univ Kansas, Dept Psychol, Lawrence, KS 66045 USA. [Smith, Kelly B.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Pirl, William F.; Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pirl, William F.; Lennes, Inga T.; Hyland, Kelly A.; Park, Elyse R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hyland, Kelly A.; Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Sporn, NJ (reprint author), Univ Kansas, Dept Psychol, 325 Fraser Hall,1415 Jayhawk Blvd, Lawrence, KS 66045 USA. EM nsporn@ku.edu FU Massachusetts General Hospital Cancer Center; Michael Smith Foundation for Health Research; Canadian Pain Society FX This study was supported by internal funds from the Massachusetts General Hospital Cancer Center.; Dr. Smith has received postdoctoral fellowship awards from the Michael Smith Foundation for Health Research and the Canadian Pain Society. NR 40 TC 9 Z9 9 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2015 VL 24 IS 9 BP 1167 EP 1173 DI 10.1002/pon.3736 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CR0FD UT WOS:000360992900024 PM 25534170 ER PT J AU Fortenbaugh, FC DeGutis, J Germine, L Wilmer, JB Grosso, M Russo, K Esterman, M AF Fortenbaugh, Francesca C. DeGutis, Joseph Germine, Laura Wilmer, Jeremy B. Grosso, Mallory Russo, Kathryn Esterman, Michael TI Sustained Attention Across the Life Span in a Sample of 10,000: Dissociating Ability and Strategy SO PSYCHOLOGICAL SCIENCE LA English DT Article DE sustained attention; response inhibition; development; aging; life span ID COGNITIVE NEUROSCIENCE; INHIBITORY CONTROL; REACTION-TIME; RISK-TAKING; BEHAVIOR; AGE; PERFORMANCE; FAILURES; MIND AB Normal and abnormal differences in sustained visual attention have long been of interest to scientists, educators, and clinicians. Still lacking, however, is a clear understanding of how sustained visual attention varies across the broad sweep of the human life span. In the present study, we filled this gap in two ways. First, using an unprecedentedly large 10,430-person sample, we modeled age-related differences with substantially greater precision than have prior efforts. Second, using the recently developed gradual-onset continuous performance test (gradCPT), we parsed sustained-attention performance over the life span into its ability and strategy components. We found that after the age of 15 years, the strategy and ability trajectories saliently diverge. Strategy becomes monotonically more conservative with age, whereas ability peaks in the early 40s and is followed by a gradual decline in older adults. These observed life-span trajectories for sustained attention are distinct from results of other life-span studies focusing on fluid and crystallized intelligence. C1 [Fortenbaugh, Francesca C.; DeGutis, Joseph; Grosso, Mallory; Russo, Kathryn; Esterman, Michael] VA Boston Healthcare Syst, GRECC & Res Serv, Dept Vet Affairs, Boston, MA 02130 USA. [Fortenbaugh, Francesca C.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [DeGutis, Joseph] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Germine, Laura] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Germine, Laura] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wilmer, Jeremy B.] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. [Esterman, Michael] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Fortenbaugh, FC (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 182 JP, Boston, MA 02130 USA. EM francescafortenbaugh@gmail.com OI Esterman, Michael/0000-0002-9000-3920; Germine, Laura/0000-0001-8690-8412 FU Department of Veterans Affairs; Department of Veterans Affairs Clinical Sciences Research and Development Service [1IK2CX000706-01A2]; Brachman Hoffman Fellowship FX This research was partially supported by the Department of Veterans Affairs. F. C. Fortenbaugh has an Advanced Geriatric Fellowship from the Department of Veterans Affairs. M. Esterman has a Career Development award from the Department of Veterans Affairs Clinical Sciences Research and Development Service (1IK2CX000706-01A2). J. B. Wilmer has a Brachman Hoffman Fellowship. NR 40 TC 8 Z9 8 U1 4 U2 19 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 SEP PY 2015 VL 26 IS 9 BP 1497 EP 1510 DI 10.1177/0956797615594896 PG 14 WC Psychology, Multidisciplinary SC Psychology GA CR2OY UT WOS:000361171200016 PM 26253551 ER PT J AU Sauser, K Vickery, KD Davis, MM AF Sauser, Kori Vickery, Katherine Diaz Davis, Matthew M. TI Bottleneck or Magnifying Glass? Monitoring the Health-Care System's Vital Signs through Emergency Departments SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID REHOSPITALIZATIONS; IMPACT AB At this time of dynamic changes in the U.S. health-care system, the emergency department (ED) has a unique vantage point from which to monitor the pulse of Americans' health and to ensure that vulnerable groups are not the victims of unintended consequences of policy and system changes. The ED has a vital, pluripotent role in the U.S. health-care system: It is a primary site of acute unscheduled care and the chief source of hospital admissions, it serves as a diagnostic center, and it is an essential strand of federal, state, and community safety nets.' With such an array of roles, the ED forms a key intersection, where clinical, social, and financial issues converge and often bottleneck. At this privileged but pressurized site, the ED is a place where early effects of policy changes may be detected, diagnosed, and addressed. Yet, the opportunity for the ED to serve this monitoring function is frequently missed. Development of a coordinated network of EDs acting as monitoring points would leverage the natural, timely advantage of the ED and its unique position in the U.S. health-care system. High-yield opportunities for taking a pulse on how our system is caring for its most vulnerable patient groups might be found in tracking ED utilization patterns, rates of left-without-being-seen patients, ED revisit rates, and rates of psychiatric boarding. By monitoring these indicators in real time, system-level alerts can capitalize on the convergence and magnification of issues in the ED by collecting data that are relevant on many levels for hospitals, health systems, and local, state, and national jurisdictions. Such a system could illuminate key issues, inform innovative solutions, and provide opportunities for early intervention. C1 [Sauser, Kori] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Sauser, Kori] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Vickery, Katherine Diaz] Hennepin Healthcare Syst, Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN USA. [Vickery, Katherine Diaz] Hennepin Healthcare Syst, Hennepin Cty Med Ctr, Dept Family Med, Minneapolis, MN USA. [Vickery, Katherine Diaz] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. [Vickery, Katherine Diaz] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Davis, Matthew M.] Univ Michigan, Robert Wood Johnson Fdn, Clin Scholars Program, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. RP Sauser, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Ste 3B, Boston, MA 02114 USA. EM ksauser@mgh.harvard.edu OI Sauser-Zachrison, Kori/0000-0001-8160-3257 NR 20 TC 1 Z9 1 U1 2 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2015 VL 130 IS 5 BP 431 EP 434 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR1KX UT WOS:000361084800004 PM 26327719 ER PT J AU Hasegawa, K Stoll, SJ Ahn, J Bittner, JC Camargo, CA AF Hasegawa, Kohei Stoll, Samantha J. Ahn, Jason Bittner, Jane C. Camargo, Carlos A., Jr. TI Prevalence of eosinophilia in hospitalized patients with asthma exacerbation SO RESPIRATORY MEDICINE LA English DT Article DE Acute asthma; Hospitalization; Prevalence; Eosinophilia; Asthma phenotypes; Biologic therapies ID MULTICENTER; MEPOLIZUMAB; PHENOTYPES; ONSET; CARE AB Background: Recent studies have identified the "eosinophilic phenotype" of asthma that is characterized by persistent eosinophilic inflammation and frequent exacerbations. However, the prevalence of eosinophilia in patients hospitalized for asthma exacerbation is not known. Methods: We performed a pilot study in two sites participating in a multicenter chart review project of children and adults hospitalized for asthma exacerbation during 2012-2013. The pilot study investigated the prevalence of blood eosinophilia in this patient population. Eosinophilia was defined as a count of >= 300 cells/microliter at some time during the hospitalization. Results: Among 80 patients hospitalized for asthma exacerbation, 47 (59%) underwent CBC with differential and had data on blood eosinophil count. These 47 comprised the analytic cohort. The median patient age was 32 years (IQR, 24-44 years), and 51% were female. Overall, 40% (95% CI, 26%-56%) of patients had eosinophilia. Although statistical power was limited, there were no statistically significant differences in patient characteristics or hospital course between patients with eosinophilia and those without (all P > 0.05). Conclusion: Our pilot study showed that 40% of patients hospitalized for asthma exacerbation had eosinophilia. The clinical meaning of this biomarker in the emergency department/inpatient setting requires further study in much larger samples with long-term follow-up; such studies appear feasible. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hasegawa, Kohei; Stoll, Samantha J.; Ahn, Jason; Bittner, Jane C.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Stoll, Samantha J.; Ahn, Jason] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Novartis Pharmaceuticals Corporation FX The study was supported, in part, by Novartis Pharmaceuticals Corporation to Massachusetts General Hospital (PI: Camargo). The sponsor had no role in the conduct of the study, or collection, management, analysis or interpretation of the data, nor preparation, review, or approval of the manuscript. NR 16 TC 7 Z9 7 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD SEP PY 2015 VL 109 IS 9 BP 1230 EP 1232 DI 10.1016/j.rmed.2015.07.011 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA CQ9HY UT WOS:000360925800018 PM 26198894 ER PT J AU Cui, J Kawai, T Irani, Z AF Cui, Jie Kawai, Tasuo Irani, Zubin TI Catheter-directed Thrombolysis in Acute Superior Vena Cava Syndrome Caused by Central Venous Catheters SO SEMINARS IN DIALYSIS LA English DT Article ID ARTERIOVENOUS GRAFTS; HEMODIALYSIS-PATIENTS; HERO; OUTCOMES; ACCESS AB Indwelling central venous catheters have been reported to increase the risk of superior venous cava (SVC) syndrome. This case report describes the development of acute SVC syndrome in a 28-year-old woman with end-stage renal disease implanted with a left-side hemodialysis reliable outflow graft and a right-side double lumen hemodialysis catheter via internal jugular veins. Her symptoms were not alleviated after catheter removal and systemic anticoagulation therapy. She was eventually treated with catheter-directed thrombolysis and a predischarge computer tomographic venogram on postthrombolytic procedure day 7 showed patent central veins and patient remained asymptomatic. This case demonstrates that catheter-directed thrombolysis can be safely employed to treat refractory catheter-induced acute SVC syndrome in end-stage renal disease patients. C1 [Cui, Jie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02115 USA. [Kawai, Tasuo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg, Boston, MA 02115 USA. [Irani, Zubin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Radiol, Boston, MA 02115 USA. RP Irani, Z (reprint author), MGH Intervent Radiol, 55 Fruits St, Boston, MA 02114 USA. EM zirani@mgh.harvard.edu FU American Society of Nephrology FX The authors thank Linda Romano RN for her assistance with patient's care coordination. Dr. Cui is supported by Ben J. Lipps Research Fellowship from American Society of Nephrology. NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP-OCT PY 2015 VL 28 IS 5 BP 548 EP 551 DI 10.1111/sdi.12362 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA CQ7SG UT WOS:000360803600016 PM 25827021 ER PT J AU Brouwers, HB Battey, TWK Musial, HH Ciura, VA Falcone, GJ Ayres, AM Vashkevich, A Schwab, K Viswanathan, A Anderson, CD Greenberg, SM Pomerantz, SR Ortiz, CJ Goldstein, JN Gonzalez, RG Rosand, J Romero, JM AF Brouwers, H. Bart Battey, Thomas W. K. Musial, Hayley H. Ciura, Viesha A. Falcone, Guido J. Ayres, Alison M. Vashkevich, Anastasia Schwab, Kristin Viswanathan, Anand Anderson, Christopher D. Greenberg, Steven M. Pomerantz, Stuart R. Ortiz, Claudia J. Goldstein, Joshua N. Gonzalez, R. Gilberto Rosand, Jonathan Romero, Javier M. TI Rate of Contrast Extravasation on Computed Tomographic Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage SO STROKE LA English DT Article DE cerebral hemorrhage; CT angiography; intracerebral hemorrhage; mortality ID ACTIVATED FACTOR-VII; SPOT SIGN SCORE; GROWTH AB Background and Purpose-In primary intracerebral hemorrhage, the presence of contrast extravasation after computed tomographic angiography (CTA), termed the spot sign, predicts hematoma expansion and mortality. Because the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation, which may reflect the rate of bleeding, predicts expansion and mortality beyond the simple presence of the spot sign. Methods-Consecutive intracerebral hemorrhage patients with first-pass CTA followed by a 90-second delayed postcontrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by 2 blinded readers. Spot sign volumes on first-pass and delayed CTA and intracerebral hemorrhage volumes were measured using semiautomated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regressions. Results-One hundred and sixty-two patients were included, 48 (30%) of whom had >= 1 spot sign. Median spot sign volume was 0.04 mL on first-pass CTA and 0.4 mL on delayed CTA. Median extravasation rate was 0.23 mL/min overall and 0.30 mL/min among expanders versus 0.07 mL/min in nonexpanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27 mL/min versus 0.04 mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (odds ratio, 1.09 [95% confidence interval, 1.04-1.18], P=0.004), 90-day mortality (odds ratio, 1.15 [95% confidence interval, 1.08-1.27]; P=0.0004), and hematoma expansion (odds ratio, 1.03 [95% confidence interval, 1.01-1.08]; P=0.047). Conclusions-Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute intracerebral hemorrhage. C1 [Brouwers, H. Bart] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurosurg, NL-3584 CX Utrecht, Netherlands. [Brouwers, H. Bart; Battey, Thomas W. K.; Musial, Hayley H.; Falcone, Guido J.; Anderson, Christopher D.; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Brouwers, H. Bart; Falcone, Guido J.; Viswanathan, Anand; Anderson, Christopher D.; Goldstein, Joshua N.; Rosand, Jonathan] Harvard Univ, Sch Med, Dept Neurol,Div Neurocrit Care & Emergency Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brouwers, H. Bart; Battey, Thomas W. K.; Musial, Hayley H.; Falcone, Guido J.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Viswanathan, Anand; Anderson, Christopher D.; Greenberg, Steven M.; Goldstein, Joshua N.; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Grp, Boston, MA USA. [Brouwers, H. Bart; Battey, Thomas W. K.; Musial, Hayley H.; Falcone, Guido J.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Viswanathan, Anand; Anderson, Christopher D.; Greenberg, Steven M.; Goldstein, Joshua N.; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr, Boston, MA USA. [Ciura, Viesha A.; Pomerantz, Stuart R.; Ortiz, Claudia J.; Gonzalez, R. Gilberto; Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Neuroradiol Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Brouwers, HB (reprint author), Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurosurg, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM H.B.Brouwers-4@umcutrecht.nl RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727, 5K23NS059774]; NIH-NINDS SPOTRIAS fellowship [P50NS051343] FX All funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the article, and in the decision to submit for publication. The project described was supported by National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) grants R01NS073344, R01NS059727, and 5K23NS059774. Drs Brouwers and Falcone were supported by the NIH-NINDS SPOTRIAS fellowship grant P50NS051343. NR 23 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2015 VL 46 IS 9 BP 2498 EP 2503 DI 10.1161/STROKEAHA.115.009659 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CQ9FZ UT WOS:000360919700028 PM 26243220 ER PT J AU Andersson, C Preis, SR Beiser, A DeCarli, C Wollert, KC Wang, TJ Januzzi, JL Vasan, RS Seshadri, S AF Andersson, Charlotte Preis, Sarah R. Beiser, Alexa DeCarli, Charles Wollert, Kai C. Wang, Thomas J. Januzzi, James L., Jr. Vasan, Ramachandran S. Seshadri, Sudha TI Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke SO STROKE LA English DT Article DE follow-up studies; growth differentiation factor-15; magnetic resonance imaging; neuroimaging; stroke ID FACTOR-15/MACROPHAGE INHIBITORY CYTOKINE-1; ACUTE CORONARY SYNDROME; RISK STRATIFICATION; SOLUBLE ST2; CARDIOVASCULAR EVENTS; MULTIPLE BIOMARKERS; EJECTION FRACTION; COGNITIVE DECLINE; ISCHEMIC-STROKE; HEART-FAILURE AB Background and Purpose-Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort. Methods-We followed 3374 stroke-and dementia-free individuals (mean age, 59.0+/-9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8+/-3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing approximate to 4.0+/-1.7 years after the sixth examination. Results-After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (beta coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (beta coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (beta for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. Conclusions-Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury. C1 [Andersson, Charlotte; Beiser, Alexa; Wang, Thomas J.; Vasan, Ramachandran S.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Andersson, Charlotte] Univ Copenhagen, Gentofte Hosp, Dept Cardiol, DK-1168 Copenhagen, Denmark. [Preis, Sarah R.; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Beiser, Alexa; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Cardiol, Boston, MA 02215 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Andersson, C (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM ca@heart.dk OI Seshadri, Sudha/0000-0001-6135-2622; Ramachandran, Vasan/0000-0001-7357-5970; Beiser, Alexa/0000-0001-8551-7778 FU National Institutes of Health Heart, Lung and Blood Institute [N01-HC-25195]; National Institute on Neurological Diseases and Stroke [NS17950]; National Institute on Aging [AG081220, AG016495]; Critical Diagnostics; Danish agency for science, technology, and innovation [FSS-11-120873]; Desanctis Clinical Scholar Endowment; Hutter Family Professorship; NIA [AG10129] FX This study was funded by the National Institutes of Health Heart, Lung and Blood Institute (contract no. N01-HC-25195, PI, Vasan) with additional support from the National Institute on Neurological Diseases and Stroke (NS17950) and the National Institute on Aging (AG081220, AG016495). The ST2 assays were provided with in-kind support from Critical Diagnostics. Dr Andersson was supported by an independent research grant from the Danish agency for science, technology, and innovation (grant number, FSS-11-120873). Dr Januzzi was supported in part by the Desanctis Clinical Scholar Endowment and the Hutter Family Professorship and NIA AG10129. NR 41 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2015 VL 46 IS 9 BP 2568 EP 2575 DI 10.1161/STROKEAHA.115.009026 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CQ9FZ UT WOS:000360919700039 PM 26219649 ER PT J AU Han, LJ Cai, W Mao, LL Liu, J Li, PY Leak, RK Xu, Y Hu, XM Chen, J AF Han, Lijuan Cai, Wei Mao, Leilei Liu, Jia Li, Peiying Leak, Rehana K. Xu, Yun Hu, Xiaoming Chen, Jun TI Rosiglitazone Promotes White Matter Integrity and Long-Term Functional Recovery After Focal Cerebral Ischemia SO STROKE LA English DT Article DE bromodeoxyuridine; inflammation; polarization; stroke; white matter ID ACTIVATED-RECEPTOR-GAMMA; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; TRAUMATIC BRAIN-INJURY; PPAR-GAMMA; OLIGODENDROCYTE DIFFERENTIATION; INTRACEREBRAL HEMORRHAGE; AGONIST ROSIGLITAZONE; NEUROPROTECTION; CELLS; PROGENITORS AB Background and Purpose-Oligodendrogenesis is essential for white matter repair after stroke. Although agonists of peroxisome proliferator-activated receptors. confer neuroprotection in models of cerebral ischemia, it is not known whether this effect extends to white matter protection. This study tested the hypothesis that the peroxisome proliferator-activated receptors. agonist rosiglitazone enhances oligodendrogenesis and improves long-term white matter integrity after ischemia/reperfusion. Methods-Male adult C57/BL6 mice (25-30 g) were subjected to 60-minute middle cerebral artery occlusion and reperfusion. Rosiglitazone (3 mg/kg) was injected intraperitoneally once daily for 14 days beginning 2 hours after reperfusion. Sensorimotor and cognitive functions were evaluated <= 21 days after middle cerebral artery occlusion. Immunostaining was used to assess infarct volume, myelin loss, and microglial activation. Bromodeoxyuridine (BrdU) was injected for measurements of proliferating NG2(+) oligodendrocyte precursor cells (OPCs) and newly generated adenomatous polyposis coli(+) oligodendrocytes. Mixed glial cultures were used to confirm the effect of rosiglitazone on oligodendrocyte differentiation and microglial polarization. Results-Rosiglitazone significantly reduced brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions for at least 21 days after middle cerebral artery occlusion. Rosiglitazone enhanced OPC proliferation and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion. Rosiglitazone treatment also reduced the numbers of Iba1(+)/CD16(+) M1 microglia and increased the numbers of Iba1(+)/CD206(+) M2 microglia after stroke. Glial culture experiments confirmed that rosiglitazone promoted oligodendrocyte differentiation, perhaps by promoting microglial M2 polarization. Conclusions-Rosiglitazone treatment improves long-term white matter integrity after cerebral ischemia, at least, in part, by promoting oligodendrogenesis and facilitating microglial polarization toward the beneficial M2 phenotype. C1 [Han, Lijuan; Xu, Yun] Nanjing Univ, Sch Med, Drum Tower Hosp, Dept Neurol, Nanjing 21008, Jiangsu, Peoples R China. [Han, Lijuan; Cai, Wei; Mao, Leilei; Hu, Xiaoming; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Liu, Jia; Li, Peiying; Hu, Xiaoming; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Liu, Jia; Li, Peiying; Hu, Xiaoming; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Cai, Wei] Sun Yat Sen Univ, Affiliated Hosp 3, Multiple Sclerosis Ctr, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM xuyun20042001@aliyun.com; chenj2@upmc.edu OI Leak, Rehana/0000-0003-2817-7417 FU National institutes of Health/National Institute of neurological disorders and stroke [NS095671, NS045048, NS036736, NS089534, NS092618]; US Department of Veterans Affairs Research Career Scientist Award and RRD Merit Review [I01RX000420]; American Heart Association [13SDG14570025]; Chinese Scholarship Council; China Natural Science Foundation [81230026, 81171085]; Science and Technology Commission of Shanghai Municipality [13ZR1452200]; National Natural Science Foundation [81400956] FX This work was supported by the National institutes of Health/National Institute of neurological disorders and stroke grants NS095671, NS045048, NS036736, and NS089534 (to Dr Chen) and NS092618 (to Dr Hu), US Department of Veterans Affairs Research Career Scientist Award and RR&D Merit Review I01RX000420 (to Dr Chen), and grant 13SDG14570025 from the American Heart Association (to Dr Hu). Dr Han was supported by predoctoral fellowship from the Chinese Scholarship Council. Dr Xu was supported by China Natural Science Foundation grants (No. 81230026 and No. 81171085). Dr Li was supported by the Science and Technology Commission of Shanghai Municipality (13ZR1452200) and National Natural Science Foundation grant (No. 81400956). NR 36 TC 11 Z9 11 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2015 VL 46 IS 9 BP 2628 EP 2636 DI 10.1161/STROKEAHA.115.010091 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CQ9FZ UT WOS:000360919700046 PM 26243225 ER PT J AU Esposito, E Hayakawa, K Maki, T Arai, K Lo, EH AF Esposito, Elga Hayakawa, Kazuhide Maki, Takakuni Arai, Ken Lo, Eng H. TI Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia SO STROKE LA English DT Article DE brain ischemia; infarction; ischemic postconditioning; neurogenesis; stroke ID BRAIN-INJURY; STROKE; RATS AB Background and Purpose-Postconditioning may be a clinically feasible way to protect the brain after a stroke. However, its effects during the recovery phase post stroke remain to be fully elucidated. Here, we examine the hypothesis that ischemic postconditioning amplifies neurogenesis and angiogenesis during stroke recovery. Methods-Male Sprague-Dawley rats were subjected to 100-minute transient middle cerebral artery occlusion (MCAO) or postconditioning (100-minute middle cerebral artery occlusion plus 10-minute reperfusion plus 10-minute reocclusion). After 2 weeks, infarct volumes, behavioral outcomes, and immunohistochemical markers of neurogenesis and angiogenesis were quantified. Results-Postconditioning significantly reduced infarction and improved neurological outcomes. Concomitantly, brains subjected to postconditioning showed an increase in doublecortin/BrdU and collagen-IV/Ki67-positive cells. Conclusions-These results suggest that therapeutic effects of postconditioning may involve the promotion of neurogenesis and angiogenic remodeling during the recovery phase after focal cerebral ischemia. C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, E Bldg 149,13th St, Charlestown, MA 02129 USA. EM eesposito@partners.org; lo@helix.mgh.harvard.edu FU National Institutes of Health; Rappaport Foundation FX This work was supported in part by grants from the National Institutes of Health and the Rappaport Foundation. NR 13 TC 7 Z9 8 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2015 VL 46 IS 9 BP 2691 EP 2694 DI 10.1161/STROKEAHA.115.009070 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CQ9FZ UT WOS:000360919700059 PM 26243221 ER PT J AU Bader, MK Wavra, T Laux, C Guanci, MM Figueroa, SA Brophy, GM Kurczewski, L Livesay, SL AF Bader, Mary Kay Wavra, Teresa Laux, Chris Guanci, Mary McKenna Figueroa, Stephen A. Brophy, Gretchen M. Kurczewski, Lisa Livesay, Sarah L. TI Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Article ID TRAUMATIC BRAIN-INJURY; CARDIAC-ARREST; MODERATE HYPOTHERMIA; SHIVERING THRESHOLD; MILD HYPOTHERMIA; NORMOTHERMIA; METAANALYSIS; INDUCTION; REDUCE; HEAD C1 [Bader, Mary Kay; Wavra, Teresa] Mission Hosp, Mission Viejo, CA 92691 USA. [Laux, Chris] Univ Washington, Harborview Med Ctr, Operat Manager Cardiac Serv, Seattle, WA 98104 USA. [Guanci, Mary McKenna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Figueroa, Stephen A.] Univ Texas SW Med Ctr Dallas, Div Neurocrit Care, Dallas, TX 75390 USA. [Brophy, Gretchen M.] Virginia Commonwealth Univ, Pharmacotherapy & Outcomes Sci & Neurosurg, Richmond, VA USA. [Kurczewski, Lisa] Virginia Commonwealth Univ Hlth Syst, Dept Pharm Serv, Crit Care, Richmond, VA USA. [Livesay, Sarah L.] Rush Univ, Coll Nursing, Chicago, IL 60612 USA. RP Bader, MK (reprint author), Mission Hosp, Mission Viejo, CA 92691 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD SEP 1 PY 2015 VL 5 IS 3 BP 177 EP 181 DI 10.1089/ther.2015.29002.mkb PG 5 WC Critical Care Medicine SC General & Internal Medicine GA CR1UC UT WOS:000361109600011 ER PT J AU Calabrese, R Gerami-Naini, B Maione, AG Smith, AE Carpinito, G Tomic-Canic, M Veves, A Mooney, DJ Garlick, JA AF Calabrese, R. Gerami-Naini, B. Maione, A. G. Smith, A. E. Carpinito, G. Tomic-Canic, M. Veves, A. Mooney, D. J. Garlick, J. A. TI Reprogramming Diabetic Foot Ulcer-Derived Fibroblasts to Restore Regenerative Potential: From iPSCs to Bioengineered 3D Tissues SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Calabrese, R.; Gerami-Naini, B.; Maione, A. G.; Smith, A. E.; Carpinito, G.; Garlick, J. A.] Tufts Dent Sch Med, Dept Oral & Maxillofacial Pathol Oral Med & Crani, Boston, MA USA. [Tomic-Canic, M.] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Miami, FL 33136 USA. [Veves, A.] Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. [Veves, A.] Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Mooney, D. J.] Harvard Univ, Sch Engn & Appl Sci, Boston, MA 02115 USA. 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S86 EP S86 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205200338 ER PT J AU Du, D Liu, Z Niu, W Weng, D Lim, TC Wang, L Kurisawa, M Spector, M AF Du, D. Liu, Z. Niu, W. Weng, D. Lim, T. C. Wang, L. Kurisawa, M. Spector, M. TI An Injectable Multifunctional Dual-Phase Microsphere-Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Du, D.; Liu, Z.; Niu, W.; Weng, D.; Lim, T. C.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Du, D.; Liu, Z.] Harbin Med Univ, Sino Russian Inst Hard Tissue Dev & Regenerat, Harbin, Peoples R China. [Lim, T. C.] MIT, Boston, MA USA. [Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 0 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S298 EP S298 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202258 ER PT J AU Frohlich, EM Prantil-Baun, R Alonso, J Arnaout, AM Charest, JL AF Frohlich, E. M. Prantil-Baun, R. Alonso, J. Arnaout, A. M. Charest, J. L. TI A Microphysiological 3D Model of the Renal Proximal Tubule to Evaluate Regenerative Therapies SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Frohlich, E. M.] Draper Lab, Micro Nano Syst Dev, Cambridge, MA USA. [Prantil-Baun, R.; Charest, J. L.] Draper Lab, Biomed Microsyst, Cambridge, MA USA. [Alonso, J.; Arnaout, A. M.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S27 EP S27 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205200099 ER PT J AU Gonzalez-Andrades, M Cruzat, A Mauris, J Alonso-Pastor, L Dohlman, C Argueso, P AF Gonzalez-Andrades, M. Cruzat, A. Mauris, J. Alonso-Pastor, L. Dohlman, C. Argueso, P. TI A Novel Human Epithelial In Vitro Wound Healing Assay for the Evaluation of Materials and Growth Factors Used in Corneal Tissue Engineering SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Gonzalez-Andrades, M.; Cruzat, A.; Dohlman, C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol, Boston, MA USA. [Mauris, J.; Argueso, P.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Alonso-Pastor, L.] MIT, Changing Places Res Grp, Media Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S203 EP S204 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201395 ER PT J AU Grottkau, BE Pang, Y AF Grottkau, B. E. Pang, Y. TI Stem Cell Transplantation into Epiphysis of Piglet Perthes' Model Promoted Restoration of Femoral Head Sphericity SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Grottkau, B. E.; Pang, Y.] Massachusetts Gen Hosp, Orthopaed, Boston, MA 02114 USA. NR 0 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S37 EP S37 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205200140 ER PT J AU Hahn, S Yang, J Yeom, J Choi, M Yun, S AF Hahn, S. Yang, J. Yeom, J. Choi, M. Yun, S. TI Bioengineered Cell-Based Sensing and Therapy using Smart Hydrogels SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Hahn, S.; Yang, J.; Yeom, J.] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang, South Korea. [Choi, M.; Yun, S.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA USA. [Choi, M.; Yun, S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S54 EP S55 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205200210 ER PT J AU Kim, D AF Kim, D. TI A 3d Human Neural Cell Culture System for Modeling Alzheimer's Disease SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Kim, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S78 EP S78 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205200304 ER PT J AU Kim, S Lee, S Choi, H AF Kim, S. Lee, S. Choi, H. TI Noninvasive Trafficking of Scaffold Degradation and Tissue Regeneration SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Kim, S.; Lee, S.] WFIRM, Winston Salem, NC USA. [Choi, H.] BIDMC, Boston, MA USA. 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S356 EP S356 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202487 ER PT J AU Lee, J Parekkadan, B AF Lee, J. Parekkadan, B. TI Implantable Microenvironments for Studying Human Tumor Metastasis SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Lee, J.] Univ Massachusetts, Inst Appl Life Sci, Dept Chem Engn, Amherst, MA 01003 USA. [Parekkadan, B.] Massachusetts Gen Hosp, Ctr Engn Med, Dept Surg, Boston, MA 02114 USA. [Parekkadan, B.] Shriners Hosp Children, Boston, MA USA. [Parekkadan, B.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S223 EP S223 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201472 ER PT J AU Lim, T Mandeville, E Weng, D Wang, L Kurisawa, M Leite-Morris, K Lo, E Spector, M AF Lim, T. Mandeville, E. Weng, D. Wang, L. Kurisawa, M. Leite-Morris, K. Lo, E. Spector, M. TI Injectable Gelatin Matrix to Enable Reconstruction of Deep Brain Lesion Cavity with Endogenous Neural Stem Cells SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Lim, T.] MIT, Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lim, T.; Weng, D.; Spector, M.] VA Boston Healthcare Syst, Tissue Engn Lab, Boston, MA USA. [Mandeville, E.; Lo, E.] Massachusetts Gen Hosp, Neurol & Radiol, Boston, MA 02114 USA. [Weng, D.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. [Leite-Morris, K.] VA Boston Healthcare Syst, Neuropharmacol Lab, Boston, MA USA. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S298 EP S298 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202257 ER PT J AU Ma, D Yao, Y Hui, Z Pang, Y Grottkau, BE AF Ma, D. Yao, Y. Hui, Z. Pang, Y. Grottkau, B. E. TI 3D Bioprinting Malignant Tumor Micro-tissues for Cancer Research SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Ma, D.; Yao, Y.; Hui, Z.; Pang, Y.; Grottkau, B. E.] Massachusetts Gen Hosp, Orthopaed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S214 EP S214 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201436 ER PT J AU Mishra, R Roux, BM Posukonis, M Bodamer, E Brey, EM Fisher, JP Dean, D AF Mishra, R. Roux, B. M. Posukonis, M. Bodamer, E. Brey, E. M. Fisher, J. P. Dean, D. TI Effect of HUVEC/hMSC Pre-culture on Vascularization of Fibrin-Loaded Poly(propylene Fumarate) Scaffolds In Vitro and In Vivo SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Mishra, R.; Posukonis, M.; Bodamer, E.; Dean, D.] Ohio State Univ, Plast Surg, Columbus, OH 43210 USA. [Roux, B. M.; Brey, E. M.] IIT, Biomed Engn, Chicago, IL 60616 USA. [Roux, B. M.; Brey, E. M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Fisher, J. P.] Univ Maryland, Bioengn, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 5 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S361 EP S361 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202506 ER PT J AU Niu, W Weng, D Alshihri, AA Lim, T Wang, L Kurisawa, M Spector, M AF Niu, W. Weng, D. Alshihri, A. A. Lim, T. Wang, L. Kurisawa, M. Spector, M. TI Behavior of Bone Marrow Mesenchymal Stem Cells in Injectable Gelatin-Hyaluronan Matrices SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Niu, W.; Weng, D.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Alshihri, A. A.] Harvard Univ, Sch Dent Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Alshihri, A. A.] King Saud Univ, Riyadh, Saudi Arabia. [Lim, T.] MIT, VA Boston Healthcare Syst, Boston, MA USA. [Lim, T.; Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 0 TC 0 Z9 0 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S308 EP S308 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202296 ER PT J AU Niu, W Kong, Q Weng, D Wang, L Kurisawa, M Spector, M AF Niu, W. Kong, Q. Weng, D. Wang, L. Kurisawa, M. Spector, M. TI Fibroblast Behavior in an Injectable Covalently Cross-Linkable Gelatin Matrix Incorporating Select Growth Factors SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Niu, W.; Kong, Q.; Weng, D.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Kong, Q.] West China Hosp, Chengdu, Peoples R China. [Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 1 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S290 EP S290 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202227 ER PT J AU Rajappa, R Rokkappanavar, S Wang, L Kurisawa, M Spector, M AF Rajappa, R. Rokkappanavar, S. Wang, L. Kurisawa, M. Spector, M. TI PDGF-BB-Loaded Injectable Gelatin Matrix in Conjunction with Extracorporeal Shock Waves for Periodontal Tissue Regeneration: In-eVitro Assessment SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Rajappa, R.; Rokkappanavar, S.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S411 EP S411 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202709 ER PT J AU Randolph, M Edwards, S Meppelink, A Gill, TJ AF Randolph, M. Edwards, S. Meppelink, A. Gill, T. J. TI Meniscal Regeneration using a Bovine Dermal Collagen Matrix SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Randolph, M.; Edwards, S.; Meppelink, A.] Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Boston, MA 02114 USA. [Gill, T. J.] Harvard Univ, Sch Med, Boston, MA USA. 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S224 EP S225 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201478 ER PT J AU Roux, BM Gandhi, JK Brey, EM AF Roux, B. M. Gandhi, J. K. Brey, E. M. TI Evaluation of MSC Source on Angiogenesis in 3D Co-Culture SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Roux, B. M.; Gandhi, J. K.; Brey, E. M.] IIT, Biomed Engn, Chicago, IL 60616 USA. [Roux, B. M.; Gandhi, J. K.; Brey, E. M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 3 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S156 EP S157 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201212 ER PT J AU Wang, Y Ortega-Martinez, A Gutierrez-Herrera, E Farinelli, WA Doukas, AG Anderson, RR Franco, W AF Wang, Y. Ortega-Martinez, A. Gutierrez-Herrera, E. Farinelli, W. A. Doukas, A. G. Anderson, R. R. Franco, W. TI A Non-contact Wide Field Method to Evaluate Epithelialization: UV Fluorescence Excitation Imaging SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Wang, Y.; Ortega-Martinez, A.; Farinelli, W. A.; Doukas, A. G.; Anderson, R. R.; Franco, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. [Gutierrez-Herrera, E.] Univ Nacl Autonoma Mexico, Ctr Ciencias Aplicadas & Desarrollo Tecnol, Mexico City 04510, DF, Mexico. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S374 EP S375 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202559 ER PT J AU Weng, D Niu, W Du, D Wang, L Kurisawa, M Spector, M AF Weng, D. Niu, W. Du, D. Wang, L. Kurisawa, M. Spector, M. TI Physical Properties of Enzymatically Cross-Linked Injectable Gelatin Matrices SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Weng, D.; Niu, W.; Du, D.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Weng, D.; Niu, W.; Du, D.; Spector, M.] VA Boston Healthcare Syst, Boston, MA USA. [Du, D.] Harbin Med Univ, Orthoped Surg, Harbin, Peoples R China. [Wang, L.; Kurisawa, M.] Inst Bioengn & Nanotechnol, Singapore, Singapore. RI KURISAWA, MOTOICHI/C-1325-2014 OI KURISAWA, MOTOICHI/0000-0003-2413-6933 NR 0 TC 0 Z9 0 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S324 EP S325 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202361 ER PT J AU Yao, Y Hui, Z Ma, D Grottkau, BE Pang, Y AF Yao, Y. Hui, Z. Ma, D. Grottkau, B. E. Pang, Y. TI A Novel 3D Bioprinted Angiogenesis System for High-throughput Screening SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Yao, Y.; Hui, Z.; Ma, D.; Grottkau, B. E.; Pang, Y.] Massachusetts Gen Hosp, Orthopaed, Boston, MA 02114 USA. NR 0 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S321 EP S321 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202347 ER PT J AU Knowlton, S Onal, S Yu, CH Zhao, JJ Tasoglu, S AF Knowlton, Stephanie Onal, Sevgi Yu, Chu Hsiang Zhao, Jean J. Tasoglu, Savas TI Bioprinting for cancer research SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID LAYER-BY-LAYER; MICROSCALE HYDROGELS; IN-VITRO; FREEFORM FABRICATION; TISSUE CONSTRUCTS; PROSTATE-CANCER; CELL-MIGRATION; LIVING CELLS; TUMOR; SCAFFOLDS AB Bioprinting offers the ability to create highly complex 3D architectures with living cells. This cutting-edge technique has significantly gained popularity and applicability in several fields. Bioprinting methods have been developed to effectively and rapidly pattern living cells, biological macromolecules, and biomaterials. These technologies hold great potential for applications in cancer research. Bioprinted cancer models represent a significant improvement over previous 2D models by mimicking 3D complexity and facilitating physiologically relevant cell-cell and cell-matrix interactions. Here we review bioprinting methods based on inkjet, microextrusion, and laser technologies and compare 3D cancer models with 2D cancer models. We discuss bioprinted models that mimic the tumor microenvironment, providing a platform for deeper understanding of cancer pathology, anticancer drug screening, and cancer treatment development. C1 [Knowlton, Stephanie; Onal, Sevgi; Tasoglu, Savas] Univ Connecticut, Dept Biomed Engn, Storrs, CT 06269 USA. [Yu, Chu Hsiang; Tasoglu, Savas] Univ Connecticut, Dept Mech Engn, Storrs, CT 06269 USA. [Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhao, Jean J.] Dana Farber Canc Inst, Canc Biol, Boston, MA 02215 USA. RP Tasoglu, S (reprint author), Univ Connecticut, Dept Biomed Engn, 260 Glenbrook Rd, Storrs, CT 06269 USA. EM savas@engr.uconn.edu FU UConn Research Excellence Program Award FX S.T. acknowledges the UConn Research Excellence Program Award. NR 89 TC 26 Z9 27 U1 13 U2 75 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD SEP PY 2015 VL 33 IS 9 BP 504 EP 513 DI 10.1016/j.tibtech.2015.06.007 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CQ9RH UT WOS:000360952200004 PM 26216543 ER PT J AU Curreri, SA Fung, C Beard, CJ AF Curreri, Stephanie A. Fung, Chunkit Beard, Clair J. TI Secondary malignant neoplasms in testicular cancer survivors SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Testicular cancer; Radiation therapy; Chemotherapy; Diagnostic imaging; Second cancer ID COMPUTED-TOMOGRAPHY; 2ND MALIGNANCIES; CHEMOTHERAPY; RISK; RADIATION; PLATINUM; SEMINOMA; TUMORS; SURVEILLANCE; CISPLATIN AB Background: Testicular cancer is the most common cancer among men aged 15 to 40 years, and the incidence of testicular cancer is steadily increasing. Despite successful treatment outcomes and the rate of survival at 5 to 10 years being 95%, survivors can experience late effects of both their cancer and the treatment they received, including secondary malignant neoplasms (SMNs). We discuss the development of non germ cell SMNs that develop after diagnosis and treatment of testicular cancer and their effect on mortality. Results: Patients diagnosed with testicular cancer frequently choose postoperative surveillance if they are diagnosed with clinical stage I disease. These patients may experience an increased risk for developing SMNs following radiation exposure from diagnostic imaging. Similarly. radiotherapy for testicular cancer is associated with increased risks of developing both solid tumors and leukemia. Studies have reported that patients exposed to higher doses of radiation have an increased risk of developing SMNs when compared with patients who received lower doses of radiation. Patients treated with chemotherapy also experience an increased risk of developing SMNs following testicular cancer. though the risk following chemotherapy and radiation therapy combined is not well described. A large population-based study concluded that the rate ratios for both cancer-specific and all-cause mortality for SMNs among testicular cancer survivors were not significantly different from those of matched first cancers. Conclusions: Although it is known that patients who receive adjuvant chemotherapy or radiotherapy or who undergo routine diagnostic or follow-up imaging for a primary testicular cancer are at an increased risk for developing SMNs, the extent of this risk is largely unknown. It is critically important that research be conducted to determine this risk and its contributing factors as accurately as possible. (C) 2015 Elsevier Inc. All rights reserved. C1 [Curreri, Stephanie A.; Beard, Clair J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fung, Chunkit] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Curreri, SA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM scurreri@lroc.harvard.edu OI Lynch, Stephanie/0000-0002-2200-1579 NR 31 TC 1 Z9 1 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD SEP PY 2015 VL 33 IS 9 BP 392 EP 398 DI 10.1016/j.urolonc.2015.05.002 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CR0TV UT WOS:000361037000024 PM 26072728 ER PT J AU Preston, MA Feldman, AS Coen, JJ McDougal, WS Smith, MR Paly, JJ Carrasquillo, R Wu, CL Dahl, DM Barrisford, GW Blute, ML Zietman, AI AF Preston, Mark A. Feldman, Adam S. Coen, John J. McDougal, W. Scott Smith, Matthew R. Paly, Jonathan J. Carrasquillo, Robert Wu, Chin-Lee Dahl, Douglas M. Barrisford, Glen W. Blute, Michael L. Zietman, Anthony I. TI Active surveillance for low-risk prostate cancer: Need for intervention and survival at 10 years SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancel; Active surveillance; Survival; Intervention ID OVERDIAGNOSIS; EXPERIENCE; MORTALITY; SELECTION; TRIGGERS; OUTCOMES; BIOPSY; PSA AB Introduction: To describe the need for treatment and cancer-specific and overall survival in a contemporary active surveillance (AS) cohort. Patients and methods: Historical cohort study of men diagnosed with localized prostate cancer between 1997 and 2009 and managed with AS at a tertiary care center. Inclusion criteria were Gleason score <= 6 (Gleason score of 7 in select patients), <= 3/12 cores positive, and prostate-specific antigen (PSA) level <20 ng/ml. Survival analyses were conducted using the Kaplan-Meier method. Results: A total of 469 men with median age at diagnosis of 68.1 years (interquartile range [IQR]: 62.5-73.4) were followed up for a median of 4.8 years (IQR: 3.4-7.3). Median PSA level at diagnosis was 5.1 ng/ml (IQR: 4.0-6.9), with 94% of them having PSA level <10 ng/ml. Overall, 98.3% (461/469) of patients had a Gleason score of 6 and 1.7% (8/469) had a Gleason score of 3 + 4 = 7, and 94.0% (441/469) had T1c stage disease. Freedom from treatment was 77% at 5 years and 62% at 10 years. A total of 116 (24.7%) patients received treatment during the course of surveillance. Reasons for treatment included 44.8% (52/116) for pathologic reclassification, 30.2% (35/116) for PSA progression, 12.1% (14/116) for patient preference, 5.2% (6/116) for digital rectal examination progression, and 4.3% (5/116) for metastatic disease. Of the patients treated, 59 (50.1%) received radiation, 26 (22.4%) underwent surgery, 17 (14.7%) received brachytherapy, and 14 (12.1%) received androgen-deprivation therapy. Cancer-specific survival was 100% at 5 and 10 years. Overall survival was 95% at 5 years and 88% at 10 years. Conclusion: In a contemporary cohort of men with low-risk prostate cancer. AS allowed avoidance of treatment most of them. Common reasons for change in management were Gleason upgrading and volume progression on prostate rebiopsy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Preston, Mark A.] Brigham & Womens Hosp, Dept Surg, Div Urol, Boston, MA 02115 USA. [Feldman, Adam S.; McDougal, W. Scott; Wu, Chin-Lee; Dahl, Douglas M.; Barrisford, Glen W.; Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Coen, John J.; Paly, Jonathan J.; Zietman, Anthony I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Carrasquillo, Robert] Boston Med Ctr, Dept Urol, Boston, MA USA. RP Feldman, AS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM afeldman@partners.org FU Prostate Cancer Foundation Young Investigator Award; Department of Defense Prostate Cancer Research Program Physician Research Training Award [W81XWH-13-1-0328] FX This work was in part funded by the Prostate Cancer Foundation Young Investigator Award (A.S.F.) and the Department of Defense Prostate Cancer Research Program Physician Research Training Award, Award no. W81XWH-13-1-0328 (A.S.F.). NR 29 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD SEP PY 2015 VL 33 IS 9 DI 10.1016/j.urolonc.2015.04.015 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CR0TV UT WOS:000361037000004 ER PT J AU Chou, LB Lerner, LB Harris, AHS Brandon, AJ Girod, S Butler, LM AF Chou, Loretta B. Lerner, Lori B. Harris, Alex H. S. Brandon, Ashley J. Girod, Sabine Butler, Lesley M. TI Cancer Prevalence among a Cross-sectional Survey of Female Orthopedic, Urology, and Plastic Surgeons in the United States SO WOMENS HEALTH ISSUES LA English DT Article ID US RADIOLOGIC TECHNOLOGISTS; C-ARM FLUOROSCOPY; RADIATION-EXPOSURE; BREAST-CANCER; MEDICAL RADIATION; RISK; CARCINOGENS; MORTALITY; WOMEN AB Background: Exposure to ionizing radiation from fluoroscopy performed during surgery, although low and within established limits, remains a health concern among surgeons. Estimates of breast cancer prevalence among women across surgery specialties with different patterns of fluoroscopy use are needed to evaluate this concern. Methods: Female U.S. surgeons in urology, plastics, and orthopedics were identified using national directories and mailed surveys to collect information on occupational and medical history, including cancer diagnoses. Standardized prevalence ratios (SPRs) and 95% CIs were calculated by dividing the observed number of cancers among female surgeons in each specialty by the expected number, based on the gender-specific, age-specific, and race-specific cancer prevalence statistics in the general U.S. population. Results: Standard fluoroscopy use more than once per week was common among urologists (54%) and orthopedists (37%); the same frequency of mini fluoroscopy use was only common among orthopedics (31%) and hardly ever used by urologists. Plastic surgeons reported very infrequent use of any fluoroscopy. For orthopedic surgeons, a significantly greater than expected prevalence of any cancer (SPR, 1.85; 95% CI, 1.19-2.76) and breast cancer (SPR, 2.90; 95% CI, 1.66-4.71) were observed. There was no difference between the observed and expected prevalence of any cancer or breast cancer for urology or plastics. Conclusions: Using the first available cancer prevalence data comparing female surgeons across three specialties, we report that orthopedic surgeons have a greater than expected prevalence of cancer that may or may not be owing to occupational exposure to ionizing radiation. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Chou, Loretta B.; Harris, Alex H. S.] Stanford Sch Med, Dept Orthopaed Surg, Redwood City, CA 94063 USA. [Lerner, Lori B.; Brandon, Ashley J.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Girod, Sabine] Stanford Univ, Dept Oral Med & Maxillofacial Surg, Palo Alto, CA 94304 USA. [Butler, Lesley M.] Univ Pittsburgh, Inst Canc, Div Canc Control & Populat Sci, Pittsburgh, PA USA. [Butler, Lesley M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Chou, LB (reprint author), Stanford Sch Med, Dept Orthopaed Surg, 450 Broadway St, Redwood City, CA 94063 USA. EM lchou@stanford.edu NR 33 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2015 VL 25 IS 5 BP 476 EP 481 DI 10.1016/j.whi.2015.05.005 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CR1CM UT WOS:000361060400009 PM 26265543 ER PT J AU Saadi, A Bond, BE Percac-Lima, S AF Saadi, Altaf Bond, Barbara E. Percac-Lima, Sanja TI Bosnian, Iraqi, and Somali Refugee Women Speak: A Comparative Qualitative Study of Refugee Health Beliefs on Preventive Health and Breast Cancer Screening SO WOMENS HEALTH ISSUES LA English DT Article ID AFRICAN-AMERICANS VIEWS; IMMIGRANT WOMEN; UNITED-STATES; CARE; DISPARITIES; BARRIERS; TRUSTWORTHINESS; ETHNICITY; ATTITUDES; SURVIVAL AB Introduction: The low uptake of preventive services in disadvantaged communities is a continuing challenge to public health. Women refugee communities are particularly vulnerable populations, and disparities in both preventive care and breast cancer screening have been documented sparsely. The objective of this qualitative study was to explore Bosnian, Iraqi, and Somali women refugees' beliefs about preventive care and breast cancer screening to inform future community interventions and best practices. Methods: In an urban community health center, 57 interviews with Bosnian, Somali, and Iraqi women refugees were conducted by native language speakers. Interview transcripts were coded and analyzed according to best practices for thematic and content analysis. The responses of three groups were compared. Findings: Similarities across participants included barriers to care such as fear of pain and diagnosis, modesty, and work and childcare commitments; facilitative factors such as outreach efforts, appointment reminders, and personal contact from health providers; perceptions of how the American medical infrastructure compared with inadequacies in their home countries; and positive attitude toward U.S. health professionals. Differences that emerged among groups were: varying degrees of medical exposure to doctors in home countries, the impact of war on health systems; and understanding preventive breast care. Conclusion: Taken together, duration of time in United States and prior exposure to Western medicine account for differences in refugee women's knowledge of preventive care. Understanding population-specific health beliefs, health information, and behavior are crucial for designing tailored prevention programs for refugee women. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Saadi, Altaf] Massachusetts Gen Hosp, Partners Neurol Residency, Boston, MA 02114 USA. [Saadi, Altaf] Brigham & Womans Hosp, Boston, MA USA. [Bond, Barbara E.] Bridgewater State Univ, Sch Social Work, Bridgewater, MA USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Chelsea, MA USA. RP Saadi, A (reprint author), Massachusetts Gen Hosp, Partners Neurol Residency, 55 Fruit St, Boston, MA 02114 USA. EM asaadi@partners.org FU Susan G. Komen MA Affiliate foundation; MGH Center for Community Health Improvement; Cancer Control Career Development Award for Primary Care Physicians from the American Cancer Society [CCCDAA-14-012-01-CCCDA]; Lazarex Cancer Foundation FX Funding: This work was funded by Susan G. Komen MA Affiliate foundation and MGH Center for Community Health Improvement. Dr. Percac-Lima is supported in part by Cancer Control Career Development Award for Primary Care Physicians, CCCDAA-14-012-01-CCCDA from the American Cancer Society and in part by grant from Lazarex Cancer Foundation. NR 39 TC 0 Z9 0 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2015 VL 25 IS 5 BP 501 EP 508 DI 10.1016/j.whi.2015.06.005 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CR1CM UT WOS:000361060400012 PM 26219676 ER PT J AU Lehavot, K O'Hara, R Washington, DL Yano, EM Simpson, TL AF Lehavot, Keren O'Hara, Ruth Washington, Donna L. Yano, Elizabeth M. Simpson, Tracy L. TI Posttraumatic Stress Disorder Symptom Severity and Socioeconomic Factors Associated with Veterans Health Administration Use among Women Veterans SO WOMENS HEALTH ISSUES LA English DT Article ID FEMALE VETERANS; PTSD RISK; CARE; VALIDITY; SAMPLE; RELIABILITY; DEPRESSION; PROJECT; NEED AB Background: The Veterans Health Administration (VA) has historically focused on treating men. Although women veterans' VA use is increasing, they remain more likely than male veterans to receive their care in non-VA settings. To date, there is limited research on factors associated with VA use among women. We examined the relationship between demographic, civilian, military, and health-related variables with past-year VA use among women veterans. Methods: Women veterans were recruited over the internet to participate in an anonymous national survey (n = 617) in 2013. An empirically derived decision tree was computed using signal detection software for iterative receiver operator characteristics (ROC) to identify variables with the best sensitivity/specificity balance associated with past-year VA use. Results: ROC analysis indicated that 85% of participants with high posttraumatic stress disorder (PTSD) and depressive symptoms and who were younger than 54 years of age used VA in the past year. Of those who were 54 years of age or older and had very high PTSD symptoms, 94% used the VA in the last year. By contrast, only 40% of participants with relatively lower PTSD symptoms had VA past-year use, although among these individuals, VA past-year use increased to 65% for those with a relatively lower income. Conclusions: Findings suggest that greater PTSD symptoms, depressive symptoms, and low income correlate with VA use, with very high PTSD symptoms in older groups, high PTSD symptoms coupled with high depressive symptoms in younger groups, and low income in those with lower PTSD symptoms each associated with greater past-year VA use. Ensuring PTSD assessment and treatment, and addressing socioeconomic factors, may be key strategies for health care delivered directly or through contract with VA facilities. Published by Elsevier Inc. C1 [Lehavot, Keren] VA Puget Sound Hlth Care Syst, HSR&D, Ctr Innovat COIN, Seattle, WA 98108 USA. [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98108 USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [O'Hara, Ruth] Palo Alto VA Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. [O'Hara, Ruth] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Washington, Donna L.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D, Ctr Study Healthcare Innovat Implementat & Policy, Sepulveda, CA USA. [Washington, Donna L.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA 98108 USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, 116-POC,1660 S Columbian Way, Seattle, WA 98108 USA. EM klehavot@uw.edu FU VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC); VA CSR&D Career Development Award [IK2 CX000867]; VA HSR&D Service Senior Research Career Scientist award [RCS 05-195] FX This research was supported by a research grant to Drs. Lehavot and Simpson from the VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC). Dr. Lehavot's effort was supported by a VA CSR&D Career Development Award (IK2 CX000867) and Dr. Yano's effort was supported by a VA HSR&D Service Senior Research Career Scientist award (Project # RCS 05-195). NR 40 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2015 VL 25 IS 5 BP 535 EP 541 DI 10.1016/j.whi.2015.05.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CR1CM UT WOS:000361060400016 PM 26123641 ER PT J AU Callegari, LS Borrero, S Reiber, GE Nelson, KM Zephyrin, L Sayre, GG Katon, JG AF Callegari, Lisa S. Borrero, Sonya Reiber, Gayle E. Nelson, Karin M. Zephyrin, Laurie Sayre, George G. Katon, Jodie G. TI Reproductive Life Planning in Primary Care: A Qualitative Study of Women Veterans' Perceptions SO WOMENS HEALTH ISSUES LA English DT Article ID SHARED DECISION-MAKING; VA HEALTH-CARE; UNITED-STATES; PRECONCEPTION HEALTH; PREFERENCES; RECOMMENDATIONS; CONTRACEPTION; EXPERIENCES; PREGNANCY; MILITARY AB Background: Women veterans using Veterans Administration (VA) health care have high rates of medical and mental health comorbidities, placing them at increased risk of poor outcomes from unplanned pregnancy. Reproductive life planning is a strategy recommended by the U.S. Centers of Disease Control and Prevention that could promote healthy pregnancies and reduce unplanned pregnancy in the VA. However, no data exist on women veterans' perceptions of reproductive life planning discussions. Methods: We trained six VA primary care physicians at two VA Women's Health Clinics to conduct reproductive life planning discussions with veterans aged 18 to 44 during primary care visits. After the visit, we performed semi-structured telephone interviews with consenting veterans to explore perceptions of 1) reproductive life planning content and 2) provider-patient communication in reproductive life planning discussions. Interviews were audio-recorded, transcribed, and analyzed using content analysis. Results: We interviewed 27 veterans with a mean age of 31 years (range, 22-42). Women veterans perceived generally reproductive life planning discussions as important opportunities to discuss reproductive goals with providers and to obtain new and relevant information about contraception, planning healthy pregnancies, and available VA reproductive health services. Perceptions of reproductive life planning content were influenced by women's pregnancy intentions. Perceptions related to provider-patient communication included preferences for provider-initiated discussions and nonjudgmental counseling that incorporates patients' values and preferences. Conclusions: Women veterans perceived reproductive life planning as valuable and important to their health. Reproductive life planning has the potential to enhance patient-centered delivery of reproductive health services in VA primary care. Published by Elsevier Inc. C1 [Callegari, Lisa S.; Reiber, Gayle E.; Nelson, Karin M.; Sayre, George G.; Katon, Jodie G.] Dept Vet Affairs VA Puget Sound Hlth Care Syst Hl, Seattle, WA USA. [Callegari, Lisa S.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Borrero, Sonya] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Reiber, Gayle E.; Nelson, Karin M.; Sayre, George G.; Katon, Jodie G.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Nelson, Karin M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Zephyrin, Laurie] Womens Hlth Serv, VA Off Patient Care Serv, Washington, DC USA. [Zephyrin, Laurie] NYU, Dept Obstet & Gynecol, Langone Sch Med, New York, NY 10016 USA. RP Callegari, LS (reprint author), VA Puget Sound Hlth Care Syst, Seattle HSR&D Ctr, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM lisa.callegari@va.gov FU Department of Veterans Affairs (VA) National Office of Patient Care Services, Office of Women's Health and Office of Public Health; VA Health Services Research and Development Postdoctoral Fellowship [TPM 61-041] FX The authors acknowledge Marie Lutton for her assistance with patient recruitment, interviewing, and data management. The authors also acknowledge the generous VA clinicians and veterans who donated their time to participate in the project. This study was supported by a quality improvement grant from the Department of Veterans Affairs (VA) National Office of Patient Care Services, Office of Women's Health and Office of Public Health. L.S.C. was supported by a VA Health Services Research and Development Postdoctoral Fellowship (TPM 61-041). NR 36 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2015 VL 25 IS 5 BP 548 EP 554 DI 10.1016/j.whi.2015.05.002 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CR1CM UT WOS:000361060400018 PM 26123640 ER PT J AU Dichter, ME Wagner, C Goldberg, EB Iverson, KM AF Dichter, Melissa E. Wagner, Clara Goldberg, Erica B. Iverson, Katherine M. TI Intimate Partner Violence Detection and Care in the Veterans Health Administration: Patient and Provider Perspectives SO WOMENS HEALTH ISSUES LA English DT Article ID WOMEN VETERANS; INTERVENTIONS; COMMUNICATION; DISCLOSURE; FRAMEWORK; SURVIVORS AB Background: Women veterans experience high rates of intimate partner violence (IPV), with associated negative health impacts. The Veterans Health Administration (VHA) has recently developed plans to implement routine IPV screening and provide IPV-related follow-up services for VHA patients. Previous research has examined barriers and facilitators to health care provider screening for IPV. The next step is to examine patients' disclosure of IPV experiences to health care providers and effective response to such disclosures. We sought to identify VHA patients' and providers' perspectives on how to facilitate effective IPV detection and care in VHA. Methods: We conducted semistructured, qualitative interviews with 25 female veteran patients and 15 VHA health care providers. We used an inductive approach to analyzing interview transcripts and identifying themes that constituted study findings. Results: Themes fell in to two broad categories: 1) barriers to disclosure and 2) barriers to an adequate response to disclosure and providing follow-up care. Barriers to disclosure of IPV to health care providers included lack of provider inquiry, lack of comfort, and concerns about the consequences of disclosure and lack of privacy. Patients and providers both indicated a need for expanded resources to respond to IPV in VHA. Conclusions: Findings support current plans for IPV program implementation in VHA and point to recommendations for practice and implications for further research. Published by Elsevier Inc. C1 [Dichter, Melissa E.; Wagner, Clara; Goldberg, Erica B.] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, VA Ctr Hlth Equ Res & Promot, 3900 Woodland Ave,Bldg 4100 Annex, Philadelphia, PA 19104 USA. EM Melissa.Dichter@va.gov FU Department of Veterans Affairs VISN 4 Center for Evaluation of Patient Aligned Care Teams [CEPACT 12-005]; Drs. Dichter's and Iverson's VA Health Services Research and Development (HSR&D) Career Development Awards [CDA 10-202, CDA 10-029] FX This research was supported by the Department of Veterans Affairs VISN 4 Center for Evaluation of Patient Aligned Care Teams (CEPACT 12-005; PI: Dichter) and as part of Drs. Dichter's and Iverson's VA Health Services Research and Development (HSR&D) Career Development Awards (Dichter: CDA 10-202; Iverson: CDA 10-029). NR 36 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2015 VL 25 IS 5 BP 555 EP 560 DI 10.1016/j.whi.2015.06.006 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CR1CM UT WOS:000361060400019 PM 26227208 ER PT J AU Maezawa, Y Paltser, G Tsui, H Cheung, R Wu, P Nicholas, AP Dosch, HM AF Maezawa, Y. Paltser, G. Tsui, H. Cheung, R. Wu, P. Nicholas, A. P. Dosch, H. -M. TI 2-Chloroacetamidine, a novel immunomodulator, suppresses antigen-induced mouse airway inflammation SO ALLERGY LA English DT Article DE animal model; asthma; protein citrullination; T cell ID PEPTIDYLARGININE-DEIMINASE; CITRULLINATED PROTEINS; T-CELLS; ASTHMA; PATHOGENESIS; INVOLVEMENT; EXPRESSION; APOPTOSIS; RESPONSES; FEATURES AB BackgroundCitrullination is a presently under-recognized posttranslational protein modification catalyzed by PAD enzymes. Immune responses to citrullinated neo-epitopes are identified in a growing number of inflammatory and autoimmune diseases. However, the involvement of hypercitrullination in the pathogenesis of bronchial asthma is still unknown. MethodsAs main experimental tool, we examined the effect of 2-chloroacetamidine (2CA), a PAD enzyme inhibitor, on OVA-immunized and airway-challenged BALB/c mice; a commonly used model of allergic airway inflammation. We also measured the effect of 2CA on exvivo lymphocytes and cell lines. ResultsIn vivo, 2CA dramatically suppressed lung tissue hypercitrullination, inflammatory cell recruitment, and airway-Th2 cytokine secretion. 2CA also suppressed systemic OVA-specific and total IgE production dramatically, effectively preventing de novo and diminishing established disease without measurably impacting general immunocompetence. In vitro, 2CA markedly inhibited the proliferation of mouse and human T cells with cell cycle block and apoptosis during a limited, postactivation phase. Conclusions2CA acts as narrow-spectrum immunosuppressant that selectively targets lymphocyte populations involved in active inflammatory tissue lesions. If hypercitrullination is generated in patients with asthma, 2CA may represent a novel disease modulator for human asthmatics/allergic diseases. C1 [Maezawa, Y.; Paltser, G.; Tsui, H.; Cheung, R.; Wu, P.; Dosch, H. -M.] Univ Toronto, Hosp Sick Children, Res Inst, Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. [Nicholas, A. P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, A. P.] Univ Alabama Birmingham, Ctr Neuroimmunol, Birmingham, AL USA. [Nicholas, A. P.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Dosch, HM (reprint author), Univ Toronto, Hosp Sick Children, NMH Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM michael.dosch@me.com NR 25 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2015 VL 70 IS 9 BP 1130 EP 1138 DI 10.1111/all.12651 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA CQ2QW UT WOS:000360447200011 PM 25969859 ER PT J AU Meara, JG Leather, AJM Hagander, L Alkire, BC Alonso, N Ameh, EA Bickler, SW Conteh, L Dare, AJ Davies, J Merisier, ED El-Halabi, S Farmer, PE Gawande, A Gillies, R Greenberg, SLM Grimes, CE Gruen, RL Ismail, EA Kamara, TB Lavy, C Lundeg, G Mkandawire, NC Raykar, NP Riesel, JN Rodas, E Rose, J Roy, N Shrime, MG Sullivan, R Verguet, S Watters, D Weiser, TG Wilson, IH Yamey, G Yip, W AF Meara, John G. Leather, Andrew J. M. Hagander, Lars Alkire, Blake C. Alonso, Nivaldo Ameh, Emmanuel A. Bickler, Stephen W. Conteh, Lesong Dare, Anna J. Davies, Justine Merisier, Eunice Derivois El-Halabi, Shenaaz Farmer, Paul E. Gawande, Atul Gillies, Rowan Greenberg, Sarah L. M. Grimes, Caris E. Gruen, Russell L. Ismail, Edna Adan Kamara, Thaim Buya Lavy, Chris Lundeg, Ganbold Mkandawire, Nyengo C. Raykar, Nakul P. Riesel, Johanna N. Rodas, Edgar Rose, John Roy, Nobhojit Shrime, Mark G. Sullivan, Richard Verguet, Stephane Watters, David Weiser, Thomas G. Wilson, Iain H. Yamey, Gavin Yip, Winnie TI Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article C1 [Meara, John G.; Greenberg, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Global Surg & Social Change,Dept Global H, Boston, MA 02163 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Otol & Laryngol, Boston, MA USA. [Meara, John G.; Greenberg, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Alkire, Blake C.] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Off Global Surg, Boston, MA USA. [Farmer, Paul E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Global Hlth & Social Med,Div Global Hlth Equ, Boston, MA USA. [Farmer, Paul E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Farmer, Paul E.] Partners Hlth, Boston, MA USA. [Gawande, Atul; Rose, John] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gawande, Atul] Harvard Univ, TH Chan Sch Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. [Raykar, Nakul P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, TH Chan Sch Publ Hlth, Boston, MA 02215 USA. [Riesel, Johanna N.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Verguet, Stephane] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Caris E.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Caris E.] Kings Coll London, London WC2R 2LS, England. [Conteh, Lesong] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Davies, Justine] The Lancet, London, England. [Sullivan, Richard] Kings Coll London, Kings Ctr Global Hlth, Kings Hlth Partners Integrated Canc Ctr, Inst Canc Policy, London WC2R 2LS, England. [Hagander, Lars] Lund Univ, Clin Sci Lund, Dept Pediat, Pediat Surg & Global Pediat, Lund, Sweden. [Alonso, Nivaldo] Univ Sao Paulo, Dept Plast Surg, Sao Paulo, Brazil. [Ameh, Emmanuel A.] Natl Hosp, Dept Surg, Div Peadiatr Surg, Abuja, Nigeria. [Bickler, Stephen W.] Rady Childrens Hosp, San Diego, CA USA. [Rose, John] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Merisier, Eunice Derivois] Dept Minist Hlth, Gressier, Ouest, Haiti. [El-Halabi, Shenaaz] Minist Hlth, Gaborone, Botswana. [Gillies, Rowan] Royal N Shore Hosp, St Leonards, NSW 2065, Australia. [Greenberg, Sarah L. M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gruen, Russell L.] Alfred Hosp, Melbourne, Vic, Australia. [Gruen, Russell L.] Monash Univ, Melbourne, Vic 3004, Australia. [Gruen, Russell L.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Watters, David] Royal Australasian Coll Surg, East Melbourne, Vic, Australia. [Watters, David] Deakin Univ, Melbourne, Vic, Australia. [Ismail, Edna Adan] Edna Adan Univ Hosp, Hargeisa, Somaliland, England. [Kamara, Thaim Buya] Connaught Hosp, Freetown, Sierra Leone. [Lavy, Chris] Univ Oxford, Dept Orthopaed Rheumatol & Musculoskeletal Sci, Oxford, England. [Yip, Winnie] Univ Oxford, Blavatnik Sch Govt, Oxford, England. [Lundeg, Ganbold] Mongolian Natl Univ Med Sci, Ulaanbaatar, Mongol Peo Rep. [Mkandawire, Nyengo C.] Univ Malawi, Coll Med, Dept Surg, Blantyre, Malawi. [Mkandawire, Nyengo C.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia. [Rodas, Edgar] Univ Cuenca, Cinterandes Fdn, Cuenca, Ecuador. [Rodas, Edgar] Univ Azuay, Cuenca, Ecuador. [Roy, Nobhojit] BARC Hosp, Bombay, Maharashtra, India. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Wilson, Iain H.] Royal Devon & Exeter Natl Hlth Serv Fdn Trust, Dept Anaesthesia, Exeter, Devon, England. [Yamey, Gavin] Univ Calif San Francisco, Global Hlth Grp, Evidence Policy Initiat, San Francisco, CA 94143 USA. RP Meara, JG (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Global Surg & Social Change,Dept Global H, Boston, MA 02163 USA. EM john.meara@childrens.harvard.edu NR 1 TC 0 Z9 0 U1 3 U2 7 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 SEP PY 2015 VL 213 IS 3 BP 338 EP 340 DI 10.1016/j.ajog.2015.04.010 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700011 PM 25985722 ER PT J AU Creanga, AA Bateman, BT Butwick, AJ Raleigh, L Maeda, A Kuklina, E Callaghan, WM AF Creanga, Andreea A. Bateman, Brian T. Butwick, Alexander J. Raleigh, Lindsay Maeda, Ayumi Kuklina, Elena Callaghan, William M. TI Morbidity associated with cesarean delivery in the United States: is placenta accreta an increasingly important contributor? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean delivery; United States ID MATERNAL MORBIDITY; ABNORMAL PLACENTATION; HYSTERECTOMY; COMPLICATIONS; MORTALITY; OUTCOMES; TERM AB OBJECTIVE: The purpose of this study was to examine cesarean delivery morbidity and its predictors in the United States. STUDY DESIGN: We used 2000-2011 Nationwide Inpatient Sample data to identify cesarean deliveries and records with 12 potential cesarean delivery complications, including placenta accreta. We estimated cesarean delivery morbidity rates and rate changes from 2000-2011, and fitted Poisson regression models to assess the relative incidence of morbidity among repeat vs primary cesarean deliveries and explore its predictors. RESULTS: From 2000-2011, 76 in 1000 cesarean deliveries (97 in 1000 primary and 48 in 1000 repeat cesarean deliveries) were accompanied by >= 1 of 12 complications. The unadjusted composite cesarean delivery morbidity rate increased by 3.6% only among women with a primary cesarean delivery (P < .001); the unadjusted rate of placenta accreta increased by 30.8% only among women with a repeat cesarean deliveries (P = .025). The adjusted rate of overall composite cesarean delivery morbidity decreased by 1% annually from 2000-2011 (P < .001). Compared with women with a primary cesarean delivery, those women who underwent a repeat cesarean delivery were one-half as likely (incidence rate ratio, 0.50; 95% CI, 0.49-0.50) to experience a complication, but 2.13 (95% CI, 1.98-2.29) times more likely to have a placenta accreta diagnosis. Both cesarean delivery morbidity and placenta accreta were positively associated with age >30 years, non-Hispanic black race/ethnicity, the presence of a chronic medical condition, and delivery in urban, teaching, or larger hospitals. CONCLUSION: Overall, cesarean delivery morbidity declined modestly from 2000-2011, but placenta accreta became an increasingly important contributor to repeat cesarean delivery morbidity. Clinicians should maintain a high index of suspicion for abnormal placentation and make adequate preparations for patients who need cesarean deliveries. C1 [Creanga, Andreea A.; Kuklina, Elena; Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30329 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.; Maeda, Ayumi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Butwick, Alexander J.; Raleigh, Lindsay] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. RP Creanga, AA (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30329 USA. EM acreanga@cdc.gov OI Butwick, Alexander/0000-0002-2048-0879 NR 29 TC 6 Z9 6 U1 0 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 SEP PY 2015 VL 213 IS 3 AR 384.e1 DI 10.1016/j.ajog.2015.05.002 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700027 PM 25957019 ER PT J AU Pilliod, RA Page, JM Burwick, RM Kaimal, AJ Cheng, YW Caughey, AB AF Pilliod, Rachel A. Page, Jessica M. Burwick, Richard M. Kaimal, Anjali J. Cheng, Yvonne W. Caughey, Aaron B. TI The risk of fetal death in nonanomalous pregnancies affected by polyhydramnios SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med DE antenatal testing; intrauterine fetal demise; polyhydramnios; stillbirth ID HYDRAMNIOS AB OBJECTIVE: The objective of the study was to evaluate the ongoing risk of intrauterine fetal demise (IUFD) in nonanomalous pregnancies affected by polyhydramnios. STUDY DESIGN: We analyzed a retrospective cohort of all singleton, nonanomalous births in California between 2005 and 2008 as recorded in a statewide birth certificate registry. We included all births between 24+0 and 41+6 weeks' gestational age, excluding multiple gestations, major congenital anomalies, and pregnancies affected by oligohydramnios. Polyhydramnios was identified by International Classification of Diseases, ninth revision, codes. chi(2) tests were used to compare the dichotomous outcomes, and multivariable logistic regression analyses were then performed to control for potential confounders. We analyzed the data for pregnancies affected and unaffected by polyhydramnios. The IUFD risk was expressed as a rate per 10,000. RESULTS: The risk of IUFD in pregnancies affected by polyhydramnios was greater at every gestational age compared with unaffected pregnancies. The IUFD risk in pregnancies affected by polyhydramnios was more than 7 times higher than unaffected pregnancies at 37 weeks at a rate of 18.0 (95% confidence interval [CI], 9.0-32.6) vs 2.4 (95% CI, 2.0-2.5) and was 11-fold higher by 40 weeks' gestational age at a rate of 66.3 (95% CI, 10.8-68.6) vs 6.0 (95% CI, 5.1-6.3) in unaffected pregnancies. When adjusted for multiple confounding variables, the presence of polyhydramnios remained associated with an increased odds of IUFD in nonanomalous singleton pregnancies, with an adjusted odds ratio of 5.5 (95% CI, 4.1-7.6). CONCLUSION: Ongoing risk of IUFD is greater in low-risk pregnancies affected by polyhydramnios at all gestational ages compared with unaffected pregnancies with the greatest increase in risk at term. Although further study is needed to explore the underlying etiology of polyhydramnios in these cases, the identification of polyhydramnios alone may warrant increased antenatal surveillance. C1 [Pilliod, Rachel A.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Page, Jessica M.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Burwick, Richard M.; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Portland, OR 97201 USA. [Cheng, Yvonne W.] Univ Calif Davis, Div Maternal Fetal Med, Dept Obstet & Gynecol, Sch Med, Sacramento, CA 95817 USA. RP Pilliod, RA (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rpilliod@partners.org NR 17 TC 1 Z9 1 U1 2 U2 6 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 SEP PY 2015 VL 213 IS 3 AR 410.e1 DI 10.1016/j.ajog.2015.05.022 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700041 PM 25981851 ER PT J AU Kao, CS Cornejo, KM Ulbright, TM Young, RH AF Kao, Chia-Sui Cornejo, Kristine M. Ulbright, Thomas M. Young, Robert H. TI Juvenile Granulosa Cell Tumors of the Testis A Clinicopathologic Study of 70 Cases With Emphasis on Its Wide Morphologic Spectrum SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; juvenile granulosa cell tumor; sex cord-stromal tumor; infants; immunohistochemistry ID CORD-STROMAL TUMORS; PREPUBERTAL TESTICULAR-TUMORS; CLINICAL BEHAVIOR; INFANTILE TESTIS; DIAGNOSIS; CHILDREN; REGISTRY; FOXL2; DIFFERENTIATION; MANAGEMENT AB The clinical and pathologic features of 70 juvenile granulosa cell tumors (JGCTs) of the testis are presented. The patients were from 30 weeks gestational age to 10 years old; 60 of 67 (90%) whose ages are known to us were 6 months old or younger. Sixty-two underwent gonadectomy, 6 wedge excision, and 2 only biopsy. Twenty-six tumors were left sided and 22 right sided. Six occurred in an undescended testis and 2 in dysgenetic gonads. The most common presentation was a testicular mass (65%), followed by an enlarging testis (25%). Six of 14 patients in whom it was measured had elevated serum -fetoprotein (AFP), likely physiologically, and 1 had gynecomastia. The tumors measured 0.5 to 5 cm (mean, 1.7 cm; median, 1.5 cm) and were most commonly well circumscribed and typically yellow-tan; approximately 2/3 had a cystic component, whereas 1/3 were entirely solid. Microscopic examination typically showed a lobular growth, punctuated in 67 cases by variably sized and shaped follicles containing material that was basophilic (21%), eosinophilic (44%), or of both characters (35%); 3 lacked follicles. In nonfollicular areas, the tumor cells typically grew diffusely but occasionally had a corded arrangement (26%) or reticular appearance (29%). The stroma was either fibrous or fibromyxoid; hemorrhage associated with hemosiderin-laden macrophages was focally seen in 16%. The tumor cells were mostly small to medium sized with round to oval nuclei containing inconspicuous nucleoli and moderate to abundant, but occasionally scant, pale to lightly eosinophilic, sometimes vacuolated, cytoplasm; nuclear grooves were infrequent (6%). Focal columnar morphology was seen in 27% of the tumors. Mitoses were plentiful in 37%, and apoptosis was prominent in 46%. Intratubular tumor was seen in 43% and entrapped seminiferous tubules in 70%. Lymphovascular invasion was present in 2 cases, rete testis involvement in 4, and necrosis in 1. Rare features/patterns included: regressed tumor with hyalinization and prominent blood vessels (13%), papillary growth (4%), basaloid morphology (1%), spindle cell predominance (1%), microcystic foci (1%), adult granulosa cell-like (1%) patterns, and hyaline globules (1%). Inhibin (16/18), calretinin (8/9), WT1 (6/7), FOXL2 (12/12), SF-1 (12/12), and SOX9 (6/11) were positive, whereas SALL4 and glypican-3 were consistently negative in the neoplastic granulosa cells. Only 1 of 10 tumors was focally positive for -fetoprotein. JGCT is a rare neoplasm with a wide morphologic spectrum that also occurs rarely in undescended testes and dysgenetic gonads. The solid and reticular patterns may pose diagnostic challenges, but the lobular appearance and follicular differentiation are characteristic. Immunohistochemical stains may aid in its distinction from other tumors of young male individuals, particularly yolk sac tumor, a neoplasm that peaks at a somewhat later age. Twenty-four patients with follow-up, including 4 of 6 patients treated with wedge resection/biopsy, had no evidence of disease (2 to 348 mo; mean, 83 mo; median, 61 mo). One additional patient was alive at 260 months, but the disease status is unknown. The benign clinical course of all cases of JGCT with follow-up, despite often frequent mitotic activity, supports testis sparing surgery when technically feasible. C1 [Kao, Chia-Sui; Cornejo, Kristine M.; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Kao, Chia-Sui; Cornejo, Kristine M.; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ulbright, Thomas M.] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 215, Boston, MA 02114 USA. EM rhyoung@partners.org NR 37 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2015 VL 39 IS 9 BP 1159 EP 1169 DI 10.1097/PAS.0000000000000450 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA CQ4QP UT WOS:000360590000001 PM 26076062 ER PT J AU Khor, TS Lauwers, GY Odze, RD Srivastava, A AF Khor, Tze S. Lauwers, Gregory Y. Odze, Robert D. Srivastava, Amitabh TI "Mass-forming" Variant of Ischemic Colitis Is A Distinct Entity With Predilection for the Proximal Colon SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ischemia; colon; colitis; carcinoma; malignancy ID CARCINOMA; PATTERNS; OUTCOMES; CANCER AB We systematically evaluated the clinicopathologic features and outcome of a rare, unusual variant of ischemic colitis that presents as a mass lesion mimicking malignancy on imaging or colonoscopy. A retrospective search was performed for cases with a histologic diagnosis of ischemic colitis and a clinical impression of malignancy. Of the 23 patients initially identified, 4 were excluded because clinical and histologic review showed mucosal prolapse (n=1), discrete colon polyp (n=2), and a diverticular mass (n=1) without concern for malignancy. The mass-forming variant of ischemic colitis (n=19) was seen predominantly in elderly (mean age 71.8 y) women (63.2%) with a striking predilection for the right colon (13/19), particularly the cecum (n=6). Abdominal pain (52.6%) and hematochezia (26.3%) were the most common presenting symptoms. A computed tomography scan showed segmental thickening suspicious for malignancy in 6/8 patients. Colonoscopy revealed an exophytic (n=16) or stricturing (n=3) mass with a mean size of 4.67 cm. Mucosal biopsies showed features typical for ischemic colitis in all cases. A colectomy was performed in 4 cases. In 2, the mass-like appearance was due to marked submucosal and mural edema, whereas in the other 2 cases, with a malignant stricture-like lesion, marked submucosal fibrosis and cholesterol emboli were present. No malignancy was identified on follow-up in any patient (mean 39.9 mo). Follow-up colonoscopy was performed in 7 patients 1 to 32 weeks after initial presentation and showed resolution of the mass in all cases. Awareness of this rare variant of ischemic colitis will prevent unnecessary resections in these patients. C1 [Khor, Tze S.] PathWest Lab Med, Dept Anat Pathol, Nedlands, WA, Australia. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Odze, Robert D.; Srivastava, Amitabh] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Srivastava, A (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM asrivastava@partners.org FU A&A Saw Medical Research Fellowship from the University of Western Australia, WA, Australia FX T.S.K. was supported by an A&A Saw Medical Research Fellowship from the University of Western Australia, WA, Australia. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 26 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2015 VL 39 IS 9 BP 1275 EP 1281 DI 10.1097/PAS.0000000000000438 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA CQ4QP UT WOS:000360590000014 PM 26034865 ER PT J AU Shih, A Lauwers, GY Balabaud, C Bioulac-Sage, P Misdraji, J AF Shih, Angela Lauwers, Gregory Y. Balabaud, Charles Bioulac-Sage, Paulette Misdraji, Joseph TI Simultaneous Occurrence of Focal Nodular Hyperplasia and HNF1A-inactivated Hepatocellular Adenoma A Collision Tumor Simulating a Composite FNH-HCA SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE liver; mixed tumor; collision tumor; focal nodular hyperplasia; hepatocellular adenoma ID ORAL-CONTRACEPTIVES; SUBTYPE CLASSIFICATION; GLUTAMINE-SYNTHETASE; LIVER ADENOMA; CARCINOMA; INACTIVATION; ASSOCIATION; EXPRESSION; VARIANT AB Mixed focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) within a single tumor mass is rarely reported, and most of these cases are examples of tumors with features intermediate between FNH and HCA. Although a few reported cases are probably examples of true mixed tumors, none was evaluated immunohistochemically or confirmed by molecular analysis. We report a mixed FNH and HCA arising in a woman with several HNF1A-inactivated adenomas. Our case is the first case of mixed FNH and HNF1A-inactivated HCA documented by immunohistochemistry. C1 [Shih, Angela; Lauwers, Gregory Y.; Misdraji, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Balabaud, Charles; Bioulac-Sage, Paulette] Univ Bordeaux, INSERM, U1053, Bordeaux, France. [Bioulac-Sage, Paulette] CHU Bordeaux, Pellegrin Hosp, Dept Pathol, Bordeaux, France. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 105, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 31 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2015 VL 39 IS 9 BP 1296 EP 1300 DI 10.1097/PAS.0000000000000477 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA CQ4QP UT WOS:000360590000017 PM 26274031 ER PT J AU Nanji, KC Orser, BA AF Nanji, Karen C. Orser, Beverley A. TI Managing Ebola: Lessons Learned from the SARS Epidemic SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Nanji, Karen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Dept Anaesth, Boston, MA 02115 USA. [Orser, Beverley A.] Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON M4N 3M5, Canada. [Orser, Beverley A.] Univ Toronto, Dept Anesthesia, Toronto, ON, Canada. RP Nanji, KC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Dept Anaesth, Boston, MA 02115 USA. EM knanji@partners.org NR 3 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2015 VL 121 IS 3 BP 834 EP 835 DI 10.1213/ANE.0000000000000748 PG 2 WC Anesthesiology SC Anesthesiology GA CQ1MA UT WOS:000360360600008 PM 26287305 ER PT J AU Zhang, Q Gray, PJ AF Zhang, Qing Gray, Phillip J. TI From bench to bedside: bipolar androgen therapy in a pilot clinical study SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID METASTATIC PROSTATE-CANCER; CASTRATION; ENZALUTAMIDE; CHEMOTHERAPY; RECEPTOR AB Prostate cancer remains a leading cause of cancer death in Europe and the United States and is an emerging problem in Asia despite significant improvements in available treatments over the last few decades. Androgen deprivation therapy (ADT) has been the core treatment of advance-staged disease since the discovery of prostate cancer's androgen dependence in 1941 by Huggins et al.(1) Options for initial medical treatment include gonadotropin-releasing hormone analogues such as leuprolide (LHRH agonist) and degarelix (LHRH antagonist) and androgen receptor (AR) binding agents such as bicalutamide. Although most patients will initially respond to either surgical or medical castration, there is almost always progression to castration-resistant prostate cancer (CRPC) necessitating treatment with more novel agents.(2) However, even drugs such as abiraterone and enzalutamide, two next-generation agents used commonly in metastatic CRPC, have failed to demonstrate persistent efficacy in most patients.(3,4) C1 [Zhang, Qing] Singapore Gen Hosp, Dept Internal Med, Singapore, Singapore. [Gray, Phillip J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Gray, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM pjgray@partners.org NR 13 TC 1 Z9 1 U1 1 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD SEP-OCT PY 2015 VL 17 IS 5 BP 767 EP 768 DI 10.4103/1008-682X.151390 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CQ5FN UT WOS:000360628800016 PM 25814159 ER PT J AU Zhao, JY An, Q Goldberg, J Quyyumi, AA Vaccarino, V AF Zhao, Jinying An, Qiang Goldberg, Jack Quyyumi, Arshed A. Vaccarino, Viola TI Promoter methylation of glucocorticoid receptor gene is associated with subclinical atherosclerosis: A monozygotic twin study SO ATHEROSCLEROSIS LA English DT Article DE DNA methylation; NR3C1; Subclinical atherosclerosis; Monozygotic twins ID SEROTONIN TRANSPORTER GENE; PITUITARY-ADRENAL AXIS; FLOW-MEDIATED DILATION; DNA METHYLATION; EPIGENETIC INHERITANCE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; BRACHIAL-ARTERY; HEART-DISEASE; RISK AB Objective: Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker of early atherosclerosis. Glucocorticoid receptor gene (NR3C1) regulates many biological processes, including stress response, behavioral, cardiometabolic and immunologic functions. Genetic variants in NR3C1 have been associated with atherosclerosis and related risk factors. This study investigated the association of NR3C1 promoter methylation with FMD, independent of genetic and family-level environmental factors. Methods: We studied 84 middle-aged, male-male monozygotic twin pairs recruited from the Vietnam Era Twin Registry. Brachial artery FMD was measured by ultrasound. DNA methylation levels at 22 CpG residues in the NR3C1 exon 1F promoter region were quantified by bisulfite pyrosequencing in genomic DNA isolated from peripheral blood leukocytes. Co-twin control analyses were conducted to examine the association of methylation variation with FMD, adjusting for smoking, physical activity, body mass index, lipids, blood pressure, fasting glucose, and depressive symptoms. Multiple testing was corrected using the false discovery rate. Results: Mean methylation level across the 22 studied CpG sites was 2.02%. Methylation alterations at 12 out of the 22 CpG residues were significantly associated with FMD. On average, a 1% increase in the intra-pair difference in mean DNA methylation was associated with 2.83% increase in the intra-pair difference in FMD (95% CI: 1.46-4.20; P < 0.0001) after adjusting for risk factors and multiple testing. Conclusion: Methylation variation in NR3C1 exon 1F promoter significantly influences subclinical atherosclerosis, independent of genetic, early family environmental and other risk factors. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Zhao, Jinying; An, Qiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [Goldberg, Jack] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Goldberg, Jack] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Quyyumi, Arshed A.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Vaccarino, Viola] Emory Univ, Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. RP Zhao, JY (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Suite 2000-SL18, New Orleans, LA 70112 USA. EM jzhao5@tulane.edu FU NIH [R01MH097018, R21HL092363, K01AG034259, K24HL077506, R01HL68630, R01AG026255]; United States Department of Veterans Affairs FX This study was supported by NIH grants R01MH097018, R21HL092363, and K01AG034259 (Dr. Zhao), and grants K24HL077506, R01HL68630 and R01AG026255 (Dr. Vaccarino).; The United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. Numerous organizations have provided invaluable assistance in the conduct of this study, including: Department of Defense; National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; National Institutes of Health; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University. Most importantly, the authors gratefully acknowledge the continued cooperation and participation of the members of the VET Registry and their families. Without their contribution this research would not have been possible. NR 48 TC 2 Z9 2 U1 0 U2 6 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 SEP PY 2015 VL 242 IS 1 BP 71 EP 76 DI 10.1016/j.atherosclerosis.2015.07.007 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900012 PM 26186654 ER PT J AU Quispe, R Manalac, RJ Faridi, KF Blaha, MJ Toth, PP Kulkarni, KR Nasir, K Virani, SS Banach, M Blumenthal, RS Martin, SS Jones, SR AF Quispe, Renato Manalac, Raoul J. Faridi, Kamil F. Blaha, Michael J. Toth, Peter P. Kulkarni, Krishnaji R. Nasir, Khurram Virani, Salim S. Banach, Maciej Blumenthal, Roger S. Martin, Seth S. Jones, Steven R. TI Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The Very Large Database of Lipids-4 (VLDL-4) study SO ATHEROSCLEROSIS LA English DT Article DE Triglycerides; High-density lipoprotein cholesterol; TG/HDL-C ratio; Lipids; Cut-off points; Remnant lipoprotein particle cholesterol ID CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; LOW-GRADE INFLAMMATION; HDL-CHOLESTEROL; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; POSTMENOPAUSAL WOMEN; REMNANT CHOLESTEROL; LDL-CHOLESTEROL; MYOCARDIAL-INFARCTION AB Background: High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. Objectives: We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. population. Methods: We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female). Results: The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C. Conclusions: In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Quispe, Renato; Manalac, Raoul J.; Faridi, Kamil F.; Blaha, Michael J.; Toth, Peter P.; Nasir, Khurram; Blumenthal, Roger S.; Martin, Seth S.; Jones, Steven R.] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21287 USA. [Toth, Peter P.] CGH Med Ctr, Dept Prevent Cardiol, Sterling, IL USA. [Toth, Peter P.] Univ Illinois, Coll Med, Peoria, IL 61656 USA. [Kulkarni, Krishnaji R.] Atherotech Diagnost Lab, Birmingham, AL USA. [Nasir, Khurram] Univ Miami, South Beach Prevent Cardiol Ctr, Miami, FL USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Banach, Maciej] Med Univ Lodz, Dept Hypertens, Lodz, Poland. RP Quispe, R (reprint author), Johns Hopkins Ciccarone Ctr Prevent Heart Dis, 600 N Wolfe St,Blalock 524-C, Baltimore, MD 21287 USA. EM jquispe1@jhmi.edu RI Banach, Maciej/A-1271-2009; OI Banach, Maciej/0000-0001-6690-6874; Virani, Salim/0000-0001-9541-6954 FU Atherotech FX Dr. Blaha served on an Advisory Board for Pfizer. Dr. Toth reports consulting for Amgen, AstraZeneca, Atherotech, GlaxoSmithKline, Kowa, Liposcience, and Merck; serving on the speakers bureau for Amarin, AstraZeneca, Genzyme, Kowa, Merck. Dr. Kulkarni is a research director at Atherotech Diagnostics Lab; owns uncashable stocks for Atherotech Diagnostics Labs; and receives modest royalties from the University of Alabama at Birmingham. Dr. Nasir served on an Advisory Board for Quest Diagnostic. Dr Jones reports serving on the medical advisory board for, and receiving grant funding from, Atherotech. Drs. Quispe, Manalac, Faridi, Virani, Banach, Blumenthal, and Martin have nothing to disclose. NR 60 TC 7 Z9 8 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2015 VL 242 IS 1 BP 243 EP 250 DI 10.1016/j.atherosclerosis.2015.06.057 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900039 PM 26232164 ER PT J AU Prudente, S Bailetti, D Mendonca, C Mannino, GC Fontana, A Andreozzi, F Hastings, T Mercuri, L Alberico, F Basile, G Copetti, M Sesti, G Doria, A Trischitta, V AF Prudente, Sabrina Bailetti, Diego Mendonca, Christine Mannino, Gaia Chiara Fontana, Andrea Andreozzi, Francesco Hastings, Timothy Mercuri, Luana Alberico, Federica Basile, Giorgio Copetti, Massimiliano Sesti, Giorgio Doria, Alessandro Trischitta, Vincenzo TI Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes SO ATHEROSCLEROSIS LA English DT Article DE Insulin sensitivity; Insulin signaling; Coronary artery disease; Type 2 diabetes mellitus; Infrequent variants ID INSULIN SIGNALING GENES; HUMAN ENDOTHELIAL-CELLS; OF-FUNCTION MUTATIONS; HEART-DISEASE; CARDIOVASCULAR EVENTS; GLUCOSE-HOMEOSTASIS; R84 VARIANT; RISK; ASSOCIATION; RESISTANCE AB Objective: Genes that modulate insulin sensitivity may also be involved in shaping the risk of coronary artery disease (CAD). The relatively common TRIB3 Q84R polymorphism (rs2295490) has been associated with abnormal insulin signaling, endothelial dysfunction, insulin resistance, and pro-atherogenic phenotypes. The aim of our study was to investigate the association between low-frequency TRIB3 coding variants and CAD in patients with type 2 diabetes (T2D). Methods: Three caseecontrol studies for CAD from Italy and US were analyzed, for a total of 1565 individuals, all with type 2 diabetes. Infrequent variants were identified by re-sequencing TRIB3 exons in 140 "extreme cases" and 140 "super-controls" and then genotyped in all study subjects. Results: TRIB3 infrequent variants (n = 8), considered according to a collapsing rare variants framework, were significantly associated with CAD in diabetic patients from Italy (n = 700, OR = 0.43, 95% CI 0.20-0.91; p = 0.027), but not from the US (n = 865, OR = 1.22, 95% CI 0.69-2.18; p = 0.49). In the Italian sets, the association was especially strong among individuals who also carried the common R84 variant. Conclusion: Although preliminary, our finding suggests a role of TRIB3 low-frequency variants on CAD among Italian patients with T2D. Further studies are needed to address the role of TRIB3 infrequent variants in other populations of both European and non-European ancestries. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Prudente, Sabrina; Bailetti, Diego; Mercuri, Luana; Alberico, Federica; Basile, Giorgio; Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza Mendel Lab, San Giovanni Rotondo, Italy. [Bailetti, Diego; Basile, Giorgio; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Mendonca, Christine; Mannino, Gaia Chiara; Hastings, Timothy; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Mannino, Gaia Chiara; Andreozzi, Francesco; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Catanzaro, Italy. [Fontana, Andrea; Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. RP Prudente, S (reprint author), CSS Mendel Inst, Viale Regina Margherita 261, I-00198 Rome, Italy. EM s.prudente@css-mendel.it; vincenzo.trischitta@uniroma1.it RI Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Mannino, Gaia/K-1580-2016; Copetti, Massimiliano/K-3186-2016; Fontana, Andrea/J-8584-2016; OI Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X; Mannino, Gaia/0000-0002-6341-4572; Copetti, Massimiliano/0000-0002-7960-5947; Fontana, Andrea/0000-0002-6660-5315; Andreozzi, Francesco/0000-0001-9375-1513 FU Italian Ministry of Health (Ricerca Corrente); National Institutes of Health [R01 HL073168, P30 DK036836]; European Union [279171-1 MEDIGENE] FX This work was supported by the Italian Ministry of Health (Ricerca Corrente 2014 and 2015 to SP and VT), the National Institutes of Health (grants R01 HL073168 to AD and P30 DK036836 to the Joslin Diabetes Research Center [Advanced Genomics and Genetics Core]) and the European Union (FP7 2007-2013, grant 279171-1 MEDIGENE to VT). NR 26 TC 2 Z9 2 U1 1 U2 4 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 SEP PY 2015 VL 242 IS 1 BP 334 EP 339 DI 10.1016/j.atherosclerosis.2015.07.030 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900052 PM 26253791 ER PT J AU Kim, E Zeng, DL Zhou, XH AF Kim, Eunhee Zeng, Donglin Zhou, Xiao-Hua TI Semiparametric transformation models for multiple continuous biomarkers in ROC analysis SO BIOMETRICAL JOURNAL LA English DT Article DE Biomarkers; ROC analysis; Nonparametric maximum likelihood estimation; Semiparametric efficiency; Transformation models ID OPERATING CHARACTERISTIC CURVE; MAXIMUM-LIKELIHOOD-ESTIMATION; CENSORED-DATA; EM ALGORITHM; INFERENCE; SUBJECT; MARKERS; CLASSIFICATION; DISEASE; LIMITS AB Recent technological advances continue to provide noninvasive and more accurate biomarkers for evaluating disease status. One standard tool for assessing the accuracy of diagnostic tests is the receiver operating characteristic (ROC) curve. Few statistical methods exist to accommodate multiple continuous-scale biomarkers in the framework of ROC analysis. In this paper, we propose a method to integrate continuous-scale biomarkers to optimize classification accuracy. Specifically, we develop semiparametric transformation models formultiple biomarkers. We assume that unknown and marker-specific transformations of biomarkers follow a multivariate normal distribution. Our models accommodate biomarkers subject to limits of detection and account for the dependence among biomarkers by including a subject-specific random effect. We also propose a diagnostic measure using an optimal linear combination of the transformed biomarkers. Our diagnostic rule does not depend on any monotone transformation of biomarkers and is not sensitive to extreme biomarker values. Nonparametric maximum likelihood estimation (NPMLE) is used for inference. We show that the parameter estimators are asymptotically normal and efficient. We illustrate our semiparametric approach using data from the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) study. C1 [Kim, Eunhee] Brown Univ, Dept Biostat, Providence, RI 02912 USA. [Kim, Eunhee] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Zeng, Donglin] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Zhou, Xiao-Hua] Univ Washington, VA Puget Sound Hlth Care Syst, HSRD Ctr Excellence, Seattle, WA 98198 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98198 USA. RP Kim, E (reprint author), Brown Univ, Dept Biostat, Providence, RI 02912 USA. EM ekim@stat.brown.edu FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child and Human Development, National Institute of Heath [NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02] FX The authors thank Zhen Chen for his valuable comments and suggestions and Youdan Wang for providing programming support. This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child and Human Development, National Institute of Heath (contracts #NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02; 10001406-02). NR 37 TC 0 Z9 0 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD SEP PY 2015 VL 57 IS 5 BP 808 EP 833 DI 10.1002/bimj.201400043 PG 26 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA CQ7CA UT WOS:000360759200006 PM 26138227 ER PT J AU Sajatovic, M Levin, JB Sams, J Cassidy, KA Akagi, K Aebi, ME Ramirez, LF Safren, SA Tatsuoka, C AF Sajatovic, Martha Levin, Jennifer B. Sams, Johnny Cassidy, Kristin A. Akagi, Kouri Aebi, Michelle E. Ramirez, Luis F. Safren, Steven A. Tatsuoka, Curtis TI Symptom severity, self-reported adherence, and electronic pill monitoring in poorly adherent patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE adherence; bipolar disorder; compliance; depression; mania; mood stabilizer ID PSYCHIATRIC RATING-SCALE; MEDICATION ADHERENCE; MOOD STABILIZERS; I DISORDER; LITHIUM; NONADHERENCE; HOSPITALIZATION; DEPRESSION; GUIDELINES; ATTITUDES AB ObjectivesThis analysis of screening and baseline data from an ongoing trial examined self-report versus automated adherence monitoring and assessed the relationship between bipolar disorder (BD) symptoms and adherence in 104 poorly adherent individuals. MethodsAdherence was measured with the Tablets Routine Questionnaire (TRQ) and the Medication Event Monitoring System (MEMS). Symptoms were measured with the Montgomery-angstrom sberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS). ResultsThe mean age of the sample was 46.3years [standard deviation (SD)=9.41 years], with 72% (n=75) women and 71% (n=74) African American subjects. Adherence improved from screening to baseline, with a mean missed drug proportion measured by TRQ of 61.43% (SD=26.48%) versus a baseline mean of 46.61% (SD=30.55%). The mean proportion of missed medication using MEMS at baseline was 66.43% (SD=30.40%). The correlation between TRQ and MEMS was 0.47. The correlation between a single index drug and all BD medications was 0.95. Symptoms were generally positively correlated with TRQ (worse adherence=more severe symptoms), but in most instances was only at a trend level (p>0.05), with the exception of the correlations between baseline TRQ and MADRS and BPRS, which were positive (r=0.20 and r=0.21, respectively) and significant (p0.05). ConclusionsIn patients with BD, monitoring increased adherence by 15%. MEMS identified 20% more non-adherence than self-report. Using a standard procedure to identify a single index drug for adherence monitoring may be one way to assess global adherence in patients with BD receiving polypharmacy treatment. Greater BD symptom severity may be a clinical indicator to assess for adherence problems. C1 [Sajatovic, Martha; Levin, Jennifer B.; Sams, Johnny; Cassidy, Kristin A.; Akagi, Kouri; Ramirez, Luis F.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. [Sajatovic, Martha; Levin, Jennifer B.; Sams, Johnny; Aebi, Michelle E.; Tatsuoka, Curtis] Univ Hosp Case Med Ctr, Neurol & Behav Outcomes Ctr, Cleveland, OH USA. [Sajatovic, Martha; Tatsuoka, Curtis] Case Western Reserve Univ, Sch Med, Dept Neurol, Cleveland, OH 44106 USA. [Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Sajatovic, M (reprint author), Case Western Reserve Univ, Sch Med, Dept Psychiat, WO Walker Bldg,7th Floor 10524 Euclid Ave, Cleveland, OH 44106 USA. EM martha.sajatovic@uhhospitals.org FU National Institute of Mental Health (NIMH) [NIMH 1R01MH093321-01A1]; Clinical and Translational Science Award (CTSC) [UL1TR 00043] FX This study was supported by a grant from the National Institute of Mental Health (NIMH) grant NIMH 1R01MH093321-01A1 (Principal Investigator: MS) and by the Clinical and Translational Science Award (CTSC) - UL1TR 00043 for REDCap. NR 48 TC 3 Z9 3 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2015 VL 17 IS 6 BP 653 EP 661 DI 10.1111/bdi.12326 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CQ8DB UT WOS:000360835300008 PM 26529124 ER PT J AU Freer, PE Slanetz, PJ Haas, JS Tung, NM Hughes, KS Armstrong, K Semine, AA Troyan, SL Birdwell, RL AF Freer, Phoebe E. Slanetz, Priscilla J. Haas, Jennifer S. Tung, Nadine M. Hughes, Kevin S. Armstrong, Katrina Semine, A. Alan Troyan, Susan L. Birdwell, Robyn L. TI Breast cancer screening in the era of density notification legislation: summary of 2014 Massachusetts experience and suggestion of an evidence-based management algorithm by multi-disciplinary expert panel SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Screening; Density; Dense breasts; Mammography; Supplemental screening ID MAMMOGRAPHIC DENSITY; DIGITAL MAMMOGRAPHY; COMMUNITY PRACTICE; ELEVATED RISK; WOMEN; ACCURACY; MRI; ULTRASOUND; COHORT; US AB Stemming from breast density notification legislation in Massachusetts effective 2015, we sought to develop a collaborative evidence-based approach to density notification that could be used by practitioners across the state. Our goal was to develop an evidence-based consensus management algorithm to help patients and health care providers follow best practices to implement a coordinated, evidence-based, cost-effective, sustainable practice and to standardize care in recommendations for supplemental screening. We formed the Massachusetts Breast Risk Education and Assessment Task Force (MA-BREAST) a multi-institutional, multi-disciplinary panel of expert radiologists, surgeons, primary care physicians, and oncologists to develop a collaborative approach to density notification legislation. Using evidence-based data from the Institute for Clinical and Economic Review, the Cochrane review, National Comprehensive Cancer Network guidelines, American Cancer Society recommendations, and American College of Radiology appropriateness criteria, the group collaboratively developed an evidence-based best-practices algorithm. The expert consensus algorithm uses breast density as one element in the risk stratification to determine the need for supplemental screening. Women with dense breasts and otherwise low risk (< 15 % lifetime risk), do not routinely require supplemental screening per the expert consensus. Women of high risk (> 20 % lifetime) should consider supplemental screening MRI in addition to routine mammography regardless of breast density. We report the development of the multi-disciplinary collaborative approach to density notification. We propose a risk stratification algorithm to assess personal level of risk to determine the need for supplemental screening for an individual woman. C1 [Freer, Phoebe E.] Massachusetts Gen Hosp, MGH Imaging, Div Breast Imaging, Boston, MA 02114 USA. [Slanetz, Priscilla J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Breast Imaging, Boston, MA 02215 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Semine, A. Alan] Newton Wellesley Hosp, Dept Radiol, Washington, DC USA. [Troyan, Susan L.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Birdwell, Robyn L.] Brigham & Womens Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02115 USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, MGH Imaging, Div Breast Imaging, Boston, MA 02114 USA. EM phoebefreer@gmail.com; pslanetz@bidmc.harvard.edu; jhaas@partners.org; ntung@bidmc.harvard.edu; kshughes@partners.org; Karmstrong6@mgh.harvard.edu; asemine@partners.org; stroyan@partners.org; rbirdwell@partners.org OI Freer, Phoebe/0000-0001-6886-7100 FU NCI NIH HHS [U54 CA163307] NR 46 TC 3 Z9 3 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2015 VL 153 IS 2 BP 455 EP 464 DI 10.1007/s10549-015-3534-9 PG 10 WC Oncology SC Oncology GA CQ5TU UT WOS:000360669400023 PM 26290416 ER PT J AU Foley, O Dizon, D Schmeler, K del Carmen, M AF Foley, Olivia Dizon, Don Schmeler, Kathleen del Carmen, Marcela TI Development of a Breast Cancer Advocacy and Access Health Program in Nicaragua SO BREAST JOURNAL LA English DT Letter C1 [Foley, Olivia; del Carmen, Marcela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol, Boston, MA USA. [Dizon, Don] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. [Schmeler, Kathleen] Univ Texas MD Anderson Canc Ctr, Div Gynecol Oncol, Houston, TX 77030 USA. RP del Carmen, M (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD SEP-OCT PY 2015 VL 21 IS 5 BP 570 EP 571 DI 10.1111/tbj.12459 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CQ7FK UT WOS:000360768200024 PM 26190769 ER PT J AU Kieran, MW Chi, S Goldman, S Onar-Thomas, A Poussaint, TY Vajapeyam, S Fahey, F Wu, SJ Turner, DC Stewart, CF Moses, M Packer, RJ Jakacki, R Banerjee, A Boyett, JM Fouladi, M Kun, L AF Kieran, Mark W. Chi, Susan Goldman, Stewart Onar-Thomas, Arzu Poussaint, Tina Young Vajapeyam, Sridhar Fahey, Frederic Wu, Shengjie Turner, David C. Stewart, Clinton F. Moses, Marsha Packer, Roger J. Jakacki, Regina Banerjee, Anu Boyett, James M. Fouladi, Maryam Kun, Larry TI A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors SO CHILDS NERVOUS SYSTEM LA English DT Article DE AZD2171; Recentin; Cediranib; Antiangiogenesis; Pediatric brain tumor ID TYROSINE KINASE INHIBITOR; CONTINUAL REASSESSMENT METHOD; BEVACIZUMAB PLUS IRINOTECAN; BRAIN-STEM GLIOMA; METRONOMIC CHEMOTHERAPY; GLIOBLASTOMA PATIENTS; PROSTATE-CANCER; F-18-FDG PET; SOLID TUMORS; GROWTH AB Cediranib (AZD2171), an oral pan-vascular endothelial growth factor (VEGF) inhibitor, was evaluated in this phase I study to determine its toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children and adolescents with recurrent or refractory primary central nervous system (CNS) tumors. Children and adolescents < 22 years were enrolled into one of two strata: stratum I-those not receiving enzyme-inducing anticonvulsant drugs (EIACD) and stratum II-those receiving EIACDs. Dose-level selection was based on the continual reassessment method (CRM). Thirty-six eligible patients with median age of 12.7 years (range, 5.4-21.7 years) in stratum I (24 males) and 12 patients (7 males) in stratum II with median age of 13.4 years (range, 8.9-19.5 years) were initially assessed over a 4-week DLT evaluation period, modified to 6 weeks during the study. An MTD of 32 mg/m(2)/day was declared; however, excessive toxicities (transaminitis, proteinuria, diarrhea, hemorrhage, palmer-planter syndrome, reversible posterior leukoencephalopathy) in the expansion cohort treated at this dose suggested that it might not be tolerated over a longer time period. An expansion cohort at 20 mg/m(2)/day also demonstrated poor longer-term tolerability. Diffusion and perfusion MRI and PET imaging variables as well as biomarker analysis were performed and correlated with outcome. At 20 mg/m(2)/day, the median plasma area under the concentration-time curve at steady state was lower than that observed in adults at similar dosages. While the MTD of once daily oral cediranib in children with recurrent or progressive CNS tumors was initially defined as 32 mg/m(2)/day, this dose and 20 mg/m(2)/day were not considered tolerable over a protracted time period. C1 [Kieran, Mark W.; Chi, Susan] Dana Farber Canc Inst, Dept Pediat Oncol, Pediat Neurooncol, Boston, MA 02215 USA. [Kieran, Mark W.; Chi, Susan] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02215 USA. [Poussaint, Tina Young; Vajapeyam, Sridhar; Fahey, Frederic] Boston Childrens Hosp, Dept Radiol, Boston, MA 02215 USA. [Kieran, Mark W.; Moses, Marsha] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02215 USA. [Goldman, Stewart] Lurie Childrens Hosp, Dept Hematol Oncol, Chicago, IL USA. [Onar-Thomas, Arzu; Wu, Shengjie; Boyett, James M.] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Turner, David C.; Stewart, Clinton F.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Kun, Larry] St Jude Childrens Res Hosp, Radiol Sci, Memphis, TN 38105 USA. [Packer, Roger J.] Childrens Natl Hlth Syst, Ctr Neurosci & Behav Med, Brain Tumor Inst, Washington, DC USA. [Jakacki, Regina] Childrens Hosp Pittsburgh, Pediat Hematol Oncol, Pittsburgh, PA 15213 USA. [Banerjee, Anu] Univ San Francisco, Pediat Oncol, San Francisco, CA 94117 USA. [Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Pediat Neurooncol, 450 Brookline Ave,Rm D3154, Boston, MA 02215 USA. EM mark_kieran@dfci.harvard.edu FU NIH for the Pediatric Brain Tumor Consortium [U01 CA81457]; American Lebanese Syrian Associated Charities; Stop & Shop Pediatric Brain Tumor Program at the Dana-Farber Cancer Institute; Boston Children's Hospital FX This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium, American Lebanese Syrian Associated Charities, and the Stop & Shop Pediatric Brain Tumor Program at the Dana-Farber Cancer Institute and Boston Children's Hospital. NR 32 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 EI 1433-0350 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD SEP PY 2015 VL 31 IS 9 BP 1433 EP 1445 DI 10.1007/s00381-015-2812-5 PG 13 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA CQ8FI UT WOS:000360841500003 PM 26188774 ER PT J AU Qadri, YJ Bortsov, AV Orrey, DC Swor, RA Peak, DA Jones, JS Rathlev, NK Lee, DC Domeier, RM Hendry, PL Mclean, SA AF Qadri, Yawar J. Bortsov, Andrey V. Orrey, Danielle C. Swor, Robert A. Peak, David A. Jones, Jeffrey S. Rathlev, Niels K. Lee, David C. Domeier, Robert M. Hendry, Phyllis L. Mclean, Samuel A. TI Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision SO CLINICAL JOURNAL OF PAIN LA English DT Article DE dopamine; DRD2; SLC6A3; genetic association; acute trauma ID PATIENT-CONTROLLED ANALGESIA; DRD2 NCOI ALLELES; PARKINSONS-DISEASE; TRANSPORTER GENE; ASSOCIATION; MIGRAINE; METOCLOPRAMIDE; SUSCEPTIBILITY; ALCOHOL; HUMANS AB Objectives:Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tested the hypothesis that genetic variants in the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter (SLC6A3) influence acute pain severity after motor vehicle collision.Materials and Methods:European Americans presenting to the emergency department after motor vehicle collision were recruited. Overall pain intensity in emergency department was assessed using a 0 to 10 numeric rating scale. DNA was extracted from blood samples and genotyping of single-nucleotide polymorphisms (SNPs) in the DRD2 and SLC6A3 gene was performed.Results:A total of 948 patients completed evaluation. After correction for multiple comparisons, SNP rs6276 at DRD2 showed significant association with pain scores, with individuals with the A/A genotype reporting lower mean pain scores (5.3; 95% confidence interval [CI], 5.1-5.5) than those with A/G (5.9; 95% CI, 5.6-6.1) or G/G (5.7; 95% CI, 5.2-6.2) genotypes (P=0.0027). Secondary analyses revealed an interaction between sex and DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with 2 minor alleles had increased pain intensity, whereas males with 2 minor alleles had less pain than individuals with a major allele (interaction P=0.0019).Discussion:Genetic variants in DRD2 are associated with acute pain after a traumatic stressful event. These results suggest that dopaminergic agents may be useful for the treatment of individuals with acute posttraumatic pain as part of a multimodal opioid-sparing analgesic regimen. C1 [Qadri, Yawar J.; Bortsov, Andrey V.; Orrey, Danielle C.; Mclean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Jones, Jeffrey S.] Spectrum Hlth Syst, Dept Emergency Med, Grand Rapids, MI USA. [Domeier, Robert M.] St Joseph Mercy Hlth Syst, Dept Emergency Med, Ypsilanti, MI USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rathlev, Niels K.] Bay State Med Ctr, Dept Emergency Med, Springfield, MA USA. [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Hendry, Phyllis L.; Mclean, Samuel A.] Univ Florida, Dept Emergency Med, Jacksonville, FL USA. RP Mclean, SA (reprint author), Univ N Carolina, Sch Med, Dept Anesthesiol, Wing C CB 7010, Chapel Hill, NC 27599 USA. EM smclean@aims.unc.edu OI McLean, Samuel/0000-0001-9482-3582 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, Bethesda, MD [R01AR056328] FX Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, Bethesda, MD; under Award Number R01AR056328. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflict of interest. NR 61 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD SEP PY 2015 VL 31 IS 9 BP 768 EP 775 DI 10.1097/AJP.0000000000000167 PG 8 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CQ1GZ UT WOS:000360346600002 ER PT J AU Anderson, JE Steiner, RW Mekeel, KL Chang, DC Hemming, AW Halldorson, JB AF Anderson, Jamie E. Steiner, Robert W. Mekeel, Kristin L. Chang, David C. Hemming, Alan W. Halldorson, Jeffrey B. TI ECD kidney transplantation outcomes are improved when matching donors to recipients using a novel creatinine clearance match ratio (CCMR) SO CLINICAL TRANSPLANTATION LA English DT Article DE creatinine clearance; end-stage renal disease; extended criteria donor; kidney transplantation; surgical outcomes ID GRAFT FUNCTION; ALLOGRAFT SURVIVAL; SERUM CREATININE; WEIGHT; SIZE; PREDICTION; IMPACT; INDEX; AGE AB Improved outcomes have been associated with various methods of size matching between expanded criteria (ECD) donors and recipients. A novel method for improved functional based matching was developed utilizing manipulation of Cockcroft-Gault estimated creatinine clearances for donor and recipient. We hypothesized that optimal clearance-based matches would have superior outcomes for both immediate graft function and long-term graft survival. For the analysis, recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) transplanted between October 1, 1987 and August 31, 2011 were included. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. A total of 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher creatinine clearance match ratio (CCMR) was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.43, p<0.001; OR 2.08, p<0.001). This study suggests that ECD kidneys have improved outcomes when the recipient/donor CCMR is optimized. C1 [Anderson, Jamie E.; Mekeel, Kristin L.; Hemming, Alan W.; Halldorson, Jeffrey B.] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Steiner, Robert W.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Chang, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Halldorson, JB (reprint author), Univ Calif San Diego, 200 W Arbor Dr 8400, San Diego, CA 92103 USA. EM jhalldorson@ucsd.edu NR 22 TC 1 Z9 2 U1 0 U2 0 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 SEP PY 2015 VL 29 IS 9 BP 738 EP 746 DI 10.1111/ctr.12555 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA CQ7NG UT WOS:000360790300005 PM 25918902 ER PT J AU Veldman, PB Dye, PK Holiman, JD Mayko, ZM Sales, CS Straiko, MD Stoeger, CG Terry, MA AF Veldman, Peter B. Dye, Philip K. Holiman, Jeffrey D. Mayko, Zachary M. Sales, Christopher S. Straiko, Michael D. Stoeger, Christopher G. Terry, Mark A. TI Stamping an S on DMEK Donor Tissue to Prevent Upside-Down Grafts: Laboratory Validation and Detailed Preparation Technique Description SO CORNEA LA English DT Article DE DMEK; endothelial keratoplasty; donor tissue preparation; S-stamp; upside-down graft ID MEMBRANE ENDOTHELIAL KERATOPLASTY; CORNEAL TISSUE; EYE; REJECTION; RISK AB Purpose:To report endothelial cell loss (ECL) caused by a novel S-stamp preparation technique for Descemet membrane endothelial keratoplasty (DMEK).Methods:Six cadaveric human corneas were prepared for DMEK transplantation using a single standardized technique, including the application of a dry ink gentian violet S-stamp to the stromal side of Descemet membrane. Endothelial cell death was evaluated and quantified using computerized analysis of vital dye staining.Results:ECL caused by the S-stamp was 0.6% (range 0.1%-1.0%), which comprised less than one-tenth of the total ECL caused by our preparation of the DMEK graft from the start to finish, including recovery, prestripping, S-stamping, and trephination (13.7% total ECL, range 9.9%-17.6%).Conclusions:Our novel S-stamp donor tissue preparation technique is intuitive to learn and holds the promise of preventing iatrogenic primary graft failure due to upside-down grafts without causing unacceptable increases in ECL. C1 [Veldman, Peter B.] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. [Veldman, Peter B.; Sales, Christopher S.; Straiko, Michael D.; Terry, Mark A.] Devers Eye Inst, Cornea Serv, Portland, OR USA. [Dye, Philip K.; Holiman, Jeffrey D.; Mayko, Zachary M.; Stoeger, Christopher G.] Lions Vis Gift, Portland, OR USA. RP Veldman, PB (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM peterbveldman@gmail.com NR 18 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD SEP PY 2015 VL 34 IS 9 BP 1175 EP 1178 DI 10.1097/ICO.0000000000000522 PG 4 WC Ophthalmology SC Ophthalmology GA CQ1HT UT WOS:000360348600034 PM 26147839 ER PT J AU Roberts, DA Steensma, DP AF Roberts, Daniel A. Steensma, David P. TI Outlook and Management of Patients with Myelodysplastic Syndromes Failed by Hypomethylating Agents SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Review DE Myelodysplastic syndromes; Azacitidine; Decitabine; DNA methyltransferase inhibitor ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; LOW-DOSE CYTARABINE; AZACITIDINE TREATMENT FAILURE; INTERNATIONAL WORKING GROUP; ACUTE MYELOGENOUS LEUKEMIA; PHASE-III; ELDERLY-PATIENTS; INTENSIVE CHEMOTHERAPY; RISK STRATIFICATION AB The DNA hypomethylating agents (HMAs) azacitidine and decitabine are currently the most frequently administered disease-modifying therapies for patients with higher-risk myelodysplastic syndromes (MDS). However, azacitidine and decitabine are not curative, the median response duration is 11-15 months, and only 10-20 % of patients experience complete hematologic and cytogenetic response. Moreover, once an HMA fails the patient, the prognosis is poor, with a median survival of less than 6 months unless the patient undergoes hematopoietic stem cell transplantation (HSCT). Recent insights into the genetic basis of MDS have enhanced biological understanding and prognostication accuracy, but these developments have not yet led to regulatory approval of new therapies. While there are multiple potential approaches to patients with MDS for whom HMAs have failed, including supportive care alone, cytotoxic therapy, lenalidomide, histone deacetylase inhibitors, and HSCT, favorable responses to these approaches are limited and new therapies are greatly needed. Here, we review clinical and biological data about the population of patients failed by HMAs, evaluate currently available approaches to patients in this clinical situation, and discuss prospects for development of novel active agents. C1 [Roberts, Daniel A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02215 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu NR 89 TC 1 Z9 1 U1 0 U2 2 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 EI 1558-822X J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD SEP PY 2015 VL 10 IS 3 BP 318 EP 328 DI 10.1007/s11899-015-0273-2 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CQ4BK UT WOS:000360548900016 PM 26126600 ER PT J AU D'Eon, SA Pober, DM Tinsley, LJ Hastings, SM King, GL Keenan, HA AF D'Eon, S. A. Pober, D. M. Tinsley, L. J. Hastings, S. M. King, G. L. Keenan, H. A. TI Lower mortality with physical activity in type 1 diabetes of extreme duration: Joslin 50-Year Medalist study SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [D'Eon, S. A.; Pober, D. M.; Tinsley, L. J.; Hastings, S. M.; King, G. L.; Keenan, H. A.] Joslin Diabet Ctr, Vasc Cell, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 308 BP S155 EP S155 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900309 ER PT J AU Dahlstrom, EH Todd, J Sandholm, N Salem, R Forsblom, C Tolonen, N Harjutsalo, V Hirschorn, J Florez, JC Groop, PH AF Dahlstrom, E. H. Todd, J. Sandholm, N. Salem, R. Forsblom, C. Tolonen, N. Harjutsalo, V. Hirschorn, J. Florez, J. C. Groop, P. -H. TI Genetic exploration of a causal role of dyslipidaemia on diabetic nephropathy in type 1 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Dahlstrom, E. H.; Sandholm, N.; Forsblom, C.; Tolonen, N.; Harjutsalo, V.; Groop, P. -H.] Folkhalsan Inst Genet, Helsinki, Finland. [Dahlstrom, E. H.; Sandholm, N.; Forsblom, C.; Tolonen, N.; Harjutsalo, V.; Groop, P. -H.] Abdominal Ctr Nephrol, Helsinki, Finland. [Todd, J.; Salem, R.; Hirschorn, J.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Todd, J.; Salem, R.; Hirschorn, J.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 1096 BP S527 EP S527 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820903063 ER PT J AU De Jesus, DF Kulkarni, RN AF De Jesus, D. F. Kulkarni, R. N. TI Metabolic reprogramming in male offspring in a non-dietary model of liver insulin resistance SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [De Jesus, D. F.; Kulkarni, R. N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02115 USA. [De Jesus, D. F.] Univ Porto, GABBA Grad Program Areas Basic & Appl Biol, Abel Salazar Biomed Sci Inst, P-4100 Oporto, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 239 BP S120 EP S121 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900240 ER PT J AU Grunberg, JR Hoffmann, JM Hedjazifar, S Nerstedt, A Jenndahl, L Castellot, J Wei, L Skrtic, SM Backhed, F Syed, I Saghetelian, A Kahn, B Hammarstedt, A Smith, U AF Grunberg, J. R. Hoffmann, J. M. Hedjazifar, S. Nerstedt, A. Jenndahl, L. Castellot, J. Wei, L. Skrtic, S. Moverare Backhed, F. Syed, I. Saghetelian, A. Kahn, B. Hammarstedt, A. Smith, U. TI Increased brown fat and insulin sensitivity in obese mice overexpressing WISP2 in the adipose tissue SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Castellot, J.] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Medford, MA USA. [Wei, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Syed, I.; Kahn, B.] Harvard Univ, Sch Med, Boston, MA USA. [Saghetelian, A.] Salk Inst, San Diego, CA 92186 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 210 BP S105 EP S106 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900211 ER PT J AU Hillary, KA Khamaisi, M Tinsley, LJ Hastings, SM D'Eon, S Pober, D Sun, JK King, GL AF Hillary, K. A. Khamaisi, M. Tinsley, L. J. Hastings, S. M. D'Eon, S. Pober, D. Sun, J. K. King, G. L. TI Protection from diabetic retinopathy, but not nephropathy SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Hillary, K. A.; Khamaisi, M.; Tinsley, L. J.; Hastings, S. M.; D'Eon, S.; Pober, D.; King, G. L.] Joslin Diabet Ctr, Vasc Cell Biol, Boston, MA 02215 USA. [Sun, J. K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 228 BP S114 EP S115 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900229 ER PT J AU Kaplan, LM Maggs, D Liao, A Chiquette, E AF Kaplan, L. M. Maggs, D. Liao, A. Chiquette, E. TI Sustained effects of duodenal-jejunal bypass liner on weight loss and glycaemic control SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Kaplan, L. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaplan, L. M.] Harvard Univ, Sch Med, Boston, MA USA. [Maggs, D.; Liao, A.; Chiquette, E.] GI Dynam, Lexington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 906 BP S437 EP S437 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820902164 ER PT J AU Sandholm, N Ahlqvist, E Deshmukh, H Van Zuydam, N Rayner, NW Harjutsalo, V Marcovecchio, ML Cooper, J McKnight, AJ Salem, RM Lajer, M Tregouet, D Hiraki, LT Pezzolesi, M Forsblom, C AF Sandholm, N. Ahlqvist, E. Deshmukh, H. Van Zuydam, N. Rayner, N. W. Harjutsalo, V. Marcovecchio, M. L. Cooper, J. McKnight, A. J. Salem, R. M. Lajer, M. Tregouet, D. Hiraki, L. T. Pezzolesi, M. Forsblom, C. TI Genome-wide association studies on kidney complications in patients with type 1 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Sandholm, N.; Forsblom, C.] Univ Helsinki, Folkhalsan Inst Genet, Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. [Sandholm, N.; Forsblom, C.] Univ Helsinki, Abdominal Ctr Nephrol, FIN-00014 Helsinki, Finland. Helsinki Univ Hosp, Helsinki, Finland. [Ahlqvist, E.] Lund Univ, Skane Univ Hosp, Malmo, Sweden. [Deshmukh, H.] Univ Dundee, Dundee DD1 4HN, Scotland. [Van Zuydam, N.; Rayner, N. W.] Wellcome Trust Ctr Human Genet, Oxford, England. [Harjutsalo, V.] Natl Inst Hlth & Welf, Helsinki, Finland. [Marcovecchio, M. L.; Cooper, J.] Univ Cambridge, Cambridge CB2 1TN, England. [McKnight, A. J.] Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. [Salem, R. M.] Broad Inst, Cambridge, MA USA. [Lajer, M.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Tregouet, D.] INSERM, UMR S 1166, Paris, France. [Hiraki, L. T.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Pezzolesi, M.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 179 BP S90 EP S91 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900180 ER PT J AU Skupien, J Smiles, AM Galecki, AT Mychaleckyj, JC Pezzolesi, MG Krolewski, AS AF Skupien, J. Smiles, A. M. Galecki, A. T. Mychaleckyj, J. C. Pezzolesi, M. G. Krolewski, A. S. TI Synergistic effect of genetic susceptibility and poor glycaemic control on renal decline in patients with type 1 diabetes and proteinuria SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Skupien, J.] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Skupien, J.; Smiles, A. M.; Pezzolesi, M. G.; Krolewski, A. S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Galecki, A. T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mychaleckyj, J. C.] Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 180 BP S91 EP S91 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900181 ER PT J AU Solheim, MH Winnay, JN Molven, A Njolstad, PR Kahn, CR AF Solheim, M. H. Winnay, J. N. Molven, A. Njolstad, P. R. Kahn, C. R. TI Impaired PI 3-kinase signalling in a mouse model of SHORT syndrome SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Solheim, M. H.; Winnay, J. N.; Kahn, C. R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Solheim, M. H.; Molven, A.; Njolstad, P. R.] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabetes Res, Bergen, Norway. [Molven, A.] Univ Bergen, Dept Clin Sci, Gade Lab Pathol, Bergen, Norway. [Njolstad, P. R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 34 BP S17 EP S17 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900035 ER PT J AU Zhu, X Waldron, R Lugea, A Li, L AF Zhu, X. Waldron, R. Lugea, A. Li, L. TI Insulin and IGF-1 promote pancreatic stellate cells activation and galectin-3 expression: potential role in promotion of pancreatic cancer SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Zhu, X.; Li, L.] Southeast Univ, Dept Endocrinol, Affiliated ZhongDa Hosp, Nanjing, Jiangsu, Peoples R China. [Waldron, R.; Lugea, A.; Li, L.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Waldron, R.; Lugea, A.; Li, L.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 699 BP S334 EP S334 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820901388 ER PT J AU Karaosmanoglu, AD Onur, MR Shirkhoda, A Ozmen, M Hahn, PF AF Karaosmanoglu, Ali Devrim Onur, Mehmet Ruhi Shirkhoda, Ali Ozmen, Mustafa Hahn, Peter F. TI Unusual benign solid neoplasms of the kidney: cross-sectional imaging findings SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article AB Kidney neoplasms are common diseases with varying prognoses depending on the subtype of the tumor. The most common solid lesion of the kidney is renal cell carcinoma, and the treatment is typically surgical removal. With increasing use of cross-sectional imaging in the last two decades, the detection of renal lesions has significantly increased, especially in asymptomatic patients who are scanned for other reasons. In this article, we present the imaging findings of rare solid benign primary kidney neoplasms including renal leiomyoma, reninoma, carcinoid tumor, metanephric adenoma, solitary fibrous tumor of the kidney, lipomatous hemangiopericytoma of the kidney, renal schwannoma, inflammatory myofibroblastic tumor of the kidney, extramedullary hematopoiesis in the kidney, and extranodal renal Rosai-Dorfman disease. Accurate preoperative or prebiopsy diagnoses of these lesions are unusual; however, informed radiologists may sometimes be able to favorably change the patient management and treatment. C1 [Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa] Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. [Shirkhoda, Ali] Univ Calif Irvine, Sch Med, Dept Radiol, Irvine, CA 92717 USA. [Hahn, Peter F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Onur, MR (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. EM ruhionur@yahoo.com NR 15 TC 1 Z9 1 U1 0 U2 7 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP-OCT PY 2015 VL 21 IS 5 BP 376 EP 381 DI 10.5152/dir.2015.14545 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ4CE UT WOS:000360551000003 PM 26200482 ER PT J AU Khalilzadeh, O Rahimian, M Batchu, V Vadvala, HV Novelline, RA Choy, G AF Khalilzadeh, Omid Rahimian, Maryam Batchu, Vinay Vadvala, Harshna V. Novelline, Robert A. Choy, Garry TI Effectiveness of second-opinion radiology consultations to reassess the cervical spine CT scans: a study on trauma patients referred to a tertiary-care hospital SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INJURIES AB PURPOSE A second opinion is a valuable resource in confirming proper medical diagnosis and treatment. This study evaluates the effectiveness of second-opinion radiology consultations to reassess the cervical spine computed tomography (CT) scans of the trauma patients referred to our hospital. METHODS Cervical spine CT scans of 301 consecutive adult trauma patients, who were referred to our hospital from outside institutions, were analyzed. The emergency radiologists at our institution completed the over-read reports on the CT images obtained at the outside facilities. A single radiologist compared the outside-and over-read reports and determined the discrepancy of the radiologic reports. RESULTS Based on the outside reports, 31% of the CT scans had cervical traumatic injury. In 92% of patients, the first-read and the over-read reports had consistent radiologic findings. About 90% of the positive, and 93% of the negative radiologic findings, were reported consistently in the over-read reports. Our analysis showed that the over-read reporting resulted in reassurance of negative findings in 63%; confirmation of positive findings in 29%; clearing a false diagnosis in 3%; and detection of a missed diagnosis in 5%. A rescan was done in 80% of patients with inconsistent and 20% of patients with consistent findings (P < 0.05). The most common missed radiologic findings in the first-reports were transverse and spinous process fractures and the most common misdiagnoses were dens fractures. CONCLUSION For a service offering second-opinion consultations on cervical spine trauma, review of outside CT studies improves diagnosis and benefits patient care. C1 [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Choy, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM gchoy@partners.org NR 18 TC 0 Z9 0 U1 0 U2 1 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP-OCT PY 2015 VL 21 IS 5 BP 423 EP 427 DI 10.5152/dir.2015.15003 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ4CE UT WOS:000360551000012 PM 26200483 ER PT J AU Prakash, SR Herrmann, BS Milojcic, R Rauch, SD Guinan, JJ AF Prakash, S. R. Herrmann, Barbara S. Milojcic, Rupprecht Rauch, Steven D. Guinan, John J. TI Evaluating Inhibition of Motoneuron Firing From Electromyogram Data to Assess Vestibular Output Using Vestibular Evoked Myogenic Potentials SO EAR AND HEARING LA English DT Article DE cVEMP; Electromyogram; EMG; oVEMP; VEMP; Vestibulocollic reflex ID MOTOR-UNIT; STERNOCLEIDOMASTOID MUSCLE; ISOMETRIC CONTRACTIONS; EMG; MODEL; GENERATION; NERVE; NOISE; NORMALIZATION; RECRUITMENT AB Objectives: Vestibular evoked myogenic potentials (VEMPs) are due to vestibular responses producing brief inhibitions of muscle contractions that are detectable in electromyographic (EMG) responses. VEMP amplitudes are traditionally measured by the peak to peak amplitude of the averaged EMG response (VEMPpp) or by a normalized VEMPpp (nVEMPpp). However, a brief EMG inhibition does not satisfy the statistical assumptions for the average to be the optimal processing strategy. Here, it is postulated that the inhibition depth of motoneuron firing is the desired metric for showing the influence of the vestibular system on the muscle system. The authors present a metric called VEMPid that estimates this inhibition depth from the EMG data obtained in a usual VEMP data acquisition. The goal of this article was to compare how well VEMPid, VEMPpp, and nVEMPpp track inhibition depth. Design: To find a robust method to compare VEMPid, VEMPpp, and nVEMPpp, realistic physiological models for the inhibition of VEMP EMG signals were made using VEMP data from four measurement sessions on each of the five normal subjects. Each of the resulting 20 EMG-production models was adjusted to match the EMG autocorrelation of an individual subject and session. Simulated VEMP traces produced by these models were used to compare how well VEMPid, VEMPpp, and nVEMPpp tracked model inhibition depth. Results: Applied to simulated and real VEMP data, VEMPid showed good test-retest consistency and greater sensitivity at low stimulus levels than VEMPpp or nVEMPpp. For large-amplitude responses, nVEMPpp and VEMPid were equivalent in their consistency across subjects and sessions, but for low-amplitude responses, VEMPid was superior. Unnormalized VEMPpp was always worse than nVEMPpp or VEMPid. Conclusions: VEMPid provides a more reliable measurement of vestibular function at low sound levels than the traditional nVEMPpp, without requiring a change in how VEMP tests are performed. The calculation method for VEMPid should be applicable whenever an ongoing muscle contraction is briefly inhibited by an external stimulus. C1 [Prakash, S. R.; Herrmann, Barbara S.; Guinan, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Prakash, S. R.; Herrmann, Barbara S.; Milojcic, Rupprecht; Rauch, Steven D.; Guinan, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Prakash, S. R.; Milojcic, Rupprecht; Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Guinan, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu NR 50 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2015 VL 36 IS 5 BP 591 EP 604 DI 10.1097/AUD.0000000000000158 PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA CQ5GI UT WOS:000360630900011 PM 25811931 ER PT J AU Tsvetkov, P Mendillo, ML Zhao, JH Carette, JE Merrill, PH Cikes, D Varadarajan, M van Diemen, FR Penninger, JM Goldberg, AL Brummelkamp, TR Santagata, S Lindquist, S AF Tsvetkov, Peter Mendillo, Marc L. Zhao, Jinghui Carette, Jan E. Merrill, Parker H. Cikes, Domagoj Varadarajan, Malini van Diemen, Ferdy R. Penninger, Josef M. Goldberg, Alfred L. Brummelkamp, Thijn R. Santagata, Sandro Lindquist, Susan TI Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome SO ELIFE LA English DT Article ID EMBRYONIC STEM-CELLS; 26S PROTEASOME; HEAT-SHOCK; SACCHAROMYCES-CEREVISIAE; STATIONARY-PHASE; OXIDATIVE STRESS; 20S PROTEASOMES; CANCER-CELLS; DEGRADATION; INHIBITORS AB Proteasomes are central regulators of protein homeostasis in eukaryotes. Proteasome function is vulnerable to environmental insults, cellular protein imbalance and targeted pharmaceuticals. Yet, mechanisms that cells deploy to counteract inhibition of this central regulator are little understood. To find such mechanisms, we reduced flux through the proteasome to the point of toxicity with specific inhibitors and performed genome-wide screens for mutations that allowed cells to survive. Counter to expectation, reducing expression of individual subunits of the proteasome's 19S regulatory complex increased survival. Strong 19S reduction was cytotoxic but modest reduction protected cells from inhibitors. Protection was accompanied by an increased ratio of 20S to 26S proteasomes, preservation of protein degradation capacity and reduced proteotoxic stress. While compromise of 19S function can have a fitness cost under basal conditions, it provided a powerful survival advantage when proteasome function was impaired. This means of rebalancing proteostasis is conserved from yeast to humans. C1 [Tsvetkov, Peter; Varadarajan, Malini; Santagata, Sandro; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Mendillo, Marc L.; Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Zhao, Jinghui; Goldberg, Alfred L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Carette, Jan E.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Merrill, Parker H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Cikes, Domagoj; Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, A-1010 Vienna, Austria. [van Diemen, Ferdy R.; Brummelkamp, Thijn R.] Netherlands Canc Inst, Dept Biochem, Amsterdam, Netherlands. [Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Santagata, Sandro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Santagata, S (reprint author), Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM ssantagata@bics.bwh.harvard.edu; lindquist_admin@wi.mit.edu RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 FU EMBO [ALTF 739-2011]; National Institutes of Health (NIH) [K08NS064168]; The Medical Foundation (TMF) FX EMBO ALTF 739-2011 Peter Tsvetkov; National Institutes of Health (NIH) K08NS064168 Sandro Santagata; The Medical Foundation (TMF) Charles A. King Trust Peter Tsvetkov NR 79 TC 6 Z9 6 U1 0 U2 7 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD SEP 1 PY 2015 VL 4 AR e08467 DI 10.7554/eLife.08467 PG 22 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CQ5QT UT WOS:000360661200001 ER PT J AU Wang, YH Scadden, DT AF Wang, Ying-Hua Scadden, David T. TI Harnessing the apoptotic programs in cancer stem-like cells SO EMBO REPORTS LA English DT Review DE apoptosis; cancer stem cells; cancer therapy ID ACUTE MYELOID-LEUKEMIA; TRAIL-INDUCED APOPTOSIS; TUMOR-INITIATING CELLS; HEPATOCELLULAR-CARCINOMA CELLS; SMALL-MOLECULE INHIBITORS; DR5 MONOCLONAL-ANTIBODY; BCL-2 FAMILY PROTEINS; HUMAN GLIOMA-CELLS; LUNG-CANCER; DOWN-REGULATION AB Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population. C1 [Wang, Ying-Hua; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Wang, Ying-Hua; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wang, Ying-Hua; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Wang, Ying-Hua; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu NR 167 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD SEP PY 2015 VL 16 IS 9 BP 1084 EP 1098 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ6LP UT WOS:000360716200008 PM 26253117 ER PT J AU Lal, D Pernhorst, K Klein, KM Reif, P Tozzi, R Toliat, MR Winterer, G Neubauer, B Nurnberg, P Rosenow, F Becker, F Lerche, H Kunz, WS Kurki, MI Hoffmann, P Becker, AJ Perucca, E Zara, F Sander, T Weber, YG AF Lal, Dennis Pernhorst, Katharina Klein, Karl Martin Reif, Philipp Tozzi, Rossana Toliat, Mohammad R. Winterer, Georg Neubauer, Bernd Nuernberg, Peter Rosenow, Felix Becker, Felicitas Lerche, Holger Kunz, Wolfram S. Kurki, Mitja I. Hoffmann, Per Becker, Albert J. Perucca, Emilio Zara, Federico Sander, Thomas Weber, Yvonne G. TI Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy SO EPILEPSIA LA English DT Article DE Copy number variation; Idiopathic; Genetic; Cryptogenic; Magnet resonance imaging negative; Lesional ID GENERALIZED EPILEPSY; MODEL; DISEASE; BRAIN; RISK AB Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self-limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)-negative epilepsy of unknown etiology with frontal and temporal origin (n=5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies. C1 [Lal, Dennis; Toliat, Mohammad R.; Winterer, Georg; Nuernberg, Peter; Sander, Thomas] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. [Lal, Dennis; Neubauer, Bernd] Univ Med Ctr Giessen & Marburg, Dept Neuropediat, Giessen, Germany. [Lal, Dennis] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany. [Pernhorst, Katharina; Becker, Albert J.] Univ Bonn, Dept Neuropathol, Bonn, Germany. [Klein, Karl Martin; Reif, Philipp; Rosenow, Felix] Univ Marburg, Dept Neurol, Marburg, Germany. [Tozzi, Rossana; Perucca, Emilio] C Mondino Natl Neurol Inst, Pavia, Italy. [Becker, Felicitas; Lerche, Holger; Weber, Yvonne G.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, D-72076 Tubingen, Germany. [Kunz, Wolfram S.] Univ Bonn, Life & Brain Ctr, Bonn, Germany. [Kurki, Mitja I.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Kurki, Mitja I.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kurki, Mitja I.] Kuopio Univ Hosp, NeuroCtr, Neurosurg, SF-70210 Kuopio, Finland. [Hoffmann, Per] Univ Bonn, Inst Human Genet, Bonn, Germany. [Hoffmann, Per] Univ Basel Hosp, Div Med Genet, CH-4031 Basel, Switzerland. [Hoffmann, Per] Univ Basel, Dept Biomed, Basel, Switzerland. [Perucca, Emilio] Univ Pavia, Dept Internal Med & Therapeut, I-27100 Pavia, Italy. [Zara, Federico] Ist Giannina Gaslini, Neurogenet Lab, Neuromuscular Dis Unit, I-16148 Genoa, Italy. RP Weber, YG (reprint author), Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Hoppe SeylerStr 3, D-72076 Tubingen, Germany. EM Yvonne.weber@uni-tuebingen.de RI Becker, Albert/F-6248-2012; OI Klein, Karl Martin/0000-0002-6654-1665 FU Italian League against Epilepsy (LICE); European Community [LSHCT-2006- 037315]; Klaus-Dieter Scharf Research Project Marburg; Stiftung P.E. Kempkes Marburg FX This study was supported by grants from the Italian League against Epilepsy (LICE) and from the European Community's Sixth Framework Programme (Integrated Project EPICURE, contract number: LSHCT-2006- 037315). In addition to the authors, the following investigators from Italian centers participated in the study: Umberto Aguglia, Angelo Labate, Institute of Neurology, University Magna Graecia, Catanzaro; Fabrizio Balestrieri, Unit of Neurology, Palagi Hospital, Firenze; Amedeo Bianchi, Division of Neurology, Ospedale S Donato, Arezzo; Francesca Beccaria, Giuseppe Capovilla, Epilepsy Center, Department of Child Neuropsychiatry, C. Poma Hospital, Mantova; Paolo Benna, Rossella Colonna, Elisa Montalenti, Division of Neurology, University of Turin; Clementina Boniver, Marilena Vecchi, Division of Pediatric Neurology, University of Padua; Roberto Campostrini, Paolo Forleo, Epilepsy Center, Ospedale Misericordia e Dolce, Prato; Maria P. Canevini, Rosanna Chifari, Epilepsy Center, S. Paolo Hospital, Milan; Barbara Chiocchetti, Giancarlo Muscas, Eleonora Rosati, 3rd Neurology Division and Epilepsy Center, Careggi Hospital, Florence; Patrizia D'Alessandro, Epilepsy Centre, Unit of Neurophysiopathology, Perugia; Christine Durisotti, Pier Gaetano Garofalo, Epilepsy Center, Civil Hospital, Vicenza; Maurizio Elia, Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina; Cinzia Fattore, C. Mondino National Neurological Institute, Pavia; Roberto Gaggero, Maria Maddalena Mancardi, Division of Neuropsychiatry, Istituto G. Gaslini, Genova; Antonio Gambardella, Institute of Neurology, University Magna Grecia, Catanzaro, Italy; Anna T. Giallonardo, Gabriella Egeo, Department of Neurological Sciences, Policlinico Umberto I, Sapienza University of Rome; Alfonso Iudice, Stella Jensen, Department of Neurosciences, University of Pisa; Angela La Neve, Nicola Specchio, Epilepsy Center, Neurology Hospital Amaducci, University of Bari; Ida Manna, Francesca Condino, Institute of Neurological Sciences, National Research Council, Mangone-Cosenza; Daniela Marino, Raffaele Rocchi, Gian Paolo Vatti, Epilepsy Centre, University of Siena; Roberto Michelucci, Stefania Testoni, Division of Neurology, Bellaria Hospital, Bologna; Roberta Paravidino, Laboratory of Human Genetics, E.O. Ospedali Galliera, Genoa; Pasquale Striano, Laboratory of Neurogenetics, Neuromuscular Disease Unit, Istituto G. Gaslini, Genoa; Francesca Vanadia, Service of Neuropsychiatry, Ospedale Civico, Palermo; Gaetano Zaccara, Unit of Neurology, Palagi Hospital, Firenze; Claudio Zucca, Clinical Neurophysiology Unit, E. Medear Scientific Institute, Lecco, Italy. This study was supported by the Klaus-Dieter Scharf Research Project Marburg and the Stiftung P.E. Kempkes Marburg. NR 12 TC 3 Z9 3 U1 0 U2 2 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 SEP PY 2015 VL 56 IS 9 BP E129 EP E133 DI 10.1111/epi.13076 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7PF UT WOS:000360795400003 PM 26174448 ER PT J AU Martin, NE AF Martin, Neil E. TI Doing It Right: How, Not Whether, To Perform Prostate-specific Antigen Screening SO EUROPEAN UROLOGY LA English DT Editorial Material ID TASK-FORCE RECOMMENDATION; FOLLOW-UP; CANCER C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Martin, NE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, ASB 1,L2,75 Francis St, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 9 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 361 EP 362 DI 10.1016/j.eururo.2015.02.035 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300011 PM 25794459 ER PT J AU DiPaola, RS Chen, YH Bubley, GJ Stein, MN Hahn, NM Carducci, MA Lattime, EC Gulley, JL Arlen, PM Butterfield, LH Wilding, G AF DiPaola, Robert S. Chen, Yu-Hui Bubley, Glenn J. Stein, Mark N. Hahn, Noah M. Carducci, Michael A. Lattime, Edmund C. Gulley, James L. Arlen, Philip M. Butterfield, Lisa H. Wilding, George TI A National Multicenter Phase 2 Study of Prostate-specific Antigen (PSA) Pox Virus Vaccine with Sequential Androgen Ablation Therapy in Patients with PSA Progression: ECOG 9802 SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Pox virus; Vaccine; PSA ID DEPRIVATION THERAPY; ONCOLOGY-GROUP; CANCER; IMMUNOTHERAPY; SURVIVAL; IMPACT; TRIAL AB Background: E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. Objective: To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Design, setting, and participants: Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte- macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Outcome measurements and statistical analysis: Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. Results and limitations: In step 1, 25 of 40 eligible patients (63%) were progression free at 6mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p = 0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade >= 4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. Conclusions: A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined withandrogenablation, supporting the feasibility of futurephase 3studies in thispopulation. Patient summary: These data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [DiPaola, Robert S.; Stein, Mark N.; Lattime, Edmund C.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hahn, Noah M.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Carducci, Michael A.] Johns Hopkins Univ, Baltimore, MD USA. [Gulley, James L.; Arlen, Philip M.] NCI, Bethesda, MD 20892 USA. [Butterfield, Lisa H.] Univ Pittsburgh, Pittsburgh, PA USA. [Wilding, George] Univ Wisconsin, UW Carbone Canc Ctr, Madison, WI USA. RP DiPaola, RS (reprint author), Rutgers Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM Robert.DiPaola@rutgers.edu RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Public Health Service [CA23318, CA66636, CA21115, CA80775, CA49883, CA16116, CA21076]; National Cancer Institute (NCI), National Institutes of Health; Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, group cochairs) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA80775, CA49883, CA16116, CA21076, and from the National Cancer Institute (NCI), National Institutes of Health, and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI. Only the first step of the study (step 1: vaccine alone) was presented at the Genitourinary American Society of Clinical Oncology Annual Meeting 2009; step 2 data (combined androgen ablation and vaccine) has not been presented. NR 19 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 365 EP 371 DI 10.1016/j.eururo.2014.12.010 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300013 PM 25533418 ER PT J AU Martin, NE AF Martin, Neil E. TI Improving What Matters SO EUROPEAN UROLOGY LA English DT Editorial Material ID LOCALIZED PROSTATE-CANCER; MORTALITY; OUTCOMES; TRIAL; MEN C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Martin, NE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 384 EP 385 DI 10.1016/j.eururo.2015.05.004 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300016 PM 26004798 ER PT J AU Nguyen, PL D'Amico, AV AF Nguyen, Paul L. D'Amico, Anthony V. TI Toward Personalizing the Use of Androgen Deprivation Therapy to Maximize Benefit and Minimize Harm SO EUROPEAN UROLOGY LA English DT Editorial Material ID PROSTATE-CANCER; CARDIOVASCULAR-DISEASE C1 [Nguyen, Paul L.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 397 EP 398 DI 10.1016/j.eururo.2014.12.019 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300018 PM 25542627 ER PT J AU Kroeger, N Pantuck, AJ Wells, JC Lawrence, N Broom, R Kim, JJ Srinivas, S Yim, J Bjarnason, GA Templeton, A Knox, J Bernstein, E Smoragiewicz, M Lee, J Rini, BI Vaishampayan, UN Woodm, LA Beuselinck, B Donskov, F Choueiri, TK Heng, DY AF Kroeger, Nils Pantuck, Allan J. Wells, J. Connor Lawrence, Nicola Broom, Reuben Kim, Jenny J. Srinivas, Sandy Yim, Jessica Bjarnason, Georg A. Templeton, Arnoud Knox, Jennifer Bernstein, Ezra Smoragiewicz, Martin Lee, Jae Rini, Brian I. Vaishampayan, Ulka N. Woodm, Lori A. Beuselinck, Benoit Donskov, Frede Choueiri, Toni K. Heng, Daniel Y. TI Characterizing the Impact of Lymph Node Metastases on the Survival Outcome for Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapies SO EUROPEAN UROLOGY LA English DT Article DE Lymph node metastases; Lymph nodes; Targeted therapies; Treatment response; Survival outcome; Renal cell carcinoma ID DATABASE CONSORTIUM; RADICAL NEPHRECTOMY; PROGNOSTIC-FACTORS; DISSECTION; LYMPHADENECTOMY; VALIDATION; CANCER; MODEL AB Background: It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients. Objective: To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT). Design, setting, and participants: Patients (n = 2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype. Additional analyses (n = 1536) were performed in subgroups of patients with supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) patients, respectively. Outcome measurements and statistical analysis: The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). Results and limitations: All patients with LNM had worse PFS (p = 0.001) and OS (p < 0.001) compared to those without LNM. Compared to patients without LNM (PFS 8.8 mo; OS 25.1 mo), any SBD LNM involvement was associated with worse PFS (SBD, 6.8 mo; p = 0.003; SPD+/SBD+, 5.5 mo; p < 0.001) and OS (SBD, 16.2 mo; p < 0.001; SPD+/SBD+, 11.5 mo; p < 0.001). Both SBD and SPD+/SBD+ LNM were retained as independent prognostic factors in multivariate analyses (MVA) for PFS (p = 0.006 and p = 0.022, respectively) and OS (both p < 0.001), while SPD LNM was not an independent risk factor. Likewise, in ccRCC, SBD LNM (19.8 mo) and SPD+/SBD+ LNM (12.85 mo) patients had the worst OS. SPD+/SBD+LNM (p = 0.006) and SBD LNM (p = 0.028) were independent prognostic factors for OS in MVA, while SPD LNM was not significant (p = 0.301). The study is limited by its retrospective design and the lack of pathologic evaluation of LNM in all cases. Conclusions: The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT. Patient summary: The presence of lymph node metastases below the diaphragm is associated with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Kroeger, Nils; Wells, J. Connor; Heng, Daniel Y.] Univ Calgary, Tom Baker Canc Ctr, Dept Med Oncol, Calgary, AB T2N 4N2, Canada. [Kroeger, Nils] Univ Med, Dept Urol, Greifswald, Germany. [Kroeger, Nils; Pantuck, Allan J.; Bernstein, Ezra] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Inst Urol Oncol, Los Angeles, CA 90095 USA. [Lawrence, Nicola; Broom, Reuben] Auckland City Hosp, Auckland, New Zealand. [Kim, Jenny J.] Johns Hopkins Univ Hosp, Dept Med Oncol, Baltimore, MD 21287 USA. [Srinivas, Sandy] Stanford Med Ctr, Div Oncol, Stanford, CA USA. [Yim, Jessica; Bjarnason, Georg A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Templeton, Arnoud; Knox, Jennifer] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. [Smoragiewicz, Martin] Univ British Columbia, British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada. [Lee, Jae] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Woodm, Lori A.] Dalhousie Univ, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada. [Beuselinck, Benoit] Katholieke Univ Leuven, Dept Gen Med Oncol, Leuven, Belgium. [Beuselinck, Benoit] Katholieke Univ Leuven, Leuven Canc Inst, Univ Hosp Leuven, Expt Oncol Lab, Leuven, Belgium. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heng, DY (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Trust family; Loker Pinard and Michael Brigham Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute FX Dr. Choueiri is supported in part by the Trust family and the Loker Pinard and Michael Brigham Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. Dr. Kroeger thanks Dr. Klatte, Department of Urology, Medical University of Vienna, for statistical advice. NR 23 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 506 EP 515 DI 10.1016/j.eururo.2014.11.054 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300035 PM 25524810 ER PT J AU Ambrecht, LA Perlman, JI McDonnell, JF Zhai, YG Qiao, L Bu, P AF Ambrecht, Lindsay A. Perlman, Jay I. McDonnell, James F. Zhai, Yougang Qiao, Liang Bu, Ping TI Protection of retinal function by sulforaphane following retinal ischemic injury SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Sulforaphane; Retinal ischemic reperfusion injury; Electroretinography; Neuroprotection; Retinal morphology ID NRF2-DEPENDENT PHASE-2 ENZYME; REPERFUSION INJURY; INDUCTION; NEURONS; ELEMENT; DAMAGE; NRF2; MICE AB Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (I% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Ambrecht, Lindsay A.; Perlman, Jay I.; McDonnell, James F.; Bu, Ping] Loyola Univ Chicago, Dept Ophthalmol, Maywood, IL 60153 USA. [Perlman, Jay I.] Loyola Univ Chicago, Dept Pathol, Maywood, IL 60153 USA. [Zhai, Yougang; Qiao, Liang] Loyola Univ Chicago, Dept Microbiol & Immunol, Maywood, IL 60153 USA. [Bu, Ping] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Perlman, Jay I.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Surg Serv, Hines, IL 60141 USA. RP Bu, P (reprint author), Loyola Univ Chicago, Dept Ophthalmol, 2160 S First Ave, Maywood, IL 60153 USA. EM pbu@luc.edu FU Richard A. Perritt Charitable Foundation; Illinois Society for the Prevention of Blindness; American Society of Cataract and Refractive Surgery FX The authors thank Dr. Xiaorong Liu for her suggestions. This work was supported by The Richard A. Perritt Charitable Foundation, Illinois Society for the Prevention of Blindness, and American Society of Cataract and Refractive Surgery. NR 21 TC 3 Z9 4 U1 2 U2 3 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 SEP PY 2015 VL 138 BP 66 EP 69 DI 10.1016/j.exer.2015.06.030 PG 4 WC Ophthalmology SC Ophthalmology GA CQ7IV UT WOS:000360777100008 PM 26142954 ER PT J AU Gonzalez, T Chiodo, C AF Gonzalez, Tyler Chiodo, Christopher TI ICD 10: A Primer for the Orthopedic Foot and Ankle Surgeon SO FOOT & ANKLE INTERNATIONAL LA English DT Review DE ICD 10; foot and ankle; orthopedic surgery; codes; billing AB The use of the 10th Revision of the International Classification of Diseases (ICD-10) will likely be required as of October 2015. ICD-10 was developed to increase the specificity and accuracy of disease and injury reporting. The number of diagnostic codes in this system has increased substantially, and approximately half of all ICD-10 codes are related to the musculoskeletal system, whereas 25% of all codes are related to fractures. For most foot and ankle injuries, the new code structure includes location, laterality, degree of healing, and encounter type. At the provider level, navigating this system will initially be a complex task. Understanding the ICD-10 code structure, properly training appropriate staff, and financially preparing for implementation will minimize potential practice disruption. C1 [Gonzalez, Tyler] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Chiodo, Christopher] Brigham & Womens Hosp, Faulkner Hosp, Div Foot & Ankle Surg, Brigham Foot & Ankle Ctr, Boston, MA 02130 USA. RP Chiodo, C (reprint author), Brigham & Womens Hosp, Faulkner Hosp, Div Foot & Ankle Surg, Brigham Foot & Ankle Ctr, 1153 Ctr St Suite 56, Boston, MA 02130 USA. EM cchiodo@partners.org NR 6 TC 0 Z9 0 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 SEP PY 2015 VL 36 IS 9 BP 1110 EP 1116 DI 10.1177/1071100715600286 PG 7 WC Orthopedics SC Orthopedics GA CQ5DU UT WOS:000360624300018 PM 26276133 ER PT J AU Osborn-Heaford, HL Murthy, S Gu, LL Larson-Casey, JL Ryan, AJ Shi, L Glogauer, M Neighbors, JD Hohl, R Carter, AB AF Osborn-Heaford, Heather L. Murthy, Shubha Gu, Linlin Larson-Casey, Jennifer L. Ryan, Alan J. Shi, Lei Glogauer, Michael Neighbors, Jeffrey D. Hohl, Raymond Carter, A. Brent TI Targeting the isoprenoid pathway to abrogate progression of pulmonary fibrosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Macrophage; Reactive oxygen species; Mitochondria; Pulmonary fibrosis; Rac1; Isoprenoid; Pathway ID COA REDUCTASE INHIBITOR; OXIDATIVE STRESS; EXTRACELLULAR-MATRIX; IN-VIVO; MACROPHAGES; RAC1; FIBROBLASTS; ACTIVATION; APOPTOSIS; SURVIVAL AB Fibrotic remodeling in lung injury is a major cause of morbidity. The mechanism that mediates the ongoing fibrosis is unclear, and there is no available treatment to abate the aberrant repair. Reactive oxygen species (ROS) have a critical role in inducing fibrosis by modulating extracellular matrix deposition. Specifically, mitochondrial hydrogen peroxide (H2O2) production by alveolar macrophages is directly linked to pulmonary fibrosis as inhibition of mitochondrial H2O2 attenuates the fibrotic response in mice. Prior studies indicate that the small GTP-binding protein, Rac1, directly mediates H2O2 generation in the mitochondrial intermembrane space. Geranylgeranylation of the C-terminal cysteine residue (Cys(189)) is required for Rac1 activation and mitochondria! import. We hypothesized that impairment of geranylgeranylation would limit mitochondrial oxidative stress and, thus, abrogate progression of pulmonary fibrosis. By targeting the isoprenoid pathway with a novel agent, digeranyl bisphosphonate (DGBP), which impairs geranylgeranylation, we demonstrate that Rac1 mitochondrial import, mitochondrial oxidative stress, and progression of the fibrotic response to lung injury are significantly attenuated. These observations reveal that targeting the isoprenoid pathway to alter Rac1 geranylgeranylation halts the progression of pulmonary fibrosis after lung injury. (C) 2015 Elsevier Inc. All rights reserved. C1 [Osborn-Heaford, Heather L.; Murthy, Shubha; Ryan, Alan J.; Hohl, Raymond; Carter, A. Brent] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Gu, Linlin; Larson-Casey, Jennifer L.; Carter, A. Brent] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Larson-Casey, Jennifer L.; Carter, A. Brent] Univ Iowa, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. [Shi, Lei; Carter, A. Brent] Univ Iowa, Human Toxicol Program, Iowa City, IA 52242 USA. [Glogauer, Michael] Univ Toronto, Canadian Inst Hlth Res Grp Matrix Dynam, Toronto, ON, Canada. [Neighbors, Jeffrey D.] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Hohl, Raymond] Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA. [Carter, A. Brent] Iowa City VA Healthcare Syst, Iowa City, IA USA. [Carter, A. Brent] Birmingham VAMC, Birmingham, AL USA. RP Carter, AB (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham VAMC, 1918 Univ Blvd,404 MCLM, Birmingham, AL 35294 USA. EM bcarter1@uab.edu OI Larson-Casey, Jennifer L./0000-0001-7238-7986 FU National Institutes of Health [2R01ES015981-07, R01ES014871]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development [1BX001135-01] FX This work was supported, in whole or in part, by National Institutes of Health Grants 2R01ES015981-07 and R01ES014871. This work was also supported by a Merit Review from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Grant 1BX001135-01. NR 58 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 2015 VL 86 BP 47 EP 56 DI 10.1016/j.freeradbiomed.2015.04.031 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CQ4JA UT WOS:000360569700005 PM 25958207 ER PT J AU Gelaye, B Barrios, YV Zhong, QY Rondon, MB Borba, CPC Sanchez, SE Henderson, DC Williams, MA AF Gelaye, Bizu Barrios, Yasmin V. Zhong, Qiu-Yue Rondon, Marta B. Borba, Christina P. C. Sanchez, Sixto E. Henderson, David C. Williams, Michelle A. TI Association of poor subjective sleep quality with suicidal ideation among pregnant Peruvian women SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Sleep quality; Suicide ideation; Suicide; Depression; Pregnancy ID RISK-FACTORS; ANXIETY DISORDERS; MAJOR DEPRESSION; POSTPARTUM WOMEN; PRETERM BIRTH; LATE-LIFE; COHORT; BEHAVIOR; PERIOD; ADULTS AB Objective: To examine the independent and joint relationships of poor subjective sleep quality and antepartum depression with suicidal ideation among pregnant women. Methods: A cross-sectional study was conducted among 641 pregnant women attending prenatal care clinics in Lima, Peru. Antepartum depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 scale. Antepartum subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression procedures were performed to estimate odds ratios (aOR) and 95% confidence intervals (95% CI) adjusted for confounders. Results: Overall, the prevalence of suicidal ideation in this cohort was 16.8% and poor subjective sleep quality was more common among women endorsing suicidal ideation as compared to their counterparts who did not (47.2% vs. 24.8%, P<.001). After adjustment for confounders including maternal depression, poor subjective sleep quality (defined using the recommended criteria of PSQI global score of >5 vs. <= 5) was associated with a 1.7-fold increased odds of suicidal ideation (aOR=1.67; 95% CI 1.02-2.71). When assessed as a continuous variable, each 1-unit increase in the global PSQI score resulted in an 18% increase in odds for suicidal ideation, even after adjusting for depression (aOR=1.18; 95% CI 1.08-1.28). Women with both poor subjective sleep quality and depression had a 3.5-fold increased odds of suicidal ideation (aOR=3.48; 95% CI 1.96-6.18) as compared with those who had neither risk factor. Conclusion: Poor subjective sleep quality was associated with increased odds of suicidal ideation. Replication of these findings may promote investments in studies designed to examine the efficacy of sleep-focused interventions to treat pregnant women with sleep disorders and suicidal ideation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gelaye, Bizu; Barrios, Yasmin V.; Zhong, Qiu-Yue; Henderson, David C.; Williams, Michelle A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rondon, Marta B.] Cayetano Heredia Peruvian Univ, Dept Med, Lima, Peru. [Borba, Christina P. C.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Borba, Christina P. C.; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sanchez, Sixto E.] Univ Peruana Ciencias Aplicadas, Lima, Peru. [Sanchez, Sixto E.] Asociac Civil PROESA, Lima, Peru. RP Gelaye, B (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,K505F, Boston, MA 02115 USA. EM bgelaye@hsph.harvard.edu OI Gelaye, Bizu/0000-0001-7934-548X FU National Institutes of Health (NIH) [R01-HD-059835, T37-MD000149, K01MH100428] FX This research was supported by an award from the National Institutes of Health (NIH; R01-HD-059835, T37-MD000149 and K01MH100428). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors wish to thank the dedicated staff members of Asociacion Civil Proyectos en Salud (PROESA), Peru and Instituto Especializado Materno Perinatal, Peru, for their expert technical assistance with this research. NR 74 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2015 VL 37 IS 5 BP 441 EP 447 DI 10.1016/j.genhosppsych.2015.04.014 PG 7 WC Psychiatry SC Psychiatry GA CQ4HD UT WOS:000360564500010 PM 25983188 ER PT J AU Gatchel, J Legesse, B Tayeb, S Murray, E Price, B AF Gatchel, Jennifer Legesse, Benalfew Tayeb, Safwan Murray, Evan Price, Bruce TI Neurosyphilis in psychiatric practice: a case-based discussion of clinical evaluation and diagnosis SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Neurosyphilis; Tabes dorsalis; Psychotic disorder; RPR ID MANIFESTATIONS; SYPHILIS AB Objective: Neurosyphilis can present with a wide range of neuropsychiatric symptoms. Hence, psychiatrists need to be familiar with tests for syphilis screening and how to interpret syphilis serologic tests. Methods: We present four cases of patients with positive syphilis tests encountered in a psychiatric hospital. Results: Two cases were treated for neurosyphilis, while the other two cases did not have active syphilis infection despite positive results. Conclusion: We thus highlight the challenges encountered by psychiatrists in screening for and diagnosing cases of neurosyphilis. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gatchel, Jennifer] MGH McLean Adult Psychiat Residency Program, Boston, MA USA. [Gatchel, Jennifer] Massachusetts Gen Hosp, Dept Psychopharmacol, Boston, MA 02114 USA. [Legesse, Benalfew] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Legesse, Benalfew] McLean Hosp, Dept Psychiat, Boston, MA USA. [Tayeb, Safwan] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Murray, Evan; Price, Bruce] Harvard Univ, Sch Med, Dept Neurol, Belmont, MA 02178 USA. [Murray, Evan; Price, Bruce] McLean Hosp, Dept Neurol, Boston, MA USA. [Murray, Evan; Price, Bruce] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Murray, Evan] Manchester VA Med Ctr, Traumat Brain Injury Serv, Manchester, NH USA. RP Legesse, B (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. EM blegesse@partners.org OI Gatchel, Jennifer/0000-0002-3892-9742 FU Jr. Foundation FX We would like to thank the Sidney R. Baer, Jr. Foundation for fellowship training support. NR 16 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2015 VL 37 IS 5 BP 459 EP 463 DI 10.1016/j.genhosppsych.2015.04.012 PG 5 WC Psychiatry SC Psychiatry GA CQ4HD UT WOS:000360564500013 PM 26022384 ER PT J AU Fei, Q Yang, XQ Jiang, H Wang, Q Yu, YY Yu, YL Yi, W Zhou, SL Chen, TP Lu, C Atadja, P Liu, XS Li, E Zhang, Y Shou, JY AF Fei, Qi Yang, Xiaoqin Jiang, Hua Wang, Qian Yu, Yanyan Yu, Yiling Yi, Wei Zhou, Shaolian Chen, Taiping Lu, Chris Atadja, Peter Liu, Xiaole Shirley Li, En Zhang, Yong Shou, Jianyong TI SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells SO GENOME RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE ESET; TRANSCRIPTIONAL NETWORK; RECOMBINANT HISTONES; METHYLATION; POLYCOMB; PLURIPOTENCY; REGULATORS; MAINTENANCE; CHROMATIN AB SETDB1, a histone methyltransferase responsible for methylation of histone H3 lysine 9 (H3K9), is involved in maintenance of embryonic stem (ES) cells and early embryonic development of the mouse. However, how SETDB1 regulates gene expression during development is largely unknown. Here, we characterized genome-wide SETDB1 binding and H3K9 trimethylation (H3K9me3) profiles in mouse ES cells and uncovered two distinct classes of SETDB1 binding sites, termed solo and ensemble peaks. The solo peaks were devoid of H3K9me3 and enriched near developmental regulators while the ensemble peaks were associated with H3K9me3. A subset of the SETDB1 solo peaks, particularly those near neural development-related genes, was found to be associated with Polycomb Repressive Complex 2 (PRC2) as well as PRC2-interacting proteins JARID2 and MTF2. Genetic deletion of Setdb1 reduced EZH2 binding as well as histone 3 lysine 27 (H3K27) trimethylation level at SETDB1 solo peaks and facilitated neural differentiation. Furthermore, we found that H3K27me3 inhibits SETDB1 methyltransferase activity. The currently identified reciprocal action between SETDB1 and PRC2 reveals a novel mechanism underlying ES cell pluripotency and differentiation regulation. C1 [Fei, Qi; Jiang, Hua; Yu, Yanyan; Yu, Yiling; Yi, Wei; Zhou, Shaolian; Lu, Chris; Atadja, Peter; Li, En; Shou, Jianyong] China Novartis Inst BioMed Res, Shanghai 201203, Peoples R China. [Yang, Xiaoqin; Wang, Qian; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Shanghai 200092, Peoples R China. [Chen, Taiping] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. [Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Shou, JY (reprint author), Lilly China Res & Dev Ctr, Shanghai 201203, Peoples R China. EM yzhang@tongji.edu.cn; shou_jian_yong@lilly.com RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU China Novartis Institutes for BioMedical Research; National Natural Science Foundation of China [31371288, 31322031]; Shanghai Rising-Star Program [13QH1402200] FX We thank Thomas Jenuwein for the H3K9me3 antibody for our initial study. We also thank Drs. Song Shi, Shannon Chuai, and Haiyan Xu for insightful discussion and suggestions. We thank Dr. Tengfei Zhang for critical reading of the paper. We thank Drs. Teddy Yang and Kehao Zhao for help with making the nucleosomes and Drs. Ling Li and Justin Gu for the help with the in vitro methylation assay. This project is sponsored by China Novartis Institutes for BioMedical Research. The fourteenth author (Y.Z.) is partially supported by the National Natural Science Foundation of China (31371288, 31322031) and the Shanghai Rising-Star Program (13QH1402200). NR 44 TC 3 Z9 3 U1 1 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD SEP PY 2015 VL 25 IS 9 BP 1325 EP 1335 DI 10.1101/gr.177576.114 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CQ6NK UT WOS:000360721000007 PM 26160163 ER PT J AU Mimiaga, MJ Biello, K Reisner, SL Crane, HM Wilson, J Grasso, C Kitahata, MM Mathews, WC Mayer, KH Safren, SA AF Mimiaga, Matthew J. Biello, Katie Reisner, Sari L. Crane, Heidi M. Wilson, Johannes Grasso, Chris Kitahata, Mari M. Mathews, Wm. Christopher Mayer, Kenneth H. Safren, Steven A. TI Latent Class Profiles of Internalizing and Externalizing Psychosocial Health Indicators Are Differentially Associated With Sexual Transmission Risk: Findings From the CFAR Network of Integrated Clinical Systems (CNICS) Cohort Study of HIV-Infected Men Engaged in Primary Care in the United States SO HEALTH PSYCHOLOGY LA English DT Article DE externalizing; HIV; internalizing; men who have sex with men; sexual risk ID RESEARCH DOMAIN CRITERIA; SUBSTANCE USE; NEGATIVE AFFECT; ANTIRETROVIRAL THERAPY; PSYCHIATRIC-DISORDERS; LONGITUDINAL DATA; ANAL INTERCOURSE; DSM-IV; BEHAVIOR; CLASSIFICATION AB Objective: To examine whether latent class indicators of negative affect and substance use emerged as distinct psychosocial risk profiles among HIV-infected men, and if these latent classes were associated with high-risk sexual behaviors that may transmit HIV. Methods: Data were from HIV-infected men who reported having anal intercourse in the past 6 months and received routine clinical care at 4 U.S. sites in the Centers for AIDS Research Network of Integrated Clinical Systems cohort (n = 1,210). Latent class membership was estimated using binary indicators for anxiety, depression, alcohol and/or drug use during sex, and polydrug use. Generalized estimating equations modeled whether latent class membership was associated with HIV sexual transmission risk in the past 6 months. Results: Three latent classes of psychosocial indicators emerged: (a) internalizing (15.3%; high probability of anxiety and major depression); (b) externalizing (17.8%; high probability of alcohol and/or drug use during sex and polydrug use); (c) low psychosocial distress (67.0%; low probability of all psychosocial factors examined). Internalizing and externalizing latent class membership were associated with HIV sexual transmission risk, compared to low psychosocial class membership; externalizing class membership was also associated with higher sexual transmission risk compared to internalizing class membership. Conclusions: Distinct patterns of psychosocial health characterize this sexually active HIV-infected male patient population and are strongly associated with HIV sexual transmission risk. Public Health intervention efforts targeting HIV sexual risk transmission may benefit from considering symptom clusters that share internalizing or externalizing properties. C1 [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Mimiaga, Matthew J.; Biello, Katie; Reisner, Sari L.; Wilson, Johannes; Grasso, Chris; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Boston, MA USA. [Biello, Katie; Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Crane, Heidi M.; Kitahata, Mari M.] Univ Washington, Sch Med, Div Infect Dis, Seattle, WA 98195 USA. [Mathews, Wm. Christopher] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Infect Dis, Boston, MA 02114 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@hsph.harvard.edu FU CNICS [R24AI067039]; PROMIS HIV grant [U01AR057954]; [R34DA031028]; [K24 MH094214] FX This work was supported in part by R34DA031028 (Matthew J. Mimiaga) and the CNICS grant R24AI067039 (Saag). Patient Reported Outcome collection in CNICS is also supported in part by the PROMIS HIV grant U01AR057954 (Heidi M. Crane). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Steven A. Safren is supported by K24 MH094214. NR 64 TC 3 Z9 3 U1 2 U2 6 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 SEP PY 2015 VL 34 IS 9 BP 951 EP 959 DI 10.1037/hea0000189 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA CQ4OO UT WOS:000360584600008 PM 25642839 ER PT J AU Leatherman, BD Khalid, A Lee, S McMains, K Peltier, J Platt, MP Stachler, RJ Toskala, E Tropper, G Venkatraman, G Lin, SY AF Leatherman, Bryan D. Khalid, Ayesha Lee, Stella McMains, Kevin Peltier, Jacques Platt, Michael P. Stachler, Robert J. Toskala, Elina Tropper, Guy Venkatraman, Giri Lin, Sandra Y. TI Dosing of sublingual immunotherapy for allergic rhinitis: evidence-based review with recommendations SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE type I allergy; subcutaneous immunotherapy; evidence-based medicine; aeroallergens; allergic conjunctivitis; allergy injections; asthma; sublingual immunotherapy ID HOUSE-DUST-MITE; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND-PLACEBO; SUB-LINGUAL IMMUNOTHERAPY; NORTH-AMERICAN ADULTS; QUALITY-OF-LIFE; GRASS-POLLEN; SWALLOW IMMUNOTHERAPY; BIRCH POLLEN AB BackgroundSince the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increased. However, 1 of the primary barriers to providing SLIT is lack of a published dosing recommendations. The purpose of this work is to provide a range of effective SLIT dosing based upon a rigorous review of the existing evidence base. An appendix with SLIT dosing recommendations is also included. MethodsA comprehensive search of the past 25 years of the medical literature using PubMed was performed for specific antigens. Inclusion criteria for articles included: randomized, placebo-controlled studies of SLIT, studies with clinical allergic rhinitis outcomes, and dosing units available to determine the micrograms per month of major allergen administered. The extracted data was used to compile a range of effective SLIT dosing for individual antigens. ResultsSeventy-five articles met the inclusion criteria, providing a range of effective dosing for some allergens. There was commonly a wide range in doses for particular antigens between the individual studies. For some antigens, there was significant overlap in dosage amount between studies showing efficacy and lack of efficacy. Clinical trials meeting inclusion criteria are not available for many allergens. ConclusionThis study provided a comprehensive review of the published sublingual dosing ranges for specific antigens. The review provided a range of effective sublingual doses for some allergens, whereas for other allergens there was insufficient published data to determine specific doses. Recommendations for SLIT dosing were produced based on the data revealed in the review and expert opinion. C1 [Leatherman, Bryan D.] Coastal Sinus & Allergy Ctr, Gulfport, MS 39503 USA. [Leatherman, Bryan D.] Coastal Ear Nose & Throat Associates, Gulfport, MS USA. [Khalid, Ayesha] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lee, Stella] Univ Pittsburgh, Med Ctr, Div Sinonasal Disorders & Allergy, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA USA. [McMains, Kevin] South Texas Vet Hlth Care Syst, Otolaryngol, San Antonio, TX USA. [Peltier, Jacques] North Oaks ENT & Allergy, Hammond, LA USA. [Platt, Michael P.] Boston Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA. [Stachler, Robert J.] Henry Ford Med Grp, Sterling Hts, MI USA. [Toskala, Elina] Temple Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. [Tropper, Guy] Avant Garde Med Care, Boucherville, PQ, Canada. [Venkatraman, Giri] Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. [Lin, Sandra Y.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. RP Leatherman, BD (reprint author), 9000 Lorraine Rd, Gulfport, MS 39503 USA. EM Leathermanmd@coastalent.net FU AAOA FX Funding sources for the study: This article is a product of a work group appointed by the American Academy of Otolaryngic Allergy (AAOA). Funding in the form of facilitating a face-to-face meeting was provided by the AAOA. NR 88 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD SEP PY 2015 VL 5 IS 9 BP 773 EP 783 DI 10.1002/alr.21561 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA CQ8BY UT WOS:000360832400002 PM 26097218 ER PT J AU Xu, WF Li, HZ Ji, ZG Yan, WG Zhang, YS Zhang, XB Li, Q AF Xu, Weifeng Li, Hanzhong Ji, Zhigang Yan, Weigang Zhang, Yushi Zhang, Xuebin Li, Qian TI Transumbilical laparoendoscopic single-site surgery versus conventional laparoscopy for the resection of retroperitoneal paragangliomas SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE laparoscopy; paraganglioma; pheochromocytoma; transumbilical laparoendoscopic single-site surgery ID CLINICAL-EXPERIENCE; PHEOCHROMOCYTOMA; ADRENALECTOMY; UROLOGY AB ObjectivesTo compare transumbilical laparoendoscopic single-site surgery with conventional laparoscopy for the resection of retroperitoneal paragangliomas. MethodsIn the present case-control study, we compared 11 transumbilical laparoendoscopic single-site surgery procedures with 22 conventional laparoscopy procedures carried out to treat retroperitoneal paragangliomas between June 2004 and October 2013 at Peking Union Medical Hospital, Beijing, China. Operative time, estimated intraoperative blood loss, blood transfusions, intraoperative hypertension, intraoperative hypotension, highest intraoperative systolic blood pressure, lowest intraoperative systolic blood pressure, postoperative fatigue time, postoperative systematic inflammation reaction syndrome, 24-h postoperative visual analog scale scores, postoperative hospital stay duration, and postoperative complications were recorded and analyzed. ResultsThere were no significant differences in patient characteristics. All surgical procedures were successfully completed in both groups. Minor complications occurred in one case in the laparoendoscopic single-site surgery group and in two cases in the conventional laparoscopy group. In the laparoendoscopic single-site surgery group, the operative time was longer than that in the conventional laparoscopy group (P=0.001). There were no significant differences in terms of intraoperative hypertension, intraoperative hypotension, highest intraoperative systolic blood pressure, lowest intraoperative systolic blood pressure, estimated blood loss, postoperative fatigue time, postoperative hospital stay or systematic inflammation reaction syndrome between the two groups. The 24-h postoperative visual analog scale score was lower in the laparoendoscopic single-site surgery group (P=0.002). No recurrence or metastases were observed over the duration of the postoperative follow up. ConclusionsIn properly selected patients, transumbilical laparoendoscopic single-site surgery is a feasible, safe and effective procedure for the surgical treatment of retroperitoneal paragangliomas. C1 [Xu, Weifeng; Li, Hanzhong; Ji, Zhigang; Yan, Weigang; Zhang, Yushi; Zhang, Xuebin] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Urol, Beijing 100730, Peoples R China. [Li, Qian] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Li, HZ (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Urol, Beijing 100730, Peoples R China. EM lihanzhongcn@163.com NR 30 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD SEP PY 2015 VL 22 IS 9 BP 844 EP 849 DI 10.1111/iju.12834 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CQ7CR UT WOS:000360760900010 PM 26119870 ER PT J AU Kohli, P Pinto-Plata, V Divo, M Malhotra, A Harris, RS Lazaar, A Flynn, A Tal-Singer, R Panettieri, RA Celli, B AF Kohli, Puja Pinto-Plata, Victor Divo, Miguel Malhotra, Atul Harris, R. Scott Lazaar, Aili Flynn, Aiden Tal-Singer, Ruth Panettieri, Reynold A., Jr. Celli, Bartolome TI Functional Capacity, Health Status, and Inflammatory Biomarker Profile in a Cohort of Patients With Chronic Obstructive Pulmonary Disease SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE biomarkers; chronic obstructive pulmonary disease; health-related quality of life; pulmonary rehabilitation ID 6-MIN WALK DISTANCE; QUALITY-OF-LIFE; CHRONIC RESPIRATORY-DISEASE; SYSTEMIC INFLAMMATION; ECLIPSE COHORT; COPD; MORTALITY; ASSOCIATION; REHABILITATION; DEPRESSION AB PURPOSE: Prior research has shown a significant relationship between 6-minute walking distance (6MWD) and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, few studies have examined this relationship above and below the 350-m threshold that prognosticates survival and whether serum biomarkers could provide insight into the causes of quality-of-life differences above and below this threshold. METHODS: Measures of lung function, 6MWD, and HRQOL were compared in patients with COPD. Differences in HRQOL domains and serum biomarkers were compared in patients whose 6MWD were > or < 350 m. RESULTS: In patients walking < 350 m, scores in the physical domains of the SF-36 and the St. George's Respiratory Questionnaire (SGRQ) were significantly different from scores of their counterparts with greater 6MWD. However, there was no association between any biomarkers and the physical domains of the SF-36 and the SGRQ. In patients walking < 350 m, only the IL-8 levels were associated with lower scores in SF-36 domains of emotional role, pain, vitality, and mental health (average r = -0.702; P = .01). In contrast, in patients walking > 350 m, surfactant protein D levels were associated with higher SF-36 scores in general pain, vitality, and social functioning (average r = 0.42; P = .04). CONCLUSIONS: In COPD, there is an association between 6MWD and the physical domains of the SF-36 and SGRQ in those patients walking < 350 m. The physical differences between patients walking < or > 350 m are not related to systemic inflammation. The association between interleukin 8 with nonphysical domains in patients with 6MWD < 350 m suggests that inflammation may play a larger role in the perceptive domain than previously recognized. C1 [Kohli, Puja; Pinto-Plata, Victor; Divo, Miguel; Celli, Bartolome] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Kohli, Puja; Harris, R. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA USA. [Malhotra, Atul] Univ Calif San Diego, Sch Med, Div Pulm & Crit Care Med, Div Sleep Med, San Diego, CA 92103 USA. [Lazaar, Aili; Flynn, Aiden; Tal-Singer, Ruth] GalaxoSmithKline, COPD Clin Discovery, King Of Prussia, PA USA. [Panettieri, Reynold A., Jr.] Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. RP Celli, B (reprint author), PBB Clin 3, 75 Francis St, Boston, MA 02115 USA. EM BCelli@copdnet.org FU GalaxoSmithKline FX Support for this research was provided by an unrestricted grant from GalaxoSmithKline. Jane Gilbert contributed to the data analysis of the manuscript. NR 42 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-7501 EI 1932-751X J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD SEP-OCT PY 2015 VL 35 IS 5 BP 348 EP 355 DI 10.1097/HCR.0000000000000123 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ5QN UT WOS:000360660600007 PM 26309192 ER PT J AU Dukkipati, SR Woollett, I McElderry, HT Bohmer, MC Doshi, SK Gerstenfeld, EP Horton, R D'Avila, A Haines, DE Valderrabano, M Mangrum, JM Ruskin, JN Natale, A Reddy, VY AF Dukkipati, Srinivas R. Woollett, Ian McElderry, H. Thomas Boehmer, Marie-Christine Doshi, Shephal K. Gerstenfeld, Edward P. Horton, Rodney D'Avila, Andre Haines, David E. Valderrabano, Miguel Mangrum, J. Michael Ruskin, Jeremy N. Natale, Andrea Reddy, Vivek Y. TI Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: Results of the US Feasibility Study SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; laser; pulmonary veins; visual guidance ID PAROXYSMAL ATRIAL-FIBRILLATION; ENDOSCOPIC ABLATION SYSTEM; CATHETER ABLATION; FOLLOW-UP; 2ND-GENERATION CRYOBALLOON; MULTICENTER; EXPERIENCE; EFFICACY; LESSONS; SAFETY AB Visually Guided PV Isolation IntroductionVisually guided laser balloon (VGLB) ablation is unique in that the operator delivers ablative energy under direct visual guidance. In this multicenter study, we sought to determine the feasibility, efficacy, and safety of performing pulmonary vein isolation (PVI) using this VGLB. MethodsPatients with symptomatic, drug-refractory paroxysmal atrial fibrillation (AF) underwent PVI using the VGLB with the majority of operators conducting their first-ever clinical VGLB cases. The primary effectiveness endpoint was defined as freedom from treatment failure that included: Occurrence of symptomatic AF episodes 1 minutes beyond the 90-day blanking, the inability to isolate 1 superior and 2 total PVs, occurrence of left atrial flutter or atrial tachycardia, or left atrial ablation/surgery during follow-up. ResultsA total of 86 patients (mean age 5610 years, 67% male) were treated with the VGLB at 10 US centers. Mean fluoroscopy, ablation, and procedure times were 39.8 +/- 24.3 minutes, 205.2 +/- 61.7 minutes, and 253.5 +/- 71.3 minutes, respectively. Acute PVI was achieved in 314/323 (97.2%) of targeted PVs. Of 84 patients completing follow-up, the primary effectiveness endpoint was achieved in 50 (60%) patients. Freedom from symptomatic or asymptomatic AF was 61%. The primary adverse event rate was 16.3% (8.1% pericarditis, phrenic nerve injury 5.8%, and cardiac tamponade 3.5%). There were no cerebrovascular events, atrioesophageal fistulas, or significant PV stenosis. ConclusionsThis multicenter study of operators in the early stage of the learning curve demonstrates that PVI can be achieved with the VGLB with a reasonable safety profile and an efficacy similar to radiofrequency ablation. C1 [Dukkipati, Srinivas R.; Boehmer, Marie-Christine; D'Avila, Andre; Reddy, Vivek Y.] Icahn Sch Med Mt Sinai, Helmsley Electrophysiol Ctr, New York, NY 10029 USA. [Woollett, Ian] Sentara Cardiovasc Res Inst, Norfolk, VA USA. [McElderry, H. Thomas] Univ Alabama Birmingham, Birmingham, AL USA. [Doshi, Shephal K.] Pacific Heart Inst, Santa Monica, CA USA. [Gerstenfeld, Edward P.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Haines, David E.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Valderrabano, Miguel] Methodist Hosp, Houston, TX 77030 USA. [Mangrum, J. Michael] Univ Virginia, Charlottesville, VA USA. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Horton, Rodney; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. RP Dukkipati, SR (reprint author), Icahn Sch Med Mt Sinai, Helmsley Electrophysiol Ctr, One Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM srinivas.dukkipati@mountsinai.org FU CardioFocus; Hansen Medical; Boston Scientific; CardioInsight; Cardiome; Gilead Sciences; Medtronic; Pfizer FX Drs. Woollett, McElderry, Doshi, Mangrum, Haines, and Reddy report participation on a research grant supported by CardioFocus. Drs. Dukkipati and McElderry report compensation for participation on a speaker's bureau and honoraria relevant to this topic; in addition, Dr. McElderry serves as consultant/advisory board member for Boston Scientific, ACT Med, Vytron US, St. Jude Medical, and Biosense Webster. Dr. Reddy serves as consultant/advisory board member for CardioFocus. Dr. Valderrabano reports research grants supported by Hansen Medical and Boston Scientific. Dr. Ruskin reports consultant fees from CardioInsight, Cardiome, Gilead Sciences, Medtronic, and Pfizer; honorarium from Sanofi Aventis; equity interest in InfoBionic and Portola. Other authors: No disclosures. NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2015 VL 26 IS 9 BP 944 EP 949 DI 10.1111/jce.12727 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ7VM UT WOS:000360813600005 ER PT J AU Sadowska, GB Chen, XD Zhang, JY Lim, YP Cummings, EE Makeyev, O Besio, WG Gaitanis, J Padbury, JF Banks, WA Stonestreet, BS AF Sadowska, Grazyna B. Chen, Xiaodi Zhang, Jiyong Lim, Yow-Pin Cummings, Erin E. Makeyev, Oleksandr Besio, Walter G. Gaitanis, John Padbury, James F. Banks, William A. Stonestreet, Barbara S. TI Interleukin-1 beta transfer across the blood-brain barrier in the ovine fetus SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; brain; cytokines; fetus; hypoxia-ischemia; sheep ID NECROSIS-FACTOR-ALPHA; PROTEIN EXPRESSION; WHITE-MATTER; NEONATAL-RAT; TRANSPORT; CYTOKINES; ISCHEMIA; INJURY; MECHANISM; MOUSE AB Pro-inflammatory cytokines contribute to hypoxic-ischemic brain injury. Blood-brain barrier (BBB) dysfunction represents an important component of hypoxic-ischemic brain injury in the fetus. Hypoxic-ischemic injury could accentuate systemic cytokine transfer across the fetal BBB. There has been considerable conjecture suggesting that systemic cytokines could cross the BBB during the perinatal period. Nonetheless, evidence to support this contention is sparse. We hypothesized that ischemia-reperfusion increases the transfer of systemic interleukin-1 beta (IL-1 beta) across the BBB in the fetus. Ovine fetuses at 127 days of gestation were studied 4 hours after 30 minutes of bilateral carotid artery occlusion and compared with a nonischemic group. Recombinant ovine IL-1 beta protein was expressed from an IL-1 beta pGEX-2 T vector in E. coli BL-21 cells and purified. The BBB function was quantified in 12 brain regions using a blood-to-brain transfer constant with intravenous I-125-radiolabeled IL-1 beta (I-125-IL-1 beta). Interleukin-1 beta crossed the intact BBB in nonischemic fetuses. Blood-to-brain transport of I-125-IL-1 beta was higher (P < 0.05) across brain regions in fetuses exposed to ischemia-reperfusion than nonischemic fetuses. We conclude that systemic IL-1 beta crosses the intact fetal BBB, and that ischemia-reperfusion increases transfer of this cytokine across the fetal BBB. Therefore, altered BBB function after hypoxia-ischemia facilitates entry of systemic cytokines into the brain of the fetus. C1 [Sadowska, Grazyna B.; Chen, Xiaodi; Zhang, Jiyong; Cummings, Erin E.; Padbury, James F.; Stonestreet, Barbara S.] Brown Univ, Alpert Med Sch, Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. [Lim, Yow-Pin] ProThera Biol Inc, Providence, RI USA. [Makeyev, Oleksandr; Besio, Walter G.] Univ Rhode Isl, Dept Elect Comp & Biomed Engn, Kingston, RI 02881 USA. [Gaitanis, John] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Neurol, Providence, RI 02905 USA. [Banks, William A.] Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Div Gerontol & Geriatr Med,Geriatr Res Educ & Cli, Seattle, WA USA. RP Stonestreet, BS (reprint author), Brown Univ, Alpert Med Sch, Women & Infants Hosp Rhode Isl, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA. EM bstonestreet@wihri.org FU National Institute of General Medical Sciences of the National Institutes of Health [1R01-HD-057100, P20 RR018728, P20GM103537]; American Heart Association [13POST16860015] FX Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number 1R01-HD-057100, by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 RR018728 and P20GM103537, and by a postdoctoral fellowship award (JZ) from the American Heart Association under grant number 13POST16860015. NR 46 TC 3 Z9 3 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2015 VL 35 IS 9 BP 1388 EP 1395 DI 10.1038/jcbfm.2015.134 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CQ6BN UT WOS:000360689500002 PM 26082012 ER PT J AU Werner, P Saur, D Zeisig, V Ettrich, B Patt, M Sattler, B Jochimsen, T Lobsien, D Meyer, PM Bergh, FT Dreyer, A Boltze, J Classen, J Fritzsch, D Hoffmann, KT Sabri, O Barthel, H AF Werner, Peter Saur, Dorothee Zeisig, Vilia Ettrich, Barbara Patt, Marianne Sattler, Bernhard Jochimsen, Thies Lobsien, Donald Meyer, Philipp M. Bergh, Florian Then Dreyer, Antje Boltze, Johannes Classen, Joseph Fritzsch, Dominik Hoffmann, Karl-Titus Sabri, Osama Barthel, Henryk TI Simultaneous PET/MRI in stroke: a case series SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Mismatch; penumbra; PET/MRI; stroke; thrombolysis ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; ISCHEMIC-STROKE; MRI; PET; METABOLISM; ALTEPLASE; PENUMBRA; TRIAL; MAPS AB Prospective studies on magnetic resonance imaging (MRI)-guided systemic thrombolysis >4.5 hours after stroke onset did not reach their primary end points. It was discussed and observed in post hoc data re-assessment that this was partly because of limited MRI accuracy to measure critical hypoperfusion. We report the first cases of simultaneous [O-15]H2O-positron emission tomography (PET)/MRI in stroke patients and an ovine model. Discrepancies between simultaneously obtained PET and MRI readouts were observed that might explain the above current limitations of stroke MRI. By offering highly complementary information, [O-15]H2O-PET/MRI might help to identify critically hypoperfused tissue resulting in an improved patient stratification in thrombolysis trials. C1 [Werner, Peter; Zeisig, Vilia; Patt, Marianne; Sattler, Bernhard; Jochimsen, Thies; Meyer, Philipp M.; Sabri, Osama; Barthel, Henryk] Univ Leipzig, Dept Nucl Med, D-04103 Leipzig, Germany. [Saur, Dorothee; Ettrich, Barbara; Bergh, Florian Then; Classen, Joseph] Univ Leipzig, Dept Neurol, D-04103 Leipzig, Germany. [Lobsien, Donald; Fritzsch, Dominik; Hoffmann, Karl-Titus] Univ Leipzig, Dept Neuroradiol, D-04103 Leipzig, Germany. [Bergh, Florian Then; Dreyer, Antje] Univ Leipzig, Univ Hosp Leipzig, Translat Ctr Regenerat Med, D-04103 Leipzig, Germany. [Dreyer, Antje; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. RP Barthel, H (reprint author), Univ Leipzig, Dept Nucl Med, Liebigstr 18, D-04103 Leipzig, Germany. EM henryk.barthel@medizin.uni-leipzig.de FU German Research Foundation [SA 669/9-1]; Max Planck Society FX The work was supported by the German Research Foundation that funded the PET/MRI system (grantcode: SA 669/9-1). The Max Planck Society co-funded the system. NR 18 TC 7 Z9 7 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2015 VL 35 IS 9 BP 1421 EP 1425 DI 10.1038/jcbfm.2015.158 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CQ6BN UT WOS:000360689500008 PM 26174332 ER PT J AU Dong, TT Zhang, Q Hamblin, MR Wu, MX AF Dong, Tingting Zhang, Qi Hamblin, Michael R. Wu, Mei X. TI Low-level light in combination with metabolic modulators for effective therapy of injured brain SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE hypoxia; lactate/pyruvate; low-level light; mitochondrial function; TBI ID RAT-LIVER MITOCHONDRIA; TREATMENT STRATEGIES; TRANSCRANIAL LASER; SPINAL-CORD; IN-VITRO; HYPOXIA; NEURONS; PYRUVATE; LACTATE; DAMAGE AB Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue-like injured brain. C1 [Dong, Tingting; Zhang, Qi; Hamblin, Michael R.; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. EM mwu5@mgh.harvard.edu FU Department of Defense/Air Force Office of Scientific Research Militory Phtomedicine Program [FA9550-11-1-0331, FA9550-13-1-0068]; Department of Defense, CDMRP/BAA [W81XWH-13-2-0067]; [CA158756] FX This work was supported by FA9550-11-1-0331 and FA9550-13-1-0068, Department of Defense/Air Force Office of Scientific Research Militory Phtomedicine Program, W81XWH-13-2-0067, Department of Defense, CDMRP/BAA, and CA158756 to MW. NR 39 TC 6 Z9 6 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2015 VL 35 IS 9 BP 1435 EP 1444 DI 10.1038/jcbfm.2015.87 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CQ6BN UT WOS:000360689500010 PM 25966949 ER PT J AU Roh, MR Kim, JM Lee, SH Jang, HS Park, KH Chung, KY Rha, SY AF Roh, Mi Ryung Kim, Jung Min Lee, Sang Hee Jang, Hong Sun Park, Kyu Hyun Chung, Kee Yang Rha, Sun Young TI Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation SO JOURNAL OF DERMATOLOGY LA English DT Article DE human HaCaT keratinocyte; matrix metalloproteinase; mitogen-activated protein kinase pathway; squamous cell carcinoma; vemurafenib ID SQUAMOUS-CELL CARCINOMA; BRAF V600E MUTATION; RAF INHIBITORS; COLORECTAL NEOPLASIA; METASTATIC MELANOMA; SKIN CARCINOGENESIS; IMPROVED SURVIVAL; PROGRESSION; EXPRESSION; METALLOPROTEINASES AB Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2mol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2mol/L vemurafenib for 24h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2mol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion. C1 [Roh, Mi Ryung; Lee, Sang Hee; Jang, Hong Sun; Chung, Kee Yang] Yonsei Univ, Coll Med, Cutaneous Biol Res Inst, Dept Dermatol, Seoul 120749, South Korea. [Roh, Mi Ryung] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02115 USA. [Kim, Jung Min; Park, Kyu Hyun; Rha, Sun Young] Yonsei Univ, Coll Med, Songdam Inst Canc Res, Seoul 120749, South Korea. [Rha, Sun Young] Yonsei Univ, Coll Med, Dept Int Med, Seoul 120749, South Korea. [Rha, Sun Young] Yonsei Univ, Coll Med, Div Med Oncol, Seoul 120749, South Korea. RP Rha, SY (reprint author), Yonsei Univ, Yonsei Canc Ctr, Dept Internal Med, Div Med Oncol,Coll Med, 50 Yonsei Ro, Seoul 120749, South Korea. EM rha7655@yuhs.ac FU Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2011-0022376]; Public Welfare and Safety Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0020841] FX This work was supported by the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Education, Science and Technology (2011-0022376) and by the Public Welfare and Safety Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (2010-0020841). NR 35 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0385-2407 EI 1346-8138 J9 J DERMATOL JI J. Dermatol. PD SEP PY 2015 VL 42 IS 9 BP 881 EP 888 DI 10.1111/1346-8138.12950 PG 8 WC Dermatology SC Dermatology GA CQ7EQ UT WOS:000360766200006 PM 26047064 ER PT J AU Hanske, J Sanchez, A Schmid, M Meyer, CP Abdollah, F Feldman, AS Kibel, AS Sammon, JD Menon, M Eswara, JR Noldus, J Trinh, QD AF Hanske, Julian Sanchez, Alejandro Schmid, Marianne Meyer, Christian P. Abdollah, Firas Feldman, Adam S. Kibel, Adam S. Sammon, Jesse D. Menon, Mani Eswara, Jairam R. Noldus, Joachim Trinh, Quoc-Dien TI A Comparison of 30-Day Perioperative Outcomes in Open Versus Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Carcinoma: Analysis of 896 Patients from the American College of Surgeons-National Surgical Quality Improvement Program Database SO JOURNAL OF ENDOUROLOGY LA English DT Article ID LYMPH-NODE DISSECTION; LAPAROSCOPIC NEPHROURETERECTOMY; RADICAL NEPHROURETERECTOMY; VENOUS THROMBOEMBOLISM; ONCOLOGIC OUTCOMES; BLOOD-TRANSFUSION; CANCER; LYMPHADENECTOMY; METAANALYSIS; EVENTS AB Background and Purpose: Minimally invasive surgery for nephroureterectomy (MINU) in patients with upper tract urothelial carcinoma (UTUC) is increasingly used among urologists with reported equivalent oncologic outcomes compared with open nephroureterectomy (ONU). Population-level data comparing perioperative outcomes between these approaches remain limited, however. We sought to compare perioperative outcomes between MINU and ONU in a prospectively collected national cohort of patients. Methods: Between 2006 and 2012, patients who underwent nephroureterectomy for UTUC within the American College of Surgeons-National Surgical Quality Improvement Program database were categorized into MINU or ONU. Our primary outcome of interest was 30-day perioperative complications. Secondary outcomes included use of lymph node dissection (LND), transfusion, reintervention and readmission rate, operative time, length of stay (LOS), and perioperative mortality. Multivariable logistic regression analyses were used to examine the association between outcomes and surgical approach. Results: A total of 599 (66.9%) and 297 (33.1%) patients underwent MINU and ONU, respectively. Overall, 12.7% of patients experienced a complication within 30 days postoperatively, and the rate did not differ among surgical approaches. Patients in the MINU group, however, had a decreased LOS (P<0.001). On multivariable analysis, patients receiving MINU were less likely to undergo a LND (OR 0.13; P<0.001), had decreased risk of thromboembolic complications (odds ratio [OR] 0.13; P=0.018), decreased need for transfusion (OR 0.39; P=0.001), and decreased need for operative reintervention (OR 0.24; P=0.024). Conclusions: Patients receiving MINU have similar overall complication rates compared with ONU. MINU, however, was associated with a decreased risk of blood transfusions, thromboembolic events, reintervention, and overall LOS compared with ONU. MINU should be considered as a primary approach in select groups of patients with UTUC. C1 [Hanske, Julian; Schmid, Marianne; Meyer, Christian P.; Kibel, Adam S.; Eswara, Jairam R.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. [Hanske, Julian; Schmid, Marianne; Meyer, Christian P.; Kibel, Adam S.; Eswara, Jairam R.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hanske, Julian; Noldus, Joachim] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Bochum, Herne, Germany. [Sanchez, Alejandro; Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Schmid, Marianne; Meyer, Christian P.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Abdollah, Firas; Sammon, Jesse D.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyst & Evaluat, Detroit, MI USA. RP Hanske, J (reprint author), Brigham & Womens Hosp, Div Urol Surg, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM j.hanske@gmx.de FU Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital; Vattikuti Urology Institute; Heinrich Hertz-Stiftung FX Quoc-Dien Trinh is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital and by an unrestricted educational grant from the Vattikuti Urology Institute. Julian Hanske is supported by a grant from the Heinrich Hertz-Stiftung. NR 27 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 EI 1557-900X J9 J ENDOUROL JI J. Endourol. PD SEP 1 PY 2015 VL 29 IS 9 BP 1052 EP 1058 DI 10.1089/end.2015.0137 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CQ4RA UT WOS:000360591100013 PM 25891843 ER PT J AU Grob, SR Campbell, AA Gross, A Cestari, DM AF Grob, Seanna R. Campbell, Ashley A. Gross, Andrew Cestari, Dean M. TI Hemorrhage Within the Optic Nerve From a Cavernous Hemangioma of the Optic Disc SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID RETINA AB A 49-year-old woman with a known right optic disc cavernous hemangioma experienced pain with eye movements and worsening of a superior visual field defect. While she retained 20/20 visual acuity in each eye, findings on magnetic resonance imaging were consistent with a hemorrhage in the anterior portion of the right intraorbital optic nerve. Her visual function stabilized spontaneously. We are unaware of previous reports of hemorrhage into the optic nerve from a cavernous hemangioma of the optic disc. C1 [Gross, Andrew; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Neuroophthalmol, Boston, MA 02114 USA. [Grob, Seanna R.; Campbell, Ashley A.; Gross, Andrew; Cestari, Dean M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Cestari, DM (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dean_cestari@meei.harvard.edu NR 9 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 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2015 VL 35 IS 3 BP 277 EP 279 DI 10.1097/WNO.0000000000000274 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CQ4DC UT WOS:000360553500010 PM 26132965 ER PT J AU Cestari, DM Lessell, S Mantopoulos, D AF Cestari, Dean M. Lessell, Simmons Mantopoulos, Dimosthenis TI Early Diagnosis of Subclinical Interferon Alpha-Associated Optic Neuropathy Using Fluorescein Angiography SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID COMBINATION THERAPY; HEPATITIS-C; RETINOPATHY; EDEMA; RIBAVIRIN AB We report a case of a 57-year-old man who presented with decreased visual acuity in the left eye secondary to nonarteritic anterior ischemic optic neuropathy (NAION) while on therapy with interferon- for hepatitis C. Fundus fluorescein angiography revealed late leakage of both optic discs, consistent with bilateral disease. One week later, the patient developed clinical signs and symptoms consistent with NAION in the fellow eye. Fluorescein angiography may play an important role in identifying subclinical NAION in patients taking interferon-. C1 [Cestari, Dean M.; Lessell, Simmons; Mantopoulos, Dimosthenis] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Neuroophthalmol Serv, Boston, MA USA. [Mantopoulos, Dimosthenis] Ohio State Univ, Wexner Med Ctr, Havener Eye Inst, Dept Ophthalmol & Visual Sci, Columbus, OH 43212 USA. RP Mantopoulos, D (reprint author), Ohio State Univ, Wexner Med Ctr, Havener Eye Inst, Dept Ophthalmol & Visual Sci, 915 Olentangy River Rd, Columbus, OH 43212 USA. EM dimosthenis.mantopoulos@osumc.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2015 VL 35 IS 3 BP 280 EP 283 DI 10.1097/WNO.0000000000000238 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CQ4DC UT WOS:000360553500011 PM 25793363 ER PT J AU Borchert, MS Lessell, S AF Borchert, Mark S. Lessell, Simmons TI Fanfare for the Uncommon Neuro-Ophthalmologist: A Tribute to Irma Miller Lessell In Memoriam SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Biographical-Item C1 [Borchert, Mark S.] USC, Keck Sch Med, Childrens Hosp Los Angeles, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Lessell, Simmons] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Borchert, MS (reprint author), USC, Keck Sch Med, Childrens Hosp Los Angeles, Dept Ophthalmol, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2015 VL 35 IS 3 BP e24 EP e25 DI 10.1097/WNO.0000000000000262 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CQ4DA UT WOS:000360553300001 PM 26505049 ER PT J AU Wang, SY Aldridge, MD Gross, CP Canavan, M Cherlin, E Johnson-Hurzeler, R Bradley, E AF Wang, Shi-Yi Aldridge, Melissa D. Gross, Cary P. Canavan, Maureen Cherlin, Emily Johnson-Hurzeler, Rosemary Bradley, Elizabeth TI Geographic Variation of Hospice Use Patterns at the End of Life SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CARE; CANCER; DEATH; QUALITY; INDICATORS; DEPRESSION; ENROLLMENT; CAREGIVERS; BENEFIT; LENGTH AB Background: Little is known about state-level variation in patterns of hospice use, an important indicator of quality of care at the end of life. Findings may identify states where targeted efforts for improving end-of-life care may be warranted. Objective: Our aim was to characterize the state-level variation in patterns of hospice use among decedents and to examine state, county, and individual factors associated with these patterns. Methods: We conducted a retrospective analysis of Medicare fee-for-service decedents. The primary outcome measures were state-level hospice use during the last 6 months of life and the state's proportion of hospice users with very short hospice enrollment (7 days), very long hospice enrollment (180 days), and hospice disenrollment prior to death. Results: In 2011, the percentage of decedents who used hospice in the last 6 months of life nationally was 47.1%, and varied across states from 20.3% in Alaska to 60.8% in Utah. Hospice utilization patterns also varied by state, with the percentage of hospice users with very short hospice enrollment ranging from 23.0% in the District of Columbia to 39.9% in Connecticut. The percentage of very long hospice use varied from 5.7% in Connecticut to 15.9% in Delaware. The percentage of hospice disenrollment ranged from 6.2% in Hawaii to 19.0% in the District of Columbia. Nationally, state-level hospice use among decedents was positively correlated with the percentage of potentially concerning patterns (including very short hospice enrollment, very long hospice enrollment, and hospice disenrollment) among hospice users (the Pearson correlation coefficient=0.52, p value<0.001). Oregon was the only state in the highest quartile of hospice use and the lowest quartiles of both very short and very long hospice enrollment. Conclusions: The percentage of decedents who use hospice may mask important state-level variation in these patterns, including the timing of hospice enrollment, a potentially important component of the quality of end-of-life care. C1 [Wang, Shi-Yi] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA. [Canavan, Maureen; Cherlin, Emily; Bradley, Elizabeth] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT 06520 USA. [Wang, Shi-Yi; Gross, Cary P.] Yale Canc Ctr, Canc Outcomes Publ Policy & Effectiveness Res COP, New Haven, CT USA. [Wang, Shi-Yi; Gross, Cary P.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Aldridge, Melissa D.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Aldridge, Melissa D.] James J Peters VA Med Ctr, Bronx, NY USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, New Haven, CT 06520 USA. [Johnson-Hurzeler, Rosemary] John D Thompson Hospice Inst Educ Training & Res, Branford, CT USA. RP Wang, SY (reprint author), Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, 60 Coll St,POB 208034, New Haven, CT 06520 USA. EM shiyi.wang@yale.edu FU National Cancer Institute [1R01CA116398-01A2]; John D. Thompson Foundation; National Institute of Nursing Research [5R01NR013499] FX This study was supported by grant 1R01CA116398-01A2 from the National Cancer Institute (Drs. Aldridge and Bradley), the John D. Thompson Foundation (Dr. Bradley), and grant 5R01NR013499 from the National Institute of Nursing Research (Dr. Aldridge). NR 23 TC 7 Z9 7 U1 2 U2 4 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 SEP 1 PY 2015 VL 18 IS 9 BP 771 EP 780 DI 10.1089/jpm.2014.0425 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CQ1LE UT WOS:000360358400010 PM 26172615 ER PT J AU Kaafarani, HMA AF Kaafarani, Haytham M. A. TI The voice of the "never-complaining" staff: the impact of hospital and residency mergers on surgical trainees SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material C1 Harvard Univ, Dept Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Dept Surg, Sch Med, Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2015 VL 198 IS 1 BP 59 EP 60 DI 10.1016/j.jss.2015.05.047 PG 2 WC Surgery SC Surgery GA CQ6IG UT WOS:000360707300010 PM 26095421 ER PT J AU Vimalananda, VG Gupte, G Seraj, SM Orlander, J Berlowitz, D Fincke, BG Simon, SR AF Vimalananda, Varsha G. Gupte, Gouri Seraj, Siamak M. Orlander, Jay Berlowitz, Dan Fincke, Benjamin G. Simon, Steven R. TI Electronic consultations (e-consults) to improve access to specialty care: A systematic review and narrative synthesis SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Review DE remote consultation; teleconsulting; telehealth; telemedicine; e-consults ID CHRONIC KIDNEY-DISEASE; SAFETY-NET; REFERRALS; IMPLEMENTATION; TECHNOLOGY; PROVIDERS; BENEFITS; SERVICE AB Background: We define electronic consultations ("e-consults") as asynchronous, consultative, provider-to-provider communications within a shared electronic health record (EHR) or web-based platform. E-consults are intended to improve access to specialty expertise for patients and providers without the need for a face-to-face visit. Our goal was to systematically review and summarize the literature describing the use and effects of e-consults. Methods: We searched PubMed, EMBASE, the Cochrane Library, and CINAHL for studies related to e-consults published between 1990 through December 2014. Three reviewers identified empirical studies and system descriptions, including articles on systems that used a shared EHR or web-based platform, connected providers in the same health system, were used for two-way provider communication, and were text-based. Results: Our final review included 27 articles. Twenty-two were research studies and five were system descriptions. Eighteen originated from one of three sites with well-developed e-consult programs. Most studies reported on workflow impact, timeliness of specialty input, and/or provider perceptions of e-consults. E-consultations are used in a variety of ways within and across medical centers. They provide timely access to specialty care and are well-received by primary care providers. Discussion: E-consults are feasible in a variety of settings, flexible in their application, and facilitate timely specialty advice. More extensive and rigorous studies are needed to inform the e-consult process and describe its effect on access to specialty visits, cost and clinical outcomes. C1 [Vimalananda, Varsha G.; Berlowitz, Dan; Fincke, Benjamin G.; Simon, Steven R.] US Dept Vet Affairs, CHOIR, Bedford, MA USA. [Vimalananda, Varsha G.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Gupte, Gouri; Seraj, Siamak M.; Berlowitz, Dan] Boston Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Orlander, Jay; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Orlander, Jay] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Simon, Steven R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vimalananda, VG (reprint author), Edith Nourse Rogers Mem VA Med Ctr 152, CHOIR, 200 Springs Rd, Bedford, MA 01730 USA. EM varsha.vimalananda@va.gov FU Department of Veterans Affairs FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This material is based upon work supported in part by the Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US Government. NR 37 TC 18 Z9 18 U1 5 U2 19 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD SEP PY 2015 VL 21 IS 6 BP 323 EP 330 DI 10.1177/1357633X15582108 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CQ8HK UT WOS:000360847500002 PM 25995331 ER PT J AU Conrad, MF Carvalho, S Ergul, E Kwolek, CJ Lancaster, RT Patel, VI Cambria, RP AF Conrad, Mark F. Carvalho, Stephanie Ergul, Emel Kwolek, Christopher J. Lancaster, R. Todd Patel, Virendra I. Cambria, Richard P. TI Late aortic remodeling persists in the stented segment after endovascular repair of acute complicated type B aortic dissection SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 27-29, 2013 CL Stowe, VT SP New England Soc Vasc Surg ID MULTICENTER CLINICAL-TRIAL; DESCENDING THORACIC AORTA; COMPOSITE DEVICE DESIGN; INTERNATIONAL REGISTRY; IRAD; MANAGEMENT; ANEURYSMS; OUTCOMES; GRAFT; EXPERIENCE AB Objective: Thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissection (AD) promotes early positive aortic remodeling. However, little is known about the long-term effect of TEVAR on the dissected aorta, which is the goal of this study. Methods: Between August 2005 and August 2009, 31 patients with complicated type B AD were treated with TEVAR and had > 1-year follow-up imaging. Computed tomography angiograms obtained at 1 month, 1 year, and long term (average, 42 months) were compared with baseline scans. The largest diameters of the stented thoracic aorta, stented true lumen, and stented false lumen were recorded at each time point, as were the values in the unstented distal thoracic aorta and the abdominal aorta. Changes over time were evaluated by a mixed effect analysis of variance model of repeated measures. Results: The average age of the cohort was 56 years, and 74% were male. Indications for TEVAR were as follows: 61% malperfusion, 32% refractory hypertension, 45% impending rupture, and 32% persistent pain; 58% had more than one indication. All patients were treated in the acute phase within 7 days of the initial presentation. The average length of aorta covered was 19 cm. Observation of the stented segment over time showed that the maximum diameter of the stented thoracic aorta was stable (P = NS), the diameter of the stented true lumen increased (P < .001), and the diameter of the stented false lumen decreased (P < .001); 84% had complete false lumen obliteration across the stented aortic segment. Observation of the uncovered thoracic aorta over time showed that the maximum diameter increased (P = .014), as did the visceral segment of the aorta (P < .001). The average growth of the visceral segment was 31% in patients with a patent false lumen vs 3% in those with a thrombosed false lumen (P = .004). One patient had aneurysmal degeneration of the false lumen and required an additional endograft at 18 months. Conclusions: TEVAR of acute AD promotes long-term remodeling across the stented segment, with false lumen obliteration in 84% of patients. However, false lumen obliteration beyond the stented segment appears necessary to prevent late aneurysmal degeneration of the distal aorta. C1 [Conrad, Mark F.; Carvalho, Stephanie; Ergul, Emel; Kwolek, Christopher J.; Lancaster, R. Todd; Patel, Virendra I.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Med Sch, Div Vasc & Endovasc Surg,Dept Surg, Cambridge, MA 02138 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, WACC 4,15 Parkman St, Boston, MA 02114 USA. EM mconrad@partners.org NR 33 TC 6 Z9 6 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2015 VL 62 IS 3 BP 600 EP 605 DI 10.1016/j.jvs.2015.03.064 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CQ1KW UT WOS:000360357500010 PM 26054588 ER PT J AU Vierthaler, L Callas, PW Goodney, PP Schanzer, A Patel, VI Cronenwett, J Bertges, DJ AF Vierthaler, Luke Callas, Peter W. Goodney, Philip P. Schanzer, Andres Patel, Virenda I. Cronenwett, Jack Bertges, Daniel J. CA Vasc Study Grp New England TI Determinants of survival and major amputation after peripheral endovascular intervention for critical limb ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 27-29, 2013 CL Stowe, VT SP New England Soc Vasc Surg ID EXTREMITY BYPASS-SURGERY; LEG BASIL TRIAL; VASCULAR-SURGERY; ARTERIAL-DISEASE; PREDICTION MODEL; FINNVASC SCORE; REVASCULARIZATION; ANGIOPLASTY; VALIDATION; STRATIFICATION AB Objective: Our objective was to analyze periprocedural and 1-year outcomes of peripheral endovascular intervention (PVI) for critical limb ischemia (CLI). Methods: We reviewed 1244 patients undergoing 1414 PVIs for CLI (rest pain, 29%; tissue loss, 71%) within the Vascular Study Group of New England (VSGNE) from January 2010 to December 2011. Overall survival (OS), amputation-free survival (AFS), and freedom from major amputation at 1 year were analyzed using the Kaplan-Meier method. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The number of arteries treated during each procedure were 1 (49%), 2 (35%), 3 (12%), and >= 4 (5%). Target arterial segments and TransAtlantic Inter-Society Consensus classifications were aortoiliac, 27% (A, 48%; B, 28%; C, 12%; and D, 12%); femoral-popliteal, 48% (A, 29%; B, 34%; C, 20%; and D, 17%); and infrapopliteal, 25% (A, 17%; B, 14%; C, 25%; D, 44%). Technical success was 92%. Complications included access site hematoma (5.0%), occlusion (0.3%), and distal embolization (2.4%). Mortality and major amputation rates were 2.8% and 2.2% at 30 days, respectively. Overall percutaneous or open reintervention rate was 8.0% during the first year. At 1-year, OS, AFS, and freedom from major amputation were 87%, 87%, and 94% for patients with rest pain and 80%, 71%, and 81% for patients with tissue loss. Independent predictors of reduced 1-year OS (C index = .74) included dialysis (HR, 3.8; 95% CI, 2.8-5.1; P < .01), emergency procedure (HR, 2.5; 95% CI, 1.0-6.2; P = .05), age > 80 years (HR, 2.2; 95% CI, 1.7-2.8; P <.01), not living at home preoperatively (HR, 2.0; 95% CI, 1.4-2.8; P <.01), creatinine > 1.8 mg/dL (HR, 1.9; 95% CI, 1.3-2.8; P <.01), congestive heart failure (HR, 1.7; 95% CI, 1.3-2.2; P <.01), and chronic beta-blocker use (HR, 1.4; 95% CI, 1.0-1.9; P = .03), whereas independent preoperative ambulation (HR, 0.7; 95% CI, 0.6-0.9; P = .014) was protective. Independent predictors of major amputation (C index[. 69) at 1 year included dialysis (HR, 2.7; 95% CI, 1.6-4.5; P <.01), tissue loss (HR, 2.0; 95% CI, 1.1-3.7; P = .02), prior major contralateral amputation (HR, 2.0; 95% CI, 1.1-3.5; P = .02), nonCaucasian race (HR, 1.7; 95% CI, 1.0-2.9; P = .045), and male gender (HR, 1.6; 95% CI, 1.1-2.6; P = .03), whereas smoking (HR,.60; 95% CI, 0.4-1.0; P = .042) was protective. Conclusions: Survival and major amputation after PVI for CLI are associated with different patient characteristics. Dialysis dependence is a common predictor that portends especially poor outcomes. These data may facilitate efforts to improve patient selection and, after further validation, enable risk-adjusted outcome reporting for CLI patients undergoing PVI. C1 [Vierthaler, Luke; Callas, Peter W.] Univ Vermont, Coll Med, Burlington, VT 05401 USA. [Goodney, Philip P.; Cronenwett, Jack] Dartmouth Hitchcock Med Ctr, Sect Vasc Surg, Lebanon, NH 03766 USA. [Schanzer, Andres] Univ Massachusetts, Med Ctr, Div Vasc Surg, Worcester, MA USA. [Patel, Virenda I.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. [Bertges, Daniel J.] Univ Vermont, Med Ctr, Div Vasc Surg, Burlington, VT 05401 USA. RP Bertges, DJ (reprint author), Univ Vermont, Med Ctr, Div Vasc Surg, 111 Colchester Ave,Smith 338, Burlington, VT 05401 USA. EM daniel.bertges@vtmednet.org FU NHLBI NIH HHS [K08 HL105676] NR 23 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2015 VL 62 IS 3 BP 655 EP U532 DI 10.1016/j.jvs.2015.04.391 PG 18 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CQ1KW UT WOS:000360357500020 PM 26215708 ER PT J AU Scali, S Bertges, D Neal, D Patel, V Eldrup-Jorgensen, J Cronenwett, J Beck, A AF Scali, Salvatore Bertges, Daniel Neal, Daniel Patel, Virendra Eldrup-Jorgensen, Jens Cronenwett, Jack Beck, Adam TI Heart rate variables in the Vascular Quality Initiative are not reliable predictors of adverse cardiac outcomes or mortality after major elective vascular surgery SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 14-17, 2015 CL Scottsdale, AZ SP So Assoc Vasc Surg ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; NONCARDIAC SURGERY; OF-CARDIOLOGY; ASSOCIATION; SOCIETY; RISK; ECHOCARDIOGRAPHY; MANAGEMENT; DISEASE; BYPASS AB Objective: Heart rate (HR) parameters are known indicators of cardiovascular complications after cardiac surgery, but there is little evidence of their role in predicting outcome after major vascular surgery. The purpose of this study was to determine whether arrival HR (AHR) and highest intraoperative HR are associated with mortality or major adverse cardiac events (MACEs) after elective vascular surgery in the Vascular Quality Initiative (VQI). Methods: Patients undergoing elective lower extremity bypass (LEB), aortofemoral bypass (AFB), and open abdominal aortic aneurysm (AAA) repair in the VQI were analyzed. MACE was defined as any postoperative myocardial infarction, dysrhythmia, or congestive heart failure. Controlled HR was defined as AHR <75 beats/min on operating room arrival. Delta HR (DHR) was defined as highest intraoperative HR - AHR. Procedure-specific MACE models were derived for risk stratification, and generalized estimating equations were used to account for clustering of center effects. HR, beta-blocker exposure, cardiac risk, and their interactions were explored to determine association with MACE or 30-day mortality. A Bonferroni correction with P < .004 was used to declare significance. Results: There were 13,291 patients reviewed (LEB, n = 8155 [62%]; AFB, n = 2629 [18%]; open AAA, n = 2629 [20%]). Rates of any preoperative beta-blocker exposure were as follows: LEB, 66.5% (n = 5412); AFB, 57% (n = 1342); and open AAA, 74.2% (n = 1949). AHR and DHR outcome association was variable across patients and procedures. AHR < 75 beats/min was associated with increased postoperative myocardial infarction risk for LEB patients across all risk strata (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.03-1.9; P = .03), whereas AHR < 75 beats/min was associated with decreased dysrhythmia risk (OR, 0.42; 95% CI, 0.28-0.63; P = .0001) and 30-day death (OR, 0.50; 95% CI, 0.33-0.77; P = .001) in patients at moderate and high cardiac risk. These HR associations disappeared in controlling for beta-blocker status. For AFB and open AAA repair patients, there was no significant association between AHR and MACE or 30-day mortality, irrespective or cardiac risk or beta-blocker status. DHR and extremes of highest intraoperative HR (>90 or 100 beats/min) were analyzed among all three operations, and no consistent associations with MACE or 30-day mortality were detected. Conclusions: The VQI AHR and highest intraoperative HR variables are highly confounded by patient presentation, operative variables, and beta-blocker therapy. The discordance between cardiac risk and HR as well as the lack of consistent correlation to outcome makes them unreliable predictors. The VQI has elected to discontinue collecting AHR and highest intraoperative HR data, given insufficient evidence to suggest their importance as an outcome measure. C1 [Scali, Salvatore; Neal, Daniel; Beck, Adam] Univ Florida, Div Vasc Surg & Endovasc Therapy, Gainesville, FL 32610 USA. [Bertges, Daniel] Univ Vermont, Div Vasc Surg, Burlington, VT USA. [Patel, Virendra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA USA. [Eldrup-Jorgensen, Jens] Maine Med Ctr, Div Vasc Surg, Portland, ME 04102 USA. [Cronenwett, Jack] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03766 USA. RP Scali, S (reprint author), Univ Florida, Sch Med, Div Vasc Surg & Endovasc Therapy, Surg, POB 100128,1600 SW Archer Rd,Ste NG 45, Gainesville, FL 32610 USA. EM salvatore.scali@surgery.ufl.edu FU NHLBI NIH HHS [5K23HL115673-02, K23 HL115673] NR 27 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2015 VL 62 IS 3 BP 710 EP U599 DI 10.1016/j.jvs.2015.03.071 PG 20 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CQ1KW UT WOS:000360357500028 PM 26067200 ER PT J AU Mehta, M Paty, PSK Kwolek, C Cambria, R Keenan, M Feustel, P AF Mehta, Manish Paty, Philip S. K. Kwolek, Christopher Cambria, Richard Keenan, Megan Feustel, Paul TI A Novel Transcarotid Artery Revascularization Procedure With Flow Reversal: 30-Day Pivotal Results of the ROADSTER IDE Trial SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT 29th Annual Meeting of the Eastern-Vascular-Society CY SEP 24-26, 2015 CL Baltimore, MD SP Eastern Vasc Soc C1 [Mehta, Manish; Paty, Philip S. K.] Vasc Hlth Partners, CCP, Glens Falls, NY USA. [Kwolek, Christopher; Cambria, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keenan, Megan] Inst Vasc Hlth & Dis, Albany, NY USA. [Feustel, Paul] Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2015 VL 62 IS 3 BP 804 EP 804 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CQ1KW UT WOS:000360357500070 ER PT J AU Creighton, FX Hapner, E Klein, A Rosen, A Jinnah, HA Johns, MM AF Creighton, Francis X. Hapner, Edie Klein, Adam Rosen, Ami Jinnah, Hyder A. Johns, Michael M. TI Diagnostic Delays in Spasmodic Dysphonia: A Call for Clinician Education SO JOURNAL OF VOICE LA English DT Article DE Larynx; Voice; Spasmodic dysphonia; Diagnostic delay ID CERVICAL DYSTONIA; RISK AB Purpose. Spasmodic dysphonia (SD) is a rare but often debilitating disease. Due to lack of awareness among practitioners and lack of well-defined diagnostic criteria, it can be difficult for patients with SD to receive a diagnosis and subsequent treatment. There is currently no literature documenting the efficacy of the medical community in recognizing and diagnosing this disorder. We aimed to quantify the patients' experiences with obtaining a diagnosis of SD. Methods. One hundred seven consecutive patients with SD completed questionnaires about their experiences with SD. Patients were recruited either during outpatient laryngology visits or during participation in a National Institutes of Health funded study investigating SD. Results. It took patients an average of 4.43 years (53.21 months) to be diagnosed with SD after first going to a physician with vocal symptoms. Patients had to see an average of 3.95 physicians to receive a diagnosis of SD. Patients (31.4%) had been prescribed medications other than botulinum toxin to treat their symptoms. Patients (30%) attempted alternative therapies for treatment of SD, such as chiropractor or dietary modification. Conclusions. Despite advances in diagnostic modalities in medicine, the diagnosis of SD still remains elusive. Objective criteria for the diagnosis of SD and increased clinician education are warranted to address this diagnostic delay. C1 [Creighton, Francis X.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Hapner, Edie; Klein, Adam; Johns, Michael M.] Emory Univ, Sch Med, Emory Voice Ctr, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30308 USA. [Rosen, Ami; Jinnah, Hyder A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30308 USA. RP Johns, MM (reprint author), Emory Univ, Emory Voice Ctr, 550 Peachtree St 9th Fl Ste 4400, Atlanta, GA 30308 USA. EM michael.johns2@emory.edu FU NIH Grant [NS065701] FX This research was supported in part by NIH Grant # NS065701. NR 5 TC 1 Z9 1 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0892-1997 EI 1873-4588 J9 J VOICE JI J. Voice PD SEP PY 2015 VL 29 IS 5 BP 592 EP 594 DI 10.1016/j.jvoice.2013.10.022 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA CQ4EI UT WOS:000360556700011 PM 25873547 ER PT J AU Ng, LC Hanlon, C Yimer, G Henderson, DC Fekadu, A AF Ng, Lauren C. Hanlon, Charlotte Yimer, Getnet Henderson, David C. Fekadu, Abebaw TI Ethics in global health research: the need for balance SO LANCET GLOBAL HEALTH LA English DT Editorial Material ID INTERNATIONAL RESEARCH; CAPACITY; COMMITTEES C1 [Ng, Lauren C.; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Ng, Lauren C.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Hanlon, Charlotte; Fekadu, Abebaw] Univ Addis Ababa, Dept Psychiat, Coll Hlth Sci, Sch Med, Addis Ababa, Ethiopia. [Yimer, Getnet] Univ Addis Ababa, Dept Pharmacol & Biochem, Coll Hlth Sci, Sch Med, Addis Ababa, Ethiopia. [Hanlon, Charlotte] Kings Coll London, Ctr Global Mental Hlth, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Fekadu, Abebaw] Kings Coll London, Ctr Affect Disorders, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Henderson, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ng, LC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. EM lng4@mgh.harvard.edu FU National Institute of Mental Health [5T32MH093310] FX This Comment was supported by grant number 5T32MH093310 from the National Institute of Mental Health. The funder had no role in the writing of the Comment or the decision to submit it for publication. We declare no competing interests. NR 9 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD SEP PY 2015 VL 3 IS 9 BP E516 EP E517 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ4FJ UT WOS:000360559500009 PM 26275322 ER PT J AU Hinton, DE Reis, R de Jong, J AF Hinton, Devon E. Reis, Ria de Jong, Joop TI The "Thinking a Lot" Idiom of Distress and PTSD: An Examination of Their Relationship among Traumatized Cambodian Refugees Using the "Thinking a Lot" Questionnaire SO MEDICAL ANTHROPOLOGY QUARTERLY LA English DT Article DE idioms of distress; "thinking a lot,"; "thinking too much,"; Cambodian refugees; PTSD ID REPETITIVE THOUGHT; CULTURAL SYNDROMES; RUMINATION; ATTACKS; CBT AB Thinking a lot (TAL)also referred to as thinking too muchis a key complaint in many cultural contexts, and the current article profiles this idiom of distress among Cambodian refugees. The article also proposes a general model of how TAL generates various types of distress that then cause PTSD-type psychopathology, a model we refer to as the TAL-PTSD model. As tested in this Cambodian refugee sample, the model is supported by the following: (1) the close connection of TAL to PTSD as shown by odds ratio (OR = 19.6), correlation (r = .86), and factor loading; and (2) the mediation of most of the effect of TAL on PTSD by TAL-caused somatic symptoms, catastrophic cognitions, trauma recall, insomnia, and irritability. The questionnaire used in the present study is provided and can be used to examine TAL in other cultural and global contexts to advance the study of this commonly encountered distress form. C1 [Hinton, Devon E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Reis, Ria] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RA Leiden, Netherlands. [Reis, Ria; de Jong, Joop] Univ Amsterdam, Amsterdam Inst Social Sci Res, NL-1012 WX Amsterdam, Netherlands. [Reis, Ria] Univ Cape Town, Childrens Inst, ZA-7700 Rondebosch, South Africa. RP Hinton, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM devon_hinton@hms.harvard.edu NR 33 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0745-5194 EI 1548-1387 J9 MED ANTHROPOL Q JI Med. Anthropol. Q. PD SEP PY 2015 VL 29 IS 3 BP 357 EP 380 DI 10.1111/maq.12204 PG 24 WC Anthropology; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Anthropology; Public, Environmental & Occupational Health; Biomedical Social Sciences GA CQ7VJ UT WOS:000360813200015 PM 25772670 ER PT J AU Rinne, ST Wong, ES Hebert, PL Au, DH Lindenauer, PK Neely, EL Sulc, CA Liu, CF AF Rinne, Seppo T. Wong, Edwin S. Hebert, Paul L. Au, David H. Lindenauer, Peter K. Neely, Emily L. Sulc, Christine A. Liu, Chuan-Fen TI Weekend Discharges and Length of Stay Among Veterans Admitted for Chronic Obstructive Pulmonary Disease SO MEDICAL CARE LA English DT Article DE weekend; COPD; length of stay; efficiency; readmission ID MYOCARDIAL-INFARCTION; HEART-FAILURE; HOSPITALS; MORTALITY; OUTCOMES; SERVICE; DELAYS; RATES AB Background:Discharge rates are substantially lower on weekends, though the impact on hospital length of stay (LOS) is not fully understood.Objectives:The primary objective was to examine the association of weekend discharges with hospital LOS. We also examined the association of weekend discharges with readmission, mortality, and postdischarge follow-up.Research Design and Methods:A cohort study of 25,301 patients who were admitted to Veterans Affairs hospitals for chronic obstructive pulmonary disease during October 01, 2008-September 30, 2010, including 3845 patients discharged on the weekend (Saturday or Sunday) and 21,456 discharged on weekdays (Monday through Friday).Results:There were significantly fewer discharges on the weekend (1922 per weekend day vs. 4279 per weekday, P<0.01). Inpatient status during the weekend at any point in hospitalization was associated with an increased LOS of 0.59 day [95% confidence interval (CI), 0.54-0.63 d]. Discharge on the weekend was not associated with increased odds of 30-day hospital readmission [odds ratio (OR)=1.00; 95% CI, 0.90-1.10] or lack of primary care follow-up visit within 14 days of discharge (OR=0.94; 95% CI, 0.85-1.03). However, weekend discharges were significantly associated with lower odds of mortality within 30 days after discharge (OR=0.80; 95% CI, 0.65-0.99).Conclusions:The presence of fewer weekend discharges was associated with significantly longer hospital lengths of stay. Weekend discharges were not associated with higher readmission rates and had lower rates of mortality compared with weekdays discharges. Identifying methods to increase weekend discharges may create an opportunity to improve hospital efficiency. C1 [Rinne, Seppo T.] VA Connecticut Hlth Care Syst, West Haven, CT USA. [Rinne, Seppo T.] Yale Univ, Dept Med, Div Pulm & Crit Care, New Haven, CT 06520 USA. [Wong, Edwin S.; Hebert, Paul L.; Au, David H.; Neely, Emily L.; Sulc, Christine A.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. [Wong, Edwin S.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care, Seattle, WA USA. [Lindenauer, Peter K.] Baystate Med Ctr, Dept Med, Springfield, MA 01199 USA. RP Rinne, ST (reprint author), 950 Campbell Ave,Bldg 35a,Room 2-234, West Haven, CT 06516 USA. EM seppo.rinne@va.gov FU Veterans Affairs clinical research grant [IIR-09-354] FX Supported by Veterans Affairs clinical research grant: IIR-09-354. NR 24 TC 2 Z9 2 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2015 VL 53 IS 9 BP 753 EP 757 DI 10.1097/MLR.0000000000000395 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CQ4QM UT WOS:000360589700003 PM 26147865 ER PT J AU Toth, M Holmes, M Van Houtven, C Toles, M Weinberger, M Silberman, P AF Toth, Matthew Holmes, Mark Van Houtven, Courtney Toles, Mark Weinberger, Morris Silberman, Pam TI Rural Medicare Beneficiaries Have Fewer Follow-up Visits and Greater Emergency Department Use Postdischarge SO MEDICAL CARE LA English DT Article DE Medicare; rural health; postacute care; readmission ID QUALITY-OF-CARE; HEART-FAILURE; TRANSITIONAL CARE; HEALTH-CARE; HOSPITAL READMISSIONS; 30-DAY READMISSION; ACCESS; RATES; DISCHARGE; OPPORTUNITIES AB Background:Hospitals are focused on improving postdischarge services for older adults, such as early follow-up care after hospitalization to reduce readmissions and unnecessary emergency department (ED) use. Rural Medicare beneficiaries face many barriers to receiving quality care, but little is known about their postdischarge care and outcomes. We hypothesize that rural Medicare beneficiaries compared with urban beneficiaries, will have fewer follow-up visits, and a greater likelihood of readmission and ED use.Methods:We conducted a retrospective analysis of elderly Medicare beneficiaries discharged home using the Medicare Current Beneficiary Survey, Cost and Use files, 2000-2010. Multivariate Cox proportional hazard models were used to assess the risk of rural residency on readmission, ED use, and follow-up care up to 30 days' postdischarge. Covariates include demographic, health, and hospital-level characteristics.Results:Compared with urban beneficiaries, Medicare beneficiaries living in isolated rural settings had a lower rate of follow-up care [hazard ratio (HR)=0.81, P<0.001]. Beneficiaries in large and small rural settings had a greater risk of an ED visit compared with urban beneficiaries (HR=1.44, P<0.001; HR=1.52, P<0.01). Rural beneficiaries did not have a greater risk of readmission, though risk of readmission was higher for beneficiaries discharged from hospitals in large and small rural settings (HR=1.33, P<0.05; HR=1.42, P<0.05).Conclusions:This study provides evidence of lower quality postdischarge care for Medicare beneficiaries in rural settings. As readmission penalties expand, hospitals serving rural beneficiaries may be disproportionately affected. This suggests a need for policies that increase follow-up care in rural settings. C1 [Toth, Matthew; Holmes, Mark; Weinberger, Morris; Silberman, Pam] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Van Houtven, Courtney] Durham VA Med Ctr, US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Van Houtven, Courtney] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27706 USA. [Toles, Mark] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. RP Toth, M (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Sheps Ctr Hlth Serv Res, 135 Dauer Dr,1101 McGavran Greeberg Hall,CB 7411, Chapel Hill, NC 27599 USA. EM tbmatthe@live.unc.edu FU T-32 National Research Service Award, Sheps Center for Health Services Research [2T32HS000032-25]; North Carolina Rural Health Research Program [UL1-TR000083, F30-HL110483, T32-GM008719]; UNC Institute on Aging FX Supported by a T-32 National Research Service Award, Sheps Center for Health Services Research, Grant #: 2T32HS000032-25. Support was also provided by the North Carolina Rural Health Research Program. UL1-TR000083, F30-HL110483, T32-GM008719, and UNC Institute on Aging pilot grant supported the purchase of the Medicare Current Beneficiary Survey. NR 47 TC 4 Z9 4 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2015 VL 53 IS 9 BP 800 EP 808 DI 10.1097/MLR.0000000000000401 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CQ4QM UT WOS:000360589700009 PM 26270827 ER PT J AU Nelson, RE Samore, MH Jones, M Greene, T Stevens, VW Liu, CF Graves, N Evans, MF Rubin, MA AF Nelson, Richard E. Samore, Matthew H. Jones, Makoto Greene, Tom Stevens, Vanessa W. Liu, Chuan-Fen Graves, Nicholas Evans, Martin F. Rubin, Michael A. TI Reducing Time-dependent Bias in Estimates of the Attributable Cost of Health Care-associated Methicillin-resistant Staphylococcus aureus Infections A Comparison of Three Estimation Strategies SO MEDICAL CARE LA English DT Article DE costs; MRSA; health care-associated infection ID LENGTH-OF-STAY; BURDEN; IMPACT AB Background:Previous estimates of the excess costs due to health care-associated infection (HAI) have scarcely addressed the issue of time-dependent bias.Objective:We examined time-dependent bias by estimating the health care costs attributable to an HAI due to methicillin-resistant Staphylococcus aureus (MRSA) using a unique dataset in the Department of Veterans Affairs (VA) that makes it possible to distinguish between costs that occurred before and after an HAI. In addition, we compare our results to those from 2 other estimation strategies.Methods:Using a historical cohort study design to estimate the excess predischarge costs attributable to MRSA HAIs, we conducted 3 analyses: (1) conventional, in which costs for the entire inpatient stay were compared between patients with and without MRSA HAIs; (2) post-HAI, which included only costs that occurred after an infection; and (3) matched, in which costs for the entire inpatient stay were compared between patients with an MRSA HAI and subset of patients without an MRSA HAI who were matched based on the time to infection.Results:In our post-HAI analysis, estimates of the increase in inpatient costs due to MRSA HAI were $12,559 (P<0.0001) and $24,015 (P<0.0001) for variable and total costs, respectively. The excess variable and total cost estimates were 33.7% and 31.5% higher, respectively, when using the conventional methods and 14.6% and 11.8% higher, respectively, when using matched methods.Conclusions:This is the first study to account for time-dependent bias in the estimation of incremental per-patient health care costs attributable to HAI using a unique dataset in the VA. We found that failure to account for this bias can lead to overestimation of these costs. Matching on the timing of infection can reduce this bias substantially. C1 [Nelson, Richard E.; Samore, Matthew H.; Jones, Makoto; Stevens, Vanessa W.; Rubin, Michael A.] Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Nelson, Richard E.; Samore, Matthew H.; Jones, Makoto; Greene, Tom; Rubin, Michael A.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA. [Stevens, Vanessa W.] Univ Utah, Coll Pharm, Dept Pharmacotherapy, Salt Lake City, UT 84112 USA. [Liu, Chuan-Fen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Graves, Nicholas] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia. [Evans, Martin F.] Lexington Vet Affairs Med Ctr, Lexington, KY USA. [Evans, Martin F.] Univ Kentucky, Dept Internal Med, Lexington, KY USA. RP Nelson, RE (reprint author), 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM richard.nelson@utah.edu OI Graves, Nicholas/0000-0002-5559-3267; Stevens, Vanessa/0000-0001-8933-5453 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-210]; Centers for Disease Control and Prevention, Safety and Healthcare Epidemiology Prevention Research Development Program [200-2011-42039] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (CDA 11-210) with R.E.N. as the principal investigator and the Centers for Disease Control and Prevention, Safety and Healthcare Epidemiology Prevention Research Development Program (contract number 200-2011-42039) with M.H.S. as the principal investigator. NR 28 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2015 VL 53 IS 9 BP 827 EP 834 DI 10.1097/MLR.0000000000000403 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CQ4QM UT WOS:000360589700012 PM 26225444 ER PT J AU Simuni, T Caspell-Garcia, C Coffey, C Chahine, LM Lasch, S Oertel, WH Mayer, G Hogl, B Postuma, R Videnovic, A Amara, AW Marek, K AF Simuni, Tanya Caspell-Garcia, Chelsea Coffey, Christopher Chahine, Lama M. Lasch, Shirley Oertel, Wolfgang H. Mayer, Geert Hoegl, Birgit Postuma, Ron Videnovic, Aleksandar Amara, Amy Willis Marek, Ken CA PPMI Sleep Working Group Behalf PP TI Correlates of Excessive Daytime Sleepiness in De Novo Parkinson's Disease: A Case Control Study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; daytime somnolence; biomarkers ID POSTURAL SWAY; BRAIN-STIMULATION; GAIT; LEVODOPA; PROGRESSION; VALIDATION; INITIATION; PEOPLE; MOTOR; RISK AB Objective: This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls. Methods: Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10. Results: Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P=0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P=0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P=0.05) but not alpha-synuclein spinal fluid levels in PD. Conclusions: This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy. (c) 2015 International Parkinson and Movement Disorder Society C1 [Simuni, Tanya] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Caspell-Garcia, Chelsea; Coffey, Christopher] Univ Iowa, Iowa City, IA USA. [Chahine, Lama M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lasch, Shirley; Marek, Ken] Inst Neurodegenerat Disorders, New Haven, CT USA. [Oertel, Wolfgang H.] Charitable Hertie Fdn, Frankfurt, Germany. [Mayer, Geert] Hephata Hess Diakoniezentrum eV, Hephata Klin, Geisenheim, Germany. [Hoegl, Birgit] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Postuma, Ron] McGill Univ, Montreal, PQ, Canada. [Videnovic, Aleksandar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amara, Amy Willis] UAB Sch Med, Birmingham, AL USA. RP Simuni, T (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, 710 North Lake Shore Dr,1126, Chicago, IL 60611 USA. EM tsimuni@nmff.org RI Singleton, Andrew/C-3010-2009; OI Amara, Amy/0000-0003-0762-9656; Standaert, David/0000-0003-2921-8348 FU Michael J. Fox Foundation for Parkinson's Research (MJFF); MJFF; Abbvie; Avid Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; Eli Lilly Co.; F. Hoffman-La Roche, Ltd.; GE Healthcare; Genentech; GlaxoSmithKline; Lundbeck; Merck; MesoScale; Piramal; Pfizer; UCB FX P.P.M.I. is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB. NR 37 TC 6 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2015 VL 30 IS 10 BP 1371 EP 1381 DI 10.1002/mds.26248 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7CD UT WOS:000360759500042 PM 26095202 ER PT J AU Ashokkumar, A Kearney, M Simpson, E Videnovic, A Cudkowicz, M AF Ashokkumar, A. Kearney, M. Simpson, E. Videnovic, A. Cudkowicz, M. TI Neurological Clinical Research Institute (NCRI) Coordinating Center Support for Multi-Center Clinical Trials: Lessons Learned to Improve Efficiency of Study Start Up SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 29th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson Disease and Other Movement Disorders CY SEP 12, 2015 CL Ft Myers, FL C1 [Ashokkumar, A.; Kearney, M.; Simpson, E.; Videnovic, A.; Cudkowicz, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2015 VL 30 IS 10 MA 22 BP E7 EP E7 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7CD UT WOS:000360759500018 ER PT J AU Chen, X Umeh, CC Maguire, M Tainsh, R Macklin, EA Buys, M Schwarzschild, MA AF Chen, X. Umeh, C. C. Maguire, M. Tainsh, R. Macklin, E. A. Buys, M. Schwarzschild, M. A. TI Serum Urate Elevation and Blood Pressure Modulation in Parkinson disease: an Exploratory Analysis SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 29th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson Disease and Other Movement Disorders CY SEP 12, 2015 CL Ft Myers, FL C1 [Chen, X.; Maguire, M.; Macklin, E. A.; Schwarzschild, M. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Umeh, C. C.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Tainsh, R.; Buys, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2015 VL 30 IS 10 MA 30 BP E10 EP E10 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7CD UT WOS:000360759500026 ER PT J AU Huang, Z Li, J Ascherio, A Cui, L Dou, N Schwarzschild, MA Wu, S Gao, X AF Huang, Z. Li, J. Ascherio, A. Cui, L. Dou, N. Schwarzschild, M. A. Wu, S. Gao, X. TI Urate and Rapid Eye Movement Sleep Behavior Disorder: A Community-Based Study. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 29th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson Disease and Other Movement Disorders CY SEP 12, 2015 CL Ft Myers, FL C1 [Huang, Z.; Li, J.; Cui, L.; Wu, S.] Kailuan Hosp, Dept Internal Med, Tangshan, Hebei, Peoples R China. [Huang, Z.; Dou, N.; Gao, X.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schwarzschild, M. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schwarzschild, M. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2015 VL 30 IS 10 BP E1 EP E2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7CD UT WOS:000360759500002 ER PT J AU Videnovic, A Marconi, A Wolfe, L Zee, PC Klerman, EB Turek, F AF Videnovic, A. Marconi, A. Wolfe, L. Zee, P. C. Klerman, E. B. Turek, F. TI Circadian Expression of Clock Genes in Parkinson's Disease - Implications for Disrupted Sleep and Daytime Sleepiness. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 29th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson Disease and Other Movement Disorders CY SEP 12, 2015 CL Ft Myers, FL C1 [Videnovic, A.] Massachusetts Gen Hosp, Movement Disorders Unit, Boston, MA 02114 USA. [Videnovic, A.; Klerman, E. B.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Marconi, A.; Wolfe, L.; Zee, P. C.] Northwestern Univ, Northwestern Univ Feinberg Sch Med, Dept Neurol, Chicago, IL USA. [Turek, F.] Northwestern Univ, Dept Neurobiol, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2015 VL 30 IS 10 BP E2 EP E2 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7CD UT WOS:000360759500003 ER PT J AU Liu, JZ van Sommeren, S Huang, HL Ng, SC Alberts, R Takahashi, A Ripke, S Lee, JC Jostins, L Shah, T Abedian, S Cheon, JH Cho, J Daryani, NE Franke, L Fuyuno, Y Hart, A Juyal, RC Juyal, G Kim, WH Morris, AP Poustchi, H Newman, WG Midha, V Orchard, TR Vahedi, H Sood, A Sung, JJY Malekzadeh, R Westra, HJ Yamazaki, K Yang, SK Barrett, JC Franke, A Alizadeh, BZ Parkes, M Thelma, BK Daly, MJ Kubo, M Anderson, CA Weersma, RK AF Liu, Jimmy Z. van Sommeren, Suzanne Huang, Hailiang Ng, Siew C. Alberts, Rudi Takahashi, Atsushi Ripke, Stephan Lee, James C. Jostins, Luke Shah, Tejas Abedian, Shifteh Cheon, Jae Hee Cho, Judy Daryani, Naser E. Franke, Lude Fuyuno, Yuta Hart, Ailsa Juyal, Ramesh C. Juyal, Garima Kim, Won Ho Morris, Andrew P. Poustchi, Hossein Newman, William G. Midha, Vandana Orchard, Timothy R. Vahedi, Homayon Sood, Ajit Sung, Joseph J. Y. Malekzadeh, Reza Westra, Harm-Jan Yamazaki, Keiko Yang, Suk-Kyun Barrett, Jeffrey C. Franke, Andre Alizadeh, Behrooz Z. Parkes, Miles Thelma, B. K. Daly, Mark J. Kubo, Michiaki Anderson, Carl A. Weersma, Rinse K. CA Int Multiple Sclerosis Genetics Co Int IBD Genetics Consortium TI Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; KAPPA-B-ZETA; ULCERATIVE-COLITIS; CROHNS-DISEASE; JAPANESE POPULATION; COMPLEX DISEASES; METAANALYSIS; VARIANTS; STRATIFICATION; ARCHITECTURE AB Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first transancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations. C1 [Liu, Jimmy Z.; Shah, Tejas; Barrett, Jeffrey C.; Anderson, Carl A.] Wellcome Trust Sanger Inst, Hinxton, England. [van Sommeren, Suzanne; Alberts, Rudi; Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. [van Sommeren, Suzanne; Franke, Lude; Westra, Harm-Jan] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Huang, Hailiang; Ripke, Stephan; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. [Ng, Siew C.; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Dept Med & Therapeut, Inst Digest Dis, LKS Inst Hlth Sci,State Key Lab Digest Dis, Hong Kong, Hong Kong, Peoples R China. [Takahashi, Atsushi] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan. [Lee, James C.; Parkes, Miles] Addenbrookes Hosp, Inflammatory Bowel Dis Res Grp, Cambridge, England. [Jostins, Luke] Univ Oxford, Wellcome Trust Ctr Human Genet, Headington, England. [Abedian, Shifteh; Poustchi, Hossein; Vahedi, Homayon; Malekzadeh, Reza] Shariati Hosp, Digest Dis Res Inst, Tehran, Iran. [Cheon, Jae Hee; Kim, Won Ho] Yonsei Univ, Coll Med, Dept Gastroenterol & Hepatol, Seoul, South Korea. [Cho, Judy] Mt Sinai Hosp, Icahn Sch Med, New York, NY 10029 USA. [Daryani, Naser E.] Emam Hosp, Dept Gastroenterol, Tehran, Iran. [Fuyuno, Yuta; Yamazaki, Keiko; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan. [Hart, Ailsa] St Marks Hosp, Inflammatory Bowel Dis Unit, Harrow, Middx, England. [Juyal, Ramesh C.] Natl Inst Immunol, New Delhi 110067, India. [Juyal, Garima; Thelma, B. K.] Univ Delhi, Dept Genet, New Delhi, India. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Newman, William G.] Univ Manchester, Manchester Ctr Genom Med, Manchester, Lancs, England. [Newman, William G.] Cent Manchester Univ Hosp Natl Hlth Serv NHS Fdn, Manchester, Lancs, England. [Midha, Vandana; Sood, Ajit] Dayanand Med Coll & Hosp, Dept Med, Ludhiana, Punjab, India. [Orchard, Timothy R.] St Marys Hosp, Dept Gastroenterol & Hepatol, London, England. [Yang, Suk-Kyun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Gastroenterol & Hepatol, Seoul, South Korea. [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Alizadeh, Behrooz Z.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. RP Anderson, CA (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. EM carl.anderson@sanger.ac.uk; r.k.weersma@umcg.nl RI Ng, Siew Chien/N-4733-2015; Rioux, John/A-9599-2015; Franke, Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009; Ellinghaus, David/G-4467-2012; Zeissig, Sebastian/B-6297-2012; Franke, Andre/B-2151-2010; Palmieri, Orazio/J-7697-2012; Silverberg, Mark/B-4183-2008; Kubo, Michiaki/N-7947-2015 OI Ziad Alizadeh, Behrooz/0000-0002-1415-8007; Laukens, Debby/0000-0002-1984-5850; Kennedy, Nicholas/0000-0003-4368-1961; Barrett, Jeffrey/0000-0002-1152-370X; Nothen, Markus/0000-0002-8770-2464; Gearry, Richard/0000-0002-2298-5141; Andersen, Vibeke/0000-0002-0127-2863; Newman, William/0000-0002-6382-4678; Ng, Siew Chien/0000-0002-6850-4454; Rioux, John/0000-0001-7560-8326; Franke, Lude/0000-0002-5159-8802; Franke, Andre/0000-0003-1530-5811; Huang, Hailiang/0000-0003-1461-5762; Lee, James/0000-0001-5711-9385; Palmieri, Orazio/0000-0002-0019-7929; FU Netherlands Organization for Scientific Research (NWO) [016.136.308]; Broad Medical Research Program of the Broad Foundation [IBD-0318]; Netherlands Organization for Scientific Research (NWO), through NWO VENI grant [916.10.135]; NWO VIDI grant [917.14.374]; European Community's Health Seventh Framework Programme [259867]; Department of Biotechnology of the government of India (New Delhi, India) [BT/01/COE/07/UDSC/2008]; Tehran University of Medical Sciences, Iran; National Association for Colitis and Crohn's Disease; Wellcome Trust; Medical Research Council UK; Peninsular College of Medicine and Dentistry, Exeter; National Institute for Health Research (NIHR) Biomedical Research Centre; Wellcome Trust [WT098017, 098051] FX R.K.W. is supported by a VIDI grant (016.136.308) from the Netherlands Organization for Scientific Research (NWO) and the Broad Medical Research Program of the Broad Foundation (IBD-0318). L.F. is supported by the Netherlands Organization for Scientific Research (NWO), through NWO VENI grant 916.10.135 and NWO VIDI grant 917.14.374. The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreement 259867. T.B.K. is supported by Centre of Excellence grant BT/01/COE/07/UDSC/2008 from the Department of Biotechnology of the government of India (New Delhi, India). The collection of Iranian samples has been supported by the Tehran University of Medical Sciences, Iran. UK case collections were supported by the National Association for Colitis and Crohn's Disease, the Wellcome Trust, the Medical Research Council UK and the Peninsular College of Medicine and Dentistry, Exeter. We also acknowledge National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy's and St Thomas' NHS Trust/King's College London and to Addenbrooke's Hospital/University of Cambridge School of Clinical Medicine. A.P.M. is supported by the Wellcome Trust under award WT098017. J.Z.L., T.S., J.C.B. and C.A.A. are supported by the Wellcome Trust (098051). NR 53 TC 121 Z9 121 U1 8 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD SEP PY 2015 VL 47 IS 9 BP 979 EP + DI 10.1038/ng.3359 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CQ1XQ UT WOS:000360394100007 PM 26192919 ER PT J AU Stachler, MD Taylor-Weiner, A Peng, SY McKenna, A Agoston, AT Odze, RD Davison, JM Nason, KS Loda, M Leshchiner, I Stewart, C Stojanov, P Seepo, S Lawrence, MS Ferrer-Torres, D Lin, J Chang, AC Gabriel, SB Lander, ES Beer, DG Getz, G Carter, SL Bass, AJ AF Stachler, Matthew D. Taylor-Weiner, Amaro Peng, Shouyong McKenna, Aaron Agoston, Agoston T. Odze, Robert D. Davison, Jon M. Nason, Katie S. Loda, Massimo Leshchiner, Ignaty Stewart, Chip Stojanov, Petar Seepo, Sara Lawrence, Michael S. Ferrer-Torres, Daysha Lin, Jules Chang, Andrew C. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Getz, Gad Carter, Scott L. Bass, Adam J. TI Paired exome analysis of Barrett's esophagus and adenocarcinoma SO NATURE GENETICS LA English DT Article ID CIRCULAR BINARY SEGMENTATION; HIGH-GRADE DYSPLASIA; PROSTATE-CANCER; COPY NUMBER; GASTROESOPHAGEAL-REFLUX; NEOPLASTIC PROGRESSION; GENOMIC INSTABILITY; PANCREATIC-CANCER; SOMATIC MUTATIONS; CLONAL EXPANSION AB Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy. Here we present whole-exome sequencing from 25 pairs of EAC and Barrett's esophagus and from 5 patients whose Barrett's esophagus and tumor were extensively sampled. Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data showed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations, with more frequent oncogenic amplification and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through the gradual accumulation of tumor-suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by the acquisition of oncogenic amplifications. C1 [Stachler, Matthew D.; Agoston, Agoston T.; Odze, Robert D.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stachler, Matthew D.; Agoston, Agoston T.; Odze, Robert D.; Loda, Massimo] Harvard Univ, Sch Med, Boston, MA USA. [Stachler, Matthew D.; Peng, Shouyong; Loda, Massimo; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Taylor-Weiner, Amaro; Leshchiner, Ignaty; Stewart, Chip; Stojanov, Petar; Seepo, Sara; Lawrence, Michael S.; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad; Carter, Scott L.; Bass, Adam J.] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. [McKenna, Aaron] Univ Washington, Seattle, WA 98195 USA. [Davison, Jon M.; Nason, Katie S.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Ferrer-Torres, Daysha; Lin, Jules; Chang, Andrew C.; Beer, David G.] Univ Michigan, Sect Thorac Surg, Ann Arbor, MI 48109 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Carter, Scott L.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Broad Inst Harvard & MIT, Joint Ctr Canc Precis Med,Dana Farber Canc Inst, Boston, MA 02115 USA. [Carter, Scott L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Carter, Scott L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Carter, SL (reprint author), Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org; scarter@broadinstitute.org; adam_bass@dfci.harvard.edu FU US National Institutes of Health [T32 HL007627]; Dana-Farber/Harvard Gastrointestinal Cancer Specialized Programs of Research Excellence [P50CA127003]; National Human Genome Research Institute (NHGRI) Large-Scale Sequencing Program [U54 HG0003067]; National Cancer Institute [U54 CA163059, P01 CA098101, U54 CA163004]; Broad Institute SPARC; American Cancer Society FX We thank the members of the Broad Institute Genome Sequencing Platform and the molecular laboratories at Brigham and Women's Hospital and Massachusetts General Hospital for their assistance. We are grateful to the patients and families who agreed to contribute their samples to enable this research and to the physicians and hospital staff whose efforts in collecting these samples are essential to this work. This work was supported by US National Institutes of Health grant T32 HL007627 and the Dana-Farber/Harvard Gastrointestinal Cancer Specialized Programs of Research Excellence P50CA127003 (M.D.S.), the National Human Genome Research Institute (NHGRI) Large-Scale Sequencing Program (U54 HG0003067; E.S.L.), National Cancer Institute grant U54 CA163059 (D.G.B.), Broad Institute SPARC funding (A.J.B., S.L.C. and G.G.), a Research Scholar Grant from the American Cancer Society (A.J.B.) and the National Cancer Institute (P01 CA098101 and U54 CA163004; A.J.B.). NR 63 TC 36 Z9 36 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD SEP PY 2015 VL 47 IS 9 BP 1047 EP + DI 10.1038/ng.3343 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CQ1XQ UT WOS:000360394100015 PM 26192918 ER PT J AU Sherrill, KR Chrastil, ER Ross, RS Erdema, UM Hasselmo, ME Stern, CE AF Sherrill, Katherine R. Chrastil, Elizabeth R. Ross, Robert S. Erdema, Ugur M. Hasselmo, Michael E. Stern, Chantal E. TI Functional connections between optic flow areas and navigationally responsive brain regions during goal-directed navigation SO NEUROIMAGE LA English DT Article DE fMRI; Hippocampus; MT; Retrosplenial cortex; V3A; V6 ID PATH-INTEGRATION; RETROSPLENIAL CORTEX; HEAD-DIRECTION; COGNITIVE MAP; VISUAL-MOTION; NEURAL BASIS; SPATIAL NAVIGATION; TEMPORAL LOBECTOMY; ENTORHINAL CORTEX; HIPPOCAMPUS AB Recent computational models suggest that visual input from optic flow provides information about egocentric (navigator-centered) motion and influences firing patterns in spatially tuned cells during navigation. Computationally, self-motion cues can be extracted from optic flow during navigation. Despite the importance of optic flow to navigation, a functional link between brain regions sensitive to optic flow and brain regions important for navigation has not been established in either humans or animals. Here, we used a beta-series correlation methodology coupled with two fMRI tasks to establish this functional link during goal-directed navigation in humans. Functionally defined optic flow sensitive cortical areas V3A, V6, and hMT+ were used as seed regions. fMRI data was collected during a navigation task in which participants updated position and orientation based on self-motion cues to successfully navigate to an encoded goal location. The results demonstrate that goal-directed navigation requiring updating of position and orientation in the first person perspective involves a cooperative interaction between optic flow sensitive regions V3A, V6, and hMT+ and the hippocampus, retrosplenial cortex, posterior parietal cortex, and medial prefrontal cortex. These functional connections suggest a dynamic interaction between these systems to support goal-directed navigation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sherrill, Katherine R.; Chrastil, Elizabeth R.; Erdema, Ugur M.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Dept Psychol & Brain Sci, Ctr Memory & Brain, Boston, MA 02215 USA. [Sherrill, Katherine R.; Chrastil, Elizabeth R.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ross, Robert S.] Univ New Hampshire, Dept Psychol, Durham, NH 03824 USA. RP Stern, CE (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington Mall,Room 109, Boston, MA 02215 USA. EM Chantal@bu.edu OI Ross, Robert/0000-0002-3987-881X; Hasselmo, Michael/0000-0002-9925-6377; Chrastil, Elizabeth/0000-0003-2544-0152 FU Office of Naval Research (ONR) Multi-disciplinary University Research Initiative (MURI) [N00014-10-1-0936]; NCRR [P41RR14075] FX This work was conducted with the support from the Office of Naval Research (ONR) Multi-disciplinary University Research Initiative (MURI) (N00014-10-1-0936). fMRI scanning was completed at the Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, MA), which receives support from NCRR P41RR14075. We would like to thank Dr. Jesse Rissman for providing his custom Matlab script of the functional connectivity analysis, Randall Newmark for assisting in fMRI data collection, Deepti Putcha for assistance with processing the optic flow data, and Dr. David Somers from the Perceptual Neuroimaging Laboratory at Boston University for providing the optic flow task. The authors declare no competing financial interests. NR 71 TC 2 Z9 2 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2015 VL 118 BP 386 EP 396 DI 10.1016/j.neuroimage.2015.06.009 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CQ5GB UT WOS:000360630200037 PM 26054874 ER PT J AU Skeide, MA Kirsten, H Kraft, I Schaadt, G Muller, B Neef, N Brauer, J Wilcke, A Emmrich, F Boltze, J Friederici, AD AF Skeide, Michael A. Kirsten, Holger Kraft, Indra Schaadt, Gesa Mueller, Bent Neef, Nicole Brauer, Jens Wilcke, Arndt Emmrich, Frank Boltze, Johannes Friederici, Angela D. TI Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children SO NEUROIMAGE LA English DT Article ID PARIETAL WHITE-MATTER; DEVELOPMENTAL DYSLEXIA; READING-ABILITY; BRAIN; ACTIVATION; MECHANISMS; REGIONS; MOTION; ADULTS; VOLUME AB Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. (C) 2015 Elsevier Inc. All rights reserved. C1 [Skeide, Michael A.; Kraft, Indra; Schaadt, Gesa; Neef, Nicole; Brauer, Jens; Friederici, Angela D.] Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, D-04103 Leipzig, Germany. [Kirsten, Holger; Mueller, Bent; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, D-04103 Leipzig, Germany. [Kirsten, Holger] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany. [Kirsten, Holger] Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04107 Leipzig, Germany. [Schaadt, Gesa] Humboldt Univ, Dept Psychol, D-12489 Berlin, Germany. [Emmrich, Frank; Boltze, Johannes] Translat Ctr Regenerat Med, D-04103 Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Boltze, Johannes] Harvard Univ, Sch Med, Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Skeide, MA (reprint author), Max Planck Inst Human Cognit & Brain Sci, Stephanstr 1a, D-04103 Leipzig, Germany. EM skeide@cbs.mpg.de OI Muller, Bent/0000-0001-8308-6193 FU Max Planck Society; Fraunhofer Society [M.FE.A.NEPF0001] FX This work was funded by the Max Planck Society and the Fraunhofer Society (grant number M.FE.A.NEPF0001). We thank Alfred Anwander for providing his expertise in diffusion-weighted magnetic resonance imaging. NR 59 TC 3 Z9 3 U1 4 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2015 VL 118 BP 414 EP 421 DI 10.1016/j.neuroimage.2015.06.024 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CQ5GB UT WOS:000360630200040 PM 26080313 ER PT J AU Duval, T McNab, JA Setsompop, K Witzel, T Schneider, T Huang, SY Keil, B Klawiter, EC Wald, LL Cohen-Adad, J AF Duval, Tanguy McNab, Jennifer A. Setsompop, Kawin Witzel, Thomas Schneider, Torben Huang, Susie Yi Keil, Boris Klawiter, Eric C. Wald, Lawrence L. Cohen-Adad, Julien TI In vivo mapping of human spinal cord microstructure at 300 mT/m SO NEUROIMAGE LA English DT Article DE Diffusion MRI; AxCaliber; Axon diameter; Quantification; Human; Spinal cord ID AXON DIAMETER DISTRIBUTION; HUMAN CONNECTOME PROJECT; DIFFUSION MRI; WHITE-MATTER; WATER DIFFUSION; HUMAN BRAIN; MAGNETIZATION-TRANSFER; TISSUE-MICROSTRUCTURE; MULTIPLE-SCLEROSIS; MULTICOMPONENT T-1 AB The ability to characterize white matter microstructure non-invasively has important applications for the diagnosis and follow-up of several neurological diseases. There exists a family of diffusion MRI techniques, such as AxCaliber, that provide indices of axon microstructure, such as axon diameter and density. However, to obtain accurate measurements of axons with small diameters (<5 mu m), these techniques require strong gradients, i.e. an order of magnitude higher than the 40-80 mT/m currently available in clinical systems. In this study we acquired AxCaliber diffusion data at a variety of different q-values and diffusion times in the spinal cord of five healthy subjects using a 300 mT/m whole body gradient system. Acquisition and processing were optimized using state-of-the-artmethods (e.g., 64-channel coil, template-based analysis). Results consistently show an average axon diameter of 4.5 +/- 1.1 mu min the spinal cord white matter. Diameters ranged from 3.0 mu m(gracilis) to 5.9 mu m (spinocerebellar tracts). Values were similar across laterality (left-right), but statistically different across spinal cord pathways (p < 10(-5)). The observed trends are similar to those observed in animal histology. This study shows, for the first time, in vivo mapping of axon diameter in the spinal cord at 300 mT/m, thus creating opportunities for applications in spinal cord diseases. (C) 2015 Elsevier Inc. All rights reserved. C1 [Duval, Tanguy; Cohen-Adad, Julien] Polytech Montreal, Inst Biomed Engn, Montreal, PQ H3T 1J4, Canada. [McNab, Jennifer A.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Setsompop, Kawin; Witzel, Thomas; Huang, Susie Yi; Keil, Boris; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Schneider, Torben] UCL Inst Neurol, Queen Sq MS Ctr, Dept Neuroinflammat, NMR Res Unit, London, England. [Klawiter, Eric C.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cohen-Adad, Julien] Univ Montreal, CRIUGM, Funct Neuroimaging Unit, Montreal, PQ, Canada. RP Cohen-Adad, J (reprint author), Polytech Montreal, Inst Biomed Engn, 2900 Edouard Montpetit Bld, Montreal, PQ H3T 1J4, Canada. EM jcohen@polymtl.ca RI Wald, Lawrence/D-4151-2009; OI DUVAL, Tanguy/0000-0002-1228-5192 FU National Institutes of Health [P41EB015896]; NIH Blueprint Initiative for Neuroscience Research [U01MH093765]; MS Society of Canada [EGID 2370]; SensoriMotor Rehabilitation Research Team (SMRRT) of the Canadian Institute of Health Research; National MS Society [FG1892A1/1]; Fonds de Recherche du Quebec - Sante (FRQS); Quebec BioImaging Network (QBIN); Natural Sciences and Engineering Research Council of Canada (NSERC) FX We would like to thank the individuals who participated in this experiment. We also thank Marc Benhamou and Benjamin De Leener for the creation of the atlas of white matter tracts and the development of registration tools. This study was founded by National Institutes of Health, NIH Blueprint Initiative for Neuroscience Research grant U01MH093765, National Institutes of Health grant P41EB015896, the MS Society of Canada [EGID 2370], the SensoriMotor Rehabilitation Research Team (SMRRT) of the Canadian Institute of Health Research, the National MS Society [FG1892A1/1], the Fonds de Recherche du Quebec - Sante (FRQS), the Quebec BioImaging Network (QBIN) and the Natural Sciences and Engineering Research Council of Canada (NSERC). NR 88 TC 8 Z9 8 U1 3 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2015 VL 118 BP 494 EP 507 DI 10.1016/j.neuroimage.2015.06.038 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CQ5GB UT WOS:000360630200047 PM 26095093 ER PT J AU Chen, JX Kozin, ED Sethi, RKV Remenschneider, AK Emerick, KS Gray, ST AF Chen, Jenny X. Kozin, Elliott D. Sethi, Rosh K. V. Remenschneider, Aaron K. Emerick, Kevin S. Gray, Stacey T. TI Increased Resident Research over an 18-Year Period: A Single Institution's Experience SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE residency; otolaryngology; work hours; research; publication ID DUTY HOUR RESTRICTIONS; ACADEMIC OTOLARYNGOLOGY; SCHOLARLY IMPACT; NECK-SURGERY; PUBLICATIONS; PRODUCTIVITY; PERSPECTIVES; APPLICANTS; HEAD AB Objectives (1) To evaluate changes in the resident publications over time, including before and after duty hour restrictions, and (2) to identify factors statistically associated with publications during residency. Study Design Retrospective review of bibliometric data. Subjects and Methods Residents who graduated from an otolaryngology residency program from 1996 to 2013 were evaluated. Thomson Reuters Web of Science was searched to determine the number of indexed peer-reviewed publications before and after implementation of resident duty hour restrictions in 2003. Resident demographics, PhD degrees, training tracks, and postgraduation plans were collected to determine factors associated with publication rate using multivariable regression analysis. Results During the studied period, 75 residents completed otolaryngology residency training and published a total of 294 papers, averaging 3.92 publications per resident during training. After work hour restrictions were implemented, the mean number of publications increased from 1.21 to 5.10 (P < .0001). First author publications, clinical publications, and basic science publications all increased (P < .001). In regression analysis, T32 grants ( = 6.98, standard error [SE] = 1.87, P = .0004) and the time period after duty hour restrictions were introduced ( = 4.72, SE = 1.73, P = .0083) were positively associated with resident publications. Gender, PhD degree, and pursuit of fellowship training were not associated with increased publications (P > .05). Conclusion There has been a significant increase in resident publications over time, coinciding with the implementation of work hour restrictions. T32 grants were most predictive of increased resident publications, while PhD degrees were not significantly associated. C1 [Chen, Jenny X.; Kozin, Elliott D.; Sethi, Rosh K. V.; Remenschneider, Aaron K.; Emerick, Kevin S.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Chen, Jenny X.; Kozin, Elliott D.; Sethi, Rosh K. V.; Remenschneider, Aaron K.; Emerick, Kevin S.; Gray, Stacey T.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Kozin, ED (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Elliott_Kozin@meei.harvard.edu NR 29 TC 1 Z9 1 U1 1 U2 4 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 SEP PY 2015 VL 153 IS 3 BP 350 EP 356 DI 10.1177/0194599815587908 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CQ5SP UT WOS:000360666300005 PM 26070509 ER PT J AU Paddle, PM Mansor, MB Song, PC Franco, RA AF Paddle, Paul M. Mansor, Masaany B. Song, Phillip C. Franco, Ramon A. TI Diagnostic Yield of Computed Tomography in the Evaluation of Idiopathic Vocal Fold Paresis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE idiopathic unilateral vocal fold paresis; computed tomography; diagnostic yield; incidental yield ID CORD PARALYSIS; IMMOBILITY; ETIOLOGY AB Objective To determine the diagnostic yield of computed tomography (CT) in establishing an etiology in patients with idiopathic unilateral vocal fold paresis (IUVFP). To determine the proportion of CT scans yielding incidental findings requiring further patient management. Study Design Case series with chart review. Setting Tertiary laryngology practice. Subjects Laryngology clinic patients under the care of the 2 senior authors. Methods All clinic patients were identified who had a diagnosis of IUVFP and underwent CT of the skull base to the upper mediastinum from 2004 to 2014. Demographic, historical, examination, and investigation data were extracted. CT reports and endoscopic recordings were reviewed. Patients were excluded if there were insufficient clinical findings recorded or if there was a known neurologic disorder, complete vocal fold immobility, or bilateral involvement. Results A total of 174 patients with IUVFP who had also undergone contrast-enhanced CT were identified. Of the 174 patients, 5 had a cause for their paresis identified on CT. This equated to a diagnostic yield of 2.9% (95% confidence interval, 0.94% to 6.6%). Of the 174 patients, 48 had other incidental lesions identified that required further follow-up, investigation, or treatment. This equated to an incidental yield of 27.6% (95% confidence interval, 21.1% to 34.9%). Conclusion This is the second and largest study to evaluate the diagnostic yield of CT in the evaluation of IUVFP. It demonstrates a low diagnostic yield and a high incidental yield. These findings suggest that the routine use of CT in the evaluation of idiopathic vocal fold paresis should be given careful consideration and that a tailored approach to investigation with good otolaryngologic follow-up is warranted. C1 [Paddle, Paul M.; Mansor, Masaany B.; Song, Phillip C.; Franco, Ramon A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Laryngol, Boston, MA 02114 USA. RP Paddle, PM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Laryngol, Boston, MA 02114 USA. EM paulpaddle@me.com NR 17 TC 0 Z9 0 U1 0 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 SEP PY 2015 VL 153 IS 3 BP 414 EP 419 DI 10.1177/0194599815593268 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CQ5SP UT WOS:000360666300014 PM 26156423 ER PT J AU Dedmon, MM Paddle, PM Phillips, J Kobayashi, L Franco, RA Song, PC AF Dedmon, Matthew M. Paddle, Paul M. Phillips, Jeananne Kobayashi, Leo Franco, Ramon A. Song, Phillip C. TI Development and Validation of a High-Fidelity Porcine Laryngeal Surgical Simulator SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE laryngology; laryngeal surgery; simulation; validation; phonomicrosurgery; education ID FOLD EXTRACELLULAR-MATRIX; SURGERY; SKILLS AB Objective Design and validate a laryngeal surgical simulator to teach phonomicrosurgical techniques. Study Design Device development and prospective validation. Setting Tertiary medical center. Subjects and Methods A novel laryngeal fixation device and custom laryngoscope were produced for use with ex vivo porcine larynx specimens. Vocal fold lesions such as nodules and keratotic lesions were simulated with silicone injections and epithelial markings. A prospective validation using postsimulation surveys, global rating scales, and procedure-specific checklists was performed with a group of 15 medical students, otolaryngology residents, fellows, and attending laryngologists. Three procedures were performed: vocal fold augmentation, excision of a simulated vocal fold nodule, and excision of a simulated vocal fold keratosis. Results Participants overwhelmingly agreed that the simulator provided a realistic dissection experience that taught skills that would transfer to real operating scenarios. Expert performance was statistically superior to novice performance for excision of simulated vocal fold nodules and keratotic lesions, while no difference was observed for injection laryngoplasty. Conclusion The ability to learn and rehearse surgical procedures in a safe environment is invaluable, particularly for delicate and highly technical phonomicrosurgical operations. We have developed a high-fidelity laryngeal surgical simulator complete with pathological lesions such as nodules and keratoses to teach these procedures. A prospective study demonstrated validity of our global rating scale and checklist assessments for vocal fold nodule and keratosis excision procedures, allowing them to be confidently incorporated into phonomicrosurgical training programs for surgeons of all levels of expertise. C1 [Dedmon, Matthew M.; Paddle, Paul M.; Phillips, Jeananne; Franco, Ramon A.; Song, Phillip C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Dedmon, Matthew M.; Paddle, Paul M.; Phillips, Jeananne; Franco, Ramon A.; Song, Phillip C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Kobayashi, Leo] Rhode Isl Hosp, Dept Emergency Med, Providence, RI USA. RP Dedmon, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM matthew_dedmon@meei.harvard.edu NR 13 TC 3 Z9 3 U1 0 U2 3 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 SEP PY 2015 VL 153 IS 3 BP 420 EP 426 DI 10.1177/0194599815590118 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CQ5SP UT WOS:000360666300015 PM 26138605 ER PT J AU Niazi, IK Sperzel, J Heist, EK Rosenberg, SP Ryu, K Yang, M D'Avila, A Singh, JP AF Niazi, Imran K. Sperzel, Johannes Heist, Edwin Kevin Rosenberg, Stuart P. Ryu, Kyungmoo Yang, Michael D'Avila, Andre Singh, Jagmeet P. TI Three-Dimensional Cardiac Mapping Characterizes Ventricular Contractile Patterns during Cardiac Resynchronization Therapy Implant: A Feasibility Study SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; contractility; electroanatomic mapping; dyssynchrony; heart failure ID HEART-FAILURE; RESYNCHRONISATION THERAPY; PACING SITES; OPTIMIZATION; TRIAL AB BackgroundElectroanatomic mapping systems track the position of electrodes in the heart. We assessed the feasibility of characterizing left ventricular (LV) performance during cardiac resynchronization therapy (CRT) implant utilizing an electroanatomic mapping system to track the motion of CRT lead electrodes, thus deriving ventricular contractility surrogates. MethodsDuring CRT implant, atrial, right ventricular (RV), and LV leads were connected to the EnSite NavX mapping system (St. Jude Medical Inc., St. Paul, MN, USA). The relative displacement of electrodes was averaged over 10 cardiac cycles during RV, LV, and biventricular (BiV) pacing in DOO mode. Three contractility surrogates indicative of ventricular performance were extracted from the RV-LV distance waveform: systolic slope (SS), time to peak systolic contraction (TPSC), and fractional shortening (FS). ResultsIn the 20 patients included, there were detectable differences in each of the three contractility surrogates responding to the different pacing configurations. Median SS varied 42%, median TPSC varied 35%, and median FS varied 19% across RV, LV, and BiV pacing interventions. The RV-LV distance waveform showed subtle sensitivity to varying pacing timing cycles when measured in a subset of patients. For all pacing configurations, RV-LV distance waveforms were stable during 2-minute recordings. ConclusionsTracking the motion of CRT pacing electrodes with a mapping system to derive contractility surrogates during implant is feasible. C1 [Niazi, Imran K.] Univ Wisconsin, Aurora Cardiovasc Serv, Aurora Sinai Aurora St Lukes Med Ctr, Sch Med & Publ Hlth, Milwaukee, WI 53215 USA. [Sperzel, Johannes] Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, Bad Nauheim, Germany. [Heist, Edwin Kevin; D'Avila, Andre; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenberg, Stuart P.; Ryu, Kyungmoo; Yang, Michael] St Jude Med, Sylmar, CA USA. RP Niazi, IK (reprint author), Univ Wisconsin, Aurora Cardiovasc Serv, Aurora Sinai Aurora St Lukes Med Ctr, Sch Med & Publ Hlth, 2801 W Kinnickinnic River Pkwy,845, Milwaukee, WI 53215 USA. EM publishing24@aurora.org FU St. Jude Medical Inc. FX This study was supported by a research grant from St. Jude Medical Inc. NR 23 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD SEP PY 2015 VL 38 IS 9 BP 1091 EP 1098 DI 10.1111/pace.12674 PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CQ5UZ UT WOS:000360672500009 PM 26096125 ER PT J AU Klein, MM Treister, R Raij, T Pascual-Leone, A Park, L Nurmikko, T Lenz, F Lefaucheur, JP Lang, M Hallett, M Fox, M Cudkowicz, M Costello, A Carr, DB Ayache, SS Oaklander, AL AF Klein, Max M. Treister, Roi Raij, Tommi Pascual-Leone, Alvaro Park, Lawrence Nurmikko, Turo Lenz, Fred Lefaucheur, Jean-Pascal Lang, Magdalena Hallett, Mark Fox, Michael Cudkowicz, Merit Costello, Ann Carr, Daniel B. Ayache, Samar S. Oaklander, Anne Louise TI Transcranial magnetic stimulation of the brain: guidelines for pain treatment research SO PAIN LA English DT Review DE Neuropathic pain; Neuromodulation; Treatment; Human; Device ID MOTOR CORTEX STIMULATION; SHAM-CONTROLLED TRIAL; SPINAL-CORD-INJURY; CHRONIC NEUROPATHIC PAIN; SYNDROME TYPE-I; THETA-BURST STIMULATION; CENTRAL POSTSTROKE PAIN; SMALL-FIBER NEUROPATHY; DOUBLE-BLIND; MULTIPLE-SCLEROSIS AB Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials. C1 [Klein, Max M.; Treister, Roi; Lang, Magdalena; Fox, Michael; Cudkowicz, Merit; Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Raij, Tommi; Fox, Michael] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Boston, MA 02114 USA. [Pascual-Leone, Alvaro; Fox, Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02114 USA. [Park, Lawrence; Costello, Ann] US FDA, Ctr Devices & Radiol Hlth, Div Neurol & Phys Med Devices, Off Device Evaluat, Bethesda, MD 20014 USA. [Park, Lawrence] NIMH, US Natl Inst Hlth, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Nurmikko, Turo] Walton Ctr NHS Fdn Trust, Pain Res Inst, Neurosci Res Ctr, Liverpool, Merseyside, England. [Lenz, Fred] Johns Hopkins Med Inst, Dept Neurosurg, Baltimore, MD 21205 USA. [Lefaucheur, Jean-Pascal; Ayache, Samar S.] Henri Mondor Hosp, Assistance Publ Hop Paris, Dept Physiol, Creteil, France. [Lefaucheur, Jean-Pascal; Ayache, Samar S.] Paris Est Creteil Univ, Fac Med, Nerve Excitabil & Therapeut Team, EA 4391, Creteil, France. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Anesthesiol, Boston, MA 02111 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Klein, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 275 Charles St Warren Bldg 310, Boston, MA 02114 USA. EM mklein@mgh.harvard.edu FU Radcliffe Institute for Advanced Study; Samuels Family Foundation; Public Health Service [K24NS059892, K23NS083741, NS38493, R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, U01NS077179]; NINDS; UK National Institute of Health Research [PB-PG-0110-20321]; Hopkins Neurosurgery Pain Research Institute; American Academy of Neurology/American Brain Foundation; Sidney R. Baer Foundation; Harvard Catalyst-Clinical and Translational Science Center [UL1 RR025758] FX Supported in part by the Radcliffe Institute for Advanced Study and the Samuels Family Foundation, the Public Health Service (K24NS059892, K23NS083741, NS38493, R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, and U01NS077179) and NINDS intramural support to M. Hallett, the UK National Institute of Health Research (PB-PG-0110-20321) to T. Nurmikko, the Hopkins Neurosurgery Pain Research Institute, the American Academy of Neurology/American Brain Foundation, the Sidney R. Baer Foundation, the Harvard Catalyst-Clinical and Translational Science Center (UL1 RR025758). NR 117 TC 16 Z9 16 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD SEP PY 2015 VL 156 IS 9 BP 1601 EP 1614 DI 10.1097/j.pain.0000000000000210 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CQ4MQ UT WOS:000360579400007 PM 25919472 ER PT J AU Woythaler, M McCormick, MC Mao, WY Smith, VC AF Woythaler, Melissa McCormick, Marie C. Mao, Wen-Yang Smith, Vincent C. TI Late Preterm Infants and Neurodevelopmental Outcomes at Kindergarten SO PEDIATRICS LA English DT Article ID CARE UTILIZATION INDEX; WEEKS GESTATION; TERM; CHILDREN; BIRTH; RISK; BORN; AGE; ACHIEVEMENT; DISPARITIES AB BACKGROUND AND OBJECTIVE: Late preterm infants (LPIs) (gestation 34 weeks and 0 days to 36 weeks and 6 days) compared with full-term infants (FTIs) are at increased risk for mortality and short- and long-term morbidity. The objective of this study was to assess the neurodevelopmental outcomes in a longitudinal cohort study of LPIs from infancy to school age and determine predictive values of earlier developmental testing compared with school-age testing. METHODS: We used general estimating equations to calculate the odds of school readiness in a nationally representative cohort of 4900 full-term and 950 late preterm infants. We generated positive and negative predictive values of the ability of the 24-month Mental Developmental Index (MDI) scores of the Bayley Short Form, Research Edition, to predict Total School Readiness Score (TSRS) at kindergarten age. RESULTS: In multivariable analysis, late preterm infants had higher odds of worse TSRSs (adjusted odds ratio 1.52 [95% confidence interval 1.06-2.18], P = .0215). The positive predictive value of a child having an MDI of <70 at 24 months and a TSRS <5% at kindergarten was 10.4%. The negative predictive value of having an MDI of >70 at 24 months and a TSRS >5% was 96.8%. Most infants improved score ranking over the study interval. CONCLUSIONS: LPIs continue to be delayed at kindergarten compared with FTIs. The predictive validity of having a TSRS in the bottom 5% given a MDI <70 at 24 months was poor. A child who tested within the normal range (>85) at 24 months had an excellent chance of testing in the normal range at kindergarten. C1 [Woythaler, Melissa] Massachusetts Gen Hosp Children, Boston, MA USA. [Woythaler, Melissa; Smith, Vincent C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [McCormick, Marie C.; Mao, Wen-Yang; Smith, Vincent C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McCormick, Marie C.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Woythaler, M (reprint author), Massachusetts Gen Hosp, Dept Newborn Med, 55 Fruit St,Founders 5, Boston, MA 02114 USA. EM mwoythaler@partners.org NR 41 TC 12 Z9 13 U1 3 U2 8 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 SEP PY 2015 VL 136 IS 3 BP 424 EP 431 DI 10.1542/peds.2014-4043 PG 8 WC Pediatrics SC Pediatrics GA CQ6IN UT WOS:000360708100029 PM 26260723 ER PT J AU Goodman, E Maxwell, S Malspeis, S Adler, N AF Goodman, Elizabeth Maxwell, Sarah Malspeis, Susan Adler, Nancy TI Developmental Trajectories of Subjective Social Status SO PEDIATRICS LA English DT Article ID SOCIOECONOMIC-STATUS GRADIENTS; SELF-RATED HEALTH; AFRICAN-AMERICANS; ADOLESCENT HEALTH; PREGNANT-WOMEN; WHITEHALL-II; INDIVIDUALS; CHILDHOOD; MOBILITY; LATINO AB BACKGROUND AND OBJECTIVE: Subjective social status (SSS), a person's sense of their (or for youth, abstract their family's) position in the socioeconomic hierarchy, is strongly related to health in adults but not health in adolescence. Understanding this developmental discrepancy requires first understanding the developmental trajectory of SSS. The objective of this study was to identify the number and shape of SSS trajectories as adolescents transition to adulthood and explore if trajectory membership affects health. METHODS: Using data from 7436 assessments from the Princeton School District Study, a decade-long cohort study of non-Hispanic black and white youth, latent class growth models with 3 to 7 SSS trajectories were developed. Model fit, trajectory structure, and shape were used to guide optimal model selection. Using this optimal model, the associations of trajectory membership with BMI and depressive symptoms in young adulthood were explored. RESULTS: The 5-class model was optimal. In this model, trajectories were persistent high (7.8%), mid-high (32.2%), middle (43.4%), low-lower (7.4%), and high-low (9.1%). Non-Hispanic black race/ethnicity, lower household income, and low parent education were associated with membership in this high-low trajectory. High-low trajectory membership was associated with higher BMI and depressive symptoms in non-Hispanic white subjects but was not associated with depressive symptoms. It was associated with lower BMI only after adjustment for BMI in adolescence in non-Hispanic black subjects. CONCLUSIONS: SSS is relatively stable in adolescence and the transition to adulthood, and it generally reflects objective markers of social advantage. However, socially disadvantaged youth with high SSS in early adolescence may be at increased health risk. C1 [Goodman, Elizabeth] MassGen Hosp Children, Boston, MA 02114 USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Maxwell, Sarah; Adler, Nancy] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. [Malspeis, Susan] Brigham & Womens Hosp, Clin Sci Sect, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Adler, Nancy] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Adler, Nancy] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Adler, Nancy] Univ Calif San Francisco, Sch Med, Ctr Hlth & Commun, San Francisco, CA USA. RP Goodman, E (reprint author), MassGen Hosp Children, Div Gen Acad Pediat, 55 Fruit St,MS-125N,Suite 860, Boston, MA 02114 USA. EM egoodman3@mgh.harvard.edu FU National Institutes of Health (NIH) [HD041527, DK59183] FX Supported, in part, by National Institutes of Health grants HD041527 and DK59183. Funded by the National Institutes of Health (NIH). NR 39 TC 1 Z9 1 U1 6 U2 20 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 SEP PY 2015 VL 136 IS 3 BP E633 EP E640 DI 10.1542/peds.2015-1300 PG 8 WC Pediatrics SC Pediatrics GA CQ6IN UT WOS:000360708100011 PM 26324868 ER PT J AU Naeser, MA Hamblin, MR AF Naeser, Margaret A. Hamblin, Michael R. TI Traumatic Brain Injury: A Major Medical Problem That Could Be Treated Using Transcranial, Red/Near-Infrared LED Photobiomodulation SO PHOTOMEDICINE AND LASER SURGERY LA English DT Editorial Material ID DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY; MICROGLIAL ACTIVATION; LASER THERAPY; LIGHT; INFLAMMATION; PERFORMANCE; CONCUSSION; RADIATION; FOREHEAD C1 [Naeser, Margaret A.] VA Boston Healthcare Syst, Boston, MA USA. [Naeser, Margaret A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst 12A, Transcranial Light Emitting Diode LED Therapy Res, Neuroimaging Aphasia Res, 150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu FU NIAID NIH HHS [R01AI050875] NR 48 TC 3 Z9 3 U1 4 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 EI 1557-8550 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD SEP 1 PY 2015 VL 33 IS 9 BP 443 EP 446 DI 10.1089/pho.2015.3986 PG 4 WC Surgery SC Surgery GA CQ4JY UT WOS:000360572200001 PM 26280257 ER PT J AU Gassman, AA Lewis, MS Bradley, JP Lee, JC AF Gassman, Andrew A. Lewis, Michael S. Bradley, James P. Lee, Justine C. TI Remote Ischemic Preconditioning Improves the Viability of Donor Lipoaspirate during Murine Fat Transfer SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID REPERFUSION INJURY; RAT MODEL; SURVIVAL; BREAST; CELLS; TRANSPLANTATION; RECONSTRUCTION; LIPOSUCTION; HARVEST; HEART AB Background: Variable results associated with fat grafting have been attributed to local trauma, inconsistencies in transfer, and ischemia before the development of recipient circulation. Remote ischemic preconditioning is an inexpensive noninvasive technique that has been used in animal models and multicenter clinical trials to protect organ systems. In this work, the authors describe a novel animal model for analyzing the efficacy of fat grafting, and investigate the effect of remote ischemic preconditioning on volume retention. Methods: Subcutaneous adipose tissue samples from green fluorescent protein/luciferase-expressing FVB mice were obtained with or without pretreatment with a temporary hind-limb tourniquet. The samples were injected into the dorsal skin folds of wild-type FVB mice. The viability of the transferred tissue was examined over a 28-day period with quantitative bioluminescence after luciferin injection. Transferred tissue was also explanted for histologic analysis. Results: The remote ischemic preconditioning group had significantly increased bioluminescence at days 0, 1, and 28. Histologic analysis at day 28 confirmed the presence of vascularized adipose in both groups. However, significant amounts of interstitial fibrosis were found in the control group, whereas substantially less was found in the remote ischemic preconditioning group. The remote ischemic preconditioning group retained a substantially greater amount of green fluorescent protein, suggesting increased survival of donor adipocytes. Conclusions: In this work, the authors describe a novel animal model for quantitative evaluation of fat grafting using in vivo bioluminescence of adipocytes from luciferase-expressing mice. The authors also demonstrate that remote ischemic preconditioning increases the viability of fat transfer and decreases interstitial fibrosis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, Dept Surg, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Dept Pathol, Los Angeles, CA USA. Temple Univ Hosp & Sch Med, Dept Surg, Div Plast & Reconstruct Surg, Philadelphia, PA USA. RP Gassman, AA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Plast Surg, 1801 Inwood Rd, Dallas, TX 75390 USA. EM Andrew.Gassman@UTsouthwestern.edu FU Plastic Surgery Foundation [274376]; Jean Perkins Foundation FX This work was supported by the Plastic Surgery Foundation (Pilot Research Grant 274376) (to A.A.G.) and the Jean Perkins Foundation (to J.C.L.). NR 26 TC 3 Z9 3 U1 2 U2 2 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 SEP PY 2015 VL 136 IS 3 BP 495 EP 502 DI 10.1097/PRS.0000000000001488 PG 8 WC Surgery SC Surgery GA CQ5YO UT WOS:000360681800005 PM 25989298 ER PT J AU Susarla, SM Lopez, J Swanson, EW Miller, D O'Brien-Coon, D Zins, JE Serletti, JM Yaremchuk, MJ Manson, PN Gordon, CR AF Susarla, Srinivas M. Lopez, Joseph Swanson, Edward W. Miller, Devin O'Brien-Coon, Devin Zins, James E. Serletti, Joseph M. Yaremchuk, Michael J. Manson, Paul N. Gordon, Chad R. TI Are Quantitative Measures of Academic Productivity Correlated with Academic Rank in Plastic Surgery? A National Study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID H-INDEX; UNITED-STATES; SCHOLARLY PRODUCTIVITY; GENDER DISPARITIES; CITATION; OTOLARYNGOLOGY; PERFORMANCE; DEPARTMENTS; AUTHORSHIP; SEARCH AB Background: The purpose of this study was to investigate the correlation between quantitative measures of academic productivity and academic rank among full-time academic plastic surgeons. Methods: Bibliometric indices were computed for all full-time academic plastic surgeons in the United States. The primary study variable was academic rank. Bibliometric predictors included the Hirsch index, I-10 index, number of publications, number of citations, and highest number of citations for a single publication. Descriptive, bivariate, and correlation analyses were computed. Multiple comparisons testing was used to calculate adjusted associations for subgroups. For all analyses, a value of p < 0.05 was considered significant. Results: The cohort consisted of 607 plastic surgeons across 91 Accreditation Council for Graduate Medical Education-approved programs. Of them, 4.1 percent were instructors/lecturers, 43.7 percent were assistant professors, 22.1 percent were associate professors, 25.7 percent were professors, and 4.4 percent were endowed professors. Mean values were as follows: Hirsch index, 10.2 9.0; I-10 index, 17.2 +/- 10.2; total number of publications, 45.5 +/- 69.4; total number of citations, 725.0 +/- 1448.8; and highest number of citations for a single work, 117.8 +/- 262.4. Correlation analyses revealed strong associations of the Hirsch index, I-10 index, number of publications, and number of citations with academic rank (r(s) = 0.62 to 0.64; p < 0.001). Conclusions: Academic rank in plastic surgery is strongly correlated with several quantitative metrics of research productivity. Although academic promotion is the result of success in multiple different areas, bibliometric measures may be useful adjuncts for assessment of research productivity. C1 Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD 21218 USA. Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Dept Neurosurg, Baltimore, MD 21218 USA. Cleveland Clin, Dept Plast Surg, Cleveland, OH USA. Univ Penn, Sch Med, Dept Surg, Div Plast Surg, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Plast Surg, Cambridge, MA 02138 USA. RP Gordon, CR (reprint author), Johns Hopkins Univ Hosp, Dept Plast Reconstruct Surg, 601 North Caroline St,JHOC 8, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu OI Susarla, Srinivas/0000-0003-0155-8260 NR 35 TC 9 Z9 9 U1 0 U2 8 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 SEP PY 2015 VL 136 IS 3 BP 613 EP 621 DI 10.1097/PRS.0000000000001531 PG 9 WC Surgery SC Surgery GA CQ5ZK UT WOS:000360684000001 PM 26313830 ER PT J AU Kunert, C Baish, JW Liao, S Padera, TP Munn, LL AF Kunert, Christian Baish, James W. Liao, Shan Padera, Timothy P. Munn, Lance L. TI Mechanobiological oscillators control lymph flow SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lymphatic; mechanobiology; computational model; control; biological oscillator ID RAT MESENTERIC LYMPHATICS; SMOOTH-MUSCLE-CELLS; LATTICE BOLTZMANN SCHEME; INDUCED CALCIUM-RELEASE; GUINEA-PIG MESENTERY; NITRIC-OXIDE; CONTRACTILE ACTIVITY; TRANSMURAL PRESSURE; COLLECTING LYMPHATICS; ENDOTHELIAL-CELLS AB The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, "emergent" behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled-at least in part-by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca2+-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca2+ and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function. C1 [Kunert, Christian; Liao, Shan; Padera, Timothy P.; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Kunert, Christian; Liao, Shan; Padera, Timothy P.; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Baish, James W.] Bucknell Univ, Biomed Engn & Mech Engn, Lewisburg, PA 17837 USA. RP Kunert, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM kuni@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Padera, Timothy/0000-0002-3453-9384 FU National Institutes of Health [R01-CA149285, R00-CA137167, R21-AI097745, DP2-OD008780, R01-HL128168]; Deutsche Forschungsgemeinschaft [Ku 2909/1] FX We thank Drs. Jonathan Song and Dennis Jones for unpublished studies that guided this project. This work was funded in part by National Institutes of Health Grants R01-CA149285 (to L.L.M.), R00-CA137167, R21-AI097745, and DP2-OD008780 (to T.P.P.), R01-HL128168 (to J.W.B., T.P.P., and L.L.M.), and Deutsche Forschungsgemeinschaft Grant Ku 2909/1 (to C.K.). NR 79 TC 8 Z9 8 U1 3 U2 8 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 SEP 1 PY 2015 VL 112 IS 35 BP 10938 EP 10943 DI 10.1073/pnas.1508330112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200047 PM 26283382 ER PT J AU Godec, J Cowley, GS Barnitz, RA Alkan, O Root, DE Sharpe, AH Haining, WN AF Godec, Jernej Cowley, Glenn S. Barnitz, R. Anthony Alkan, Ozan Root, David E. Sharpe, Arlene H. Haining, W. Nicholas TI Inducible RNAi in vivo reveals that the transcription factor BATF is required to initiate but not maintain CD8(+) T-cell effector differentiation (vol 112, pg 512, 2015) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Correction C1 [Godec, Jernej; Barnitz, R. Anthony; Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cowley, Glenn S.; Alkan, Ozan; Root, David E.; Sharpe, Arlene H.; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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 SEP 1 PY 2015 VL 112 IS 35 BP E4968 EP E4968 DI 10.1073/pnas.1514097112 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200020 ER PT J AU Woerman, AL Stohr, J Aoyagi, A Rampersaud, R Krejciova, Z Watts, JC Ohyama, T Patel, S Widjaja, K Oehler, A Sanders, DW Diamond, MI Seeley, WW Middleton, LT Gentleman, SM Mordes, DA Sudhof, TC Giles, K Prusiner, SB AF Woerman, Amanda L. Stoehr, Jan Aoyagi, Atsushi Rampersaud, Ryan Krejciova, Zuzana Watts, Joel C. Ohyama, Takao Patel, Smita Widjaja, Kartika Oehler, Abby Sanders, David W. Diamond, Marc I. Seeley, William W. Middleton, Lefkos T. Gentleman, Steve M. Mordes, Daniel A. Suedhof, Thomas C. Giles, Kurt Prusiner, Stanley B. TI Propagation of prions causing synucleinopathies in cultured cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alpha-synuclein; multiple system atrophy; neurodegeneration; strains; Parkinson's disease ID MULTIPLE SYSTEM ATROPHY; PATHOLOGICAL ALPHA-SYNUCLEIN; GLIAL CYTOPLASMIC INCLUSIONS; SPORADIC PARKINSONS-DISEASE; A-BETA PRIONS; ALZHEIMERS-DISEASE; TRANSGENIC MICE; LEWY BODIES; IN-VIVO; STRAINS AB Increasingly, evidence argues that many neurodegenerative diseases, including progressive supranuclear palsy (PSP), are caused by prions, which are alternatively folded proteins undergoing self-propagation. In earlier studies, PSP prions were detected by infecting human embryonic kidney (HEK) cells expressing a tau fragment [TauRD(LM)] fused to yellow fluorescent protein (YFP). Here, we report on an improved bioassay using selective precipitation of tau prions from human PSP brain homogenates before infection of the HEK cells. Tau prions were measured by counting the number of cells with TauRD(LM)-YFP aggregates using confocal fluorescence microscopy. In parallel studies, we fused alpha-synuclein to YFP to bioassay alpha-synuclein prions in the brains of patients who died of multiple system atrophy (MSA). Previously, MSA prion detection required similar to 120 d for transmission into transgenic mice, whereas our cultured cell assay needed only 4 d. Variation in MSA prion levels in four different brain regions from three patients provided evidence for three different MSA prion strains. Attempts to demonstrate alpha-synuclein prions in brain homogenates from Parkinson's disease patients were unsuccessful, identifying an important biological difference between the two synucleinopathies. Partial purification of tau and alpha-synuclein prions facilitated measuring the levels of these protein pathogens in human brains. Our studies should facilitate investigations of the pathogenesis of both tau and alpha-synuclein prion disorders as well as help decipher the basic biology of those prions that attack the CNS. C1 [Woerman, Amanda L.; Stoehr, Jan; Aoyagi, Atsushi; Rampersaud, Ryan; Krejciova, Zuzana; Watts, Joel C.; Patel, Smita; Widjaja, Kartika; Giles, Kurt; Prusiner, Stanley B.] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA. [Stoehr, Jan; Watts, Joel C.; Seeley, William W.; Giles, Kurt; Prusiner, Stanley B.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Aoyagi, Atsushi; Ohyama, Takao] Daiichi Sankyo Co Ltd, Tokyo 1408710, Japan. [Oehler, Abby; Seeley, William W.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Sanders, David W.; Diamond, Marc I.] Univ Texas SW Med Ctr Dallas, Ctr Alzheimers & Neurodegenerat Dis, Dallas, TX 75390 USA. [Middleton, Lefkos T.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ageing Res Unit, London SW7 2AZ, England. [Gentleman, Steve M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Neuroinflammat & Neurodegenerat, London SW7 2AZ, England. [Mordes, Daniel A.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Prusiner, Stanley B.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Prusiner, SB (reprint author), Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA. EM stanley@ind.ucsf.edu FU National Institutes of Health (NIH) [AG002132, AG010770, AG021601, AG031220]; Rainwater Charitable Foundation; Sherman Fairchild Foundation; Dana Foundation; Mary Jane Brinton Fund; NIH [AG023501, AG19724]; Tau Consortium; Consortium for Frontotemporal Dementia Research; Parkinson's UK, a charity registered in England [948776]; Parkinson's UK, a charity registered in Wales [948776]; Parkinson's UK, a charity registered in Scotland [SC037554]; University of Miami Brain Endowment Bank FX This work was supported by grants from the National Institutes of Health (NIH) (AG002132, AG010770, AG021601, and AG031220) as well as the Rainwater Charitable Foundation, the Sherman Fairchild Foundation, the Dana Foundation, and the Mary Jane Brinton Fund. PSP tissue samples were received from the University of California, San Francisco Neurodegenerative Disease Brain Bank, which is supported by the NIH (AG023501 and AG19724 to W.W.S.), the Tau Consortium, and the Consortium for Frontotemporal Dementia Research. Additional tissue samples were supplied by the neuropathology core of the Massachusetts Alzheimer's Disease Research Center (AG005134); the Parkinson's UK Tissue Bank at Imperial College London, funded by Parkinson's UK, a charity registered in England and Wales (948776) and in Scotland (SC037554); and the University of Miami Brain Endowment Bank. DNA for WT and A53T mutated human a-synuclein was kindly provided by Dr. Robert Nussbaum. We thank the Hunter's Point animal facility staff for their assistance with animal experiments and Marta Gavidia for mouse genotyping. Additional thanks to Dr. Joel Gever for optimizing the cell assay conditions and to Ana Serban for the production of the K18 fragment of tau and the anti-Tau-12 antibody. NR 75 TC 27 Z9 27 U1 4 U2 18 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 SEP 1 PY 2015 VL 112 IS 35 BP E4949 EP E4958 DI 10.1073/pnas.1513426112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200018 PM 26286986 ER PT J AU Nakagawa, A Williams, A Sado, M Oguchi, Y Mischoulon, D Smith, F Mimura, M Sato, Y AF Nakagawa, Atsuo Williams, Aya Sado, Mitsuhiro Oguchi, Yoshiyo Mischoulon, David Smith, Felicia Mimura, Masaru Sato, Yuji TI Comparison of treatment selections by Japanese and US psychiatrists for major depressive disorder: A case vignette study SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE Japan; major depressive disorder; medical education; psychiatric residency; USA ID SYSTEMATIC ANALYSIS; BENZODIAZEPINE USE; GLOBAL BURDEN; ANTIDEPRESSANTS; INJURIES; DISEASES AB AimsA review of the published work on treatments for major depressive disorder suggests that there is an alarming gap between guideline recommendations and actual clinical practices worldwide. The purpose of this study was to compare early-career psychiatrists' selections of treatment for mild to moderate major depression in Japan and the USA. MethodsThe authors surveyed 120 early-career psychiatrists from two residency programs in Japan and the USA using web-based questionnaires. In response to two case vignettes of mild to moderate major depression, the subjects selected treatment modalities and first- and second-line pharmacotherapy. ResultsEighty-one psychiatrists (68%) returned surveys, of whom 42 (52%) were Japanese and 39 (48%) American. Fewer Japanese subjects selected psychotherapy than Americans. The Japanese psychiatrists favored benzodiazepine monotherapy for the treatment of mild depression, whereas the American psychiatrists favored antidepressant monotherapy. For the initial treatment of moderate depression, approximately half of the Japanese selected antidepressant monotherapy, and a quarter selected benzodiazepine monotherapy, whereas the Americans unanimously selected selective serotonin reuptake inhibitors monotherapy. As a second-line strategy, the Japanese were more likely to augment medication and less likely to increase dosage for moderate depression than their American counterparts. ConclusionsDifferences were found between the treatment selections of early-career psychiatrists in Japan and the USA, despite comparable guidelines and postgraduate training. The results suggest that the gap between guidelines and practice may also be shaped by physician workload, attitudes toward side-effects, and the sociocultural contexts in which clinical decisions are made. C1 [Nakagawa, Atsuo; Williams, Aya; Sato, Yuji] Keio Univ, Clin Res Ctr, Sch Med, Tokyo 1608582, Japan. [Sado, Mitsuhiro; Oguchi, Yoshiyo; Mimura, Masaru] Keio Univ, Dept Neuropsychiat, Sch Med, Tokyo 1608582, Japan. [Mischoulon, David; Smith, Felicia] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Nakagawa, A (reprint author), Keio Univ, Clin Res Ctr, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM anakagawa@z2.keio.jp FU Health Labor Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [H25-Seishin-Shitei-011, H26-Seishin-Shitei-001] FX This study was made possible by a Health Labor Sciences Research Grant (H25-Seishin-Shitei-011, H26-Seishin-Shitei-001) from the Japanese Ministry of Health, Labour, and Welfare. The authors would also like to thank Dr Nhi-Ha Trinh and Dr Justin Chen from the MGH Depression Clinical and Research Program for their contributions to the study design and recruitment. The authors report no conflict of interest. NR 29 TC 2 Z9 2 U1 4 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-1316 EI 1440-1819 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PD SEP PY 2015 VL 69 IS 9 BP 553 EP 562 DI 10.1111/pcn.12273 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CQ7UV UT WOS:000360811400006 PM 25601043 ER PT J AU Carper, TL Mills, MA Steenkamp, MM Nickerson, A Salters-Pedneault, K Litz, BT AF Carper, Teresa L. Mills, Mary Alice Steenkamp, Maria M. Nickerson, Angela Salters-Pedneault, Kristalyn Litz, Brett T. TI Early PTSD Symptom Sub-Clusters Predicting Chronic Posttraumatic Stress Following Sexual Assault SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; sexual assault; trauma ID CONFIRMATORY FACTOR-ANALYSIS; COGNITIONS INVENTORY PTCI; PSYCHOMETRIC PROPERTIES; DISORDER SYMPTOMS; VETERANS; TRAUMA; RESILIENCE; SURVIVORS; MODELS; TRAJECTORIES AB Contemporary models of PTSD disaggregate this disorder into sub-clusters that differentially impact functioning. Severity of different types of PTSD symptoms in the acute posttrauma period may be predictive of the course of PTSD over time. Few research studies, however, have examined the predictive utility of PTSD sub-clusters. This study sought to determine the relative predictive validity of 4 sub-clusters, namely reexperiencing, strategic avoidance, emotional numbing, and hyperarousal, assessed within 1 month of a sexual assault. Women (N = 120) who had been sexually assaulted completed self-report measures at 1 and 4 months postassault. Linear regression analyses revealed that early reexperiencing and emotional numbing sub-clusters uniquely contributed to the prediction of PTSD symptoms at month 4 (strategic avoidance and hyperarousal did not). To help explain and contextualize these findings, we explored the extent to which posttraumatic cognitions mediated the relationship between acute reexperiencing and emotional numbing and later PTSD symptoms. Simultaneous multiple mediation analyses revealed that general negative cognitions about the self significantly mediated the relationship between both reexperiencing and emotional numbing and month 4 PTSD symptoms. These findings have significant clinical implications, pointing to the importance of targeting posttraumatic cognitions in the acute posttrauma phase. C1 [Carper, Teresa L.] Orlando VA Med Ctr, Orlando, FL USA. [Mills, Mary Alice; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Steenkamp, Maria M.] NYU, Dept Psychiat, New York, NY 10003 USA. [Nickerson, Angela] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT USA. RP Carper, TL (reprint author), Orlando VA Med Ctr Mental Hlth, 5201 Raymond St, Orlando, FL 32803 USA. EM teresa.carper@va.gov NR 35 TC 1 Z9 1 U1 0 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2015 VL 7 IS 5 BP 442 EP 447 DI 10.1037/tra0000060 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CQ4PO UT WOS:000360587300005 PM 26121173 ER PT J AU Maguire, E Macdonald, A Krill, S Holowka, DW Marx, BP Woodward, H Burns, T Taft, CT AF Maguire, Emily Macdonald, Alexandra Krill, Sarah Holowka, Darren W. Marx, Brian P. Woodward, Halley Burns, Tony Taft, Casey T. TI Examining Trauma and Posttraumatic Stress Disorder Symptoms in Court-Mandated Intimate Partner Violence Perpetrators SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE intimate partner violence; trauma; posttraumatic stress disorder ID LIFE EVENTS QUESTIONNAIRE; DOMESTIC VIOLENCE; EXPOSURE; AGGRESSION; MILITARY; VETERANS; SYMPTOMATOLOGY; METAANALYSIS; ABUSE AB There is a dearth of empirical literature characterizing the various forms of trauma experienced by men court mandated to intervention for intimate partner violence (IPV) perpetration. We investigated the potentially traumatic events (PTEs) experienced by men (N = 217) court mandated to enroll in a 41-week group IPV perpetrator program, as well as the relationships between PTEs, posttraumatic stress disorder (PTSD) symptoms, and IPV. Findings indicated that 94% of participants reported experiencing at least 1 PTE in their lifetime, and participants experienced an average of over 6 out of 14 types of PTEs. A significant association was found between the number of PTEs experienced and frequency of self-reported perpetration of physical and psychological IPV. PTSD symptoms were also related to both forms of IPV perpetration and mediated the relationship between experiencing PTEs and psychological IPV perpetration. Our findings have implications for understanding how trauma and PTSD symptoms may increase risk for IPV and for developing trauma-informed interventions for this population. C1 [Maguire, Emily; Macdonald, Alexandra; Holowka, Darren W.; Marx, Brian P.; Woodward, Halley; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Macdonald, Alexandra; Holowka, Darren W.; Marx, Brian P.; Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Krill, Sarah] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Burns, Tony] Common Purpose Inc, Boston, MA USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B, 150 South Huntington Ave, Jamaica Plain, MA 02130 USA. EM casey.taft@va.gov NR 30 TC 4 Z9 4 U1 2 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2015 VL 7 IS 5 BP 473 EP 478 DI 10.1037/a0039253 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CQ4PO UT WOS:000360587300009 PM 26010114 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 Veterans' PTSD Symptoms and Their Partners' Desired Changes in Key Relationship Domains SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE veteran; PTSD; intimacy; shared activities; responsibilities ID POSTTRAUMATIC-STRESS-DISORDER; EX-PRISONERS; INTIMACY; WAR; SATISFACTION; QUALITY; BURDEN AB There is a growing literature investigating the connection between veterans' posttraumatic stress disorder (PTSD) symptoms and intimate relationship problems. Little to no work, however, has examined the connection between veterans' PTSD symptoms and their partners' perceptions of specific relationship areas in need of change. We examined associations between overall PTSD symptoms and symptom cluster scores with partners' desired changes in the areas of intimacy, shared activities, and responsibilities. The sample consisted of 249 male veterans of different service eras and their female partners. Results indicated that veterans' PTSD symptoms were associated with greater desired changes from their partners in the veterans' intimacy behaviors and participation in shared activities. When examining the contribution of each symptom cluster individually, only the veterans' emotional numbing symptoms emerged as a significant unique predictor and were associated with partners' desired changes in intimacy. The findings suggest that intimacy and shared activities may be relevant areas to address in PTSD treatment for veterans and their partners and highlight the particular significance of emotional numbing symptoms to intimacy in veterans' relationships. C1 [LaMotte, Adam D.; Taft, Casey T.; Reardon, Annemarie F.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 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, Natl Ctr PTSD, Behav Sci Div, 150 South Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov FU National Institute of Mental Health [R01 MH079806] FX Funding for this study was provided by National Institute of Mental Health Award R01 MH079806 to Mark W. Miller. NR 27 TC 0 Z9 0 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2015 VL 7 IS 5 BP 479 EP 484 DI 10.1037/tra0000052 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CQ4PO UT WOS:000360587300010 PM 26010109 ER PT J AU Hill, PL Turiano, NA Spiro, A Mroczek, DK AF Hill, Patrick L. Turiano, Nicholas A. Spiro, Avron, III Mroczek, Daniel K. TI Understanding Inter-Individual Variability in Purpose: Longitudinal Findings From the VA Normative Aging Study SO PSYCHOLOGY AND AGING LA English DT Article DE purpose in life; personality; health; older adulthood ID DWELLING OLDER PERSONS; LIFE; MORTALITY; ADULTHOOD; CONSCIENTIOUSNESS; DECLINE; HEALTH; RISK; MEN; AGE AB Research has demonstrated the importance of having a purpose in older adulthood; however, little is known about whether and how individuals vary on sense of purpose over time. The current study examined patterns of mean- and individual-level change in purpose among men in the Veterans Affairs Normative Aging Study (n = 587, M-age = 74 years) across a 3-year span. Findings demonstrate that while little mean- level change was present, there was interindividual variability in change. Further research is needed to understand why these changes occur, as age, health status, and personality failed to predict individual fluctuations in purpose. C1 [Hill, Patrick L.] Carleton Univ, Dept Psychol, Ottawa, ON K1S 5B6, Canada. [Turiano, Nicholas A.] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. [Spiro, Avron, III] Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. [Mroczek, Daniel K.] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA. [Mroczek, Daniel K.] Northwestern Univ, Dept Med Social Sci, Evanston, IL 60208 USA. RP Hill, PL (reprint author), Carleton Univ, Dept Psychol, A515 Loeb Bldg,1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada. EM patrick.hill@carleton.ca FU National Institutes of Health [R01-AG018436]; Clinical Science Research and Development Service, U.S. Department of Veterans Affairs; VA Cooperative Studies Program/Epidemiological Research and Information Centers (MAVERIC) FX The current work was supported by National Institutes of Health Grant R01-AG018436, and by a Senior Research Career Scientist Award to Avron Spiro from the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (VA). The VA Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) and is supported by the VA Cooperative Studies Program/Epidemiological Research and Information Centers. The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. NR 36 TC 3 Z9 3 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 EI 1939-1498 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 2015 VL 30 IS 3 BP 529 EP 533 DI 10.1037/pag0000020 PG 5 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA CQ4OY UT WOS:000360585600004 PM 26146887 ER PT J AU Cao, JX Dai, XP Wan, LX Wang, HS Zhang, JF Goff, PS Sviderskaya, EV Xuan, ZY Xu, ZX Xu, XW Hinds, P Flaherty, KT Faller, DV Goding, CR Wang, YJ Wei, WY Cui, RT AF Cao, Juxiang Dai, Xiangpeng Wan, Lixin Wang, Hongshen Zhang, Jinfang Goff, Philip S. Sviderskaya, Elena V. Xuan, Zhenyu Xu, Zhixiang Xu, Xiaowei Hinds, Philip Flaherty, Keith T. Faller, Douglas V. Goding, Colin R. Wang, Yongjun Wei, Wenyi Cui, Rutao TI The E3 ligase APC/C-Cdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth SO SCIENCE SIGNALING LA English DT Article ID CELL-CYCLE; WAARDENBURG-SYNDROME; GENOMIC STABILITY; TUMOR SUPPRESSION; BREAST-CANCER; EXPRESSION; CDH1; DEGRADATION; MITF; DIFFERENTIATION AB The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/C-Cdh1) is an E3 ubiquitin ligase involved in the control of the cell cycle. Here, we identified sporadic mutations occurring in the genes encoding APC components, including Cdh1, in human melanoma samples and found that loss of APC/C-Cdh1 may promote melanoma development and progression, but not by affecting cell cycle regulatory targets of APC/C. Most of the mutations we found in CDH1 were those associated with ultraviolet light (UV)-induced melanomagenesis. Compared with normal human skin tissue and human or mouse melanocytes, the abundance of Cdh1 was decreased and that of the transcription factor PAX3 was increased in human melanoma tissue and human or mouse melanoma cell lines, respectively; Cdh1 abundance was further decreased with advanced stages of human melanoma. PAX3 was a substrate of APC/C-Cdh1 in melanocytes, and APC/C-Cdh1-mediated ubiquitylation marked PAX3 for proteolytic degradation in a manner dependent on the D-box motif in PAX3. Either mutating the D-box in PAX3 or knocking down Cdh1 prevented the ubiquitylation and degradation of PAX3 and increased proliferation and melanin production in melanocytes. Knocking down Cdh1 in melanoma cells in culture or before implantation in mice promoted doxorubicin resistance, whereas reexpressing wild-type Cdh1, but not E3 ligase-deficient Cdh1 or a mutant that could not interact with PAX3, restored doxorubicin sensitivity in melanoma cells both in culture and in xenografts. Thus, our findings suggest a tumor suppressor role for APC/C-Cdh1 in melanocytes and that targeting PAX3 may be a strategy for treating melanoma. C1 [Cao, Juxiang; Wang, Hongshen; Cui, Rutao] Boston Univ, Sch Med, Ctr Canc, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA. [Dai, Xiangpeng; Wan, Lixin; Zhang, Jinfang; Wei, Wenyi] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Wang, Hongshen; Wang, Yongjun; Cui, Rutao] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 20032, Peoples R China. [Goff, Philip S.; Sviderskaya, Elena V.] Univ London, Canadian Canc Soc Res Inst, Mol Cell Sci Res Ctr, London SW17 0RE, England. [Xuan, Zhenyu] Univ Texas Dallas, Dept Mol & Cell Biol, Dallas, TX 75080 USA. [Xu, Zhixiang] Univ Alabama Birmingham, Sch Med, Dept Med, Div Hematol & Oncol, Birmingham, AL 35233 USA. [Xu, Xiaowei] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hinds, Philip] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Med, Boston, MA 02114 USA. [Faller, Douglas V.] Boston Univ, Sch Med, Ctr Canc, Boston, MA 02118 USA. [Goding, Colin R.] Univ Oxford, Ludwig Inst Canc Res, Oxford OX3 7DQ, England. RP Wang, YJ (reprint author), Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 20032, Peoples R China. EM yjwang88@hotmail.com; wwei@bidmc.harvard.edu; rutaocui@bu.edu OI Goff, Philip/0000-0003-4371-5527 FU NIH [1RO1CA137098, GM089763]; American Cancer Society [RSG-09-022-01-CNE]; Harry J. Lloyd Charitable Trust; Wellcome Trust grant [078327]; National Basic Research Program of China [2010CB530400]; National Natural Science Foundation of Major International Cooperation Projects in China [81220108027]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1270]; Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China [81428025]; Longhua Medical Project; Ludwig Institute for Cancer Research; American Cancer Society FX This work was supported by the NIH (1RO1CA137098 to R.C. and GM089763 to W.W.); the American Cancer Society (RSG-09-022-01-CNE); the Harry J. Lloyd Charitable Trust (to R.C.); a Wellcome Trust grant (078327 to E.V.S.); the National Basic Research Program of China (2010CB530400 to Y.W.); the National Natural Science Foundation of Major International Cooperation Projects in China (81220108027 to Y.W.); the Program for Changjiang Scholars and Innovative Research Team in University (IRT1270 to Y.W.); the Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China (81428025 to R.C.); and the Longhua Medical Project (to R.C.). C.R.G. is funded by the Ludwig Institute for Cancer Research, and R.C. and W.W. are American Cancer Society Research Scholars. NR 49 TC 1 Z9 1 U1 3 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD SEP 1 PY 2015 VL 8 IS 392 AR ra87 DI 10.1126/scisignal.aab1995 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ7UE UT WOS:000360809300002 PM 26329581 ER PT J AU Bishop, JA Lewis, JS Rocco, JW Faquin, WC AF Bishop, Justin A. Lewis, James S., Jr. Rocco, James W. Faquin, William C. TI HPV-related squamous cell carcinoma of the head and neck: An update on testing in routine pathology practice SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE HPV; Human papillomavirus; Non-keratinizing squannous cell carcinoma; p16; In situ hybridization; Head and neck ID RISK HUMAN-PAPILLOMAVIRUS; IN-SITU HYBRIDIZATION; CAPTURE 2 ASSAY; OROPHARYNGEAL CANCER; ORAL-CAVITY; FAVORABLE PROGNOSIS; SINONASAL TRACT; UNITED-STATES; TUMOR-ORIGIN; DNA AB Oropharyngeal squamous cell carcinoma caused by high-risk types of human papillomavirus (HPV) is now a well-recognized tumor entity whose incidence is on the rise. Most HPV-related oropharyngeal squamous cell carcinomas have a distinct histomorphology, and most patients fit a typical clinical profile. Importantly, HPV-related oropharyngeal carcinoma patients overall have significantly improved outcomes when compared to their HPV-negative counterparts, and the differences in tumor biology may soon lead to modifications in how they are treated. While high-risk HPV can be detected in a significant minority of head and neck squamous cell carcinomas across anatomic subsites in the head and neck, it has become clear in recent years that the biologically and clinically favorable features are limited to tumors that harbor transcriptionally active, high-risk HPV, something that occurs predominantly (but certainly not exclusively) in the oropharynx. It is now acknowledged that detecting transcriptionally active, high-risk HPV is a necessity in routine clinical practice, but there is considerable confusion among pathologists and clinicians alike about the subsites and settings in which HPV testing should be performed. Compounding this lack of clarity is the fact that there are multiple HPV testing options available, but currently there is no clear consensus on which test or combination of tests is optimal for routine diagnostic use. This review serves as an update for practicing pathologists on the current status of HPV (and surrogate marker) testing in head and neck cancers. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bishop, Justin A.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Bishop, Justin A.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Lewis, James S., Jr.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Lewis, James S., Jr.] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Rocco, James W.; Faquin, William C.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rocco, James W.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@mgh.harvard.edu NR 60 TC 14 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD SEP PY 2015 VL 32 IS 5 BP 344 EP 351 DI 10.1053/j.semdp.2015.02.013 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA CQ7JM UT WOS:000360779300004 PM 25724476 ER PT J AU Suri, P Pashova, H Heagerty, PJ Jarvik, JG Turner, JA Comstock, BA Bauer, Z Annaswamy, TM Nedeljkovic, SS Wasan, AD Friedly, JL AF Suri, Pradeep Pashova, Hristina Heagerty, Patrick J. Jarvik, Jeffrey G. Turner, Judith A. Comstock, Bryan A. Bauer, Zoya Annaswamy, Thiru M. Nedeljkovic, Srdjan S. Wasan, Ajay D. Friedly, Janna L. TI Short-term Improvements in Disability Mediate Patient Satisfaction After Epidural Corticosteroid Injections for Symptomatic Lumbar Spinal Stenosis SO SPINE LA English DT Article DE glucocorticoid; transforaminal; interlaminar; neurogenic; claudication; radiculopathy; randomized controlled trial; low back pain; outcomes ID LOW-BACK-PAIN; SICKNESS IMPACT PROFILE; STEROID INJECTIONS; VALIDITY; TRIAL; SCALE AB Study Design. Secondary analysis of data from a double-blind randomized controlled trial. Objective. To identify mediators of the effect of lumbar epidural injections of corticosteroid plus lidocaine on patient satisfaction at 6 weeks postinjection in patients with lumbar spinal stenosis. We hypothesized that short-term (3 wk) change in leg pain would be a significant mediator of satisfaction. Summary of Background Data. No prior studies have identified mediators of effects of epidural injections on patient satisfaction with treatment of lumbar spinal stenosis. Methods. We used mediation analysis methods to examine selected intermediate variables (adverse events and change in leg pain, back pain, disability, depression, and fatigue at 3 wk) as potential mediators of the effect of lumbar epidural injections of corticosteroid plus lidocaine on patient satisfaction with treatment. We used the overall satisfaction item from the Swiss Spinal Stenosis Questionnaire as our primary outcome to measure patient satisfaction with the injection procedure at 6 weeks. Results. Among 400 patients randomized to receive epidural injections with corticosteroid plus lidocaine or with lidocaine alone, 369 had complete data for the satisfaction outcome and potential mediators and served as the analysis sample. Contrary to our expectations, 3-week change in leg pain intensity did not have significant mediation effects on patient satisfaction. Three-week change in disability as measured by the Roland-Morris Disability Questionnaire was a significant mediator of the effects of lumbar epidural corticosteroid injections on patient satisfaction at 6 weeks, explaining 48% to 60% of the treatment effect on satisfaction. Changes in pain intensity in the leg and back together explained very little of the treatment effect on satisfaction beyond the information contributed by disability change alone. We did not find other intermediate variables to be mediators of patient satisfaction. Conclusion. These findings support the current approach of examining disability as a primary patient-reported outcome in comparative effectiveness studies of lumbar spinal stenosis. Level of Evidence: 2 C1 [Suri, Pradeep] VA Puget Sound Hlth Care Syst, Div Rehabil Care Serv, Seattle, WA 98108 USA. [Suri, Pradeep] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr ERIC, Seattle, WA 98108 USA. [Suri, Pradeep; Turner, Judith A.; Friedly, Janna L.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Pashova, Hristina; Heagerty, Patrick J.; Comstock, Bryan A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heagerty, Patrick J.; Jarvik, Jeffrey G.; Turner, Judith A.; Comstock, Bryan A.; Bauer, Zoya; Friedly, Janna L.] Univ Washington, Comparat Effectiveness Cost & Outcomes Res Ctr, Seattle, WA 98195 USA. [Jarvik, Jeffrey G.; Bauer, Zoya] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Turner, Judith A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Annaswamy, Thiru M.] VA North Texas Hlth Care Syst, Dept Phys Med & Rehabil, Dallas, TX USA. [Annaswamy, Thiru M.] UT Southwestern Med Ctr, Dallas, TX USA. [Nedeljkovic, Srdjan S.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Nedeljkovic, Srdjan S.] Harvard Vanguard Med Associates, Spine Unit, Boston, MA USA. [Wasan, Ajay D.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Wasan, Ajay D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Suri, P (reprint author), VA Puget Sound Hlth Care Syst, Div Rehabil Care Serv, S-152-ERIC,1660 S Columbian Way, Seattle, WA 98108 USA. EM pradeep.suri@va.gov FU Agency for Healthcare Research and Quality (AHRQ) [1R01HS019222-01, 1R01HS022972-01]; Patient-Centered Outcomes Research Institute (PCORI) Program Award [CE-12-11-4469]; VA Puget Sound Health Care System FX Agency for Healthcare Research and Quality (AHRQ), award numbers 1R01HS019222-01 and1R01HS022972-01, funds were received to support this work. Also partially supported through a Patient-Centered Outcomes Research Institute (PCORI) Program Award (CE-12-11-4469). Dr. Suri's participation is this study was funded by VA Puget Sound Health Care System. NR 23 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD SEP 1 PY 2015 VL 40 IS 17 BP 1363 EP 1370 DI 10.1097/BRS.0000000000001000 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CQ5QW UT WOS:000360661500007 PM 26010037 ER PT J AU Pitman, JT Thapa, GB Harris, NS AF Pitman, Justin T. Thapa, Ghan B. Harris, N. Stuart TI Field Ultrasound Evaluation of Central Volume Status and Acute Mountain Sickness SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Article DE acute mountain sickness; intravascular volume ID ALTITUDE PULMONARY-EDEMA; CRITICALLY-ILL PATIENTS; FLUID RESPONSIVENESS; DIAGNOSIS; ILLNESS; ASCENT AB Objective.-To investigate whether ultrasonography can be used for field volume status assessment and to determine whether a detectable difference in intravascular volume exists in individuals with acute mountain sickness (AMS) compared with those without. Methods.-Study was performed at the Himalayan Rescue Association Clinic in Manang, Nepal, located on the Annapurna trekking circuit at an altitude of 3519 m (11545 feet). A convenience sample was taken from individuals trekking over 5 to 8 days from 760 m (2490 feet) to 3519 m (11,545 feet), comparing asymptomatic trekkers vs those who experienced AMS. Subjects were evaluated for AMS based on the Lake Louise AMS Questionnaire (LLS >= 3 indicates AIMS). After medical screening examination, both groups (control, n = 51; AIMS, n = 18) underwent ultrasonography to obtain measurements of inferior vena cava collapsibility index (IVC CI) and left ventricular outflow tract velocity-time integral (LVOT VTI) before and after a passive leg raise (PLR) maneuver. Results.-There was no statistically significant difference between groups regarding change in heart rate before and after PLR, or IVC CI; however, there was a statistically significant greater increase in LVOT VTI after PLR maneuver in control group subjects compared with those with AMS (18.96% control vs 11.71% AMS; P < .01). Conclusions.-Ultrasonography is a useful tool in the assessment of intravascular volume at altitude. In this sample, we found ultrasonographic evidence that subjects with AIMS have a higher intravascular volume than asymptomatic individuals. These data support the hypothesis that individuals with AMS have decreased altitude-related diuresis compared with asymptomatic individuals. C1 [Pitman, Justin T.; Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Thapa, Ghan B.] Mt Med Soc Nepal, Kathmandu, Bagmati, Nepal. RP Pitman, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Zero Emerson,Suite 3B, Boston, MA 02114 USA. EM jpitman@mgh.harvard.edu NR 32 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 1080-6032 EI 1545-1534 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD SEP PY 2015 VL 26 IS 3 BP 319 EP 326 PG 8 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA CQ7JX UT WOS:000360781100006 PM 25864086 ER PT J AU Matthews, LT Moore, L Milford, C Greener, R Mosery, FN Rifkin, R Psaros, C Safren, SA Harrison, A Wilson, IB Bangsberg, DR Smit, JA AF Matthews, L. T. Moore, L. Milford, C. Greener, R. Mosery, F. N. Rifkin, R. Psaros, C. Safren, S. A. Harrison, A. Wilson, I. B. Bangsberg, D. R. Smit, J. A. TI "If I don't use a condom aEuro broken vertical bar I would be stressed in my heart that I've done something wrong": Routine Prevention Messages Preclude Safer Conception Counseling for HIV-Infected Men and Women in South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Safer conception; Client-provider; communication; HIV prevention; South Africa ID FAMILY-PLANNING-SERVICES; REPRODUCTIVE DECISION-MAKING; SERO-DISCORDANT COUPLES; PREEXPOSURE PROPHYLAXIS; POSITIVE WOMEN; ANTIRETROVIRAL THERAPY; FERTILITY INTENTIONS; NEGATIVE WOMEN; MALE CIRCUMCISION; RANDOMIZED-TRIAL AB Intended conception likely contributes to a significant proportion of new HIV infections in South Africa. Safer conception strategies require healthcare provider-client communication about fertility intentions, periconception risks, and options to modify those risks. We conducted in-depth interviews with 35 HIV-infected men and women accessing care in South Africa to explore barriers and promoters to patient-provider communication around fertility desires and intentions. Few participants had discussed personal fertility goals with providers. Discussions about pregnancy focused on maternal and child health, not sexual HIV transmission; no participants had received tailored safer conception advice. Although participants welcomed safer conception counseling, barriers to client-initiated discussions included narrowly focused prevention messages and perceptions that periconception transmission risk is not modifiable. Supporting providers to assess clients' fertility intentions and offer appropriate advice, and public health campaigns that address sexual HIV transmission in the context of conception may improve awareness of and access to safer conception strategies. C1 [Matthews, L. T.; Rifkin, R.; Bangsberg, D. R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, L. T.; Rifkin, R.; Bangsberg, D. R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, L. T.; Psaros, C.; Safren, S. A.; Bangsberg, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Moore, L.; Milford, C.; Greener, R.; Mosery, F. N.; Smit, J. A.] Univ Witwatersrand, MatCH Res Maternal Adolescent & Child Hlth Res, Durban, South Africa. [Psaros, C.; Safren, S. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Harrison, A.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Wilson, I. B.] Brown Univ, Dept Med, Providence, RI 02912 USA. 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]; Canadian African Sub-Saharan Africa AIDS Network; NIH Grant [K23 MH095655, K24MH87227, K24MH094214, K23MH096651] FX This study was supported by the NICHD (R03-HD072602) and the Canadian African Sub-Saharan Africa AIDS Network. The analysis was also supported by NIH Grants K23 MH095655, K24MH87227, K24MH094214, and K23MH096651. The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 71 TC 7 Z9 7 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD SEP PY 2015 VL 19 IS 9 BP 1666 EP 1675 DI 10.1007/s10461-015-1026-x PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CQ2EG UT WOS:000360411600012 PM 25711300 ER PT J AU Liu, DF Chen, HB AF Liu, Dongfang Chen, Huabiao TI Structured Illumination Microscopy Improves Visualization of Lytic Granules in HIV-1 Specific Cytotoxic T-Lymphocyte Immunological Synapses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material C1 [Liu, Dongfang] Texas Childrens Hosp, Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA. [Chen, Huabiao] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [Chen, Huabiao] Jiangsu Univ, Sch Med, Jiangsu Key Lab Clin Lab Med, Zhenjiang, Jiangsu, Peoples R China. RP Chen, HB (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, 400 Technol Sq, Cambridge, MA 02139 USA. EM huabiao.chen@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 1 PY 2015 VL 31 IS 9 BP 866 EP 867 DI 10.1089/aid.2014.0363 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA CQ1VJ UT WOS:000360388000002 PM 25831465 ER PT J AU Evens, AM Kanakry, JA Sehn, LH Kritharis, A Feldman, T Kroll, A Gascoyne, RD Abramson, JS Petrich, AM Hernandez-Ilizaliturri, FJ Al-Mansour, Z Adeimy, C Hemminger, J Bartlett, NL Mato, A Caimi, PF Advani, RH Klein, AK Nabhan, C Smith, SM Fabregas, JC Lossos, IS Press, OW Fenske, TS Friedberg, JW Vose, JM Blum, KA AF Evens, Andrew M. Kanakry, Jennifer A. Sehn, Laurie H. Kritharis, Athena Feldman, Tatyana Kroll, Aimee Gascoyne, Randy D. Abramson, Jeremy S. Petrich, Adam M. Hernandez-Ilizaliturri, Francisco J. Al-Mansour, Zeina Adeimy, Camille Hemminger, Jessica Bartlett, Nancy L. Mato, Anthony Caimi, Paolo F. Advani, Ranjana H. Klein, Andreas K. Nabhan, Chadi Smith, Sonali M. Fabregas, Jesus C. Lossos, Izidore S. Press, Oliver W. Fenske, Timothy S. Friedberg, Jonathan W. Vose, Julie M. Blum, Kristie A. TI Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: Characteristics, outcomes, and prognostication among a large multicenter cohort SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID DISEASE AB Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P=0.0001); more often had bone marrow involvement (19% versus 0%, P=0.001); >1 extranodal site (27% versus 8%, P=0.014); and advanced stage disease (81% versus 13%, P=0.0001); but they had less bulk (8% versus 44%, P=0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P=0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P=0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P=0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen. Am. J. Hematol. 90:778-783, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Evens, Andrew M.; Kritharis, Athena; Klein, Andreas K.] Tufts Med Ctr, Boston, MA USA. [Kanakry, Jennifer A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sehn, Laurie H.; Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Feldman, Tatyana; Mato, Anthony] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Kroll, Aimee] Univ Massachusetts, Quantitat Hlth Sci, Worcester, MA 01605 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Petrich, Adam M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Al-Mansour, Zeina] UMASS, Hematol Oncol, Amherst, MA USA. [Adeimy, Camille] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Hemminger, Jessica; Blum, Kristie A.] Ohio State Univ, Columbus, OH 43210 USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Caimi, Paolo F.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Advani, Ranjana H.] Stanford Univ, Palo Alto, CA 94304 USA. [Nabhan, Chadi; Smith, Sonali M.] Univ Chicago, Chicago, IL 60637 USA. [Fabregas, Jesus C.; Lossos, Izidore S.] Univ Miami, Sch Med, Miami, FL USA. [Press, Oliver W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Fenske, Timothy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Evens, AM (reprint author), Div Hematol Oncol, 800 Washington St, Boston, MA 02111 USA. EM AEvens@tuftsmedicalcenter.org FU Millennium; Genentech; Seattle Genetics; Bristol-Myers Squibb; Pfizer; ImaginAb; Janssen Research Foundation; AstraZeneca; Millennium Takeda; Genentech Roche; Allos Therapeutics; Pharmacyclics; Janssen Pharmaceuticals; Idera Pharmaceuticals; Celgene; Agensys; PreSage; Spectrum Pharmaceuticals; Janssen Biotech, Inc.; Janssen; Novartis; Gilead; Cephalon FX AME-Honoraria: Seattle Genetics, Celgene; Advisory role: Celgene; Speakers' Bureau: Celgene; Research funding: Millennium. LHS-Honoraria and consulting: Genentech. RDD-Honoraria and consulting: Genentech; Speakers' Bureau: Seattle Genetics. JSA-Honoraria and consulting: Gilead; Research funding: Genentech; Honoraria, consulting, and Speakers' Bureau: Seattle Genetics; Consulting: Millennium. NLB-Consulting: Seattle Genetics and Pfizer; Research funding: Seattle Genetics, Bristol-Myers Squibb, Pfizer, ImaginAb, Genentech, Janssen Research Foundation, and AstraZeneca; Honoraria: Millennium Takeda, Eisai Co. Ltd., and General Electric/Clarient; Research funding: Millennium Takeda, Seattle Genetics, Genentech Roche, Allos Therapeutics, Pharmacyclics, Janssen Pharmaceuticals, Idera Pharmaceuticals, Celgene, and Agensys; SMS-Celgene and Janssen Oncology; Consulting or advisory role: Genentech/Roche, Celgene, Onyx, Seattle Genetics, Immunogenix, TG Therapeutics, Gilead Pharmacyclics, and Pharmacyclics; Speakers' Bureau: Spectrum and Janssen Oncology. OWP-Stock or other ownership: PhaseRx and Emergent Biosolutions; Consulting or advisory role: BIND Biosciences, Algeta, Adaptive Biotechnologies, and Roche; Research funding: PreSage and Genentech. JWF-Consulting or advisory role: Trubion, Kite Pharmaceuticals, and Bayer; Research funding: Seattle Genetics, Millennium, Genentech, and Janssen Pharmaceuticals. JMV-Honoraria: Sanofi Adventis; Consulting or advisory role: Kite Pharma, Foundation Medicine, Seattle Genetics, Bank of America, KEW Group, and Bioconnections; Research funding: Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen Biotech, Inc., and Pharmacyclics. KAB-Research funding: Seattle Genetics, Millennium, Pharmacyclics, Janssen, Novartis, Gilead, Celgene, and Cephalon. NR 16 TC 12 Z9 12 U1 0 U2 5 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 SEP PY 2015 VL 90 IS 9 BP 778 EP 783 DI 10.1002/ajh.24082 PG 6 WC Hematology SC Hematology GA CP9MI UT WOS:000360218000019 PM 26044261 ER PT J AU Paschkis, Z Potter, ML AF Paschkis, Zoe Potter, Mertie L. TI Acute Pain Management for Inpatients with Opioid Use Disorder Overcoming misconceptions and prejudices. SO AMERICAN JOURNAL OF NURSING LA English DT Article DE acute pain; addiction; evidence-based practice; opioid; opioid use disorder; pain; pain management; substance use disorder ID SUBSTANCE USE DISORDERS; ACUTE POSTOPERATIVE PAIN; METHADONE-MAINTENANCE; HEALTH-PROFESSIONALS; DRUG-USERS; ATTITUDES; NURSES; THERAPY; SOCIETY AB Overview Like most hospital inpatients, those with opioid use disorder (OUD) often experience acute pain during their hospital stay and may require opioid analgesics. Unfortunately, owing to clinicians' misconceptions about opioids and negative attitudes toward patients with OUD, such patients may be inadequately medicated and thus subjected to unrelieved pain and unnecessary suffering. This article reviews current literature on the topic of acute pain management for inpatients with OUD and dispels common myths about opioids and OUD. C1 [Paschkis, Zoe; Potter, Mertie L.] Massachusetts Gen Hosp Inst Hlth Profess, Boston, MA 02114 USA. [Potter, Mertie L.] Merrimack Valley Counseling Ctr, Nashua, NH USA. RP Paschkis, Z (reprint author), Massachusetts Gen Hosp Inst Hlth Profess, Boston, MA 02114 USA. EM zpaschkis@gmail.com NR 54 TC 0 Z9 0 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-936X EI 1538-7488 J9 AM J NURS JI Am. J. Nurs. PD SEP PY 2015 VL 115 IS 9 BP 24 EP 32 DI 10.1097/01.NAJ.0000471243.30951.92 PG 9 WC Nursing SC Nursing GA CP9IP UT WOS:000360207900001 PM 26273927 ER PT J AU Gautam, S Kim, T Shoda, T Sen, S Deep, D Luthra, R Ferreira, MT Pinho, MG Spiegel, DA AF Gautam, Samir Kim, Taehan Shoda, Takuji Sen, Sounok Deep, Deeksha Luthra, Ragini Ferreira, Maria Teresa Pinho, Mariana G. Spiegel, David A. TI An Activity-Based Probe for Studying Crosslinking in Live Bacteria SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bacteria; biosensors; crosslinking; fluorescent probes; peptidoglycans ID PENICILLIN-BINDING PROTEINS; CELL-WALL SYNTHESIS; STAPHYLOCOCCUS-AUREUS; PEPTIDOGLYCAN BIOSYNTHESIS; BACILLUS-SUBTILIS; DIVISION; REVEAL; RESISTANT; PBP2; TRANSPEPTIDASE AB Penicillin-binding proteins (PBPs) catalyze the crosslinking of peptidoglycan (PG), an essential process for bacterial growth and survival, and a common antibiotic target. Yet, despite its importance, little is known about the spatiotemporal aspects of crosslinkinglargely because of a lack of experimental tools for studying the reaction in live bacteria. Here we introduce such a tool: an activity-based probe that enables visualization and relative quantitation of crosslinking in vivo. In Staphylococcus aureus, we show that fluorescent mimics of the natural substrate of PBPs (PG stem peptide) are covalently incorporated into the cell wall, installing fluorophores in place of natural crosslinks. These fluorescent stem peptide mimics (FSPMs) are selectively recognized by a single PBP in S. aureus: PBP4. Thus, we were able to use FSPM pulse-labeling to localize PBP4 activity in live cells, showing that it is recruited to the septum in a manner dependent on wall teichoic acid. C1 [Gautam, Samir] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. [Gautam, Samir; Kim, Taehan; Shoda, Takuji; Sen, Sounok; Deep, Deeksha; Luthra, Ragini; Spiegel, David A.] Yale Univ, Dept Chem, New Haven, CT 06511 USA. [Shoda, Takuji] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan. [Sen, Sounok] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sen, Sounok] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ferreira, Maria Teresa; Pinho, Mariana G.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal. RP Spiegel, DA (reprint author), Yale Univ, Dept Chem, 225 Prospect St, New Haven, CT 06511 USA. EM david.spiegel@yale.edu RI Pinho, Mariana/B-9192-2008 OI Pinho, Mariana/0000-0002-7132-8842 FU Camille and Henry Dreyfus Foundation; Novartis; Alfred P. Sloan Foundation [BR2011-117]; NIH [1DP2OD002913-01]; NIH MSTP [T32GM07205] FX This work was supported by a Camille and Henry Dreyfus Foundation New Faculty Award (to D.A.S.), a Novartis Early Career Award in Organic Chemistry (to D.A.S.), an Alfred P. Sloan Foundation Fellowship (BR2011-117 to D.A.S.), an NIH New Innovator Award (1DP2OD002913-01 to D.A.S.), and an NIH MSTP training grant (T32GM07205 to S.G.). We appreciate Dr. Thihan Padukkavidana's helpful suggestions in the preparation of this manuscript and Ambrose Cheung's generosity in sharing the S. aureus PBP mutant strains. D.A.S. is a paid consultant for Bristol-Myers Squibb. NR 30 TC 2 Z9 2 U1 5 U2 46 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD SEP 1 PY 2015 VL 54 IS 36 BP 10492 EP 10496 DI 10.1002/anie.201503869 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CQ0UL UT WOS:000360312800014 PM 26204841 ER PT J AU Liu, JX Park, YMM Berkowitz, SA Hu, QW Han, K Ortaglia, A McKeown, RE Liese, AD AF Liu, Junxiu Park, Yong-Moon Mark Berkowitz, Seth A. Hu, Qingwei Han, Kyungdo Ortaglia, Andrew McKeown, Robert E. Liese, Angela D. TI Gender differences in the association between food insecurity and insulin resistance among US adults: National Health and Nutrition Examination Survey, 2005-2010 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Food insecurity; Insulin resistance; Gender difference; NHANES ID HOMEOSTASIS MODEL ASSESSMENT; DIETARY ENERGY DENSITY; METABOLIC SYNDROME; NORMAL-WEIGHT; CARDIOVASCULAR-DISEASE; SEX-HORMONES; LOW-INCOME; BODY-FAT; OBESITY; WOMEN AB Purpose: To examine gender-specific associations between food insecurity and insulin resistance in a representative U.S. population. Methods: Data on 5533 adults of 20 years of age or more (2742 men and 2791 women) without diabetes from the 2005-2010 National Health and Nutrition Examination Survey were analyzed. Respondents were categorized as having full, marginal, low, or very low food security using a validated scale. Insulin-resistant individuals were defined as those with a homeostasis model assessment of insulin resistance value 2.5 or more. Results: Insulin resistance was higher in both normal-weight (P =.001) and overweight or obese (P <.001) women with lower food security, but no linear trend was found in men. In multiple logistic regression analyses, however, very low food security compared with full food security was associated with insulin resistance in normal-weight men (odds ratio, 3.99; 95% confidence interval, 1.71-9.33), and marginal food insecurity was associated with insulin resistance in overweight or obese men (odds ratio, 2.07; 95% confidence interval, 1.18-3.64) after adjusting for potential confounders. In women, the association between food insecurity and insulin resistance was no longer significant after adjustment. Conclusions: Food insecurity is associated with insulin resistance in adults without diabetes, and this effect varies by gender in normal-weight and overweight or obese populations. Improving food security status may help reduce insulin resistance, an underlying risk factor for diabetes and cardiovascular disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Liu, Junxiu; Park, Yong-Moon Mark; Hu, Qingwei; Ortaglia, Andrew; McKeown, Robert E.; Liese, Angela D.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Berkowitz, Seth A.] Harvard Univ, Sch Med, Boston, MA USA. [Han, Kyungdo] Catholic Univ Korea, Coll Med, Dept Biostat, Seoul, South Korea. RP Liu, JX (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. EM Junxiuliu99@gmail.com RI Nguyen, Giang/D-9027-2016; OI PARK, YONG-MOON/0000-0002-5879-6879; Berkowitz, Seth/0000-0003-1030-4297 FU Institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; Division of General Internal Medicine at Massachusetts General Hospital FX S.A.B. was supported by an Institutional National Research Service Award T32HP10251, the Ryoichi Sasakawa Fellowship Fund, and the Division of General Internal Medicine at Massachusetts General Hospital. Otherwise, the authors declare that there are no conflicts of interest. NR 47 TC 2 Z9 2 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2015 VL 25 IS 9 BP 643 EP 648 DI 10.1016/j.annepidem.2015.06.003 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP9AV UT WOS:000360187000002 PM 26189664 ER PT J AU Glenn, KR Slaughter, JC Fowke, JH Buchowski, MS Matthews, CE Signorello, LB Blot, WJ Lipworth, L AF Glenn, Kimberly R. Slaughter, James C. Fowke, Jay H. Buchowski, Maciej S. Matthews, Charles E. Signorello, Lisa B. Blot, William J. Lipworth, Loren TI Physical activity, sedentary behavior and all-cause mortality among blacks and whites with diabetes SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Physical activity; Diabetes; Low income; Sedentary behaviors; Cardiovascular disease; Mortality ID SOUTHERN COMMUNITY COHORT; CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-HEART-DISEASE; LEISURE-TIME; EXERCISE CAPACITY; HEALTH DISPARITIES; AFRICAN-AMERICANS; OLDER-ADULTS; MELLITUS; RISK AB Purpose: The study objective was to examine the role of physical activity (PA) and sedentary time (ST) on mortality risk among a population of low-income adults with diabetes. Methods: Black (n = 11,137) and white (n = 4508) men and women with diabetes from the Southern Community Cohort Study self-reported total PA levels and total ST. Participants were categorized into quartiles of total PA and total ST. Hazard ratios (HRs) and 95% confidence intervals (CIs) for subsequent mortality risk were estimated from Cox proportional hazards analysis with adjustment for potential confounders. Results: During follow-up, 2370 participants died. The multivariable risk of mortality was lower among participants in the highest quartile of PA compared with those in the lowest quartile (HR, 0.64; 95% CI: 0.57-0.73). Mortality risk was significantly increased among participants in the highest compared with the lowest quartile of ST after adjusting for PA (HR, 1.21; 95% CI: 1.08-1.37). Across sex and race groups, similar trends of decreasing mortality with rising PA and increasing mortality with rising ST were observed. Conclusions: Although causality cannot be established from these observational data, the current findings suggest that increasing PA and decreasing ST may help extend survival among individuals with diabetes irrespective of race and sex. (C) 2015 Elsevier Inc. All rights reserved. C1 [Glenn, Kimberly R.; Fowke, Jay H.; Blot, William J.; Lipworth, Loren] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA. [Slaughter, James C.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37212 USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Signorello, Lisa B.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. RP Glenn, KR (reprint author), Off Healthcare Stat Policy Planning & Assessment, Tennessee Dept Hlth, 710 James Robertson Pkwy, Nashville, TN 37243 USA. EM kimberly.glenn@tn.gov RI Dey, Kamalesh/E-6568-2017; OI Glenn, Kimberly/0000-0002-6765-5592; Slaughter, James/0000-0002-8770-980X FU NCI NIH HHS [R01 CA092447]; NIDDK NIH HHS [P30 DK092986] NR 37 TC 4 Z9 4 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2015 VL 25 IS 9 BP 649 EP 655 DI 10.1016/j.annepidem.2015.04.006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP9AV UT WOS:000360187000003 PM 26141652 ER PT J AU Blosnich, JR Gordon, AJ Fine, MJ AF Blosnich, John R. Gordon, Adam J. Fine, Michael J. TI Associations of sexual and gender minority status with health indicators, health risk factors, and social stressors in a national sample of young adults with military experience SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Veterans health; Sexuality; Transgendered persons; Health surveys; Minority health; Mental health; Military personnel ID UNITED-STATES; BISEXUAL POPULATIONS; TRANSGENDER VETERANS; WOMEN VETERANS; SAME-SEX; ORIENTATION DISPARITIES; PROBABILITY SAMPLE; SUICIDAL IDEATION; CARE UTILIZATION; MENTAL-HEALTH AB Purpose: To assess the associations of self-identified lesbian, gay, bisexual, and questioning sexual orientation or transgender status (LGBTQ) and military experience with health indicators. Methods: We used data from the Fall 2012 National College Health Assessment. The survey included self-identified sociodemographic characteristics, mental (e.g., depression) and physical (e.g., human immunodeficiency virus) conditions, health risk behaviors (e.g., smoking), and social stressors (e.g., victimization). We used modified Poisson regression models, stratified by self-reported military service, to examine LGBTQ-related differences in health indicators, whereas adjusting for sociodemographic characteristics. Results: Of 27,176 in the sample, among the military-experienced group, LGBTQ individuals had increased adjusted risks of reporting a past-year suicide attempt (adjusted risk ratio [aRR] = 4.37; 95% confidence interval [CI] = 1.39-13.67), human immunodeficiency virus (aRR = 9.90; 95% CI = 1.04-79.67), and discrimination (aRR = 4.67; 95% CI = 2.05-10.66) than their non-LGBTQ peers. Among LGBTQ individuals, military experience was associated with a nearly four-fold increased risk of reporting a past-year suicide attempt (aRR = 3.61; 95% CI = 1.46-8.91) adjusting for age, sex, race and ethnicity, marital status, depression, and other psychiatric diagnoses. Conclusions: Military experience may moderate health indicators among LGBTQ populations, and likewise, LGBTQ status likely modifies health conditions among military-experienced populations. Results suggest that agencies serving military populations should assess how and if the health needs of LGBTQ individuals are met. Published by Elsevier Inc. C1 [Blosnich, John R.; Gordon, Adam J.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Gordon, Adam J.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Dept Vet Affairs, Ctr Hlth Equity Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System FX The authors thank the American College Health Association for use of the Fall 2012 survey data set. This work was partially supported by a postdoctoral fellowship to J.R. Blosnich 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. The opinions expressed in this work are those of the authors and do not represent the funders, institutions, the Department of Veterans Affairs, or the U.S. government. NR 63 TC 3 Z9 3 U1 8 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2015 VL 25 IS 9 BP 661 EP 667 DI 10.1016/j.annepidem.2015.06.001 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP9AV UT WOS:000360187000005 PM 26184439 ER PT J AU Bird, TD Swanson, PD AF Bird, Thomas D. Swanson, Phillip D. TI Congenital insensitivity to pain with anhidrosis SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Bird, Thomas D.] Univ Washington, Seattle, WA 98195 USA. [Bird, Thomas D.; Swanson, Phillip D.] VA Puget Sound Hlth Care, GRECC, Seattle, WA USA. RP Bird, TD (reprint author), Univ Washington, Seattle, WA 98195 USA. FU CSRD VA [I01 CX001006] NR 4 TC 0 Z9 1 U1 2 U2 7 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 SEP PY 2015 VL 78 IS 3 BP 500 EP 500 DI 10.1002/ana.24450 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CP9MQ UT WOS:000360218800017 PM 26032179 ER PT J AU Lin, YT Nouizi, F Kwong, TC Gulsen, G AF Lin, Yuting Nouizi, Farouk Kwong, Tiffany C. Gulsen, Gultekin TI Simulation-based evaluation of the resolution and quantitative accuracy of temperature-modulated fluorescence tomography SO APPLIED OPTICS LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; A-PRIORI INFORMATION; PHOTOACOUSTIC TOMOGRAPHY; SYSTEM; LIGHT AB Conventional fluorescence tomography (FT) can recover the distribution of fluorescent agents within a highly scattering medium. However, poor spatial resolution remains its foremost limitation. Previously, we introduced a new fluorescence imaging technique termed "temperature-modulated fluorescence tomography" (TM-FT), which provides high-resolution images of fluorophore distribution. TM-FT is a multimodality technique that combines fluorescence imaging with focused ultrasound to locate thermo-sensitive fluorescence probes using a priori spatial information to drastically improve the resolution of conventional FT. In this paper, we present an extensive simulation study to evaluate the performance of the TM-FT technique on complex phantoms with multiple fluorescent targets of various sizes located at different depths. In addition, the performance of the TM-FT is tested in the presence of background fluorescence. The results obtained using our new method are systematically compared with those obtained with the conventional FT. Overall, TM-FT provides higher resolution and superior quantitative accuracy, making it an ideal candidate for in vivo preclinical and clinical imaging. For example, a 4 mm diameter inclusion positioned in the middle of a synthetic slab geometry phantom (D:40 mm x W:100 mm) is recovered as an elongated object in the conventional FT (x = 4.5 mm; y = 10.4 mm), while TM-FT recovers it successfully in both directions (x = 3.8 mm; y = 4.6 mm). As a result, the quantitative accuracy of the TM-FT is superior because it recovers the concentration of the agent with a 22% error, which is in contrast with the 83% error of the conventional FT. (C) 2015 Optical Society of America C1 [Lin, Yuting; Nouizi, Farouk; Kwong, Tiffany C.; Gulsen, Gultekin] Univ Calif Irvine, Dept Radiol Sci, Tu & Yuen Ctr Funct Onco Imaging, Irvine, CA 92697 USA. [Gulsen, Gultekin] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. [Lin, Yuting] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lin, Yuting] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gulsen, G (reprint author), Univ Calif Irvine, Dept Radiol Sci, Tu & Yuen Ctr Funct Onco Imaging, Irvine, CA 92697 USA. EM ggulsen@uci.edu FU National Institutes of Health (NIH) [R21 EB013387, 1R21CA191389, R01EB008716, P30CA062203, SBIR HHSN261201300068C, 1F31CA171915-01A1]; UCI Eugene Cota-Robles Fellowship FX National Institutes of Health (NIH) (R21 EB013387, 1R21CA191389, R01EB008716, P30CA062203, SBIR HHSN261201300068C, 1F31CA171915-01A1); UCI Eugene Cota-Robles Fellowship. NR 48 TC 1 Z9 1 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD SEP 1 PY 2015 VL 54 IS 25 BP 7612 EP 7621 DI 10.1364/AO.54.007612 PG 10 WC Optics SC Optics GA CQ1GB UT WOS:000360344200022 PM 26368884 ER PT J AU Ogdie, A Shah, AA Makris, UE Jiang, YH Nelson, AE Kim, AHJ Angeles-Han, ST Castelino, FV Golding, A Muscal, E Kahlenberg, JM Barg, FK AF Ogdie, Alexis Shah, Ami A. Makris, Una E. Jiang, Yihui Nelson, Amanda E. Kim, Alfred H. J. Angeles-Han, Sheila T. Castelino, Flavia V. Golding, Amit Muscal, Eyal Kahlenberg, J. Michelle Barg, Frances K. CA Amer Coll Rheumatology Early Caree TI Barriers to and Facilitators of a Career as a Physician-Scientist Among Rheumatologists in the US SO ARTHRITIS CARE & RESEARCH LA English DT Article ID NATIONAL-SURVEY; MENTORSHIP; MEDICINE AB ObjectiveTo determine perceived barriers to and facilitators of a career in rheumatology research, examine factors leading rheumatologists to leave an academic research career, and solicit ways to best support young physician-scientists. MethodsA web-based survey was conducted among the domestic American College of Rheumatology (ACR) membership from January through March 2014. Inclusion criteria were ACR membership and an available e-mail address. Non-rheumatologists were excluded. The survey assessed demographics, research participation, barriers to and facilitators of a career in research, reasons for leaving a research career (when applicable), and ways in which the ACR could support junior investigators. Content analysis was used to extract relevant themes. ResultsAmong 5,448 domestic ACR members, 502 responses were obtained (9.2% response rate). After exclusions (38 incomplete, 2 duplicates, 32 non-rheumatologists), 430 responses were analyzed. Participants included fellows, young investigators, established investigators, mentors, clinicians, and those who previously pursued a research career but have chosen a different career path. Funding and mentoring were the most highly ranked barriers and facilitators. Protection from clinical and administrative duties, institutional support, and personal characteristics such as resilience and persistence were also ranked highly. The most commonly cited reasons for leaving an academic research career were difficulty obtaining funding and lack of department or division support. ConclusionThis is the first study to examine barriers to and facilitators of a career in rheumatology research from the perspectives of diverse groups of rheumatologists. Knowledge of such barriers and facilitators may assist in designing interventions to support investigators during vulnerable points in their career development. C1 [Ogdie, Alexis; Jiang, Yihui; Barg, Frances K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shah, Ami A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Makris, Una E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Makris, Una E.] Dallas Vet Affairs Med Ctr, Dallas, TX USA. [Nelson, Amanda E.] Univ N Carolina, Chapel Hill, NC USA. [Kim, Alfred H. J.] Washington Univ, Sch Med, St Louis, MO USA. [Angeles-Han, Sheila T.] Emory Univ, Sch Med, Atlanta, GA USA. [Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golding, Amit] Baltimore Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Muscal, Eyal] Texas Childrens Hosp, Houston, TX 77030 USA. [Muscal, Eyal] Baylor Coll Med, Houston, TX 77030 USA. [Kahlenberg, J. Michelle] Univ Michigan, Ann Arbor, MI 48109 USA. RP Ogdie, A (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Div Rheumatol, Philadelphia, PA 19104 USA. EM alexis.ogdie@uphs.upenn.edu OI Ogdie, Alexis/0000-0002-4639-0775; Kahlenberg, J. Michelle/0000-0002-4006-8945 FU NIH [K23-AR-063764, K23-AR-061439, K23-AR-O61406, K08-AR-062592, K08-AR-063668]; Rheumatology Research Foundation/ASP; Center for Translational Medicine; NIH/National Center for Advancing Translational Science [KL2-TR-001103, UL1-TR-001105]; Rheumatology Research Foundation; National Eye Institute [K23-EY-021760]; US Department of Veterans Affairs Clinical Sciences Research and Development Program [IK2-CX-000649]; Pfizer; Janssen; Amgen FX Dr. Ogdie's work was supported by NIH grant K23-AR-063764. Dr. Shah's work was supported by NIH grant K23-AR-061439. Dr. Makris's work was supported by the Rheumatology Research Foundation/ASP Junior Career Development Award in Geriatric Medicine, the Center for Translational Medicine, and the NIH/National Center for Advancing Translational Science (grants KL2-TR-001103 and UL1-TR-001105). Dr. Nelson's work was supported by NIH grant K23-AR-O61406. Dr. Kim's work was supported by an Investigator Award from the Rheumatology Research Foundation. Dr. Angeles-Han's work was supported by the National Eye Institute (grant K23-EY-021760). Dr. Castelino's work was supported by NIH grant K08-AR-062592. Dr. Golding's work was supported by a Career Development Award (grant IK2-CX-000649) from the US Department of Veterans Affairs Clinical Sciences Research and Development Program. Dr. Kahlenberg's work was supported by NIH grant K08-AR-063668.; Dr. Kim has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, Janssen, and Amgen. NR 17 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2015 VL 67 IS 9 BP 1191 EP 1201 DI 10.1002/acr.22569 PG 11 WC Rheumatology SC Rheumatology GA CQ1WH UT WOS:000360390400002 PM 25708626 ER PT J AU Chang, HH Dwivedi, N Nicholas, AP Ho, IC AF Chang, Hui-Hsin Dwivedi, Nishant Nicholas, Anthony P. Ho, I-Cheng TI The W620 Polymorphism in PTPN22 Disrupts Its Interaction With Peptidylarginine Deiminase Type 4 and Enhances Citrullination and NETosis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; CELL ACTIVATION; GENETIC-VARIATION; ALLELIC VARIANT; AUTOIMMUNITY; EXPRESSION; NEUTROPHILS; DISEASE AB Objective. A C-to-T single-nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase PTPN22 complementary DNA carries the highest risk of rheumatoid arthritis (RA) among all non-HLA genetic variants. This C1858T SNP converts an arginine (R620) to a tryptophan (W620), but it is unclear why it has such a strong impact on RA, a disease characterized by anti-citrullinated protein antibodies. The aim of this study was to test the hypothesis that PTPN22 regulates protein citrullination. Methods. The level of citrullinated proteins in immune cells was quantified by Western blotting. The physical interaction between PTPN22 and peptidyl arginine deiminase type 4 (PAD-4), which is one of the enzymes that catalyzes protein citrullination, was examined by coimmunoprecipitation. Neutrophils were collected from healthy donors carrying the C1858T SNP and healthy donors not carrying this SNP. The formation of neutrophil extracellular traps (NETs) was examined by immunocytochemistry. Results. PTPN22 physically interacted with PAD-4, and a deficiency in PTPN22 enhanced protein citrullination. This abnormality was reversed by exogenous wild-type PTPN22 or catalytically dead mutant PTPN22. The R-to-W conversion rendered PTPN22 unable to interact with PAD-4 and suppress citrullination. The C1858T SNP was associated with hypercitrullination in peripheral blood mononuclear cells and a heightened propensity for spontaneous formation of NETs, which is a PAD-4-dependent process. Conclusion. PTPN22 is an inhibitor of PAD-4 and protein citrullination. This function of PTPN22 is independent of its phosphatase activity but requires R620. Our data not only establish a molecular link between PTPN22 and PAD-4, but also suggest that the C1858T SNP increases the risk of RA by enhancing protein citrullination and spontaneous formation of NETs. C1 [Chang, Hui-Hsin; Dwivedi, Nishant; Ho, I-Cheng] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chang, Hui-Hsin; Dwivedi, Nishant; Ho, I-Cheng] Harvard Univ, Sch Med, Boston, MA USA. [Nicholas, Anthony P.] Univ Alabama Birmingham, Birmingham, AL USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Ho, IC (reprint author), Brigham & Womens Hosp, One Jimmy Fund Way, Boston, MA 02115 USA. EM iho@partners.org FU US Department of Defense [W81XWH-11-1-0492] FX Supported by the US Department of Defense (grant W81XWH-11-1-0492 to Dr. Ho). NR 48 TC 15 Z9 15 U1 0 U2 6 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 SEP PY 2015 VL 67 IS 9 BP 2323 EP 2334 DI 10.1002/art.39215 PG 12 WC Rheumatology SC Rheumatology GA CQ1SP UT WOS:000360379500005 PM 26019128 ER PT J AU Wallace, ZS Deshpande, V Mattoo, H Mahajan, VS Kulikova, M Pillai, S Stone, JH AF Wallace, Zachary S. Deshpande, Vikram Mattoo, Hamid Mahajan, Vinay S. Kulikova, Maria Pillai, Shiv Stone, John H. TI IgG4-Related Disease Clinical and Laboratory Features in One Hundred Twenty-Five Patients SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SERUM IGG4 CONCENTRATIONS; AUTOIMMUNE PANCREATITIS; EXTRAPANCREATIC LESIONS; SYSTEMIC-DISEASE; SIALADENITIS; MULTICENTER; MANAGEMENT; STATEMENT; RITUXIMAB; DIAGNOSIS AB Objective. IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. Prior studies have focused on individual cases of IgG4-RD or small case series. This study was undertaken to report detailed clinical and laboratory findings in a larger group of patients with IgG4-RD whose diagnosis was established by strict clinicopathologic correlation. Methods. The baseline features of 125 patients with biopsy-proven IgG4-RD were reviewed. The diagnosis was confirmed by pathologists' review, based on consensus diagnostic criteria and correlation with clinicopathologic features. Disease activity and damage were assessed using the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts. Results. Of the 125 patients, 107 had active disease and 86 were not receiving treatment for IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher IgG4-RD RI score, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 concentrations (P < 0.01 for all comparisons). The correlation between IgG4+ plasmablast levels and the IgG4-RD RI of disease activity (Spearman's rho = 0.45, P = 0.003) was stronger than the correlation between total plasmablast levels and the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant differences according to sex were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed to produce sustained remission in 77% of patients. Conclusion. Nearly 50% of this patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to identify a subset of patients with a more severe disease phenotype. In addition, the levels of IgG4+ plasmablasts correlated well with the extent of disease activity. C1 [Wallace, Zachary S.; Deshpande, Vikram; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deshpande, Vikram; Pillai, Shiv; Stone, John H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mattoo, Hamid; Mahajan, Vinay S.; Kulikova, Maria; Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU NIH (National Institute of Allergy and Infectious Diseases, Autoimmune Disease Center of Excellence Program award for IgG4-related disease toMassachusetts General Hospital); Genentech; Abide Therapeutics; Roche FX Supported by the NIH (National Institute of Allergy and Infectious Diseases, Autoimmune Disease Center of Excellence Program award for IgG4-related disease toMassachusetts General Hospital).; Dr. Pillai has received consulting fees from Genentech and Abide Therapeutics (less than $10,000 each). Dr. Stone has received consulting fees from Genentech and Roche (less than $10,000 each) and a grant from Genentech for a clinical trial of rituximab in IgG4-related disease. NR 42 TC 41 Z9 46 U1 2 U2 6 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 SEP PY 2015 VL 67 IS 9 BP 2466 EP 2475 DI 10.1002/art.39205 PG 10 WC Rheumatology SC Rheumatology GA CQ1SP UT WOS:000360379500023 PM 25988916 ER PT J AU Rice, T Hoffman, L Sher, L AF Rice, Timothy Hoffman, Leon Sher, Leo TI Portrayal of violent male psychiatric patients by entertainment media and the stigma of psychiatric illness SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Rice, Timothy; Hoffman, Leon; Sher, Leo] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Hoffman, Leon] New York Psychoanalyt Soc & Inst, New York, NY USA. [Sher, Leo] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. RP Rice, T (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM Timothy.rice@mssm.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2015 VL 49 IS 9 BP 849 EP 849 DI 10.1177/0004867415579465 PG 1 WC Psychiatry SC Psychiatry GA CQ2FE UT WOS:000360414000018 PM 25829483 ER PT J AU Chen, YB Li, SL Fisher, DC Driscoll, J Del Rio, C Abramson, J Armand, P Barnes, J Brown, J Cutler, C El-Jawahri, A Ho, VT Hochberg, E McAfee, S Takvorian, R Spitzer, TR Antin, JH Soiffer, R Jacobsen, E AF Chen, Yi-Bin Li, Shuli Fisher, David C. Driscoll, Jessica Del Rio, Candice Abramson, Jeremy Armand, Philippe Barnes, Jeffrey Brown, Jennifer Cutler, Corey El-Jawahri, Areej Ho, Vincent T. Hochberg, Ephraim McAfee, Steven Takvorian, Ronald Spitzer, Thomas R. Antin, Joseph H. Soiffer, Robert Jacobsen, Eric TI Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Lymphoma; Tandem transplant; Reduced-intensity conditioning; Auto-allo ID NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; HEMATOLOGIC MALIGNANCIES; FOLLICULAR LYMPHOMA; PROGNOSTIC-FACTORS; BONE-MARROW; RITUXIMAB; OUTCOMES; PROGRESSION; SURVIVAL AB Many patients with lymphoma relapse after autologous stem cell transplantation (AutoSCT). These patients are often considered for allogeneic stem cell transplantation (AlloSCT) if remission can be achieved. If a tandem approach was organized, some cases of relapse might be prevented. We conducted a phase II trial of tandem AutoSCT followed by reduced-intensity conditioning (RIC) AlloSCT for patients with high-risk lymphoma. High-dose chemotherapy was given with busulfan, cyclophosphamide, and etoposide. AlloSCT was composed of RIC with busulfan/fludarabine and tacrolimus, sirolimus, and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Donors were fully matched related or unrelated donors. AlloSCT was performed any time between 40 days and 6 months after AutoSCT. Forty-two patients were enrolled, and all patients underwent AutoSCT. RIC AlloSCT was performed in 29 patients. In the 29 patients who underwent tandem transplant, median time from AutoSCT to AlloSCT was 96 days (range, 48 to 169). The 6-month cumulative incidence of grades II to IV acute GVHD was 13.8% (90% confidence interval [CI], 5.3% to 26.3%). Cumulative incidence of chronic GVHD at 1 year was 37.9% (90% CI, 23.1% to 52.7%). Nonrelapse mortality at 2 years after AlloSCT was 11.1% (90% CI, 3.5% to 23.6%). At a median follow-up of 30 months (range, 17.1 to 51.5) for the entire group, the 2-year progression-free survival rate was 64% (90% CI, 50% to 75%) and the 2-year overall survival rate was 69% (90% CI, 43% to 85%). For the 29 patients who underwent tandem SCT, the 2-year progression-free survival rate was 72% (90% CI, 55% to 83%) and the 2-year OS rate was 89% (90% CI, 74% to 96%). Tandem AutoSCT-RIC AlloSCT appears to be safe and effective in patients with high-risk lymphoma. Prospective trials using such an approach in specific lymphoma subtypes are warranted. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Chen, Yi-Bin; Driscoll, Jessica; Del Rio, Candice; Abramson, Jeremy; Barnes, Jeffrey; El-Jawahri, Areej; Hochberg, Ephraim; McAfee, Steven; Takvorian, Ronald; Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Li, Shuli] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fisher, David C.; Armand, Philippe; Brown, Jennifer; Cutler, Corey; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert; Jacobsen, Eric] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Yawkey 9E-9052,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU Otsuka Pharmaceuticals, Inc. FX Financial disclosure and Conflict of interest statement: Dr. Chen reports receiving support for this clinical trial in terms of funding and drug supply from Otsuka Pharmaceuticals, Inc. The remaining authors report no relevant conflicts of interest. NR 30 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2015 VL 21 IS 9 BP 1583 EP 1588 DI 10.1016/j.bbmt.2015.05.016 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CQ0AB UT WOS:000360255900008 PM 26009261 ER PT J AU Bachanova, V Burns, LJ Ahn, KW Laport, GG Akpek, G Kharfan-Dabaja, MA Nishihori, T Agura, E Armand, P Jaglowski, SM Cairo, MS Cashen, AF Cohen, JB D'Souza, A Freytes, CO Gale, RP Ganguly, S Ghosh, N Holmberg, LA Inwards, DJ Kanate, AS Lazarus, HM Malone, AK Munker, R Mussetti, A Norkin, M Prestidge, TD Rowe, JM Satwani, P Siddiqi, T Stiff, PJ William, BM Wirk, B Maloney, DG Smith, SM Sureda, AM Carreras, J Hamadani, M AF Bachanova, Veronika Burns, Linda J. Ahn, Kwang Woo Laport, Ginna G. Akpek, Goerguen Kharfan-Dabaja, Mohamed A. Nishihori, Taiga Agura, Edward Armand, Philippe Jaglowski, Samantha M. Cairo, Mitchell S. Cashen, Amanda F. Cohen, Jonathon B. D'Souza, Anita Freytes, Cesar O. Gale, Robert Peter Ganguly, Siddhartha Ghosh, Nilanjan Holmberg, Leona A. Inwards, David J. Kanate, Abraham S. Lazarus, Hillard M. Malone, Adriana K. Munker, Reinhold Mussetti, Alberto Norkin, Maxim Prestidge, Tim D. Rowe, Jacob M. Satwani, Prakash Siddiqi, Tanya Stiff, Patrick J. William, Basem M. Wirk, Baldeep Maloney, David G. Smith, Sonali M. Sureda, Anna M. Carreras, Jeanette Hamadani, Mehdi CA Ctr Int Blood Marrow Transplant TI Impact of Pretransplantation F-18-fluorodeoxy Glucose-Positron Emission Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Non-Hodgkin lymphoma; Allogeneic transplantation; Positron emission tomography ID LONG-TERM OUTCOMES; RESPONSE ASSESSMENT; PREDICT SURVIVAL; SCAN; DONOR; CHEMOTHERAPY; MALIGNANCIES; CONSENSUS; CLASSIFICATION; INDOLENT AB Assessment with F-18-fluorodeoxy glucose (FDG) positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non-Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with increased mortality (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL. 2015 American Society for Blood and Marrow Transplantation. C1 [Bachanova, Veronika] Univ Minnesota, Blood & Marrow Transplant Program, Med Ctr, Minneapolis, MN 55455 USA. [Burns, Linda J.] Natl Marrow Donor Program Be The Match, Hlth Serv Res, Minneapolis, MN USA. [Ahn, Kwang Woo; D'Souza, Anita; Carreras, Jeanette; Hamadani, Mehdi] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Laport, Ginna G.] Stanford Hosp & Clin, Div Bone Marrow Transplant, Stanford, CA USA. [Akpek, Goerguen] Banner MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy Program, Gilbert, AZ USA. [Kharfan-Dabaja, Mohamed A.; Nishihori, Taiga] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. [Agura, Edward] Baylor Univ, Med Ctr, Blood Serv, Dallas, TX USA. [Agura, Edward] Baylor Univ, Med Ctr, Marrow Transplant Serv, Dallas, TX USA. [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jaglowski, Samantha M.] Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Cashen, Amanda F.] Barnes Jewish Hosp, Dept BMT Oncol, St Louis, MO 63110 USA. [Cohen, Jonathon B.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA USA. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Ganguly, Siddhartha] Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA. [Ghosh, Nilanjan] Carolinas Healthcare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Holmberg, Leona A.; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Inwards, David J.] Mayo Clin, Div Hematol, Rochester, MN USA. [Kanate, Abraham S.] W Virginia Univ, Osborn Hematopoiet Malignancy & Transplantat Prog, Morgantown, WV 26506 USA. [Lazarus, Hillard M.; William, Basem M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Malone, Adriana K.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA. [Munker, Reinhold] Louisiana State Univ Hlth Shreveport, Dept Internal Med, Sect Hematol Oncol, Shreveport, LA USA. [Mussetti, Alberto] Fdn IRCCS Inst Nazl Tumori, SC Ematol & Trapianto Midollo Osseo, Milan, Italy. [Mussetti, Alberto] Univ Milan, Milan, Italy. [Norkin, Maxim] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA. [Prestidge, Tim D.] Starship Childrens Hosp, Blood & Canc Ctr, Auckland, New Zealand. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel. [Satwani, Prakash] Columbia Univ, Dept Pediat, Med Ctr, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY 10027 USA. [Siddiqi, Tanya] City Hope Natl Med Ctr, Dept Hematol Oncol, Duarte, CA 91010 USA. [Stiff, Patrick J.] Loyola Univ, Med Ctr, Dept Hematol Oncol, Chicago, IL 60611 USA. [Wirk, Baldeep] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA. [Smith, Sonali M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Sureda, Anna M.] Hosp Duran & Reynals, Serv Hematol, Inst Catara Oncol, Barcelona, Spain. [Sureda, Anna M.] European Grp Blood & Marrow Transplantat, Istanbul, Turkey. RP Bachanova, V (reprint author), Univ Minnesota, Blood & Marrow Transplant Program, Mayo Mail Code 480,420 Delaware St SE, Minneapolis, MN 55455 USA. RI William, Basem/E-1868-2016; Jaglowski, Samantha/E-3304-2011; Mussetti, Alberto/C-9500-2017 OI Mussetti, Alberto/0000-0002-4088-036X FU Public Health Service from the National Cancer Institute [U24-CA076518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute [5U10HL069294]; National Cancer Institute; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; 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; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co., Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah; Well Point FX The CIBMTR is supported by Public Health Service grant/cooperative agreement [U24-CA076518] from the National Cancer Institute, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement [5U10HL069294] from National Heart, Lung, and Blood Institute and National Cancer Institute; a contract [HHSH250201200016C] with Health Resources and Services Administration; 2 grants [N00014-12-1-0142] and [N00014-13-1-0039] from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen; 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; 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; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; 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; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos; University of Minnesota; University of Utah; and *Well Point. 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 or any other agency of the US Government. NR 26 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2015 VL 21 IS 9 BP 1605 EP 1611 DI 10.1016/j.bbmt.2015.05.007 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CQ0AB UT WOS:000360255900011 PM 25983043 ER PT J AU Shah, NN Kucharczuk, CR Mitra, N Hirsh, R Svoboda, J Porter, D Loren, A Frey, N Schapira, MM AF Shah, Nirav N. Kucharczuk, Colleen R. Mitra, Nandita Hirsh, Rebecca Svoboda, Jakub Porter, David Loren, Alison Frey, Noelle Schapira, Marilyn M. TI Implementation of an Advanced Practice Provider Service on an Allogeneic Stem Cell Transplant Unit: Impact on Patient Outcomes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic transplant; Outcomes; APPs ID PRACTITIONERS; CANCER AB Allogeneic stem cell transplantation (ASCT) is a complex medical procedure for some patients with hematologic malignancies. Most ASCTs occur at academic centers where either medical residents (house staff [HS]) or advanced practice providers (APPs) provide daily care. As a result of increasing work-hour regulations, APPs have assumed greater responsibilities, including those traditionally held by HS. In this study we evaluate ASCT patient outcomes by inpatient provider service. A retrospective, single-center chart review of ASCT patients was performed. ASCT patients admitted to an HS service from May 2011 to May 2012 (N = 86) were compared with ASCT patients admitted to a newly formed APP service from October 2012 to October 2013 (N = 81). As part of a secondary sensitivity analysis, we compared ASCT patients on the APP service to a subset of ASCT patients admitted to the HS service also from October 2012 to October 2013 (n = 27). Our primary outcomes were 100-day survival and relapse-free survival rates. Additional outcomes included length of stay (LOS), inpatient complications, and ordering behavior. Our primary pre- and post-analyses found no differences in 100-day overall survival and 100-day relapse-free survival rate between the services. The rate of pneumonia was lower on the APP service (15% versus 28%, P = .04), with no significant differences in other infectious complications. HS ordered more blood cultures (6.7 versus 4.2, P = .03) per patient than the APP service. There was no difference in LOS, readmission rates, or inpatient mortality. With regards to our secondary sensitivity analysis, no differences were found in 100-day overall survival and 100-day relapse-free survival rates between the services. There was a decreased LOS on the APP service (29.4 versus 37.2 days, P = .01). HS ordered more blood cultures (9.3 versus 4.2, P < .01) and more radiological films (8.1 versus 5.2, P = .05) per patient than the APP service. This increased ordering and LOS was associated with an increase in mean hospital charges on the HS service (P = .04). ASCT patients on an APP service had similar 100-day outcomes as those on the HS service. In the setting of limited resources, APPs are potential alternative providers for complex transplant inpatients. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Shah, Nirav N.; Kucharczuk, Colleen R.; Hirsh, Rebecca; Svoboda, Jakub; Porter, David; Loren, Alison; Frey, Noelle] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19103 USA. [Shah, Nirav N.; Kucharczuk, Colleen R.; Hirsh, Rebecca; Svoboda, Jakub; Porter, David; Loren, Alison; Frey, Noelle] Hosp Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19103 USA. [Schapira, Marilyn M.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19103 USA. [Schapira, Marilyn M.] Philadelphia VA Med Ctr, Div Gen Internal Med, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Shah, NN (reprint author), Univ Penn, Div Hematol Oncol, 1930 Chestnut Apt,9B, Philadelphia, PA 19103 USA. EM nirav.shah@uphs.upenn.edu FU Cancer Center Research Training Program [NCI 5-T32 CA09615-25] FX Financial disclosure: Fellowship funding support was provided by the Cancer Center Research Training Program (NCI 5-T32 CA09615-25) as salary support via a T32 training grant to N.N.S. NR 24 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2015 VL 21 IS 9 BP 1692 EP 1698 DI 10.1016/j.bbmt.2015.05.021 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CQ0AB UT WOS:000360255900022 PM 26028503 ER PT J AU Sierra-Mercado, D Deckersbach, T Arulpragasam, AR Chou, TN Rodman, AM Duffy, A McDonald, EJ Eckhardt, CA Corse, AK Kaur, N Eskandar, EN Dougherty, DD AF Sierra-Mercado, Demetrio Deckersbach, Thilo Arulpragasam, Amanda R. Chou, Tina Rodman, Alexandra M. Duffy, Amanda McDonald, Eric J. Eckhardt, Christine A. Corse, Andrew K. Kaur, Navneet Eskandar, Emad N. Dougherty, Darin D. TI Decision making in avoidance-reward conflict: a paradigm for non-human primates and humans SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Anxiety; Animal model; Obsessive-compulsive disorder (OCD); Bipolar disorder ID OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; DEEP BRAIN-STIMULATION; HUMAN AMYGDALA ACTIVATION; CONDITIONED FEAR; DOPAMINE NEURONS; VENTRAL STRIATUM; BIPOLAR DISORDER; BEHAVIORAL-CONTROL AB Decision making in both animals and humans is influenced by the anticipation of reward and/or punishment. Little is known about how reward and punishment interact in the context of decision making. The Avoidance-Reward Conflict (ARC) Task is a new paradigm that varies the degree of reward and the probability of punishment in a single paradigm that can be used in both non-human primates (NHPs) and humans. This study examined the behavioral pattern in the ARC task in both NHPs and humans. Two adult male NHPs (macaca mulatta) and 20 healthy human volunteers (12 females) participated in the ARC task. NHPs and humans perform similarly on the ARC task. With a high probability of punishment (an aversive air puff to the eye), both NHPs and humans are more likely to forgo reward if it is small or medium magnitude than when it is large. Both NHPs and humans perform similarly on the same behavioral task suggesting the reliability of animal models in predicting human behavior. C1 [Sierra-Mercado, Demetrio; McDonald, Eric J.; Eckhardt, Christine A.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio; McDonald, Eric J.; Eckhardt, Christine A.; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio] Univ Puerto Rico, Dept Anat & Neurobiol, San Juan, PR 00936 USA. [Deckersbach, Thilo; Arulpragasam, Amanda R.; Chou, Tina; Rodman, Alexandra M.; Duffy, Amanda; Corse, Andrew K.; Kaur, Navneet; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Charlestown, MA 02129 USA. [Deckersbach, Thilo; Arulpragasam, Amanda R.; Chou, Tina; Rodman, Alexandra M.; Duffy, Amanda; Corse, Andrew K.; Kaur, Navneet; Dougherty, Darin D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Chou, Tina; Rodman, Alexandra M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, 149 13th St, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU Conte Project Grant [P50-MH086400]; Brain and Behavior Research Foundation (NARSAD); Northeastern University Provost Award; Conte Project Summer Fellowship; HHMI fellowship FX This study was supported by Conte Project Grant (P50-MH086400) to ENE and DDD, a supplement for under-represented minorities from DA026297 and a Young Investigator Grant from the Brain and Behavior Research Foundation (NARSAD) to DS-M, a Northeastern University Provost Award and Conte Project Summer Fellowship to EJM, and an HHMI fellowship to CAE. We thank the animal care staff of the Center for Comparative Medicine. NR 80 TC 2 Z9 2 U1 3 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD SEP PY 2015 VL 220 IS 5 BP 2509 EP 2517 DI 10.1007/s00429-014-0796-7 PG 9 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA CP7LM UT WOS:000360069200003 PM 24969127 ER PT J AU Heck, N Dos Santos, M Amairi, B Salery, M Besnard, A Herzog, E Boudier, T Vanhoutte, P Caboche, J AF Heck, Nicolas Dos Santos, Marc Amairi, Brahim Salery, Marine Besnard, Antoine Herzog, Etienne Boudier, Thomas Vanhoutte, Peter Caboche, Jocelyne TI A new automated 3D detection of synaptic contacts reveals the formation of cortico-striatal synapses upon cocaine treatment in vivo SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Cocaine; Striatum; Dendritic spine; Axonal bouton; 3D segmentation; VGLUT1 ID NUCLEUS-ACCUMBENS; DENDRITIC SPINES; IMAGE-ANALYSIS; PLASTICITY; NEURONS; CONNECTIVITY; ORGANIZATION; ADDICTION; GLUTAMATE; MICROSCOPE AB Addiction can be considered as a form of neuronal adaptation within the reward circuitry. Upon psychostimulant administration, long-term behavioral adaptations are associated with synaptic plasticity and morphological changes of medium spiny neurons (MSN) from the striatum. Increased spine density onto MSN in response to chronic cocaine exposure in mice has been described for more than a decade, but no evidence indicates that these newly formed spines establish connections. We developed a method for labeling, automated detection and morphological analysis of synaptic contacts. Individual labeling of neurons in mice that express the Vesicular GLUtamate Transporter-1 fused to Venus allows visualization of both dendritic spines and axonal boutons. Automated three-dimensional segmentation and morphometric analysis retrieve information on thousands of synapses at high resolution. We used this method to demonstrate that new cortico-striatal connections are formed in the striatum upon chronic cocaine. We also show that the cortical input weight is preserved over other cerebral inputs and that the newly formed spines contact pre-existing axonal boutons. Our results pave the way for other studies, since our method can be applied to any other neuronal type as demonstrated herein for glutamatergic connections on pyramidal neurons and Purkinje cells. C1 [Heck, Nicolas; Dos Santos, Marc; Amairi, Brahim; Salery, Marine; Besnard, Antoine; Vanhoutte, Peter; Caboche, Jocelyne] INSERM, UMR S 1130, Neurosci Paris Seine, F-75005 Paris, France. [Heck, Nicolas; Dos Santos, Marc; Amairi, Brahim; Salery, Marine; Besnard, Antoine; Vanhoutte, Peter; Caboche, Jocelyne] CNRS, UMR 8246, Neurosci Paris Seine, F-75005 Paris, France. [Heck, Nicolas; Dos Santos, Marc; Amairi, Brahim; Salery, Marine; Besnard, Antoine; Boudier, Thomas; Vanhoutte, Peter; Caboche, Jocelyne] Univ Paris 06, Sorbonne Univ, UMR S 8246, Neurosci Paris Seine, F-0675005 Paris, France. [Besnard, Antoine] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Herzog, Etienne] Univ Bordeaux, Inst Interdisciplinaire Neurosci, F-33000 Bordeaux, France. [Herzog, Etienne] CNRS, Inst Interdisciplinaire Neurosci, UMR 5297, F-33000 Bordeaux, France. RP Heck, N (reprint author), INSERM, UMR S 1130, Neurosci Paris Seine, F-75005 Paris, France. EM nicolas.heck@snv.jussieu.fr RI HERZOG, Etienne/D-8997-2015 OI HERZOG, Etienne/0000-0002-0058-6959 FU Centre National pour la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (INSERM); University Pierre and Marie Curie (UPMC); Agence Nationale pour la Recherche (ANR) [ANR-08-BLAN-0287]; Fondation Jerome Lejeune; Labex Bio-Psy cluster of excellence FX This work was supported by Centre National pour la Recherche Scientifique (CNRS), Institut National de la Sante et de la Recherche Medicale (INSERM), University Pierre and Marie Curie (UPMC), Agence Nationale pour la Recherche (ANR, ANR-08-BLAN-0287) and Fondation Jerome Lejeune and the Labex Bio-Psy cluster of excellence. We wish to thank Dr. Susanne Bolte and Richard Schwartzmann from the Cellular Imaging facility of the IBPS (Institut de Biologie Paris-Seine) for expert assistance on microscopy and metrological analysis of the setup. We thank Dr. Katlin Slim the care of the VGLUT1 venus mouse line and Dr. Ann Lohof for intracellular filling of Purkinje cells. NR 49 TC 7 Z9 7 U1 0 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD SEP PY 2015 VL 220 IS 5 BP 2953 EP 2966 DI 10.1007/s00429-014-0837-2 PG 14 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA CP7LM UT WOS:000360069200031 PM 25001083 ER PT J AU Robert, MC Khreim, N Todani, A Melki, SA AF Robert, Marie-Claude Khreim, Nour Todani, Amit Melki, Samir A. TI Anterior chamber gas bubble emergence pattern during femtosecond LASIK-flap creation SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Angle; Anterior chamber; Treatment Lasers ID INNER-WALL ENDOTHELIUM; IN-SITU KERATOMILEUSIS; LASER; OPHTHALMOLOGY AB Aim To characterise the emergence pattern of cavitation bubbles into the anterior chamber (AC) following femtosecond laser-assisted in situ keratomileusis (LASIK)-flap creation Methods Retrospective review of patients undergoing femtosecond LASIK surgery at Boston Laser, a private refractive surgery practice in Boston, Massachusetts, between December 2008 and February 2014. Patient charts were reviewed to identify all cases with gas bubble migration into the AC. Surgical videos were examined and the location of bubble entry was recorded separately for right and left eyes. Results Five thousand one hundred and fifty-eight patients underwent femtosecond LASIK surgery. Air bubble migration into the AC, presumably via the Schlemm's canal and trabecular meshwork, occurred in 1% of cases. Patients with AC bubbles had an average age of 338years with a measured LASIK flap thickness of 96 +/- 21m. The occurrence of gas bubbles impaired iris registration in 64% of cases. Gas bubbles appeared preferentially in the nasal or inferior quadrants for right (92% of cases) and left (100% of cases) eyes. This bubble emergence pattern is significantly different from that expected with a random distribution (p<0.0001) and did not seem associated with decentration of the femtosecond laser docking system. Conclusions The migration of gas bubbles into the AC is a rare occurrence during femtosecond laser flap creation. The preferential emergence of gas bubbles into the nasal and inferior quadrants of the AC may indicate a distinctive anatomy of the nasal Schlemm's canal. C1 [Robert, Marie-Claude; Melki, Samir A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Khreim, Nour; Todani, Amit; Melki, Samir A.] Boston Eye Grp, Brookline, MA USA. RP Robert, MC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2015 VL 99 IS 9 BP 1201 EP 1205 DI 10.1136/bjophthalmol-2014-306307 PG 5 WC Ophthalmology SC Ophthalmology GA CQ2VL UT WOS:000360460000011 PM 25947557 ER PT J AU Thoma, B Mohindra, R Woods, RA AF Thoma, Brent Mohindra, Rohit Woods, Robert A. TI Enhanced training in emergency medicine: the search and application process SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material DE Fellowship; enhanced training; emergency medicine; residency C1 [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent; Woods, Robert A.] Univ Saskatchewan, Emergency Med, Saskatoon, SK, Canada. [Mohindra, Rohit] McGill Univ, Emergency Med Residency Training Program, Montreal, PQ, Canada. RP Thoma, B (reprint author), Royal Univ Hosp, Residency Training Program, Room 2688,103 Hosp Dr, Saskatoon, SK S7N 0W8, Canada. EM brent.thoma@usask.ca OI Thoma, Brent/0000-0003-1124-5786 NR 13 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1481-8035 EI 1481-8043 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD SEP PY 2015 VL 17 IS 5 BP 565 EP 568 DI 10.1017/cem.2015.61 PG 4 WC Emergency Medicine SC Emergency Medicine GA CQ2PZ UT WOS:000360444800012 PM 26013910 ER PT J AU Li, DK Chung, RT AF Li, Darrick K. Chung, Raymond T. TI Impact of hepatitis C virus eradication on hepatocellular carcinogenesis SO CANCER LA English DT Review DE chronic hepatitis C; cirrhosis; direct-acting antivirals; hepatocellular carcinoma; risk factors; sustained virological response ID GENOTYPE 1 INFECTION; SUSTAINED VIROLOGICAL RESPONSE; TREATMENT-NAIVE PATIENTS; UNITED-STATES; PEGYLATED INTERFERON; CARCINOMA DEVELOPMENT; COST-EFFECTIVENESS; CANCER STATISTICS; GENE-EXPRESSION; PLUS RIBAVIRIN AB Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. Infection with hepatitis C virus (HCV) represents one of the most common risk factors for HCC development, and cases of HCV-related complications have been rising over the last 2 decades. Although the standard for HCV therapy has been interferon (IFN)-based for many years, the therapeutic revolution spurred by the development of direct-acting antivirals (DAAs) promises to usher in a new era in which chronic HCV becomes a rare disease. On the basis of long-term follow-up of patients experiencing IFN-based sustained virological responses (SVRs), it can be expected that rates of HCV-associated HCC will decrease significantly after the widespread adoption of DAAs, but there remains a persistent risk for HCC even among some patients with advanced fibrosis who have achieved SVR. As such, individuals treated for HCV with advanced fibrosis should continue to be screened regularly for HCC after SVR. Furthermore, as the population of SVR patients grows, it will become imperative to accurately identify those individuals at high risk for developing HCC, appropriately allocate resources for screening, and consider cost-effective chemopreventive strategies. Risk factors include preexisting advanced fibrosis/cirrhosis, older age, diabetes mellitus, and ethanol use. In addition, laboratory biomarkers and genetic signatures are currently being identified that not only predict the likelihood of HCC development in SVR patients but also may serve as dynamic indicators of therapeutic response. Cancer 2015;121:2874-2882. (c) 2015 American Cancer Society. C1 [Li, Darrick K.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Ctr Liver, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [DK078772] FX This study was funded by the National Institutes of Health (grant DK078772 to Raymond T. Chung). NR 68 TC 17 Z9 17 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2015 VL 121 IS 17 BP 2874 EP 2882 DI 10.1002/cncr.29528 PG 9 WC Oncology SC Oncology GA CP9VU UT WOS:000360244100008 PM 26079399 ER PT J AU Ussar, S Griffin, NW Bezy, O Fujisaka, S Vienberg, S Softic, S Deng, LX Bry, L Gordon, JI Kahn, CR AF Ussar, Siegfried Griffin, Nicholas W. Bezy, Olivier Fujisaka, Shiho Vienberg, Sara Softic, Samir Deng, Luxue Bry, Lynn Gordon, Jeffrey I. Kahn, C. Ronald TI Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome SO CELL METABOLISM LA English DT Article ID INTESTINAL MICROBIOTA; INSULIN SENSITIVITY; WIDE ASSOCIATION; SYSTEMS BIOLOGY; MICE; DISEASE; INDIVIDUALS; HOMEOSTASIS; METAGENOME; RESISTANCE AB Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. C1 [Ussar, Siegfried; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ussar, Siegfried; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Ussar, Siegfried] Helmholtz Ctr Munich, Helmholtz Diabet Ctr, Inst Diabet & Obes, D-85764 Munich, Germany. [Griffin, Nicholas W.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA. [Griffin, Nicholas W.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Gut Microbiome & Nutr Res, St Louis, MO 63108 USA. [Deng, Luxue; Bry, Lynn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Clin & Translat Metagen,Dept Pathol, Boston, MA 02111 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Softic, Samir/0000-0003-1419-9789 FU NIH [DK31036, DK33201, DK82659, DK30292, DK70977, DK78669]; Crohn's and Colitis Foundation of America; Mary K. Iacocca Professorship; HFSP long-term fellowship; iMed; Helmholtz Initiative on Personalized Medicine; German Center for Diabetes Research (DZD); NIH T32 postdoctoral fellowship training grant [DK007120]; Sunstar Foundation postdoctoral fellowship FX The authors wish to thank Graham Smyth and Michael Rourk for their assistance in management of the animal studies. The authors also wish to thank Jonathan Dreyfuss of the Joslin DRC Bioinformatics Core (NIH P30DK036836) for help with data analysis, and the Center for Clinical and Translational Metagenomics for the Harvard Digestive Disease Center (NIH P30DK034854) for help with the gnotobiotic experiments. This work was supported by grants from the NIH: DK31036, DK33201, and DK82659 to C.R.K.; and DK30292, DK70977, and DK78669 to J.I.G. The authors also thank the Crohn's and Colitis Foundation of America (J.I.G.) and the Mary K. Iacocca Professorship (C.R.K.) for their support. S.U. was supported by a HFSP long-term fellowship, iMed, the Helmholtz Initiative on Personalized Medicine, and the German Center for Diabetes Research (DZD). N.W.G. was supported by a NIH T32 postdoctoral fellowship training grant (DK007120). S.F. was supported by the Sunstar Foundation postdoctoral fellowship. J.I.G. is a cofounder of Matatu, Inc., a company characterizing the role of diet-by-microbiota interactions in animal health. NR 44 TC 45 Z9 47 U1 13 U2 92 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD SEP 1 PY 2015 VL 22 IS 3 BP 516 EP 530 DI 10.1016/j.cmet.2015.07.007 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CQ2TJ UT WOS:000360453900023 PM 26299453 ER PT J AU Das, PP Hendrix, DA Apostolou, E Buchner, AH Canver, MC Beyaz, S Ljuboja, D Kuintzle, R Kim, W Karnik, R Shao, Z Xie, HF Xu, J De Los Angeles, A Zhang, YY Choe, J Jun, DLJ Shen, XH Gregory, RI Daley, GQ Meissner, A Kellis, M Hochedlinger, K Kim, J Orkin, SH AF Das, Partha Pratim Hendrix, David A. Apostolou, Effie Buchner, Alice H. Canver, Matthew C. Beyaz, Semir Ljuboja, Damir Kuintzle, Rachael Kim, Woojin Karnik, Rahul Shao, Zhen Xie, Huafeng Xu, Jian De Los Angeles, Alejandro Zhang, Yingying Choe, Junho Jun, Don Leong Jia Shen, Xiaohua Gregory, Richard I. Daley, George Q. Meissner, Alexander Kellis, Manolis Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. TI PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells SO CELL REPORTS LA English DT Article ID REPRESSIVE COMPLEX 2; IMPRINTED GENES; CHROMATIN; GENOME; RNAS; BINDING; DNMT3A; TRANSCRIPTION; PLURIPOTENCY; MECHANISMS AB Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency. C1 [Das, Partha Pratim; Buchner, Alice H.; Canver, Matthew C.; Beyaz, Semir; Ljuboja, Damir; Kim, Woojin; Shao, Zhen; Xie, Huafeng; Xu, Jian; De Los Angeles, Alejandro; Jun, Don Leong Jia; Shen, Xiaohua; Daley, George Q.; Kim, Jonghwan; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Das, Partha Pratim; Buchner, Alice H.; Canver, Matthew C.; Beyaz, Semir; Ljuboja, Damir; Kim, Woojin; Shao, Zhen; Xie, Huafeng; Xu, Jian; De Los Angeles, Alejandro; Jun, Don Leong Jia; Shen, Xiaohua; Daley, George Q.; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Dana Farber Canc Inst, Dept Pediat Oncol, Harvard Stem Cell Inst,Med Sch, Boston, MA 02115 USA. [Das, Partha Pratim; Daley, George Q.; Hochedlinger, Konrad; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Hendrix, David A.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Apostolou, Effie; Karnik, Rahul; Zhang, Yingying; Meissner, Alexander; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Apostolou, Effie; Karnik, Rahul; Zhang, Yingying; Meissner, Alexander; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Apostolou, Effie; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Apostolou, Effie; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA. [Buchner, Alice H.] Univ Gottingen, Int Max Planck Res Sch, Program Mol Biol, D-37077 Gottingen, Germany. [Karnik, Rahul; Zhang, Yingying; Meissner, Alexander] Broad Inst, Cambridge, MA 02142 USA. [Choe, Junho; Gregory, Richard I.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston Childrens Hosp, Stem Cell Program,Harvard Stem Cell Inst,Med Sch, Boston, MA 02115 USA. [Choe, Junho; Gregory, Richard I.] Harvard Univ, Dept Pediat, Boston Childrens Hosp, Harvard Stem Cell Inst,Med Sch, Boston, MA 02115 USA. [Jun, Don Leong Jia] Singapore Polytech, Sch Chem & Life Sci, Singapore 139651, Singapore. [Hendrix, David A.; Kuintzle, Rachael] Oregon State Univ, Sch Elect Engn & Comp Sci, Dept Biochem & Biophys, Corvallis, OR 97331 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Karnik, Rahul/0000-0002-0400-635X; Beyaz, Semir/0000-0003-4730-4012 FU NIH [HLBI U01HL100001, F30 DK103359-01A1] FX We thank Pratibha Tripathi; Glenn MacLean for reagents; Fieda Abderazzaq and Renee Rubio at the Center for Cancer Computational Biology (CCCB) sequencing facility, DFCI, for Illumina HiSeq2000 Sequencing; and the late Edward Fox at the Microarray Core of DFCI for microarray and small RNA-seq. This work was supported by funding from NIH grant HLBI U01HL100001. S.H.O. is an Investigator of the HHMI. M.C.C. was supported by NIH grant F30 DK103359-01A1. NR 48 TC 5 Z9 7 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD SEP 1 PY 2015 VL 12 IS 9 BP 1456 EP 1470 DI 10.1016/j.celrep.2015.07.053 PG 15 WC Cell Biology SC Cell Biology GA CQ4KS UT WOS:000360574200010 PM 26299972 ER PT J AU Chatterjee, NA Lubitz, SA AF Chatterjee, Neal A. Lubitz, Steven A. TI Systemic Embolic Events (SEE) in Atrial Fibrillation SEEing Embolic Risk More Clearly SO CIRCULATION LA English DT Editorial Material DE Editorials; arrhythmias; cardiac; atrial fibrillation; atrial flutter; embolism ID THROMBOEMBOLISM; STROKE; CLOPIDOGREL; ASPIRIN C1 [Chatterjee, Neal A.; Lubitz, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Lubitz, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM slubitz@mgh.harvard.edu FU NHLBI NIH HHS [K23 HL114724, K23HL114724] NR 20 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 2015 VL 132 IS 9 BP 787 EP 789 DI 10.1161/CIRCULATIONAHA.115.018172 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ0VE UT WOS:000360315000001 PM 26224812 ER PT J AU Merchant, FM Salerno-Uriarte, JA Caravati, F Falcone, S Molon, G Marangoni, D Raczak, G Danilowicz-Szymanowicz, L Pedretti, RFE Braga, SS Ikeda, T Calo, L Martino, A Erciyes, D Piancastelli, M Maury, P Cohen, RJ Armoundas, AA AF Merchant, Faisal M. Salerno-Uriarte, Jorge A. Caravati, Fabrizio Falcone, Stefania Molon, Giulio Marangoni, Daniele Raczak, Grzegorz Danilowicz-Szymanowicz, Ludmila Pedretti, Roberto F. E. Braga, Simona Sarzi Ikeda, Takanori Calo, Leonardo Martino, Annamaria Erciyes, Demet Piancastelli, Maurizio Maury, Philippe Cohen, Richard J. Armoundas, Antonis A. TI Prospective Use of Microvolt T-Wave Alternans Testing to Guide Primary Prevention Implantable Cardioverter Defibrillator Therapy SO CIRCULATION JOURNAL LA English DT Article DE Implantable cardioverter defibrillator; Microvolt T wave alternans; Primary prevention; Risk stratification; Sudden cardiac death ID SUDDEN CARDIAC DEATH; ISCHEMIC CARDIOMYOPATHY; RISK STRATIFICATION; HEART-FAILURE; MYOCARDIAL-INFARCTION; CLINICAL-USE; FOLLOW-UP; ARRHYTHMIAS; MORTALITY; BENEFIT AB Background: We hypothesized that a negative microvolt T-wave alternans (MTWA) test would identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillator (ICD) therapy in a prospective cohort. Methods and Results: Data were pooled from 8 centers where MTWA testing was performed specifically for the purpose of guiding primary prevention ICD implantation. Cohorts were included if the ratio of ICDs implanted in patients who were MTWA "non-negative" to patients who were MTWA negative was >2: 1, indicating that MTWA testing had a significant impact on the decision to implant an ICD. The pooled cohort included 651 patients: 371 MTWA non-negative and 280 MTWA negative. Among non-negative patients, 62% underwent ICD implantation whereas only 13% of MTWA-negative patients received an ICD (P<0.01). Despite a substantially lower prevalence of ICDs, long-term survival (6.9 years) was significantly better among MTWA-negative patients (68.2% non-negative vs. 87.1% negative, P=0.026). Conclusions: MTWA-negative patients had significantly better survival than MTWA non-negative patients, the majority of whom had ICDs. Despite a very low prevalence of ICDs, long-term survival among patients with left ventricular ejection fraction <= 40% and a negative MTWA test was better than in the ICD arm of any study to date that has demonstrated a benefit of ICDs. This provides further evidence that MTWA-negative patients are unlikely to benefit from primary prevention ICD therapy. C1 [Merchant, Faisal M.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Salerno-Uriarte, Jorge A.; Caravati, Fabrizio; Falcone, Stefania] Univ Insubria, Dept Heart Sci, Osped Circolo, Varese, Italy. [Salerno-Uriarte, Jorge A.; Caravati, Fabrizio; Falcone, Stefania] Univ Insubria, Dept Heart Sci, Fdn Macchi, Varese, Italy. [Molon, Giulio; Marangoni, Daniele] S Cuore Hosp, Dept Cardiol, Negrar, Italy. [Raczak, Grzegorz; Danilowicz-Szymanowicz, Ludmila] Med Univ Gdansk, Dept Cardiol & Electrotherapy, Gdansk, Poland. [Pedretti, Roberto F. E.; Braga, Simona Sarzi] Sci Inst Tradate, IRCCS Fdn Salvatore Maugeri, Tradate, Italy. [Ikeda, Takanori] Toho Univ, Div Cardiovasc Med, Fac Med & Med Ctr, Tokyo, Japan. [Calo, Leonardo; Martino, Annamaria] Policlin Casilino, Rome, Italy. [Erciyes, Demet] Florence Nightingale Hosp, Istanbul, Turkey. [Piancastelli, Maurizio] S Maria della Croci, Ravena, Turkey. [Maury, Philippe] Univ Hosp Rangueil Toulouse, Toulouse, France. [Cohen, Richard J.; Armoundas, Antonis A.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org RI Calo, Leonardo/R-1892-2016 OI Calo, Leonardo/0000-0002-6062-5286 NR 22 TC 2 Z9 2 U1 0 U2 1 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 SEP PY 2015 VL 79 IS 9 BP 1912 EP 1919 DI 10.1253/circj.CJ-15-0253 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP7SX UT WOS:000360089500015 PM 26073692 ER PT J AU Shiota, S Reddy, R Alsarraj, A El-Serag, HB Graham, DY AF Shiota, Seiji Reddy, Rita Alsarraj, Abeer El-Serag, Hashem B. Graham, David Y. TI Antibiotic Resistance of Helicobacter pylori Among Male United States Veterans SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Gastritis; Bacterial Resistance; Drug; Eradication Therapy ID ANTIMICROBIAL RESISTANCE; RISK-FACTORS; STREPTOCOCCUS-PNEUMONIAE; PRESCRIPTION RATES; TRIPLE-THERAPY; METRONIDAZOLE; INFECTIONS; CLARITHROMYCIN; ERADICATION; PREVALENCE AB BACKGROUND & AIMS: The most recent information published on resistance of Helicobacter pylori to antibiotics in a large population in the United States is more than 10 years old. We assessed the susceptibility of H pylori to antibiotics among patients in a large metropolitan hospital, as well as demographic, clinical, and lifestyle factors associated with antimicrobial resistance. METHODS: We performed a cross-sectional study of a random sample of 656 patients (90.2% men) from a cohort of 1559 undergoing esophagogastroduodenoscopy with collection of gastric biopsies from 2009 through 2013 at the Houston Veterans Affairs Medical Center. We performed culture analyses of gastric tissues to detect H pylori. The minimum inhibitory concentrations of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were determined by the Epsilometer test. Logistic regression analysis was performed to estimate the association between risk factors and antimicrobial resistance. RESULTS: Biopsies from 135 subjects (20.6%) tested positive for H pylori; 128 of these were from men (94.8%). Only 65 strains were susceptible to all 5 antibiotics. The prevalence of resistance to levofloxacin was 31.3% (95% confidence interval [CI], 23.1%-39.4%), to metronidazole it was 20.3% (95% CI, 13.2%-27.4%), to clarithromycin it was 16.4% (95% CI, 9.9%-22.9%), and to tetracycline it was 0.8% (95% CI, 0.0%-2.3%). No isolate was resistant to amoxicillin. Clarithromycin resistance increased from 9.1% in 2009-2010 to 24.2% in 2011-2013. In multivariate analysis, prior treatment of H pylori infection and use of fluoroquinolones were significantly associated with clarithromycin and levofloxacin resistance, respectively. CONCLUSIONS: H pylori resistance to clarithromycin increased between 2009 and 2013; resistance to metronidazole remains high in infected men in the United States. The high frequency of resistance to levofloxacin is a new and concerning finding. C1 [Shiota, Seiji; Reddy, Rita; Alsarraj, Abeer; El-Serag, Hashem B.; Graham, David Y.] Michael E DeBakey VA Med Ctr, Sect Gastroenterol & Hepatol, Dept Med, Houston, TX USA. [Shiota, Seiji; Alsarraj, Abeer; El-Serag, Hashem B.; Graham, David Y.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Shiota, Seiji; Alsarraj, Abeer; El-Serag, Hashem B.; Graham, David Y.] Baylor Coll Med, Dept Med, Sect Hepatol, Houston, TX 77030 USA. [Alsarraj, Abeer; El-Serag, Hashem B.] Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Houston, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu FU NIDDK NIH HHS [DK58338]; PHS HHS [NCI R01 116845, NIDDK K24-04-107] NR 43 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2015 VL 13 IS 9 BP 1616 EP 1624 DI 10.1016/j.cgh.2015.02.005 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP7TG UT WOS:000360090400016 PM 25681693 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Can Colonoscopy Reduce the Risk of Colon Cancer and Mortality in Patients With Inflammatory Bowel Disease? Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02115 USA. NR 2 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2015 VL 13 IS 9 BP 1703 EP 1704 DI 10.1016/j.cgh.2015.05.009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP7TG UT WOS:000360090400035 PM 25970734 ER PT J AU Jenkins, RW Oxnard, GR Elkin, S Sullivan, EK Carter, JL Barbie, DA AF Jenkins, Russell W. Oxnard, Geoffrey R. Elkin, Sheryl Sullivan, E. Kelly Carter, Jennifer L. Barbie, David A. TI Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET Splice Site Mutation SO CLINICAL LUNG CANCER LA English DT Article DE Crizotinib; Lung adenocarcinoma; MET; Splice site mutation ID C-MET; GROWTH-FACTOR; CANCER; INHIBITORS; GENE AB Lung adenocarcinoma has been increasingly subdivided based on the presence of certain driver oncogenes that confer susceptibility to targeted therapy. Similar to ALK and ROS1 rearranged lung adenocarcinomas, those that harbor MET amplification were recently found to respond to the multitargeted tyrosine kinase inhibitor crizotinib. We describe clinical activity of crizotinib in a patient with lung adenocarcinoma with a MET splice site mutation. Although these mutations occur at nearly twice the frequency of MET amplification, special attention is required to detect them on clinical next-generation sequencing platforms. Our findings suggest the need to expand efforts to identify these mutations and evaluate responsiveness to c-Met inhibition in genotype-directed clinical trials. (C) 2015 Elsevier Inc. All rights reserved. C1 [Jenkins, Russell W.; Oxnard, Geoffrey R.; Barbie, David A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Elkin, Sheryl; Sullivan, E. Kelly; Carter, Jennifer L.] N Of One Inc, Lexington, MA USA. RP Barbie, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D819, Boston, MA 02215 USA. EM dbarbie@partners.org FU Wong Family Award; US National Institutes of Health [K08 CA138918-01A1]; Uniting Against Lung Cancer; GTM Fund for Lung Cancer Research FX This work was supported by the Wong Family Award to G.O., and grants from the US National Institutes of Health (K08 CA138918-01A1, D.B.), Uniting Against Lung Cancer (D.B.), and the GTM Fund for Lung Cancer Research (D.B.). NR 14 TC 19 Z9 20 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 EI 1938-0690 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD SEP PY 2015 VL 16 IS 5 BP E101 EP E104 DI 10.1016/j.cllc.2015.01.009 PG 4 WC Oncology SC Oncology GA CP8YY UT WOS:000360182100010 PM 25769807 ER PT J AU Foster, AM Jackson, CB LaRoche, KJ Simmonds, K Taylor, D AF Foster, Angel M. Jackson, Courtney B. LaRoche, Kathryn J. Simmonds, Katherine Taylor, Diana TI From qualified physician to licensed health care professional: the time has come to change mifepristone's label SO CONTRACEPTION LA English DT Editorial Material ID CONTROLLED EQUIVALENCE TRIAL; ADVANCED PRACTICE CLINICIAN; ABORTION SERVICES; MEDICAL ABORTION; NURSE-MIDWIVES; UNITED-STATES; PROVIDERS; ASSISTANTS; SAFETY; PRACTITIONERS C1 [Foster, Angel M.; LaRoche, Kathryn J.] Univ Ottawa, Fac Hlth Sci, Ottawa, ON K1N 6N5, Canada. [Jackson, Courtney B.] New View Data Solut, Arlington, MA USA. [Simmonds, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Taylor, Diana] Univ Calif San Francisco, Advancing New Stand Reprod Hlth, San Francisco, CA 94143 USA. RP Foster, AM (reprint author), Univ Ottawa, Fac Hlth Sci, Ottawa, ON K1N 6N5, Canada. EM angel.foster@uottawa.ca OI Foster, Angel/0000-0001-8848-203X NR 27 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD SEP PY 2015 VL 92 IS 3 BP 200 EP 202 DI 10.1016/j.contraception.2015.06.022 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CP9YL UT WOS:000360251700008 PM 26134281 ER PT J AU Madden, K Wolfe, J Collura, C AF Madden, Kevin Wolfe, Joanne Collura, Christopher TI Pediatric Palliative Care in the Intensive Care Unit SO CRITICAL CARE NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Pediatrics; Palliative care; Intensive care; Intensive care units; neonatal; Quality of life ID OF-LIFE CARE; EXTREMELY PREMATURE-INFANTS; ILL CANCER-PATIENTS; SEDATION THERAPY; HOSPITALIZED CHILDREN; PROSPECTIVE MULTICENTER; GESTATIONAL-AGE; TERMINAL CANCER; END; DEATH AB The chronicity of illness that afflicts children in Pediatric Palliative Care and the medical technology that has improved their lifespan and quality of life make prognostication extremely difficult. The uncertainty of prognostication and the available medical technologies make both the neonatal intensive care unit and the pediatric intensive care unit locations where many children will receive Pediatric Palliative Care. Health care providers in the neonatal intensive care unit and pediatric intensive care unit should integrate fundamental Pediatric Palliative Care principles into their everyday practice. C1 [Madden, Kevin] Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Houston, TX 77030 USA. [Wolfe, Joanne] Harvard Univ, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care,Childrens, Pediat Palliat Care,Pediat Palliat Care Serv,Med, Boston, MA 02215 USA. [Collura, Christopher] Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Div Neonatal Med, Rochester, MN 55902 USA. RP Madden, K (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, 1515 Holcombe Blvd,Unit 1414, Houston, TX 77030 USA. EM kmadden@mdanderson.org NR 80 TC 0 Z9 0 U1 3 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0899-5885 EI 1558-3481 J9 CRIT CARE NURS CLIN JI Crit. Care Nurs. Clin. N. Am. PD SEP PY 2015 VL 27 IS 3 BP 341 EP + DI 10.1016/j.cnc.2015.05.005 PG 15 WC Nursing SC Nursing GA CQ0GB UT WOS:000360272200006 PM 26333755 ER PT J AU Gonzalez, R Schuster, RM Mermelstein, RM Diviak, KR AF Gonzalez, Raul Schuster, Randi M. Mermelstein, Robin M. Diviak, Kathleen R. TI The role of decision-making in cannabis-related problems among young adults SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cannabis; Decision-making; Addiction ID IOWA GAMBLING TASK; VENTROMEDIAL PREFRONTAL CORTEX; SUBSTANCE USE DISORDER; MARIJUANA USE; RISK-TAKING; NEUROPSYCHOLOGICAL PERFORMANCE; FUTURE CONSEQUENCES; EXECUTIVE FUNCTIONS; NEURAL MECHANISMS; EPISODIC MEMORY AB Background: Deficits in decision-making and episodic memory are often reported among heavy cannabis users, yet little is known on how they influence negative consequences from cannabis use. Individual differences in decision-making may explain, in part, why some individuals experience significant problems from their cannabis use whereas others do not. We hypothesized that poor decision-making would moderate relationships between amount of cannabis use and problems from cannabis use whereas episodic memory performance would not. Method: Young adult cannabis users (n = 52) with cannabis as their drug of choice and with minimal comorbidities completed semi-structured interviews, self-report questionnaires, and measures of neurocognitive functioning, with decision-making accessed via the Iowa Gambling Task (IGT), episodic memory via the Hopkins Verbal Learning Test - Revised (HVLT) and problems from cannabis use with the Marijuana Problems Scale. Results: Strong relationships were observed between amount of cannabis use (lifetime, 12-month, and 30-day) and problems reported from use, but only among participants with low (impaired) decision-making (R-2 = .39 to.51; p < .01). No significant relationships were observed among those with better (low average to high average) decision-making performance (p > .05). In contrast, episodic memory performance was not a significant moderator of the relationship between amount of cannabis use and cannabis problems (p >.05). Conclusions: Cannabis users with poor decision-making may be at greater risk for experiencing significant negative consequences from their cannabis use. Our results lend further support to emerging evidence of decision-making as a risk factor for addiction and extend these findings to cannabis users. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Gonzalez, Raul] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Gonzalez, Raul] Florida Int Univ, Ctr Children & Families, Miami, FL 33199 USA. [Schuster, Randi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mermelstein, Robin M.] Univ Illinois, Dept Psychol, Chicago, IL 60607 USA. [Mermelstein, Robin M.; Diviak, Kathleen R.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60608 USA. RP Gonzalez, R (reprint author), Florida Int Univ, 11200 SW 8th St,AHC-4,Room 461, Miami, FL 33199 USA. EM raul.gonzalezjr@fiu.edu FU National Institute on Drug Abuse; National Cancer Institute of the National Institutes of Health [K23 DA023560, R01 DA031176, R01 DA033156, F31 DA032244, P01 CA098262] FX Research reported in this article was supported by National Institute on Drug Abuse and the National Cancer Institute of the National Institutes of Health under grant number K23 DA023560, R01 DA031176, R01 DA033156 to Dr. Gonzalez, F31 DA032244 to Dr. Schuster, and P01 CA098262 to Dr. Mermelstein. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 88 TC 2 Z9 2 U1 8 U2 25 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2015 VL 154 BP 214 EP 221 DI 10.1016/j.drugalcdep.2015.06.046 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CQ2HB UT WOS:000360419600028 PM 26199058 ER PT J AU Barocas, JA Baker, L Hull, SJ Stokes, S Westergaard, RP AF Barocas, Joshua A. Baker, Lisa Hull, Shawnika J. Stokes, Scott Westergaard, Ryan P. TI High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE People who inject drugs; Overdose; Risky health behaviors; Take-home naloxone; Correctional facilities ID INJECTION-DRUG USERS; FOLLOW-UP; RELEASE; PRISON; DEATHS; MORTALITY AB Background: Incarceration is common among people who inject drugs. Prior research has shown that incarceration is a marker of elevated risk for opioid overdose, suggesting that the criminal justice system may be an important, under-utilized venue for implementing overdose prevention strategies. To better understand the feasibility and acceptability of such strategies, we evaluated the utilization of naloxone-based overdose prevention training among people who inject drugs with and without a history of incarceration. Methods: We surveyed clients who utilize a multi-site syringe exchange program (SEP) in 2 cities in the Midwestern United States. Participants completed an 88-item, computerized survey assessing history of incarceration, consequences associated with injection, injecting practices, and uptake of harm reduction strategies. Results: Among 543 respondents who injected drugs in the prior 30 days, 243 (43%) reported prior incarceration. Comparing those with and without a history of incarceration, there were no significant differences with respect to age, gender, or race. Those who observed an overdose, experienced overdose, and received training to administer or have administered naloxone were more likely to report incarceration. Overall, 69% of previously incarcerated clients had been trained to administer naloxone. Conclusion: People who inject drugs with a history of incarceration appear to have a higher risk of opioid overdose than those never incarcerated, and are more willing to utilize naloxone as an overdose prevention strategy. Naloxone training and distribution is an important component of comprehensive prevention services for persons with opioid use disorders. Expansion of services for persons leaving correctional facilities should be considered. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Barocas, Joshua A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Barocas, Joshua A.; Baker, Lisa; Westergaard, Ryan P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. [Hull, Shawnika J.] Univ Wisconsin, Sch Journalism Mass Commun, Madison, WI 53705 USA. [Stokes, Scott] AIDS Resource Ctr Wisconsin, Milwaukee, WI 53208 USA. [Westergaard, Ryan P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. RP Barocas, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GrJ 504, Boston, MA 02114 USA. EM jbarocas@partners.org; Imbaker@medicine.wisc.edu; sjhull@wisc.edu; Scott.Stokes@arcw.org; rpw@medicine.wisc.edu FU Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; NIH [K23DA032306] FX This manuscript was supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. RPW is supported by NIH grant K23DA032306. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 16 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 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2015 VL 154 BP 283 EP 286 DI 10.1016/j.drugalcdep.2015.06.023 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CQ2HB UT WOS:000360419600038 PM 26143300 ER PT J AU Blashill, AJ Safren, SA Jampel, JD AF Blashill, Aaron J. Safren, Steven A. Jampel, Jonathan D. TI Sexual risk behaviors and steroid use among sexual minority adolescent boys SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Sexual risk; Adolescent boys; Steroids; Sexual orientation; Substance use ID ANABOLIC-ANDROGENIC STEROIDS; BISEXUAL MEN; HEALTH; HIV; ORIENTATION; MUSCULARITY; MODEL; GAY AB Background: Previous research has extensively examined the relationship between the use of alcohol and illicit substances with sexual risk behaviors among sexual minority (i.e., gay and bisexual) male youth; however, no known studies have assessed the association of steroid use to risk behaviors among this population. Methods: Participants were 556 sexually active sexual minority adolescent boys (M age= 16.2, SD =13), taken from a pooled dataset of the 14 jurisdictions from the 2005 and 2007 Youth Risk Behavior Surveys that assessed sexual orientation. The association between lifetime use of steroids and sexual risk behaviors were examined. Results: Controlling for number of sexual partners, depression, victimization, and race, boys who reported increased steroid use were at increased odds of engaging in condomless sex, OR= 1.55, p =.003, and use of alcohol/drugs during sex, OR= 1.48, p =.002. Conclusions: Steroid use among sexual minority adolescent boys is prevalent and associated with HIV/STI sexual transmission risk behaviors. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Blashill, Aaron J.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Blashill, Aaron J.; Safren, Steven A.; Jampel, Jonathan D.] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Blashill, AJ (reprint author), San Diego State Univ, Dept Psychol, 6363 Alvarado Court,Suite 103, San Diego, CA 92120 USA. EM aaron.blashill@sdsu.edu; ssafren@mgh.harvard.edu; jjampel@fenwayhealth.org FU [K23MH096647] FX Some investigator time was supported by K23MH096647 (A.J.B.). NIH had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. NR 27 TC 0 Z9 0 U1 4 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2015 VL 154 BP 287 EP 290 DI 10.1016/j.ijhydene.2015.06.025 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CQ2HB UT WOS:000360419600039 PM 26144592 ER PT J AU Greenstein, RJ Cameron, DW Brown, ST AF Greenstein, Robert J. Cameron, D. William Brown, Sheldon T. TI Yet Another Flawed "Placebo Controlled" Study in Crohn's Disease? SO FOODBORNE PATHOGENS AND DISEASE LA English DT Letter ID SUBSPECIES PARATUBERCULOSIS C1 [Greenstein, Robert J.] James J Peters Vet Affairs Med Ctr, Dept Surg, Bronx, NY 10468 USA. [Cameron, D. William] Ottawa Hosp Res Inst, Dept Med, Ottawa, ON, Canada. [Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Div Infect Dis, Bronx, NY 10468 USA. [Brown, Sheldon T.] Inchan Sch Med Mt Sinai, New York, NY USA. RP Greenstein, RJ (reprint author), James J Peters Vet Affairs Med Ctr, Lab Mol Surg Res, Res Block 4F 05,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Greenstein.Robert@gmail.com NR 5 TC 0 Z9 0 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SEP 1 PY 2015 VL 12 IS 9 BP 812 EP 812 DI 10.1089/fpd.2015.1999 PG 1 WC Food Science & Technology SC Food Science & Technology GA CP9KX UT WOS:000360214100012 PM 26110358 ER PT J AU Baxt, LA Xavier, RJ AF Baxt, Leigh A. Xavier, Ramnik J. TI Role of Autophagy in the Maintenance of Intestinal Homeostasis SO GASTROENTEROLOGY LA English DT Review DE IBD; Pathogenesis; Cell Biology; Genetics ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; DENDRITIC CELLS; SELECTIVE AUTOPHAGY; HOST-DEFENSE; PANETH CELLS; ANTIMICROBIAL DEFENSE; ANTIGEN PRESENTATION; EPITHELIAL-CELLS; LYSOSOME FUSION AB Genome-wide association studies of inflammatory bowel disease have identified several risk loci in genes that regulate autophagy, and studies have provided insight into the functional effects of these polymorphisms. We review the mechanisms by which autophagy contributes to intestinal homeostasis, focusing on its cell type-specific roles in regulating gut ecology, restricting pathogenic bacteria, and controlling inflammation. Based on this information, we are beginning to understand how alterations in autophagy can contribute to intestinal inflammation. C1 [Baxt, Leigh A.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Baxt, Leigh A.; Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Baxt, Leigh A.; Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02138 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu FU NIAID NIH HHS [U19 AI109725]; NIDDK NIH HHS [DK043351, DK092405, DK097485, DK102557, P30 DK043351, R01 DK092405, R01 DK097485, U54 DK102557] NR 85 TC 12 Z9 13 U1 2 U2 26 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2015 VL 149 IS 3 BP 553 EP 562 DI 10.1053/j.gastro.2015.06.046 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0FE UT WOS:000360269800024 PM 26170139 ER PT J AU Yurgelun, MB Allen, B Kaldate, RR Bowles, KR Judkins, T Kaushik, P Roa, BB Wenstrup, RJ Hartman, AR Syngal, S AF Yurgelun, Matthew B. Allen, Brian Kaldate, Rajesh R. Bowles, Karla R. Judkins, Thaddeus Kaushik, Praveen Roa, Benjamin B. Wenstrup, Richard J. Hartman, Anne-Renee Syngal, Sapna TI Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome SO GASTROENTEROLOGY LA English DT Article DE Hereditary Nonpolyposis Colorectal Cancer; HNPCC; Colon Cancer Genetics; Inherited Cancer ID NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH REPAIR GENE; ASHKENAZI JEWISH POPULATION; MUTYH-ASSOCIATED POLYPOSIS; GERMLINE MUTATIONS; RISK-ASSESSMENT; ADENOMATOUS POLYPOSIS; UNCLASSIFIED VARIANTS; CLINICAL MANAGEMENT; FOUNDER MUTATION AB BACKGROUND & AIMS: Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. METHODS: We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. RESULTS: Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6% - 10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4% - 7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). CONCLUSIONS: In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many of which were unexpected based on patients' histories. Parallel sequencing also detected a high number of potentially uninformative germline findings, including VUS. C1 [Yurgelun, Matthew B.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. [Yurgelun, Matthew B.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Yurgelun, Matthew B.; Syngal, Sapna] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Allen, Brian; Kaldate, Rajesh R.; Bowles, Karla R.; Judkins, Thaddeus; Kaushik, Praveen; Roa, Benjamin B.; Wenstrup, Richard J.; Hartman, Anne-Renee] Myriad Genet Labs, Salt Lake City, UT USA. RP Yurgelun, MB (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA. EM Matthew_Yurgelun@DFCI.Harvard.edu FU NCI NIH HHS [K24 CA113433, K24CA113433, R01 CA132829, R01CA132829] NR 95 TC 30 Z9 30 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2015 VL 149 IS 3 BP 604 EP + DI 10.1053/j.gastro.2015.05.006 PG 30 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0FE UT WOS:000360269800030 PM 25980754 ER PT J AU Mehta, RS Chong, DQ Song, MY Meyerhardt, JA Ng, K Nishihara, R Qian, ZR Morikawa, T Wu, K Giovannucci, EL Fuchs, CS Ogino, S Chan, AT AF Mehta, Raaj S. Chong, Dawn Q. Song, Mingyang Meyerhardt, Jeffrey A. Ng, Kimmie Nishihara, Reiko Qian, Zhirong Morikawa, Teppei Wu, Kana Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji Chan, Andrew T. TI Association Between Plasma Levels of Macrophage Inhibitory Cytokine-1 Before Diagnosis of Colorectal Cancer and Mortality SO GASTROENTEROLOGY LA English DT Article DE Cyclooxygenase; Colon Cancer Risk Factor; Immunity; GDF15 ID EXPRESSION; RISK; MIC-1/GDF15; NAG-1/GDF15; NEOPLASIA; SURVIVAL; SULINDAC; ASPIRIN; WOMEN; COX-2 AB BACKGROUND & AIMS: Patients with colorectal cancer (CRC) have high circulating levels of macrophage inhibitory cytokine-1 (MIC1 or growth differentiation factor 15), a marker of inflammation that might be involved in carcinogenesis. We analyzed blood samples collected from individuals before they were diagnosed with CRC to determine whether levels of MIC1 were associated with mortality. METHODS: We collected data on survival of 618 participants diagnosed with CRC who provided prediagnosis blood specimens in 1990 (Nurses' Health Study) and 1994 (Health Professionals' Follow-up Study) and were followed through 2010. Levels of MIC1 were measured by enzyme-linked immunosorbent assay and then were categorized into quartiles based on the known distribution of MIC1 levels among previously matched individuals without CRC (controls) within each cohort. We then examined the association of MIC1 levels with overall and CRC-specific mortality using Cox proportional hazards models, with adjustments for mortality-associated risk factors and other plasma markers of inflammation. We also assessed the relationship between levels of MIC1 and levels of prostaglandin-endoperoxide synthase 2 expression (PTGS2 or cyclooxygenase-2), measured in 245 tumor samples by immunohistochemistry. RESULTS: Compared with participants in the lowest quartile for plasma level of MIC1, the multivariate hazard ratio for CRC-specific death for participants in the highest quartile of MIC1 level was 2.40 (95% confidence interval: 1.33 - 4.34; P for linear trend = .009). The association of MIC1 with survival varied with level of PTGS2 expression in tumor samples (Pinteraction = .04). For individuals with PTGS2-positive tumors, the hazard ratio for CRC-specific death among those with high levels of MIC1 (equal to or greater than the median) was 2.13 (95% confidence interval: 0.99 - 4.58) compared with participants with low levels of MIC1 (below the median). In individuals with PTGS2-negative CRC, a high level of MIC1 was not associated with an increased risk of CRC-specific death (multivariate hazard ratio = 0.61; 95% confidence interval: 0.13 - 2.93). CONCLUSIONS: Based on an analysis of blood and colorectal tumor samples from 2 large studies, high plasma levels of MIC1 (growth differentiation factor 15) before diagnosis of CRC are associated with greater CRC-specific mortality, particularly in individuals with PTGS2-positive tumors. C1 [Mehta, Raaj S.; Chong, Dawn Q.; Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Mehta, Raaj S.; Chong, Dawn Q.; Song, Mingyang; Meyerhardt, Jeffrey A.; Ng, Kimmie; Nishihara, Reiko; Qian, Zhirong; Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Mehta, Raaj S.; Chong, Dawn Q.; Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Chong, Dawn Q.] Natl Canc Ctr Singapore, Singapore, Singapore. [Song, Mingyang; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Song, Mingyang; Nishihara, Reiko; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA. [Meyerhardt, Jeffrey A.; Ng, Kimmie; Nishihara, Reiko; Qian, Zhirong; Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Giovannucci, Edward L.; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, GRJ 825C, Boston, MA 02114 USA. EM achan@mgh.harvard.edu RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU Howard Hughes Medical Institute; NCI NIH HHS [R35 CA197735, K07 CA148894, K07 CA190673, P01 CA087969, P01 CA87969, P50 CA127003, R01 CA118553, R01 CA137178, R01 CA151993, R01 CA169141, UM1 CA167552, UM1 CA186107]; NIDDK NIH HHS [K24 DK 098311, K24 DK098311] NR 29 TC 7 Z9 7 U1 4 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2015 VL 149 IS 3 BP 614 EP 622 DI 10.1053/j.gastro.2015.05.038 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0FE UT WOS:000360269800031 PM 26026393 ER PT J AU Berry, K Ioannou, GN AF Berry, Kristin Ioannou, George N. TI Comparison of Liver Transplant-Related Survival Benefit in Patients With Versus Without Hepatocellular Carcinoma in the United States SO GASTROENTEROLOGY LA English DT Article DE Liver Cancer; UNOS; Priority; Exception Points ID ALLOCATION SYSTEM; WAITING-LIST; MORTALITY; POLICY; MODEL; CANDIDATES; OUTCOMES AB BACKGROUND & AIMS: Patients with T2 hepatocellular carcinoma (HCC) can obtain an exception that allows them to undergo liver transplantation with much lower actual Model for End-Stage Liver Disease (MELD) scores than patients without HCC. We compared patients who received liver transplants, with and without HCC, with regard to transplantation-related survival benefit. METHODS: We modeled the post-transplantation survival of adult, first-time liver transplant recipients with HCC (n = 9135) or without (n = 25,890) from 2002 through 2013 using Cox proportional hazards regression. We modeled waitlist survival of patients listed for transplantation with HCC (n = 15,605) or without (n = 85,229) using competing risks analysis and combined outcomes of death or liver failure (defined as MELD score >= 30). We used these survival models to calculate monthly transition probabilities and 5-year life expectancies. Survival benefit was calculated as the difference between post-transplantation and waitlist life expectancy. RESULTS: The 5-year survival benefit increased with actual MELD score for patients with and without HCC, ranging from just a few months in patients with low MELD scores (ie, 6 - 8) to 4 years in patients with the highest MELD scores (ie, 36 - 40). The survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score, irrespective of tumor burden or serum level of a-fetoprotein. However, because patients with HCC received liver transplants when they had a lower mean MELD score (13.3 +/- 6.2) than patients without HCC (21.8 +/- 8.0), a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient). CONCLUSIONS: The HCC MELD exception policy has unintentionally resulted in a large reduction in transplantation-related survival benefit. C1 [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 22 TC 12 Z9 12 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2015 VL 149 IS 3 BP 669 EP 680 DI 10.1053/j.gastro.2015.05.025 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0FE UT WOS:000360269800036 PM 26021233 ER PT J AU Bowman, SK AF Bowman, Sarah K. TI Discovering enhancers by mapping chromatin features in primary tissue SO GENOMICS LA English DT Review DE Enhancers; Chromatin; Cell separation; ChIP-seq; DNase-seq; Model organism ID RNA-POLYMERASE-II; GENE-EXPRESSION; CELL-TYPES; HYPERSENSITIVE SITES; REGULATORY ELEMENTS; ACTIVE ENHANCERS; GENOME; NUCLEI; CHIP; TRANSCRIPTION AB Enhancers work with promoters to refine the timing, location, and level of gene expression. As they perform these functions, active enhancers generate a chromatin environment that is distinct from other areas of the genome. Therefore, profiling enhancer-associated chromatin features can produce genome-wide maps of potential regulatory elements. This review focuses on current technologies used to producemaps of potential tissue-specific enhancers by profiling chromatin from primary tissue. First, cells are separated from whole organisms either by affinity purification, automated cell sorting, or microdissection. Isolating the tissue prior to analysis ensures that the molecular signature of active enhancers will not become lost in an averaged signal from unrelated cell types. After cell isolation, the molecular feature that is profiled will depend on the abundance and quality of the harvested material. The combination of tissue isolation plus genome-wide chromatin profiling has successfully identified enhancers in several pioneering studies. In the future, the regulatory apparatus of healthy and diseased tissues will be explored in this manner, as researchers use the combined techniques to gain insight into how active enhancers may influence disease progression. (C) 2015 Published by Elsevier Inc. C1 [Bowman, Sarah K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Bowman, Sarah K.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Bowman, SK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 45 TC 1 Z9 1 U1 1 U2 8 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 SEP PY 2015 VL 106 IS 3 BP 140 EP 144 DI 10.1016/j.ygeno.2015.06.006 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CQ2RD UT WOS:000360447900002 PM 26079656 ER PT J AU Li, E Greenberg, PB Krzystolik, MG AF Li, Emily Greenberg, Paul B. Krzystolik, Magdalena G. TI Nurse-administered intravitreal injections: a systematic review SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter DE Intravitreal injections; Nurses; Ranibizumab; Exudative age-related macular degeneration; Diabetic macular edema ID PRACTITIONERS C1 [Li, Emily; Greenberg, Paul B.] Brown Univ, Warren Alpert Med Sch, Div Ophthalmol, Providence, RI 02912 USA. [Greenberg, Paul B.; Krzystolik, Magdalena G.] Providence VA Med Ctr, Sect Ophthalmol, Providence, RI 02908 USA. [Krzystolik, Magdalena G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02115 USA. RP Krzystolik, MG (reprint author), Providence VA Med Ctr, Sect Ophthalmol, 830 Chalkstone, Providence, RI 02908 USA. EM magdalena_krzystolik@meei.harvard.edu NR 9 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X EI 1435-702X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD SEP PY 2015 VL 253 IS 9 BP 1619 EP 1621 DI 10.1007/s00417-014-2921-y PG 3 WC Ophthalmology SC Ophthalmology GA CQ0MQ UT WOS:000360290700025 PM 25588804 ER PT J AU Rovida, E Di Maira, G Tusa, I Cannito, S Paternostro, C Navari, N Vivoli, E Deng, XM Gray, NS Esparis-Ogando, A David, E Pandiella, A Dello Sbarba, P Parola, M Marra, F AF Rovida, Elisabetta Di Maira, Giovanni Tusa, Ignazia Cannito, Stefania Paternostro, Claudia Navari, Nadia Vivoli, Elisa Deng, Xianming Gray, Nathanael S. Esparis-Ogando, Azucena David, Ezio Pandiella, Atanasio Dello Sbarba, Persio Parola, Maurizio Marra, Fabio TI The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma SO GUT LA English DT Article ID HEPATIC STELLATE CELLS; CANCER-CELLS; GENE-EXPRESSION; PHARMACOLOGICAL INHIBITION; HEPATOCYTE PROLIFERATION; SIGNAL-TRANSDUCTION; KAPPA-B; HYPOXIA; FAK; MECHANISMS AB Objective The extracellular signal-regulated kinase 5 (ERK5 or BMK1) is involved in tumour development. The ERK5 gene may be amplified in hepatocellular carcinoma (HCC), but its biological role has not been clarified. In this study, we explored the role of ERK5 expression and activity in HCC in vitro and in vivo. Design ERK5 expression was evaluated in human liver tissue. Cultured HepG2 and Huh-7 were studied after ERK5 knockdown by siRNA or in the presence of the specific pharmacological inhibitor, XMD8-92. The role of ERK5 in vivo was assessed using mouse Huh-7 xenografts. Results In tissue specimens from patients with HCC, a higher percentage of cells with nuclear ERK5 expression was found both in HCC and in the surrounding cirrhotic tissue compared with normal liver tissue. Inhibition of ERK5 decreased HCC cell proliferation and increased the proportion of cells in G0/G1 phase. These effects were associated with increased expression of p27 and p15 and decreased CCND1. Treatment with XMD8-92 or ERK5 silencing prevented cell migration induced by epidermal growth factor or hypoxia and caused cytoskeletal remodelling. In mouse xenografts, the rate of tumour appearance and the size of tumours were significantly lower when Huh-7 was silenced for ERK5. Moreover, systemic treatment with XMD8-92 of mice with established HCC xenografts markedly reduced tumour growth and decreased the expression of the protooncogene c-Rel. Conclusions ERK5 regulates the biology of HCC cells and modulates tumour development and growth in vivo. This pathway should be investigated as a possible therapeutic target in HCC. C1 [Rovida, Elisabetta; Tusa, Ignazia; Dello Sbarba, Persio] Univ Florence, Dipartimento Sci Biomed Sperimentali & Clin, I-50134 Florence, Italy. [Di Maira, Giovanni; Navari, Nadia; Vivoli, Elisa; Marra, Fabio] Univ Florence, Dipartimento Med Sperimentale & Clin, I-50134 Florence, Italy. [Cannito, Stefania; Paternostro, Claudia; Parola, Maurizio] Univ Turin, Dipartimento Med & Oncol Sperimentali, I-10124 Turin, Italy. [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Deng, Xianming] Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China. [Esparis-Ogando, Azucena; Pandiella, Atanasio] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain. [David, Ezio] Osped San Giovanni Battista, Pathol Unit, Turin, Italy. RP Marra, F (reprint author), Univ Florence, Dipartimento Med Sperimentale & Clin, Largo Brambilla 3, I-50134 Florence, Italy. EM elisabetta.rovida@unifi.it; fabio.marra@unifi.it RI Marra, Fabio/K-7263-2016; Rovida, Elisabetta/F-3565-2015; OI Marra, Fabio/0000-0001-8629-0878; Rovida, Elisabetta/0000-0002-5949-3239; Tusa, Ignazia/0000-0002-9198-2630; Parola, Maurizio/0000-0001-7720-5141 FU Associazione Italiana per la Ricerca sul Cancro Istituto Toscano Tumori [IG-13466, IG-9084]; Fondazione Umberto Veronesi; Ministero della Salute (Ricerca Finalizzata) [RF-TOS-2008-1163728]; Regione Toscana (Programma per la Ricerca in Materia di Salute); Associazione Italiana per la Lotta contro le Leucemie e i Linfomi (sezione di Prato); Fondazione Cassa di Risparmio di Volterra; Fondazione Oretta Bartolomei-Corsi FX This work was supported by Associazione Italiana per la Ricerca sul Cancro (IG-13466 and IG-9084) Istituto Toscano Tumori, Fondazione Umberto Veronesi, Ministero della Salute (Ricerca Finalizzata, grant # RF-TOS-2008-1163728), Regione Toscana (Programma per la Ricerca in Materia di Salute), Associazione Italiana per la Lotta contro le Leucemie e i Linfomi (sezione di Prato), Fondazione Cassa di Risparmio di Volterra, Fondazione Oretta Bartolomei-Corsi. NR 51 TC 8 Z9 8 U1 1 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD SEP PY 2015 VL 64 IS 9 BP 1454 EP U160 DI 10.1136/gutjnl-2014-306761 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1WB UT WOS:000360389800015 PM 25183205 ER PT J AU Nielsen, JB Kuhl, JT Pietersen, A Graff, C Lind, B Struijk, JJ Olesen, MS Sinner, MF Bachmann, TN Haunso, S Nordestgaard, BG Ellinor, PT Svendsen, JH Kofoed, KF Kober, L Holst, AG AF Nielsen, Jonas B. Kuehl, Jorgen T. Pietersen, Adrian Graff, Claus Lind, Bent Struijk, Johannes J. Olesen, Morten S. Sinner, Moritz F. Bachmann, Troels N. Haunso, Stig Nordestgaard, Borge G. Ellinor, Patrick T. Svendsen, Jesper H. Kofoed, Klaus F. Kober, Lars Holst, Anders G. TI P-wave duration and the risk of atrial fibrillation: Results from the Copenhagen ECG Study SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; P-wave; Electrocardiography; Death; Stroke ID REGISTRY; POPULATION; PREDICTION; MORTALITY; DIAGNOSIS; VALIDITY; ALCOHOL; FLUTTER; STROKE; MODEL AB BACKGROUND Results on the association between P-wave duration and the risk of atrial fibrillation (AF) are conflicting. OBJECTIVE The purpose of this study was to obtain a detailed description of the relationship between P-wave duration and the risk of AF. METHODS Using computerized analysis of electrocardiograms from a large primary care population, we evaluated the association between P-wave duration and the risk of AF. Secondary end-points were death from cardiovascular causes and putative ischemic stroke. Data on drug use, comorbidity, and outcomes were collected from administrative registries. RESULTS A total of 285,933 individuals were included. During median follow-up period of 6.7 years, 9550 developed AF, 9371 died of a cardiovascular cause, and 8980 had a stroke. Compared with the reference group (100-105 ms), individuals with very short (<= 89 ms; hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.41-1.81), intermediate (112-119 ms; HR 1.22, 950/0 CI 1.13-1.31), Long (120-129 ms; HR 1.50, 95% CI 1.39-1.62), and very long P-wave duration (>= 130 ms; HR 2.06, 95% CI 1.89-2.23) had an increased risk of incident AF. With respect to death from cardiovascular causes, we found an increased risk for very short (<= 89 ms; HR 1.20, 95% CI 1.06-1.34), Long (120-129 ms; HR 1.11, 95% CI 1.04-1.19), and very long P-wave duration (>= 130 ms; HR 1.30, 95% CI 1.21-1.40) compared with the reference group (106-111 ms). Similar but weaker associations were found between P-wave duration and the risk of putative ischemic stroke. CONCLUSION In a large primary care population we found both short and Long P-wave duration to be robustly associated with an increased risk of AF. C1 [Nielsen, Jonas B.; Olesen, Morten S.; Bachmann, Troels N.; Haunso, Stig; Svendsen, Jesper H.; Holst, Anders G.] Danish Natl Res Fdn, Ctr Cardiac Arrhythmia DARC, Copenhagen, Denmark. [Nielsen, Jonas B.; Olesen, Morten S.; Bachmann, Troels N.; Haunso, Stig; Svendsen, Jesper H.; Holst, Anders G.] Univ Copenhagen, Rigshosp, Ctr Heart, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark. [Kuehl, Jorgen T.; Haunso, Stig; Svendsen, Jesper H.; Kofoed, Klaus F.; Kober, Lars] Univ Copenhagen, Fac Hlth Sci, Dept Clin Med, Copenhagen, Denmark. [Pietersen, Adrian; Lind, Bent] Copenhagen Gen Practitioners Lab, Copenhagen, Denmark. [Graff, Claus; Struijk, Johannes J.] Aalborg Univ, Dept Hlth Sci & Technol, Aalborg, Denmark. [Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Munich, Munich, Germany. [Nordestgaard, Borge G.] Univ Copenhagen, Herlev Hosp, Dept Clin Biochem, Copenhagen Univ Hosp,Fac Hlth & Med Sci, DK-2730 Herlev, Denmark. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Nielsen, JB (reprint author), Rigshosp, Dept Cardiol, Lab Mol Cardiol, 9312,Juliane Mariesvej 20, DK-2100 Copenhagen O, Denmark. EM jonas.bille.nielsen@gmail.com OI Struijk, Johannes/0000-0002-8713-1913; Svendsen, Jesper Hastrup/0000-0001-8466-8515 FU University of Copenhagen; Danish National Research Foundation; Danish Council for Independent Research [11-107456]; John and Birthe Meyer Foundation; Beckett Foundation; Copenhagen Medical Society (DMSK); Foundation of Copenhagen University Hospital, Rigshospitalet; A.P. Moller and Wife Chastine McKinney Moller's Foundation FX This study was supported by the University of Copenhagen; the Danish National Research Foundation; The Danish Council for Independent Research (Grant No 11-107456); The John and Birthe Meyer Foundation; The Foundation of 17-12-1981; The Beckett Foundation; the Copenhagen Medical Society (DMSK), Foundation of Copenhagen University Hospital, Rigshospitalet; and the A.P. Moller and Wife Chastine McKinney Moller's Foundation. Dr. Holst is an employee of Novo Nordisk A/S, Denmark. NR 27 TC 12 Z9 13 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD SEP PY 2015 VL 12 IS 9 BP 1887 EP 1895 DI 10.1016/j.hrthm.2015.04.026 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LK UT WOS:000360359000009 PM 25916567 ER PT J AU Simon, TG Chung, RT AF Simon, Tracey G. Chung, Raymond T. TI The new hepatitis C virus bottleneck: Can delaying therapy be justified? SO HEPATOLOGY LA English DT Editorial Material ID LIVER FIBROSIS PROGRESSION; UNITED-STATES; COST-EFFECTIVENESS; INFECTION; REGIMENS; DISEASE; IMPACT C1 [Simon, Tracey G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 16 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2015 VL 62 IS 3 BP 666 EP 667 DI 10.1002/hep.27931 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1RB UT WOS:000360375100001 PM 26058922 ER PT J AU Chung, RT Davis, GL Jensen, DM Masur, H Saag, MS Thomas, DL Aronsohn, AI Charlton, MR Feld, JJ Fontana, RJ Ghany, MG Godofsky, EW Graham, CS Kim, AY Kiser, JJ Kottilil, S Marks, KM Martin, P Mitruka, K Morgan, TR Naggie, S Raymond, D Reau, NS Schooley, RT Sherman, KE Sulkowski, MS Vargas, HE Ward, JW Wyles, DL AF Chung, Raymond T. Davis, Gary L. Jensen, Donald M. Masur, Henry Saag, Michael S. Thomas, David L. Aronsohn, Andrew I. Charlton, Michael R. Feld, Jordan J. Fontana, Robert J. Ghany, Marc G. Godofsky, Eliot W. Graham, Camilla S. Kim, Arthur Y. Kiser, Jennifer J. Kottilil, Shyam Marks, Kristen M. Martin, Paul Mitruka, Kiren Morgan, Timothy R. Naggie, Susanna Raymond, Daniel Reau, Nancy S. Schooley, Robert T. Sherman, Kenneth E. Sulkowski, Mark S. Vargas, Hugo E. Ward, John W. Wyles, David L. CA AASLD IDSA HCV Guidance Panel TI Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus SO HEPATOLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; SOFOSBUVIR PLUS RIBAVIRIN; GENOTYPE 1 INFECTION; TREATMENT-EXPERIENCED PATIENTS; ALL-CAUSE MORTALITY; LIVER FIBROSIS; ANTIVIRAL THERAPY; UNITED-STATES; NATURAL-HISTORY; TREATMENT-NAIVE C1 [Chung, Raymond T.] Massachusetts Gen Hosp, Hepatol, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. [Davis, Gary L.] Baylor Univ, Med Ctr, Hepatol, Dallas, TX USA. [Davis, Gary L.] Baylor Univ, Med Ctr, Liver Transplantat, Dallas, TX USA. [Jensen, Donald M.; Reau, Nancy S.] Univ Chicago, Med Ctr, Med, Chicago, IL 60637 USA. [Masur, Henry] NIH, Dept Crit Care Med, Med, Bethesda, MD 20892 USA. [Saag, Michael S.] Univ Alabama Birmingham, Sch Med, Med, Birmingham, AL USA. [Saag, Michael S.] Univ Alabama Birmingham, Sch Med, Global Hlth, Birmingham, AL USA. [Thomas, David L.; Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Med, Baltimore, MD USA. [Thomas, David L.] Johns Hopkins Univ, Sch Med, Infect Dis, Baltimore, MD USA. [Aronsohn, Andrew I.] Univ Chicago, Med Ctr, Med, Chicago, IL 60637 USA. [Charlton, Michael R.] Intermt Med Ctr, Hepatol, Murray, KY USA. [Charlton, Michael R.] Intermt Med Ctr, Liver Transplantat, Murray, KY USA. [Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Med, Toronto, ON M5T 2S8, Canada. [Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Med, Gastroenterol, Toronto, ON M5T 2S8, Canada. [Fontana, Robert J.] Univ Michigan, Sch Med, Med, Ann Arbor, MI USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Liver Transplantat, Ann Arbor, MI USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Godofsky, Eliot W.] Bach & Godofsky, Infect Dis, Bradenton, FL USA. [Graham, Camilla S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Med, Boston, MA 02215 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, ID Div, Viral Hepatitis Clin, Boston, MA 02114 USA. [Kiser, Jennifer J.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Pharmacol, Aurora, CO USA. [Kiser, Jennifer J.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Ctr Translat Pharmacokinet & Pharmacogen, Aurora, CO USA. [Kottilil, Shyam] Univ Maryland, Inst Human Virol, Med, Baltimore, MD 21201 USA. [Kottilil, Shyam] Univ Maryland, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA. [Marks, Kristen M.] Weill Cornell Med Coll, Med, New York, NY USA. [Martin, Paul] Univ Miami, Sch Med, Med, Miami, FL USA. [Martin, Paul] Univ Miami, Sch Med, Div Hepatol, Miami, FL USA. [Mitruka, Kiren; Ward, John W.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Morgan, Timothy R.] Vet Affairs Long Beach Healthcare Syst, Hepatol, Long Beach, CA USA. [Naggie, Susanna] Duke Univ, Sch Med, Durham, NC USA. [Naggie, Susanna] Duke Clin Res Inst, Infect Dis Res, Durham, NC USA. [Raymond, Daniel] Community Representat, Harm Reduct Coalit, New York, NY USA. [Schooley, Robert T.] Univ Calif San Diego, Med, La Jolla, CA 92093 USA. [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA. [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Med, Cincinnati, OH USA. [Sherman, Kenneth E.] Univ Cincinnati, Div Digest Dis, Coll Med, Cincinnati, OH USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Viral Hepatitis Ctr, Baltimore, MD USA. [Vargas, Hugo E.] Mayo Clin, Coll Med, Med, Phoenix, AZ USA. [Wyles, David L.] Univ Calif San Diego, Med, La Jolla, CA 92093 USA. RP Davis, GL (reprint author), 201 S Ocean Grande Dr,PH4, Ponte Vedra Beach, FL 32082 USA. EM rtchung@partners.org; davisgl@sbcglobal.net NR 127 TC 169 Z9 171 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2015 VL 62 IS 3 BP 932 EP 954 DI 10.1002/hep.27950 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1RB UT WOS:000360375100028 ER PT J AU Verrier, ER Wieland, S Baumert, TF AF Verrier, Eloi R. Wieland, Stefan Baumert, Thomas F. TI Retinoic acid-inducible gene 1 and sensing of hepatitis B virus revisited SO HEPATOLOGY LA English DT Editorial Material C1 [Verrier, Eloi R.; Baumert, Thomas F.] INSERM, Inst Rech Malad Virales & Hepat, U1110, Strasbourg, France. [Verrier, Eloi R.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Wieland, Stefan] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Baumert, Thomas F.] Inst Hosp Univ, Nouvel Hop Civil, Pole Hepatodigestif, Strasbourg, France. [Baumert, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. RP Verrier, ER (reprint author), INSERM, Inst Rech Malad Virales & Hepat, U1110, Strasbourg, France. NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2015 VL 62 IS 3 BP 970 EP 972 DI 10.1002/hep.27935 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1RB UT WOS:000360375100032 PM 26096066 ER PT J AU Liu, SY Erkkinen, MG Healey, ML Xu, YS Swett, KE Chow, HM Braun, AR AF Liu, Siyuan Erkkinen, Michael G. Healey, Meghan L. Xu, Yisheng Swett, Katherine E. Chow, Ho Ming Braun, Allen R. TI Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process SO HUMAN BRAIN MAPPING LA English DT Article DE creativity; poetry composition; fMRI; neurocognitive model; cognitive disinhibition ID PREFRONTAL CORTEX; FUNCTIONAL-ORGANIZATION; COGNITIVE NEUROSCIENCE; DECISION-MAKING; DEFAULT NETWORK; BASAL GANGLIA; FMRI; IMPROVISATION; GENERATION; INSIGHT AB Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase-dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re-engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain. Hum Brain Mapp 36:3351-3372, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Liu, Siyuan; Xu, Yisheng; Chow, Ho Ming; Braun, Allen R.] NIDCD, Language Sect, NIH, Bethesda, MD 20892 USA. [Erkkinen, Michael G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Healey, Meghan L.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA. [Swett, Katherine E.] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Chow, Ho Ming] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Braun, AR (reprint author), NIH, 10 Ctr Dr,Bldg 10,5D-37, Bethesda, MD 20892 USA. EM brauna@nidcd.nih.gov FU NIH intramural research funds [DC-000031-19] FX Contract grant sponsor: NIH intramural research funds; Contract grant number: DC-000031-19 (to A. R. B.) NR 71 TC 8 Z9 9 U1 7 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2015 VL 36 IS 9 BP 3351 EP 3372 DI 10.1002/hbm.22849 PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP9IY UT WOS:000360209000005 PM 26015271 ER PT J AU Kucyi, A Hove, MJ Biederman, J Van Dijk, KRA Valera, EM AF Kucyi, Aaron Hove, Michael J. Biederman, Joseph Van Dijk, Koene R. A. Valera, Eve M. TI Disrupted functional connectivity of cerebellar default network areas in attention-deficit/hyperactivity disorder SO HUMAN BRAIN MAPPING LA English DT Article DE cerebellum; attention-deficit; hyperactivity disorder; default mode network; functional connectivity; inattention; resting state ID DEFICIT-HYPERACTIVITY DISORDER; RESTING STATE FMRI; GLOBAL SIGNAL REGRESSION; MODE NETWORK; CEREBRAL-CORTEX; WORKING-MEMORY; BRAIN NETWORKS; SPONTANEOUS COGNITION; ANTERIOR CINGULATE; MOTION CORRECTION AB Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. Hum Brain Mapp 36:3373-3386, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Kucyi, Aaron; Hove, Michael J.; Biederman, Joseph; Valera, Eve M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kucyi, Aaron; Hove, Michael J.; Biederman, Joseph; Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Van Dijk, Koene R. A.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Valera, EM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 Thirteenth St,Room 2660, Charlestown, MA 02129 USA. EM eve_valera@hms.harvard.edu RI Van Dijk, Koene/G-3317-2012 OI Van Dijk, Koene/0000-0001-6137-4282 FU National Institute of Health [R01 HD067744-01A1, T32 MH16259, NCRR P41RR14075, P41 EB015896]; Pediatric Psychopharmacology Council Fund FX Contract grant sponsor: National Institute of Health; Contract grant number: R01 HD067744-01A1 (E.M.V.), T32 MH16259 (M.J.H.), and NCRR P41RR14075 and P41 EB015896 (Athinoula A. Martinos Center for Biomedical Imaging); Contract grant sponsor: Pediatric Psychopharmacology Council Fund (J.B.). NR 91 TC 10 Z9 10 U1 3 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2015 VL 36 IS 9 BP 3373 EP 3386 DI 10.1002/hbm.22850 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP9IY UT WOS:000360209000006 PM 26109476 ER PT J AU Iscan, Z Jin, TB Kendrick, A Szeglin, B Lu, H Trivedi, M Fava, M McGrath, PJ Weissman, M Kurian, BT Adams, P Weyandt, S Toups, M Carmody, T McInnis, M Cusin, C Cooper, C Oquendo, MA Parsey, RV DeLorenzo, C AF Iscan, Zafer Jin, Tony B. Kendrick, Alexandria Szeglin, Bryan Lu, Hanzhang Trivedi, Madhukar Fava, Maurizio McGrath, Patrick J. Weissman, Myrna Kurian, Benji T. Adams, Phillip Weyandt, Sarah Toups, Marisa Carmody, Thomas McInnis, Melvin Cusin, Cristina Cooper, Crystal Oquendo, Maria A. Parsey, Ramin V. DeLorenzo, Christine TI Test-retest reliability of freesurfer measurements within and between sites: Effects of visual approval process SO HUMAN BRAIN MAPPING LA English DT Article DE multisite MRI; cerebral cortical thickness; cerebral cortical volume; cerebral cortical surface area; test-retest reliability; FreeSurfer ID CORTICAL THICKNESS MEASUREMENTS; STATISTICAL POWER ANALYSIS; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; IMAGE REGISTRATION; MAJOR DEPRESSION; MR ARTIFACTS; HUMAN BRAIN; DISEASE AB In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of intermediate processing. In this work, structural MRIs of 40 healthy controls who were scanned twice were used to determine the test-retest reliability of FreeSurfer-derived cortical measures in four groups of subjectsthose 25 that passed visual inspection (approved), those 15 that failed visual inspection (disapproved), a combined group, and a subset of 10 subjects (Travel) whose test and retest scans occurred at different sites. Test-retest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and Desikan-Killiany (DK) atlases. In the approved subjects, reliability of cortical thickness/surface area/volume (DK atlas only) were: TRC (0.82/0.88/0.88), ICC (0.81/0.87/0.88), PD (0.86/1.19/1.39), which represent a significant improvement over these measures when disapproved subjects are included. Travel subjects' results show that cortical thickness reliability is more sensitive to site differences than the cortical surface area and volume. To determine the effect of visual inspection on sample size required for studies of MRI-derived cortical thickness, the number of subjects required to show group differences was calculated. Significant differences observed across imaging sites, between visually approved/disapproved subjects, and across regions with different sizes suggest that these measures should be used with caution. Hum Brain Mapp 36:3472-3485, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Iscan, Zafer] Natl Res Univ Higher Sch Econ, Ctr Cognit & Decis Making, Moscow, Russia. [Jin, Tony B.; Kendrick, Alexandria; Szeglin, Bryan; Parsey, Ramin V.; DeLorenzo, Christine] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Lu, Hanzhang; Trivedi, Madhukar; Kurian, Benji T.; Weyandt, Sarah; Toups, Marisa; Carmody, Thomas; Cooper, Crystal] UT Southwestern, Dept Psychiat, Med Ctr, Dallas, TX USA. [Fava, Maurizio; Cusin, Cristina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McGrath, Patrick J.; Adams, Phillip; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Weissman, Myrna; DeLorenzo, Christine] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. [McInnis, Melvin] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Iscan, Z (reprint author), Natl Res Univ Higher Sch Econ, Ctr Cognit & Decis Making, Moscow, Russia. EM ziscan@hse.ru RI Parsey, Ramin/J-8254-2014; Szeglin, Bryan/G-1494-2015; OI Szeglin, Bryan/0000-0002-7866-7548; Jin, Tony/0000-0003-0504-5817; Iscan, Zafer/0000-0001-9832-6591 FU National Institute of Mental Health (NIMH) [U01 MH092250, K01MH091354] FX Contract grant sponsor: National Institute of Mental Health (NIMH); Contract grant number: U01 MH092250 and K01MH091354 NR 50 TC 5 Z9 5 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2015 VL 36 IS 9 BP 3472 EP 3485 DI 10.1002/hbm.22856 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP9IY UT WOS:000360209000012 PM 26033168 ER PT J AU Hsu, YC Lo, YC Chen, YJ Wedeen, VJ Tseng, WYI AF Hsu, Yung-Chin Lo, Yu-Chun Chen, Yu-Jen Wedeen, Van Jay Tseng, Wen-Yih Isaac TI NTU-DSI-122: A diffusion spectrum imaging template with high anatomical matching to the ICBM-152 space SO HUMAN BRAIN MAPPING LA English DT Article DE diffusion template; diffusion spectrum imaging; white matter ID HUMAN BRAIN; TENSOR MRI; INDUCED DISTORTION; SPIN-ECHO; REGISTRATION; NORMALIZATION; IMAGES AB A diffusion-weighted (DW) template in a standard coordinate system is often necessary for the analysis of white matter (WM) structures using DW images. Although several DW templates have been constructed in the ICBM-152 space, a template for diffusion spectrum imaging (DSI) is still lacking. In this study, we developed a DSI template in the ICBM-152 space from 122 healthy adults. This high quality template, NTU-DSI-122, was built through incorporating the macroscopic anatomical information using high-resolution T-1-weighted images and the microscopic structural information obtained from DSI datasets. Two evaluations were conducted to examine the quality of NTU-DSI-122. The first evaluation examined the anatomical consistency of NTU-DSI-122 in matching to the ICBM-152 coordinate system. The results showed that this template matched to the ICBM-152 templates very well across the whole brain, not only in the deep white matter regions as other DW templates but also in the superficial white matter regions. In the second evaluation, a large number of independent diffusion tensor imaging (DTI) datasets were registered to the DTI template derived from NTU-DSI-122. The examination was performed by quantifying the anatomical consistency among the registered DTI datasets. The results showed that using NTU-DSI-122 as the registration template the registered DTI datasets can achieve high anatomical alignment. Both evaluations demonstrate that NTU-DSI-122 is a useful high quality DW template. Therefore, NTU-DSI-122 can serve as a representative DSI dataset for a healthy adult population, and will be of potential value for brain research and clinical applications. The NTU-DSI-122 template is available at //www.nitrc.org/projects/ntu-dsi-122/. Hum Brain Mapp 36:3528-3541, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Hsu, Yung-Chin; Lo, Yu-Chun; Chen, Yu-Jen; Tseng, Wen-Yih Isaac] Natl Taiwan Univ, Grad Inst Med Devices & Imaging Syst, Coll Med, Taipei 10051, Taiwan. [Wedeen, Van Jay] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Wedeen, Van Jay] MGH, Massachusetts Inst Technol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tseng, Wen-Yih Isaac] Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei, Taiwan. [Tseng, Wen-Yih Isaac] Natl Taiwan Univ, Grad Inst Brain & Mind Sci, Coll Med, Taipei 10051, Taiwan. [Tseng, Wen-Yih Isaac] Natl Taiwan Univ, Mol Imaging Ctr, Taipei 10764, Taiwan. RP Tseng, WYI (reprint author), Natl Taiwan Univ, Grad Inst Med Devices & Imaging Syst, Coll Med, 1,Sec 1,Jen Ai Rd, Taipei 10051, Taiwan. EM wytseng@ntu.edu.tw OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU Ministry of Science and Technology, Taiwan [MOST 104-2325-B-002-013, NSC101-2321-B-002-079]; National Health Research Institute, Taiwan [NHRI-EX101-10145NI]; Ministry of Economic Affairs, Taiwan [100-EC-17-A-19-S1-175]; National Institute of Mental Health, USA [1U01MH093765-01] FX Contract grant sponsor: Ministry of Science and Technology, Taiwan (MOST 104-2325-B-002-013, NSC101-2321-B-002-079); Contract grant sponsor: National Health Research Institute, Taiwan; Contract grant number: NHRI-EX101-10145NI; Contract grant sponsor: Ministry of Economic Affairs, Taiwan; Contract grant number: 100-EC-17-A-19-S1-175; Contract grant sponsor: National Institute of Mental Health, USA; Contract grant number: 1U01MH093765-01. NR 34 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2015 VL 36 IS 9 BP 3528 EP 3541 DI 10.1002/hbm.22860 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP9IY UT WOS:000360209000016 PM 26095830 ER PT J AU Muriel, A Penuelas, O Frutos-Vivar, F Arroliga, AC Abraira, V Thille, AW Brochard, L Nin, N Davies, AR Amin, P Du, B Raymondos, K Rios, F Violi, DA Maggiore, SM Soares, MA Gonzalez, M Abroug, F Bulow, HH Hurtado, J Kuiper, MA Moreno, RP Zeggwagh, AA Villagomez, AJ Jibaja, M Soto, L D'Empaire, G Matamis, D Koh, Y Anzueto, A Ferguson, ND Esteban, A AF Muriel, Alfonso Penuelas, Oscar Frutos-Vivar, Fernando Arroliga, Alejandro C. Abraira, Victor Thille, Arnaud W. Brochard, Laurent Nin, Nicolas Davies, Andrew R. Amin, Pravin Du, Bin Raymondos, Konstantinos Rios, Fernando Violi, Damian A. Maggiore, Salvatore M. Soares, Marco Antonio Gonzalez, Marco Abroug, Fekri Buelow, Hans-Henrik Hurtado, Javier Kuiper, Michael A. Moreno, Rui P. Zeggwagh, Amine Ali Villagomez, Asisclo J. Jibaja, Manuel Soto, Luis D'Empaire, Gabriel Matamis, Dimitrios Koh, Younsuck Anzueto, Antonio Ferguson, Niall D. Esteban, Andres TI Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis SO INTENSIVE CARE MEDICINE LA English DT Article DE Noninvasive positive pressure ventilation; Acute respiratory failure Sedation; Analgesia; Mortality ID ACUTE RESPIRATORY-FAILURE; MECHANICAL VENTILATION; SUPPORT VENTILATION; RISK-FACTORS; DEXMEDETOMIDINE; MIDAZOLAM; EFFICACY AB There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV. We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation). 842 patients were included in the analysis. Of these, 165 patients (19.6 %) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95 % confidence interval 0.6-5.4) or sedatives (odds ratio 2.8, 95 % CI 0.85-9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95 % CI 1.8-18.4). Slightly less than 20 % of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV. C1 [Muriel, Alfonso; Abraira, Victor] Hosp Ramon & Cajal, Unidad Bioestadist Clin, Inst Ramon & Cajal Invest Sanitarias, E-28034 Madrid, Spain. [Muriel, Alfonso; Abraira, Victor] Ctr Invest Red Epidemiol & Salud Publ CIBERESP, Madrid, Spain. [Penuelas, Oscar] Hosp Infanta Cristina, Ctr Invest Biomed Red Enfermedades Resp CIBERES, Parla, Spain. [Frutos-Vivar, Fernando; Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Getafe 28905, Spain. [Frutos-Vivar, Fernando; Esteban, Andres] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Getafe 28905, Spain. [Arroliga, Alejandro C.] Scott & White Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [Thille, Arnaud W.] Univ Hosp Poitiers, Poitiers, France. [Brochard, Laurent] St Michaels Hosp, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Brochard, Laurent] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Nin, Nicolas] Hosp Espanol Montevideo, Montevideo, Uruguay. [Nin, Nicolas] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Montevideo, Uruguay. [Davies, Andrew R.] Monash Univ, Melbourne, Vic 3004, Australia. [Amin, Pravin] Bombay Hosp Inst Med Sci, Bombay, Maharashtra, India. [Du, Bin] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Raymondos, Konstantinos] Hannover Med Sch, Hannover, NH, Germany. [Rios, Fernando] Hosp Nacl Alejandro Posadas, Buenos Aires, DF, Argentina. [Violi, Damian A.] Hosp HIGA Guemes, Haedo, Argentina. [Maggiore, Salvatore M.] Univ Cattolica Sacro Cuore, Policlin Agostino Gemelli, Rome, Italy. [Soares, Marco Antonio] Hosp Univ Sao Jose, Belo Horizonte, MG, Brazil. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Abroug, Fekri] Hosp Fattouma Bourguina, Monastir, Tunisia. [Buelow, Hans-Henrik] Reg Zealand Univ Copenhagen, Holbaek Hosp, Copenhagen, Denmark. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Kuiper, Michael A.] Med Ctr Leeuwarden, Leeuwarden, Netherlands. [Moreno, Rui P.] Hosp Sao Jose, Ctr Hosp Lisboa Cent, Lisbon, Portugal. [Zeggwagh, Amine Ali] Hop Ibn Sina, Rabat, Morocco. [Villagomez, Asisclo J.] Hosp Reg Octubre, Inst Seguridad & Serv Social Trabajadores Estado, Mexico City, DF, Mexico. [Jibaja, Manuel] Hosp Eugenio Espejo, Quito, Ecuador. [Soto, Luis] Inst Nacl Torax Santiago, Santiago, Chile. [D'Empaire, Gabriel] Hosp Clin Caracas, Caracas, Venezuela. [Matamis, Dimitrios] Papageorgiou Hosp, Thessaloniki, Greece. [Koh, Younsuck] Univ Ulsan, Asan Med Ctr, Seoul, South Korea. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. RP Frutos-Vivar, F (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo, Km 12-5, Getafe 28905, Spain. EM ffrutos@ucigetafe.com RI Soares, Marcio/B-3083-2013; OI Soares, Marcio/0000-0003-2503-6088; MAGGIORE, Salvatore Maurizio/0000-0002-1828-9143; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264; Muriel, Alfonso /0000-0002-4805-4011 NR 22 TC 7 Z9 7 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2015 VL 41 IS 9 BP 1586 EP 1600 DI 10.1007/s00134-015-3854-6 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA CQ0VD UT WOS:000360314900007 PM 25971392 ER PT J AU Sharma, A Shi, QH Hoover, DR Anastos, K Tien, PC Young, MA Cohen, MH Golub, ET Gustafson, D Yin, MT AF Sharma, Anjali Shi, Qiuhu Hoover, Donald R. Anastos, Kathryn Tien, Phyllis C. Young, Mary A. Cohen, Mardge H. Golub, Elizabeth T. Gustafson, Deborah Yin, Michael T. TI Increased Fracture Incidence in Middle-Aged HIV-Infected and HIV-Uninfected Women: Updated Results From the Women's Interagency HIV Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article ID BONE-MINERAL DENSITY; POPULATION-BASED COHORT; ANTIRETROVIRAL THERAPY; RISK-FACTORS; OSTEOPOROSIS; PREVALENCE; INITIATION; MEN AB Background: We previously reported that fracture incidence rates did not differ by HIV status among predominantly premenopausal Women's Interagency HIV Study participants. We now conduct a follow-up study with 5 additional observation years to further characterize fracture risk associated with HIV infection in women as they age. Methods: We measured time to first new fracture at any site in 2375 (1713 HIV-infected and 662 HIV-uninfected) Women's Interagency HIV Study participants, with median 10-year follow-up. Fractures were self-reported semiannually. Proportional hazards models assessed predictors of incident fracture. Results: At index visit, HIV-infected women were older [median age of 40 years (IQR: 34-46) vs. 35 (27-43), P < 0.0001] and more likely to be postmenopausal, hepatitis C virus infected, and weigh less than HIV-uninfected women. Among HIV-infected women, mean CD4(+) count was 480 cells per microliter and 63% were taking highly active antiretroviral therapy. Unadjusted incidence rates of any fracture were higher in HIV-infected than in HIV-uninfected women [2.19/100 person-years (py) vs. 1.54/100 py, P = 0.002]. In multivariate models, HIV status, older age, white (vs. black) race, prior fracture, history of cocaine use, and history of injection drug use were significant predictors of incident fracture. Among HIV-infected women, age, white race, prior fracture, smoking, and prior AIDS were predictors of new fracture. Conclusions: Middle-aged HIV-infected women had a higher adjusted fracture rate than HIV-uninfected women. Cocaine use and injection drug use were also associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture associated with cocaine use relates to increased rate of falls or direct effects on bone metabolism. C1 [Sharma, Anjali; Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Shi, Qiuhu] New York Med Coll, Dept Epidemiol & Community Hlth, Valhalla, NY 10595 USA. [Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Tien, Phyllis C.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Young, Mary A.] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gustafson, Deborah] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Yin, Michael T.] Columbia Univ, Med Ctr, Div Infect Dis, New York, NY USA. RP Sharma, A (reprint author), Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave,Block Bldg 305, Bronx, NY 10461 USA. EM anjali.sharma@einstein.yu.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Institute of Dental and Craniofacial Research (NIDCR); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Deafness and other Communication Disorders (NIDCD); NIH Office of Research on Women's Health; National Institutes of Health [AI095089, K23AR06199301] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (K.A.); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Chicago Consortium (M.H.C.); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is provided by the National Center for Research Resources (UCSF-CTSI Grant No. UL1 RR024131). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). This research was also supported by National Institutes of Health AI095089 (M.T.Y.) and K23AR06199301 (A.S.). NR 31 TC 14 Z9 14 U1 0 U2 2 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 SEP 1 PY 2015 VL 70 IS 1 BP 54 EP 61 DI 10.1097/QAI.0000000000000674 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CQ1HM UT WOS:000360347900007 PM 26322667 ER PT J AU Gellad, WF Flynn, KE Alexander, GC AF Gellad, Walid F. Flynn, Kathryn E. Alexander, G. Caleb TI Evaluation of Flibanserin Science and Advocacy at the FDA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Gellad, Walid F.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Flynn, Kathryn E.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Flynn, Kathryn E.] Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA. [Alexander, G. Caleb] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Drug Safety & Effectiveness, Baltimore, MD USA. [Alexander, G. Caleb] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Alexander, G. Caleb] Johns Hopkins Med, Dept Med, Gen Internal Med Sect, Baltimore, MD USA. RP Gellad, WF (reprint author), Div Gen Internal Med, Univ Dr 151C, Pittsburgh, PA 15240 USA. EM walid.gellad@pitt.edu NR 6 TC 11 Z9 11 U1 0 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 1 PY 2015 VL 314 IS 9 BP 869 EP 870 DI 10.1001/jama.2015.8405 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CQ1WX UT WOS:000360392100008 PM 26148201 ER PT J AU Biffi, A Anderson, CD Battey, TWK Ayres, AM Greenberg, SM Viswanathan, A Rosand, J AF Biffi, Alessandro Anderson, Christopher D. Battey, Thomas W. K. Ayres, Alison M. Greenberg, Steven M. Viswanathan, Anand Rosand, Jonathan TI Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; PROGRESS TRIAL; STROKE; METAANALYSIS; PREVENTION; GUIDELINES; DISEASE AB IMPORTANCE Intracerebral hemorrhage (ICH) is the most severe form of stroke. Survivors are at high risk of recurrence, death, and worsening functional disability. OBJECTIVE To investigate the association between blood pressure (BP) after index ICH and risk of recurrent ICH. DESIGN, SETTING, AND PARTICIPANTS Single-site, tertiary care referral center observational study of 1145 of 2197 consecutive patients with ICH presenting from July 1994 to December 2013. A total of 1145 patients with ICH survived at least 90 days and were followed up through December 2013 (median follow-up of 36.8 months [minimum, 9.8 months]). EXPOSURES Blood pressure measurements at 3, 6, 9, and 12 months, and every 6 months thereafter, obtained from medical personnel (inpatient hospital or outpatient clinic medical or nursing staff) or via patient self-report. Exposure was characterized in 3 ways: (1) recorded systolic and diastolic measurements; (2) classification as adequate or inadequate BP control based on American Heart Association/American Stroke Association recommendations; and (3) stage of hypertension based on Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 criteria. MAIN OUTCOMES AND MEASURES Recurrent ICH and its location within the brain (lobar vs nonlobar). RESULTS There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up adequate BP control was achieved on at least 1 measurement by 625 patients (54.6% of total [range, 49.2%-58.7%]) and consistently (ie, at all available time points) by 495 patients (43.2% of total [range, 34.5%-51.0%]). The event rate for lobar ICH was 84 per 1000 person-years among patients with inadequate BP control compared with 49 per 1000 person-years among patients with adequate BP control. For nonlobar ICH the event rate was 52 per 1000 person-years with inadequate BP control compared with 27 per 1000 person-years for patients with adequate BP control. In analyses modeling BP control as a time-varying variable, inadequate BP control was associated with higher risk of recurrence of both lobar ICH (hazard ratio [HR], 3.53 [95% CI, 1.65-7.54]) and nonlobar ICH (HR, 4.23 [95% CI, 1.02-17.52]). Systolic BP during follow-up was associated with increased risk of both lobar ICH recurrence (HR, 1.33 per 10-mm Hg increase [95% CI, 1.02-1.76]) and nonlobar ICH recurrence (HR, 1.54 [95% CI, 1.03-2.30]). Diastolic BP was associated with increased risk of nonlobar ICH recurrence (HR, 1.21 per 10-mm Hg increase [95% CI, 1.01-1.47]) but not with lobar ICH recurrence (HR, 1.36 [95% CI, 0.90-2.10]). CONCLUSIONS AND RELEVANCE In this observational single-center cohort study of ICH survivors, reported BP measurements suggesting inadequate BP control during follow-up were associated with higher risk of both lobar and nonlobar ICH recurrence. These data suggest that randomized clinical trials are needed to address the benefits and risks of stricter BP control in ICH survivors. C1 [Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Ayres, Alison M.; Greenberg, Steven M.; Viswanathan, Anand; Rosand, Jonathan] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Greenberg, Steven M.; Viswanathan, Anand; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org OI Anderson, Christopher/0000-0002-0053-2002 FU National Institute of Neurological Disorders and Stroke [R01 NS063925, R01 NS059727, P50 NS051343, K23 NS086873, AG26484] FX The authors' work on this study was supported by funding from the National Institute of Neurological Disorders and Stroke (R01 NS063925, R01 NS059727, P50 NS051343, K23 NS086873, and AG26484). NR 20 TC 19 Z9 19 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 1 PY 2015 VL 314 IS 9 BP 904 EP 912 DI 10.1001/jama.2015.10082 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CQ1WX UT WOS:000360392100017 PM 26325559 ER PT J AU Calleo, JS Amspoker, AB Sarwar, AI Kunik, ME Jankovic, J Marsh, L York, M Stanley, MA AF Calleo, Jessica S. Amspoker, Amber B. Sarwar, Aliya I. Kunik, Mark E. Jankovic, Joseph Marsh, Laura York, Michele Stanley, Melinda A. TI A Pilot Study of a Cognitive-Behavioral Treatment for Anxiety and Depression in Patients With Parkinson Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE anxiety; depression; cognitive-behavioral therapy; Parkinson disease ID STRUCTURED INTERVIEW GUIDE; QUALITY-OF-LIFE; CONTROLLED-TRIAL; OLDER-ADULTS; RANDOMIZED-TRIAL; RATING-SCALE; PRIMARY-CARE; THERAPY; DISORDER; PREVALENCE AB Anxiety and depression often remain unrecognized or inadequately treated in patients with Parkinson disease (PD). Cognitive-behavioral therapy (CBT) is effective, but limited evidence supports its use for anxiety and depression in patients with PD. Sixteen patients with PD having significant anxiety and/or depressive symptoms were assigned to CBT or enhanced usual care. Assessments occurred at baseline, posttreatment, and 1-month follow-up. The CBT intervention included tools for anxiety, depression, and healthy living with PD symptoms. Individual sessions were delivered by telephone or in person, based on patient preference. Treatment was feasible with participants choosing 67% of sessions by telephone and 80% completed treatment. The between-group effect sizes for change scores from baseline to posttreatment and baseline to 1-month follow-up were large (posttreatment: d = 1.49 for depression and 1.44 for anxiety; 1-month follow-up: d = .73 for depression and 1.24 for anxiety), although only the posttreatment effect size for depression was significant. This pilot CBT program is feasible for treatment of anxiety and depression in patients with PD. C1 [Calleo, Jessica S.; Amspoker, Amber B.; Kunik, Mark E.; Stanley, Melinda A.] Ctr Innovat Qual Effectiveness & Safety, Houston VA Hlth Serv Res & Dev HSR&D, Houston, TX USA. [Calleo, Jessica S.; Sarwar, Aliya I.; Kunik, Mark E.; Marsh, Laura; York, Michele; Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr 152, Houston, TX 77030 USA. [Calleo, Jessica S.; Amspoker, Amber B.; Sarwar, Aliya I.; Kunik, Mark E.; Jankovic, Joseph; Marsh, Laura; York, Michele; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA. [Kunik, Mark E.; Stanley, Melinda A.] VA South Cent Mental Illness Res Educ & Clin Ctr, North Little Rock, AR USA. RP Calleo, JS (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM jcalleo@bcm.edu FU Parkinson Study Group; Parkinson's Disease Foundation's Advancing Parkinson Treatments Innovations Grant; Veteran Affairs South Central Mental Illness Research Education and Clinical Center; Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN-13-413] 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 the Parkinson Study Group and the Parkinson's Disease Foundation's Advancing Parkinson Treatments Innovations Grant; a grant from the Veteran Affairs South Central Mental Illness Research Education and Clinical Center; and the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN-13-413). The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, US Government or Baylor College of Medicine. NR 30 TC 2 Z9 2 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2015 VL 28 IS 3 BP 210 EP 217 DI 10.1177/0891988715588831 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CQ0JA UT WOS:000360280100007 PM 26047635 ER PT J AU Karjalainen, MK Ojaniemi, M Haapalainen, AM Mahlman, M Salminen, A Huusko, JM Maatta, TA Kaukola, T Anttonen, J Ulvila, J Haataja, R Teramo, K Kingsmore, SF Palotie, A Muglia, LJ Ramet, M Hallman, M AF Karjalainen, Minna K. Ojaniemi, Marja Haapalainen, Antti M. Mahlman, Mari Salminen, Annamari Huusko, Johanna M. Maatta, Tomi A. Kaukola, Tuula Anttonen, Julia Ulvila, Johanna Haataja, Ritva Teramo, Kari Kingsmore, Stephen F. Palotie, Aarno Muglia, Louis J. Ramet, Mika Hallman, Mikko TI CXCR3 Polymorphism and Expression Associate with Spontaneous Preterm Birth SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MATERNAL-FETAL INTERFACE; DIFFERENTIAL EXPRESSION; GESTATIONAL-AGE; ALLOGRAFT-REJECTION; FAMILIAL PATTERNS; GENE-EXPRESSION; UP-REGULATION; LABOR; TERM; RECEPTOR AB Spontaneous preterm birth (SPTB) is a major factor associating with deaths and with lowered quality of life in humans. Environmental and genetic factors influence the susceptibility. Previously, by analyzing families with recurrent SPTB in linkage analysis, we identified a linkage peak close to the gene encoding CXCR3. Present objectives were to investigate the association of CXCR3 with SPTB in Finnish mothers (n = 443) and infants (n = 747), to analyze CXCR3 expression levels in human placenta and levels of its ligands in umbilical cord blood, and to verify the influence of Cxcr3 on SPTB-associating cytokines in mice. We detected an association between an intronic CXCR3 polymorphism, rs2280964, and SPTB in infants from families with recurrent preterm births (p = 0.009 versus term controls, odds ratio 0.52, 95% confidence interval 0.32-0.86). The minor allele was protective and undertransmitted to SPTB infants (p = 0.007). In the placenta and fetal membranes, the rs2280964 major allele homozygotes had higher expression levels than minor allele homozygotes; decidual trophoblasts showed strong CXCR3 immunoreactivity. Expression was higher in SPTB placentas compared with those from elective deliveries. Concentration of a CXCR3 ligand, CXCL9, was increased in cord blood from SPTB, and the protective rs2280964 allele was associated with low CXCL9. In CXCR3-deficient mice (Mus musculus), SPTB-associating cytokines were not acutely increased in amniotic fluid after preterm birth-inducing dose of maternal LPS. Our results indicate that CXCR3 contributes to SPTB. Activation of CXCR3 signaling may disturb the maternal-fetal tolerance, and this may promote labor. C1 Univ Oulu, PEDEGO Res Ctr, Oulu 90014, Finland. [Karjalainen, Minna K.; Ojaniemi, Marja; Haapalainen, Antti M.; Mahlman, Mari; Salminen, Annamari; Huusko, Johanna M.; Maatta, Tomi A.; Kaukola, Tuula; Anttonen, Julia; Ulvila, Johanna; Ramet, Mika; Hallman, Mikko] Univ Oulu, Med Res Ctr Oulu, Oulu 90014, Finland. [Karjalainen, Minna K.; Ojaniemi, Marja; Haapalainen, Antti M.; Mahlman, Mari; Salminen, Annamari; Huusko, Johanna M.; Maatta, Tomi A.; Kaukola, Tuula; Anttonen, Julia; Ulvila, Johanna; Ramet, Mika; Hallman, Mikko] Oulu Univ Hosp, Dept Children & Adolescents, Oulu 90029, Finland. [Haataja, Ritva] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland. [Teramo, Kari] Univ Helsinki, Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Teramo, Kari] Helsinki Univ Hosp, Helsinki 00290, Finland. [Kingsmore, Stephen F.] Ctr Pediat Genom Med, Kansas City, MO 64108 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Palotie, Aarno] Broad Inst & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Muglia, Louis J.] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Ctr Prevent Preterm Birth, Cincinnati, OH 45229 USA. [Ramet, Mika] Tampere Univ, BioMediTech, Tampere 33014, Finland. [Ramet, Mika] Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland. RP Karjalainen, MK (reprint author), Univ Oulu, Inst Clin Med, Dept Children & Adolescents, SF-90220 Oulu, Finland. EM minna.k.karjalainen@oulu.fi OI Hallman, Mikko/0000-0002-8172-729X FU Jane and Aatos Erkko Foundation; Sigrid Juselius Foundation; Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital; Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital; Stiftelsen Alma och K.A. Snellman Foundation; March of Dimes Prematurity Research Center Ohio Collaborative; Nordic Centre of Excellence in Disease Genetics FX This work was supported by the Jane and Aatos Erkko Foundation (to M.H. and M.R.); the Sigrid Juselius Foundation (to M.H.); the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (to M.R.); the Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital (to M.R.); the Stiftelsen Alma och K.A. Snellman Foundation (to M.K.K. and M.R.); and the March of Dimes Prematurity Research Center Ohio Collaborative (to L.J.M.). Studies with the anonymous Finnish population controls were supported by the Nordic Centre of Excellence in Disease Genetics. NR 78 TC 1 Z9 1 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2015 VL 195 IS 5 BP 2187 EP 2198 DI 10.4049/jimmunol.1501174 PG 12 WC Immunology SC Immunology GA CP6QY UT WOS:000360014200031 PM 26209629 ER PT J AU Thiele, M Kerschbaumer, RJ Tam, FWK Volkel, D Douillard, P Schinagl, A Kuhnel, H Smith, J McDaid, JP Bhangal, G Yu, MC Pusey, CD Cook, HT Kovarik, J Magelky, E Bhan, A Rieger, M Mudde, GC Ehrlich, H Jilma, B Tilg, H Moschen, A Terhorst, C Scheiflinger, F AF Thiele, Michael Kerschbaumer, Randolf J. Tam, Frederick W. K. Voelkel, Dirk Douillard, Patrice Schinagl, Alexander Kuehnel, Harald Smith, Jennifer McDaid, John P. Bhangal, Gurjeet Yu, Mei-Ching Pusey, Charles D. Cook, H. Terence Kovarik, Josef Magelky, Erica Bhan, Atul Rieger, Manfred Mudde, Geert C. Ehrlich, Hartmut Jilma, Bernd Tilg, Herbert Moschen, Alexander Terhorst, Cox Scheiflinger, Friedrich TI Selective Targeting of a Disease-Related Conformational Isoform of Macrophage Migration Inhibitory Factor Ameliorates Inflammatory Conditions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR MIF; REGULATORY ROLE; FACTOR EXPRESSION; IL-10(-/-) MICE; BOWEL-DISEASE; SEVERE SEPSIS; IN-VIVO; CELL; GLOMERULONEPHRITIS; ACTIVATION AB Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy. C1 [Thiele, Michael; Kerschbaumer, Randolf J.; Voelkel, Dirk; Douillard, Patrice; Schinagl, Alexander; Kuehnel, Harald; Rieger, Manfred; Mudde, Geert C.; Ehrlich, Hartmut; Scheiflinger, Friedrich] Baxter Innovat GmbH, Baxter Biomed Res Ctr, A-2304 Orth, Austria. [Tam, Frederick W. K.; Smith, Jennifer; McDaid, John P.; Bhangal, Gurjeet; Yu, Mei-Ching; Pusey, Charles D.; Cook, H. Terence] Hammersmith Hosp, Imperial Coll Renal & Transplant Ctr, London W12 0NN, England. [Kovarik, Josef] Wilhelminenspital Stadt Wien, Dept Nephrol, A-1160 Vienna, Austria. [Magelky, Erica; Terhorst, Cox] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Immunol, Boston, MA 02215 USA. [Bhan, Atul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. [Jilma, Bernd] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria. [Tilg, Herbert; Moschen, Alexander] Med Univ Innsbruck, Dept Internal Med Endocrinol Gastroenterol & Meta, A-6020 Innsbruck, Austria. RP Kerschbaumer, RJ (reprint author), Baxter Innovat GmbH, Baxter Biomed Res Ctr, Uferstr 15, A-2304 Orth, Austria. EM randolf_kerschbaumer@baxter.com OI Moschen, Alexander/0000-0003-3598-7848 FU Baxter Healthcare FX This work was supported by Baxter Healthcare. NR 53 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2015 VL 195 IS 5 BP 2343 EP 2352 DI 10.4049/jimmunol.1500572 PG 10 WC Immunology SC Immunology GA CP6QY UT WOS:000360014200047 PM 26209628 ER PT J AU Lanktree, MB Elbers, CC Li, Y Zhang, GS Duan, Q Karczewski, KJ Guo, YR Tragante, V North, KE Cushman, M Asselbergs, FW Wilson, JG Lange, LA Drenos, F Reiner, AP Barnes, MR Keating, BJ AF Lanktree, Matthew B. Elbers, Clara C. Li, Yun Zhang, Guosheng Duan, Qing Karczewski, Konrad J. Guo, Yiran Tragante, Vinicius North, Kari E. Cushman, Mary Asselbergs, Folkert W. Wilson, James G. Lange, Leslie A. Drenos, Fotios Reiner, Alex P. Barnes, Michael R. Keating, Brendan J. TI Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration SO JOURNAL OF LIPID RESEARCH LA English DT Article DE high density lipoprotein; genetics; vascular biology; exocyst complex component 3-like 1 ID GENOME-WIDE ASSOCIATION; EXOCYST COMPLEX; CELLS; CHOLESTEROL; POPULATIONS; COMPONENTS AB Meta-analyses of European populations has successfully identified genetic variants in over 150 loci associated with lipid levels, but results from additional ethnicities remain limited. Previously, we reported two novel lipid loci identified in a sample of 7,657 African Americans using a gene-centric array including 50,000 SNPs in 2,100 candidate genes. Initial discovery and follow-up of signals with P < 10(-5) in additional African American samples confirmed CD36 and ICAM1. Using an additional 8,244 African American female samples from the Women's Health Initiative SNP Health Association Resource genome-wide association study dataset, we further examined the previous meta-analyses results by attempting to replicate 20 additional putative lipid signals with P < 10(-4). Replication confirmed rs868213, located in a splice donor region of exocyst complex component 3-like 1 (EXOC3L1) as a novel signal for HDL (additive allelic effect = 0.02; P = 1.4 x 10(-8); meta-analyses of discovery and replication). EXOC3L1 is strongly expressed in vascular endothelium and forms part of the exocyst complex, a key facilitator of the trafficking of lipid receptors. Increasing sample sizes for genetic studies in nonEuropean populations will continue to improve our understanding of lipid metabolism. C1 [Lanktree, Matthew B.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Elbers, Clara C.; Keating, Brendan J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Elbers, Clara C.] Univ Med Ctr Utrecht, Dept Med Genet DBG, Complex Genet Sect, Utrecht, Netherlands. [Tragante, Vinicius; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Tragante, Vinicius] Univ Med Ctr Utrecht, Dept Med Genet, Biomed Genet, Utrecht, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Li, Yun; Zhang, Guosheng; Duan, Qing] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Karczewski, Konrad J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Karczewski, Konrad J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Guo, Yiran] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Cushman, Mary] Univ Vermont, Dept Med, Colchester, VT USA. [Cushman, Mary] Univ Vermont, Dept Pathol, Colchester, VT USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Lange, Leslie A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Drenos, Fotios] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England. [Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Barnes, Michael R.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. [Keating, Brendan J.] Univ Penn, Dept Surg, Div Transplantat, Philadelphia, PA 19104 USA. RP Lanktree, MB (reprint author), McMaster Univ, Dept Med, Hamilton, ON, Canada. EM matthew.lanktree@medportal.ca; bkeating@mail.med.upenn.edu RI Guo, Yiran/H-4120-2011; OI Guo, Yiran/0000-0002-6549-8589; Karczewski, Konrad/0000-0003-2878-4671 FU Rubicon grant from The Netherlands Organization for Scientific Research (NWO); National Institutes of Health [R01HG006292, R01HG006703]; portfolio of translational research of the National Institutes for Health Research Biomedical Research Unit at Barts; London School of Medicine and Dentistry; National Heart, Lung, and Blood Institute FX C.C.E. was supported by a Rubicon grant from The Netherlands Organization for Scientific Research (NWO). Y.L., G.Z., and Q.D. were supported by National Institutes of Health Grants R01HG006292 and R01HG006703. M.R.B. was funded by the portfolio of translational research of the National Institutes for Health Research Biomedical Research Unit at Barts and The London School of Medicine and Dentistry. The WHI SNP Health Association Resource CWAS was funded by the National Heart, Lung, and Blood Institute. NR 25 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2015 VL 56 IS 9 BP 1781 EP 1786 DI 10.1194/jlr.P059477 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ1ZQ UT WOS:000360399500014 PM 26199122 ER PT J AU Fiorella, D Mocco, J Arthur, AS Lavine, S Albuquerque, FC Frei, D Turner, RD Turk, A Siddiqui, AH Mack, WJ Alexandrov, A Hirsch, JA Tarr, RW AF Fiorella, David Mocco, J. Arthur, Adam S. Lavine, Sean Albuquerque, Felipe C. Frei, Don Turner, Raymond D. Turk, Aquilla Siddiqui, Adnan H. Mack, William J. Alexandrov, Andrei Hirsch, Joshua A. Tarr, Robert W. TI Too much guidance SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material DE Thrombectomy ID ACUTE ISCHEMIC-STROKE; 1ST PASS TECHNIQUE; INTRAVENOUS T-PA; ENDOVASCULAR TREATMENT; IMAGING SELECTION; THROMBECTOMY; TRIAL; MANAGEMENT; GUIDELINE; THERAPY C1 [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Mocco, J.] NYC, Mt Sinai Hosp, New York, NY USA. [Arthur, Adam S.] Univ Tennessee, Semmes Murphey Neurol & Spine Clin, Memphis, TN USA. [Lavine, Sean] New York Presbyterian Hosp, New York, NY USA. [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Frei, Don] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Turner, Raymond D.] Univ S Carolina, Dept Neurosci, Mt Pleasant, SC USA. [Turk, Aquilla] Med Univ S Carolina, Charleston, SC 29425 USA. [Siddiqui, Adnan H.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Siddiqui, Adnan H.] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [Siddiqui, Adnan H.] SUNY Stony Brook, Toshiba Stroke Res Ctr, Stony Brook, NY 11794 USA. [Mack, William J.] Univ So Calif, Dept Neurosurg, Los Angeles, CA USA. [Alexandrov, Andrei] Univ Tennessee, Dept Neurol, Memphis, TN USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Tarr, Robert W.] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH USA. RP Fiorella, D (reprint author), SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. EM David.Fiorella@sbumed.org OI Arthur, Adam/0000-0002-1536-1613 NR 15 TC 4 Z9 4 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2015 VL 7 IS 9 BP 626 EP 627 DI 10.1136/neurintsurg-2015-011957 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CQ1ZL UT WOS:000360399000004 PM 26206804 ER PT J AU Deipolyi, AR Alexander, B Rho, J Hirsch, JA Oklu, R AF Deipolyi, Amy R. Alexander, Bailin Rho, Jun Hirsch, Joshua A. Oklu, Rahmi TI Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article DE Angiography; Vein; MRI; Tumor ID DEPENDENT CUSHINGS-SYNDROME; DIFFERENTIAL-DIAGNOSIS; PITUITARY; DISEASE AB Background Bilateral inferior petrosal sinus sampling (BIPSS) following corticotropic-releasing hormone (CRH) stimulation is the current gold standard technique in the diagnosis of Cushing disease. However, as a result of CRH shortage, desmopressin (DDAVP) has been used instead for BIPSS. We present the experience of a single tertiary care center using the modified BIPSS protocol and compare the results obtained with DDAVP with those obtained with CRH. Methods Using the radiology department's electronic database, BIPSS procedures performed at our institution using DDAVP and CRH were identified. Electronic medical records and imaging studies were reviewed and the clinical history, demographic data, endocrine test results, complications of BIPSS, and patient outcomes were recorded. BIPSS data were analyzed for centralization and lateralization of pituitary adrenocorticotropic hormone (ACTH) source. We identified 20 BIPSS cases (16 women, mean age 38years) performed using DDAVP between 2012 and 2013. Results The 20 cases demonstrated conventional inferior petrosal sinus anatomy and were successfully cannulated bilaterally. Of these, 18 met the criteria for both centralization and lateralization. A total of 18 patients underwent trans-sphenoidal tumor resection; one patient was lost to follow-up and one is still being followed. There were no complications resulting from the use of DDAVP, specifically no thromboembolic events. Calculated sensitivity for BIPSS with DDAVP was 94.5%. There was also no significant difference in the biochemical results produced by BIPSS using either DDAVP or CRH. All 18 patients demonstrated an ACTH-secreting adenoma on pathology review. Conclusions DDAVP is a safe alternative to CRH, producing comparable diagnostic results. C1 [Deipolyi, Amy R.; Alexander, Bailin; Rho, Jun; Oklu, Rahmi] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Deipolyi, Amy R.; Alexander, Bailin; Rho, Jun; Hirsch, Joshua A.; Oklu, Rahmi] Harvard Univ, Sch Med, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 290A, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu OI Deipolyi, Amy/0000-0003-3144-386X FU NIBIB NIH HHS [L30 EB012342] NR 15 TC 3 Z9 4 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2015 VL 7 IS 9 BP 690 EP 693 DI 10.1136/neurintsurg-2014-011262 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CQ1ZL UT WOS:000360399000015 PM 24996436 ER PT J AU Mangnus, L Meijer, DT Stufkens, SA Mellema, JJ Steller, EP Kerkhoffs, GMMJ Doornberg, JN AF Mangnus, Lukas Meijer, Diederik T. Stufkens, Sjoerd A. Mellema, Jos J. Steller, Ernst Ph. Kerkhoffs, Gino M. M. J. Doornberg, Job N. TI Posterior Malleolar Fracture Patterns SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; OF-THE-LITERATURE; DELTOID LIGAMENT; ANKLE FRACTURES; RADIAL HEAD; QUANTITATIVE MEASUREMENTS; CLASSIFICATION-SYSTEM; CORONOID PROCESS; PILON FRACTURES; TIBIAL PLAFOND AB Objective: To characterize posterior malleolar fracture morphology using Cole fracture mapping and to study reliability of quantification of 3-dimensional computed tomography (CT)-modeling for posterior malleolar fractures with respect to quantification of fragment size (in cubic millimeter) and true articular involvement (in square millimeter). Methods: CT scans of a consecutive series of 45 patients with an ankle fracture involving the posterior malleolus were reconstructed to calculate (1) fracture maps, (2) fragment volume, (3) articular surface of the posterior malleolar fragment, (4) articular surface of intact tibia, and (5) articular surface of the medial malleolus by 3 independent observers. Three-dimensional animation of this technique is shown on [GRAPHICS] . Results: Fracture mapping revealed (1) a continuous spectrum of posterolateral oriented fracture lines and (2) fragments with posterolateral to posteromedial oriented fracture lines extending into the medial malleolus. Reliability of measurements of the volume and articular surface of posterior malleolar fracture fragments was defined as almost perfect according to the categorical system of Landis (interclass coefficient, range, 0.978-1.000). Conclusions: Mapping of posterior malleolar fractures revealed a continuous spectrum of Haraguchi III to I fractures and identified Haraguchi type II as a separate pattern. Quantification of 3-dimensional CT-modeling is reliable to assess fracture characteristics of posterior malleolar fracture fragments. Morphology might be more important than posterior malleolar fracture size alone for clinical decision making. C1 [Mangnus, Lukas; Meijer, Diederik T.; Stufkens, Sjoerd A.; Mellema, Jos J.; Doornberg, Job N.] Acad Med Ctr Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands. [Stufkens, Sjoerd A.] Univ Amsterdam, Orthopaed Residency Program PGY5, NL-1100DD Amsterdam, Netherlands. [Mellema, Jos J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trauma Serv, Boston, MA USA. [Steller, Ernst Ph.] Sint Lucas Andreas Ziekenhuis, Dept Surg, Amsterdam, Netherlands. [Kerkhoffs, Gino M. M. J.] Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Amsterdam, Netherlands. [Doornberg, Job N.] Univ Amsterdam, Orthopaed Residency Program PGY4, NL-1100DD Amsterdam, Netherlands. RP Doornberg, JN (reprint author), Univ Amsterdam, Orthopaed Residency Program PGY4, Orthotrauma Res Ctr Amsterdam, Acad Med Ctr,Secretariaat Orthopaedie, G4 Noord,Meibergdreef 9, NL-1100DD Amsterdam, Netherlands. EM jobdoornbergortho@gmail.com FU Marti-Keuning Eckhart Foundation FX D. Meijer and J. N. Doornberg have received an unrestricted research grant from the Marti-Keuning Eckhart Foundation. The remaining authors report no conflict of interest. NR 43 TC 10 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD SEP PY 2015 VL 29 IS 9 BP 428 EP 435 DI 10.1097/BOT.0000000000000330 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CQ1HH UT WOS:000360347400009 PM 25785358 ER PT J AU Nelson, H Mott, S Kleinman, ME Goldstein, RD AF Nelson, Harriett Mott, Sandra Kleinman, Monica E. Goldstein, Richard D. TI Parents' Experiences of Pediatric Palliative Transports: A Qualitative Case Series SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Pediatric; compassionate extubation; location of death; critical care transport; palliative care ID INTENSIVE-CARE-UNIT; OF-LIFE; DEATH; HOME; LOCATION; CHILDREN; END; CANCER; PLACE; TEAM AB Context. Pediatric palliative transports, the practice of transporting critically ill children home for end-of-life care including extubation, are an option for children requiring high levels of medical support at end of life. Little is known about the experience from the perspective of the children and families. Objectives. To understand parents' perspectives on the experience of pediatric palliative transports. Methods. Open-ended interviews were conducted using a qualitative descriptive design. Each parent was asked to reflect on the process of bringing their child home to die. Conventional content analysis was used for data analysis. Results. Nine parents participated. The decision to transport the child home was a process motivated by promises to the child or a conviction that it was the right thing to do. The parents were gratified by the attention to safety and detail involved, but the actual transport home was stressful to them. The arrival home was typically recounted as a celebration. Being home provided time with the child in the context of their family and contributed to their lives. Memories of the experience brought comfort and a sense of fulfillment. Conclusion. Each parent found the experience positive and meaningful. The child's experiences when alive, not events at the time of death, were remembered. All parents recommended palliative transports, emphasizing the importance of home and family, when desired. These interviews strongly suggest that palliative transports make a positive, important contribution to the care of at least some children facing end of life, and their families. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Nelson, Harriett] Crit Care Transport Team, Boston, MA USA. [Mott, Sandra] Cardiovasc Program, Boston, MA USA. [Mott, Sandra] Crit Care Program, Boston, MA USA. [Kleinman, Monica E.] Boston Childrens Hosp, Dept Crit Care Med, Boston, MA USA. [Goldstein, Richard D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Boston Childrens Hosp, Boston, MA USA. [Kleinman, Monica E.; Goldstein, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldstein, RD (reprint author), Dana Farber Canc Inst, Dana 2008,450 Brookline Ave, Boston, MA 02115 USA. EM richard_goldstein@dfci.harvard.edu FU Program for Patient Safety & Quality at Boston Children's Hospital FX This study was supported by a grant from the Program for Patient Safety & Quality at Boston Children's Hospital. The funding source was not involved in the conduct of the study. The authors declare no conflicts of interest. NR 19 TC 5 Z9 5 U1 2 U2 4 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 SEP PY 2015 VL 50 IS 3 BP 375 EP 380 DI 10.1016/j.jpainsymman.2015.04.004 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CP7QZ UT WOS:000360084300017 PM 25891665 ER PT J AU Ruggiero, KJ Price, M Adams, Z Stauffacher, K McCauley, J Danielson, CK Knapp, R Hanson, RF Davidson, TM Amstadter, AB Carpenter, MJ Saunders, BE Kilpatrick, G Resnick, HS AF Ruggiero, Kenneth J. Price, Matthew Adams, Zachary Stauffacher, Kirstin McCauley, Jenna Danielson, Carla Kmett Knapp, Rebecca Hanson, Rochelle F. Davidson, Tatiana M. Amstadter, Ananda B. Carpenter, Matthew J. Saunders, Benjamin E. Kilpatrick, G. Resnick, Heidi S. TI Web Intervention for Adolescents Affected by Disaster: Population-Based Randomized Controlled Trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE disaster mental health; technology; posttraumatic stress; depression ID INTERNET-BASED INTERVENTION; POSTTRAUMATIC-STRESS; SUBSTANCE-ABUSE; CHILDREN; DEPRESSION; YOUTH; RISK AB Objective: To assess the efficacy of Bounce Back Now (BBN), a modular, Web-based intervention for disaster-affected adolescents and their parents. Method: A population-based randomized controlled trial used address-based sampling to enroll 2,000 adolescents and parents from communities affected by tornadoes in Joplin, MO, and several areas in Alabama. Data collection via baseline and follow-up semi-structured telephone interviews was completed between September 2011 and August 2013. All families were invited to access the BBN study Web portal irrespective of mental health status at baseline. Families who accessed the Web portal were assigned randomly to 1 of 3 groups: BBN, which featured modules for adolescents and parents targeting adolescents' mental health symptoms; BBN plus additional modules targeting parents' mental health symptoms; or assessment only. The primary outcomes were adolescent symptoms of posttraumatic stress disorder (PTSD) and depression. Results: Nearly 50% of families accessed the Web portal. Intent-to-treat analyses revealed time x condition interactions for PTSD symptoms (B = -0.24, SE = 0.08, p < .01) and depressive symptoms (B = -0.23, SE = 0.09, p < .01). Post hoc comparisons revealed fewer PTSD and depressive symptoms for adolescents in the experimental versus control conditions at 12-month follow-up (PTSD: B = -0.36, SE = 0.19, p = .06; depressive symptoms: B = -0.42, SE = 0.19, p = 0.03). A time x condition interaction also was found that favored the BBN versus BBN + parent self-help condition for PTSD symptoms (B = 0.30, SE = 0.12, p = .02) but not depressive symptoms (B = 0.12, SE = 0.12, p = .33). Conclusion: Results supported the feasibility and initial efficacy of BBN as a scalable disaster mental health intervention for adolescents. Technology-based solutions have tremendous potential value if found to reduce the mental health burden of disasters. C1 [Ruggiero, Kenneth J.; Adams, Zachary; McCauley, Jenna; Danielson, Carla Kmett; Knapp, Rebecca; Hanson, Rochelle F.; Davidson, Tatiana M.; Carpenter, Matthew J.; Saunders, Benjamin E.; Kilpatrick, G.; Resnick, Heidi S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Stauffacher, Kirstin; Davidson, Tatiana M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Price, Matthew] Univ Vermont, Burlington, VT 05405 USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, 99 Jonathan Lucas St, Charleston, SC 29425 USA. EM ruggierk@musc.edu FU National Institute of Mental Health (NIMH) [R01 MH081056]; NIDA [K12DA031794]; NIAAA [K02AA023239]; [R21 MH086313] FX This research was supported by National Institute of Mental Health (NIMH) Grant R01 MH081056 (PI: Ruggiero). This includes a Diversity supplement awarded to T.M.D. Grant R21 MH086313 (PI .Danielson) also supported some elements of this work The preparation of this manuscript was supported by NIDA Grant K12DA031794 (PI: Brady; support to J.M., Z.A.) and NIAAA K02AA023239 (PI: Amstadter). All views and opinions expressed herein are those of the authors and do not necessarily reflect those of the funding agency or respective institutions. NR 30 TC 5 Z9 5 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2015 VL 54 IS 9 BP 709 EP 717 DI 10.1016/j.jaac.2015.07.001 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CQ0BL UT WOS:000360259500005 PM 26299292 ER PT J AU Hagstrom, EL Patel, S Karimkhani, C Boyers, LN Williams, HC Hay, RJ Weinstock, MA Armstrong, AW Dunnick, CA Margolis, DJ Dellavalle, RP AF Hagstrom, Erika L. Patel, Shivani Karimkhani, Chante Boyers, Lindsay N. Williams, Hywel C. Hay, Roderick J. Weinstock, Martin A. Armstrong, April W. Dunnick, Cory A. Margolis, David J. Dellavalle, Robert P. TI Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE dermatitis; disability-adjusted life years; disease burden; leprosy; melanoma; National Institutes of Health; priority setting; skin conditions ID GLOBAL BURDEN; ATOPIC-DERMATITIS; CONTINUING CHALLENGES; BIOMEDICAL-RESEARCH; SYSTEMATIC ANALYSIS; ANIMAL RESEARCH; INJURIES; LIFE; PRIORITIES; MELANOMA AB Background: Disease burden should be an important component for guiding research funding. Objective: We sought to examine the relationship between dermatologic research funded from 2012 to 2013 by the National Institutes of Health (NIH) and US skin disease burden as measured by disabilityadjusted life years in the Global Burden of Disease 2010 study. Methods: A cross-sectional analysis was independently performed by 2 researchers who matched projects from the 2012 to 2013 NIH Research Portfolio Online Reporting Tools with 15 skin conditions and their respective disability-adjusted life years from Global Burden of Disease 2010. Results: The NIH funded 1108 projects spanning the 15 skin conditions. Melanoma received almost half of the total skin condition budget (49.5%). Melanoma, nonmelanoma skin cancer, and leprosy were funded above what would be suggested by their disease burden, whereas dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared underfunded. Bacterial skin diseases, viral skin diseases, and psoriasis were well matched with disease burden. Limitations: Disease burden is one of many factors that may be used to guide priority-setting decisions. Conclusion: Skin disease burden measured by disability-adjusted life year metrics partially correlates with NIH funding prioritization. Comparing US disease burden with NIH funding suggests possible underfunded and overfunded skin diseases. C1 [Hagstrom, Erika L.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Patel, Shivani] Med Univ S Carolina, Charleston, SC USA. [Karimkhani, Chante] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Hay, Roderick J.] Kings Coll Hosp Natl Hlth Serv Trust, Dept Dermatol, London, England. [Weinstock, Martin A.] Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. [Weinstock, Martin A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. [Weinstock, Martin A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Armstrong, April W.; Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO USA. [Armstrong, April W.; Dunnick, Cory A.; Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, Denver, CO USA. [Dunnick, Cory A.] Univ Penn, Dept Biostat & Epidemiol & Dermatol, Philadelphia, PA 19104 USA. [Margolis, David J.; Dellavalle, Robert P.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), US Dept Vet Affairs, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu FU Bill and Melinda Gates Foundation; US Department of Veterans Affairs; Centers for Disease Control and Prevention [3U48DP001938-04S1]; National Institutes of Health (NIH) [NCI R21 CA173654]; NIH FX The Global Burden of Disease Study 2010 was supported in part by the Bill and Melinda Gates Foundation. Drs Dellavalle, Weinstock, Dunnick, and Armstrong receive a salary from the US Department of Veterans Affairs. Dr Dellavalle is also supported by grants from the Centers for Disease Control and Prevention (Grant 3U48DP001938-04S1) and National Institutes of Health (NIH) (Grant NCI R21 CA173654). Drs Dellavalle, Weinstock, and Margolis previously received NIH funding for research grants. All other authors have no relevant funding/support. NR 42 TC 3 Z9 3 U1 3 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP 383 EP + DI 10.1016/j.jaad.2015.04.039 PG 10 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500020 PM 26051697 ER PT J AU Vedak, P Kroshinsky, D AF Vedak, Priyanka Kroshinsky, Daniela TI Squaric acid sensitization is not required for response in the treatment of alopecia areata SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE alopecia areata; squaric acid dibutylester; topical immunotherapy ID IMMUNOTHERAPY; DIBUTYLESTER; THERAPY AB Background: Topical immunotherapy using potent contact allergens, such as squaric acid dibutylester (SADBE), can be used to treat alopecia areata. However, there are conflicting reports regarding the best protocol for its administration, particularly with regard to the necessity of an eczematous response after the initial sensitization treatment. Objectives: We sought to assess the impact of initial sensitization on subsequent hair regrowth. Methods: This is a retrospective review of the use of SADBE in the treatment of alopecia areata in 14 patients. Results: Eleven of 14 patients underwent initial sensitization before initiating treatment. Three of these patients had an eczematous reaction after 1 attempt, 5 after >= 2 attempts, and 3 failed to develop a clinical reaction. Four of 14 initiated treatment without a clinical reaction or a previous sensitization. Eleven of 14 patients experienced regrowth, 7 with previous sensitization and 4 without. Limitations: This observational study is limited by sample size. Conclusions: SADBE sensitization regimens and reactions vary widely, and the absence of an initial eczematous reaction to sensitization does not predict a failed response with continued SADBE treatment. C1 [Vedak, Priyanka; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Boston, MA USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. EM dkroshinsky@partners.org NR 13 TC 1 Z9 1 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP 471 EP 476 DI 10.1016/j.jaad.2015.04.064 PG 6 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500032 PM 26282797 ER PT J AU Mochel, MC Hammond, MR Frederick, DT Alora-Palli, MB Piris, A Flaherty, KT Hoang, MP AF Mochel, Mark C. Hammond, Marc R. Frederick, Dennie T. Alora-Palli, Maria B. Piris, Adriano Flaherty, Keith T. Hoang, Mai P. TI Melanocytic nevi excised during B-Raf proto-oncogene (BRAF) inhibitor therapy: A study of 19 lesions from 10 patients SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE B-Raf proto-oncogene inhibition; CD4; CD8; melanocytic nevi; phosphorylated extracellular signal-regulated kinase; phosphorylated protein kinase B ID METASTATIC MELANOMA; V600E MUTATION; OPEN-LABEL; FOLLOW-UP; VEMURAFENIB; PROLIFERATIONS; BRAF(V600E); MULTICENTER; DABRAFENIB; DERMOSCOPY AB Background: There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy. Objective: We sought to identify their distinctive features. Methods: Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi. Results: BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8 1 in comparison with CD4(+) T lymphocytes within the dermal infiltrates. Limitation: This is a retrospective study of a small and heterogeneous group. Conclusion: The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melanin pigmentation and deep HMB-45 expression. C1 [Mochel, Mark C.; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hammond, Marc R.; Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Alora-Palli, Maria B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Piris, Adriano] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Alora-Palli, Maria B.; Piris, Adriano; Flaherty, Keith T.; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@mgh.harvard.edu NR 34 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP 491 EP + DI 10.1016/j.jaad.2015.06.006 PG 11 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500035 PM 26190239 ER PT J AU Pascoe, VL Kimball, AB AF Pascoe, Vanessa Lindsay Kimball, Alexandra Boer TI Seasonal variation of acne and psoriasis: A 3-year study using the Physician Global Assessment severity scale SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Pascoe, Vanessa Lindsay; Kimball, Alexandra Boer] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Pascoe, Vanessa Lindsay] Johns Hopkins Univ, Sch Med, Baltimore, MD 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 5 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP 523 EP 525 DI 10.1016/j.jaad.2015.06.001 PG 4 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500042 PM 26282801 ER PT J AU Donigan, JM Pascoe, VL Kimball, AB AF Donigan, Jessica M. Pascoe, Vanessa L. Kimball, Alexa B. TI Psoriasis and herpes simplex virus are highly stigmatizing compared with other common dermatologic conditions: A survey-based study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID FEELINGS C1 [Donigan, Jessica M.; Pascoe, Vanessa L.; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, Boston, MA 02114 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 5 TC 3 Z9 3 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP 525 EP 526 DI 10.1016/j.jaad.2015.06.035 PG 3 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500043 PM 26282802 ER PT J AU Hwang, E Dehesa, LA Kowalewski, CL AF Hwang, Elisha Dehesa, Luis A. Kowalewski, Catherine L. TI Brown hyperpigmentation of the hands and chest in a patient with lung cancer and muscle weakness SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 [Hwang, Elisha; Dehesa, Luis A.] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, San Antonio, TX 78229 USA. [Kowalewski, Catherine L.] Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX USA. RP Hwang, E (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, 7979 Wurzbach Dr,Grossman Bldg,3rd Fl, San Antonio, TX 78229 USA. EM elishahwang@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2015 VL 73 IS 3 BP E89 EP E90 DI 10.1016/j.jaad.2015.03.032 PG 2 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500003 PM 26282820 ER PT J AU Levy, C AF Levy, Cari TI Expectation Conversations About the Very Predictable Events in Advanced Dementia SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID NURSING-HOME RESIDENTS; FEEDING-TUBE INSERTION; ADVANCED COGNITIVE IMPAIRMENT; OF-LIFE ISSUES; DECISION-MAKING; HOSPICE CARE; END; PNEUMONIA; MANAGEMENT; SURVIVAL C1 [Levy, Cari] Univ Colorado Denver, Dept Med, Denver, CO 80220 USA. [Levy, Cari] Denver Vet Affairs Med Ctr, Div Hlth Care Policy & Res, Denver, CO 80220 USA. RP Levy, C (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM cari.levy@va.gov NR 36 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP 1 PY 2015 VL 16 IS 9 BP 724 EP 727 DI 10.1016/j.jamda.2015.05.003 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CQ0XC UT WOS:000360320100004 PM 26115816 ER PT J AU Fontenot, TE Randolph, GW Setton, TE Alsaleh, N Kandil, E AF Fontenot, Tatyana E. Randolph, Gregory W. Setton, Tedhar E. Alsaleh, Nuha Kandil, Emad TI Does intraoperative nerve monitoring reliably aid in staging of total thyroidectomies? SO LARYNGOSCOPE LA English DT Article DE Thyroid cancer; complications of thyroid surgery; recurrent laryngeal nerve injury; intraoperative neuromonitoring; patient outcomes ID RECURRENT LARYNGEAL NERVE; THYROID ASSOCIATION STATEMENT; SURGERY; INJURY; GOITER; SIGNAL; PALSY AB Objectives/HypothesisDemonstrate whether intraoperative nerve monitoring is an effective tool in staging bilateral thyroid and neck surgeries in cases of intraoperative injury to the recurrent laryngeal nerve on the side of initial dissection. We hypothesized that IONM provides reliable and appropriate feedback on the functional status of the RLN on side of initial dissection during total thyroidectomy and central neck surgery. Study DesignCase series with planned data collection. MethodsAll patients receiving total thyroidectomies or central neck surgeries were reviewed. The outcomes of patients treated whose procedures were staged based on intraoperative nerve monitoring are described. ResultsTen (4.9%) of 206 procedures were staged based on unfavorable signal change including six patients with thyroid cancers and four with compressive substernal goiters. The overall signal drop in the 10 patients with unfavorable signal change was 63%. Three patients had complete loss of signal. In the other seven patients, the signal dropped by a mean of 48%. In the eight patients with laryngoscopy-proven vocal fold paresis, the signal dropped by a mean of 68%. ConclusionsIntraoperative nerve monitoring results accurately indicated postoperative ipsilateral vocal cord dysfunction with high reliability. Intraoperative nerve monitoring is a reliable tool in staging thyroid surgery. Level of Evidence4. Laryngoscope, 125:2232-2235, 2015 C1 [Fontenot, Tatyana E.; Setton, Tedhar E.; Alsaleh, Nuha; Kandil, Emad] Tulane Univ, Sch Med, Dept Surg, New Orleans, LA 70112 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. RP Kandil, E (reprint author), Tulane Otolaryngol Head & Neck Surg, 1430 Tulane Ave,SL 59, New Orleans, LA 70112 USA. EM ekandil@tulane.edu OI Fontenot, Tatyana/0000-0001-7664-5014 NR 21 TC 5 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2015 VL 125 IS 9 BP 2232 EP 2235 DI 10.1002/lary.25133 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CP9RH UT WOS:000360231700050 PM 25601586 ER PT J AU Dowdall, JR Sadow, PM Hartnick, C Vinarsky, V Mou, H Zhao, R Song, PC Franco, RA Rajagopal, J AF Dowdall, Jayme R. Sadow, Peter M. Hartnick, Christopher Vinarsky, Vladimir Mou, Hongmei Zhao, Rui Song, Phillip C. Franco, Ramon A. Rajagopal, Jayaraj TI Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold SO LARYNGOSCOPE LA English DT Article DE Vocal fold; true vocal cord; epithelium; stratified squamous; biomarkers; cytokeratin; larynx; involucrin; proliferation; basal cell; differentiation; histology ID STEM-CELLS; VIMENTIN EXPRESSION; DIFFERENTIATION; INVOLUCRIN; MUCOSA; CYTOKERATIN; CARCINOMA; MARKER; SKIN AB Objectives/HypothesisA precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study DesignQualitative study with adult human larynges. MethodsHistologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). ResultsWe demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. ConclusionWe have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of EvidenceN/A. Laryngoscope, 125:E313-E319, 2015 C1 [Dowdall, Jayme R.; Hartnick, Christopher; Song, Phillip C.; Franco, Ramon A.; Rajagopal, Jayaraj] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Dowdall, Jayme R.; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Boston, MA USA. [Dowdall, Jayme R.; Sadow, Peter M.; Hartnick, Christopher; Song, Phillip C.; Franco, Ramon A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, CPZN 4240,185 Cambridge St, Boston, MA 02114 USA. EM jrajagopal@partners.org FU Massachusetts Life Sciences Center; Massachusetts Eye and Ear Infirmary; Massachusetts Life Sciences; Massachusetts Eye and Ear Infirmary, NIH-NIDCD Loan Repayment Grant; NHLBI Progenitor Cell Biology Consortium [5U01HL099997-04]; NIH/NHLBI [1R01HL116756-01a]; NIH-NHLBI Early Career Research New Faculty (P30) award [5P30HL101287-02]; Harvard Stem Cell Institute Junior Investigator Grant; New York Stem Cell Foundation-Robertson Investigator Grant FX The Massachusetts Life Sciences Center and the Massachusetts Eye and Ear Infirmary supported this work. This study was also supported by the following: grant from the Massachusetts Life Sciences (R.A.F); Massachusetts Eye and Ear Infirmary, NIH-NIDCD Loan Repayment Grant (J.R.D); grant from NHLBI Progenitor Cell Biology Consortium (5U01HL099997-04), R01 (1R01HL116756-01a) from NIH/NHLBI; NIH-NHLBI Early Career Research New Faculty (P30) award (5P30HL101287-02); Harvard Stem Cell Institute Junior Investigator Grant, and New York Stem Cell Foundation-Robertson Investigator Grant (J.R.). The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 29 TC 4 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2015 VL 125 IS 9 BP E313 EP E319 DI 10.1002/lary.25264 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CP9RH UT WOS:000360231700004 PM 25988619 ER PT J AU Sternthal, E Underwood, P Mantzoros, CS AF Sternthal, Elliot Underwood, Patricia Mantzoros, Christos S. TI Slip sliding away: the need for continued discussion of the use of insulin sliding scale in hospitalized patients SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID GLYCEMIC CONTROL; MEDICAL INPATIENTS; MANAGEMENT; THERAPY; TRIAL C1 [Sternthal, Elliot; Underwood, Patricia; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Sternthal, Elliot] Boston Univ, Sect Endocrinol Diabet & Nutr, Med Ctr, Boston, MA 02118 USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Sternthal, E (reprint author), Boston Univ, Sect Endocrinol Diabet & Nutr, Med Ctr, 88 E Newton St, Boston, MA 02118 USA. EM elsternthal@gmail.com NR 13 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 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2015 VL 64 IS 9 BP 935 EP 936 DI 10.1016/j.metabol.2015.06.012 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP7XJ UT WOS:000360102600001 PM 26159821 ER PT J AU Jennings, AS Lovett, AJ George, TM Jennings, JS AF Jennings, Anthony S. Lovett, Alexandra J. George, Tina M. Jennings, Jonathan S. TI Getting to goal in newly diagnosed type 2 diabetes using combination drug "subtraction therapy" SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Type 2 diabetes; Combination drug therapy; Treatment efficacy; Subtraction therapy; Durability ID BETA-CELL FUNCTION; INSULIN SENSITIVITY; GLUCOSE-PRODUCTION; GLYCEMIC CONTROL; METFORMIN; MELLITUS; THIAZOLIDINEDIONES; REPAGLINIDE; METABOLISM; RESISTANCE AB Background. The treatment of newly diagnosed type 2 diabetes mellitus is diverse, with no clear consensus regarding the initial drug regimen or dosing to achieve optimal glycemic control. Methods. We treated 44 consecutive patients with newly diagnosed type 2 diabetes with maximally tolerated doses of pioglitazone 45 mg/day, metformin 1000-2000 mg/day, and repaglinide 1-4 mg before meals. The doses and drugs were subsequently decreased ("subtraction therapy") to achieve optimal glycemic control and minimize side effects. Three primary outcomes were measured: the short term HbA(1c) response, the long term HbA(1c), response, and the incidence of hypoglycemia. Results. All 44 patients responded with a rapid, progressive decline in their HbA(1c) levels from 11.43 +/- 2.3% to 6.17 +/- 0.72% (101 +/- 25.1 mmol/mol to 44 +/- 7.9 mmol/mol) by three months, and remained stable thereafter. An HbA(1c) <= 7.0% (<= 53 mmol/mol) was reached within 1-4 months in 42 of 44 patients, and in every patient by 12 months. Each patient's lowest HbA(1c) level, 5.65 +/- 0.6% (38 +/- 6.6 mmol/mol), was reached over 6.3 +/- 2.9 months. Patients with initial HbA(1c) levels >10% (>86 mmol/mol) (n = 33) responded similarly as those with HbA(1c) levels <10% (<86 mmol/mol) (n = 11). Combination drug therapy maintained HbA(1c) levels between 5.0 and 7.0% (31 and 53 mmol/mol) for up to 14.83 years. Only one clinically significant hypoglycemic event occurred during 261.08 person-years of follow-up. Conclusions. In our experience, combination drug "subtraction therapy" was safe and effective for treating all newly diagnosed type 2 diabetic patients. (C) 2015 Elsevier Inc. All rights reserved. C1 [Jennings, Anthony S.; George, Tina M.; Jennings, Jonathan S.] Virtua Hlth Syst, Covered Bridge Med Ctr, Cherry Hill, NJ 08034 USA. [Lovett, Alexandra J.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Neurol Partners Program, Boston, MA 02114 USA. RP Jennings, AS (reprint author), 27 Covered Bridge Med Bldg, Cherry Hill, NJ 08034 USA. EM anthonysjennings111@gmail.com NR 27 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 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2015 VL 64 IS 9 BP 1005 EP 1012 DI 10.1016/j.metabol.2015.04.008 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP7XJ UT WOS:000360102600010 PM 26003501 ER PT J AU Cooke, AB Toli, E Gomez, YH Mutter, AF Eisenberg, MJ Mantzoros, CS Daskalopoulou, SS AF Cooke, Alexandra B. Toli, Eirini Gomez, Yessica-Haydee Mutter, Andrew F. Eisenberg, Mark J. Mantzoros, Christos S. Daskalopoulou, Stella S. TI From rest to stressed: endothelin-1 levels in young healthy smokers and non-smokers SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Endothelin-1; Smoking; Nicotine; Exercise; Endothelium ID CIGARETTE-SMOKING; PLASMA ENDOTHELIN-1; BLOOD-FLOW; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE; NITRIC-OXIDE; EXERCISE; EXPRESSION; NICOTINE; RELEASE AB Introduction. Endothelin-1 (ET-1) is a potent vasoconstrictor produced by vascular endothelial cells, and a known marker of endothelial dysfunction. However, the acute and chronic effects of smoking and nicotine gum on the ET-1 response to acute physical stress in young healthy smokers have not been investigated. Methods. Healthy smokers (n = 35) and non-smokers (n = 35) underwent an exercise test to exhaustion (maximal oxygen consumption) on a treadmill. Smokers were assessed a) after 12 h smoking abstinence (termed chronic smoking), b) immediately after smoking one cigarette (termed acute smoking), and c) immediately after chewing nicotine gum. Blood was drawn immediately pre-exercise, and 3 minutes post-exercise. During exercise, cardiorespiratory parameters were obtained breath-by-breath using an automated metabolic cart. Plasma ET-1 levels were quantified using enzyme-linked immunosorbent-assay. The above protocol was designed to incorporate exercise as a vascular stressor to reveal changes that would not be detected at rest. Results. Mean age was 28.6 +/- 7.2 years and body mass index (BMI) was 23.6 +/- 3.2 kg/m(2). Post-exercise ET-1 levels were significantly lower than pre-exercise levels in non-smokers (P < 0.001) and smokers under all three conditions (P = 0.005, P < 0.001, P = 0.001, respectively). There were no differences in post-exercise ET-1 levels between non-smokers and smokers under all three conditions, however the absolute and relative decrease in ET-1 levels was significantly smaller in chronic smokers compared with non-smokers (P = 0.007 and P = 0.004). Chronic smokers had a significantly lower exercise-induced change in tidal volume (P = 0.050), fraction of expired CO2 (P = 0.021), oxygen consumption (P = 0.005), carbon dioxide elimination (P = 0.004) and peak expiratory flow (P = 0.003) compared with non-smokers. Furthermore, the decrease in ET-1 observed in non-smokers in response to exercise was significantly associated with exercise induced-changes in inspiratoiy time, time for a tidal volume cycle, respiratory frequency, inspired minute ventilation and peak inspiratory flow. Conclusions. An acute decrease of circulating ET-1 in response to acute maximal exercise in young healthy individuals was noted. Chronic smokers had a significantly diminished decrease in ET-1 compared with non-smokers, however there were no significant differences in the ET-1 response between smokers under the three smoking conditions. Smokers were not able to achieve the same exercise-induced changes in cardiorespiratory parameters as nonsmokers. By incorporating exercise as a vascular stressor in our study, we have taken a novel approach to provide evidence of an altered ET-1 and cardiorespiratory response that would not otherwise be observed at rest in young active healthy smokers. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cooke, Alexandra B.; Mutter, Andrew F.; Daskalopoulou, Stella S.] McGill Univ, Fac Med, Dept Med, Div Expt Med, Montreal, PQ H3A 1A3, Canada. [Toli, Eirini; Gomez, Yessica-Haydee; Daskalopoulou, Stella S.] McGill Univ, Ctr Hlth, Div Internal Med, Dept Med,Fac Med,Res Inst, Montreal, PQ H3G 1A4, Canada. [Eisenberg, Mark J.] McGill Univ, Fac Med, Dept Med, Div Cardiol, Montreal, PQ H3G 1Y6, Canada. [Eisenberg, Mark J.] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Dept Med,Fac Med, Montreal, PQ H3T 1E2, Canada. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, VA Sect Endocrinol, Boston, MA USA. RP Daskalopoulou, SS (reprint author), Montreal Gen Hosp, Med, 1650 Cedar Ave,C2-101-4, Montreal, PQ H3G 1A4, Canada. EM stella.daskalopoulou@mcgill.ca FU Canadian Institutes of Health Research (MOP) [102626]; Fonds de recherche du Quebec-Sante (FRQS) FX This study was funded by a grant from the Canadian Institutes of Health Research (MOP#102626) to SSD. SSD is a Chercheur-Boursier Clinicien supported by a Fonds de recherche du Quebec-Sante (FRQS) salary award. NR 40 TC 3 Z9 3 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2015 VL 64 IS 9 BP 1103 EP 1111 DI 10.1016/j.metabol.2015.06.009 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP7XJ UT WOS:000360102600021 PM 26141182 ER PT J AU Luttrell, LM Maudsley, S Bohn, LM AF Luttrell, Louis M. Maudsley, Stuart Bohn, Laura M. TI Fulfilling the Promise of "Biased" G Protein-Coupled Receptor Agonism SO MOLECULAR PHARMACOLOGY LA English DT Review ID MU-OPIOID RECEPTOR; ARRESTIN-MEDIATED ACTIVATION; SEROTONIN 2A RECEPTOR; BETA-ARRESTIN; IN-VIVO; FUNCTIONAL SELECTIVITY; PARATHYROID-HORMONE; BETA(2)-ADRENERGIC RECEPTOR; PHARMACOLOGICAL AGONISM; SIGNALING PATHWAYS AB The fact that over 30% of current pharmaceuticals target heptahelical G protein-coupled receptors (GPCRs) attests to their tractability as drug targets. Although GPCR drug development has traditionally focused on conventional agonists and antagonists, the growing appreciation that GPCRs mediate physiologically relevant effects via both G protein and non-G protein effectors has prompted the search for ligands that can " bias" downstream signaling in favor of one or the other process. Biased ligands are novel entities with distinct signaling profiles dictated by ligand structure, and the potential prospect of biased ligands as better drugs has been pleonastically proclaimed. Indeed, preclinical proof-of-concept studies have demonstrated that both G protein and arrestin pathwayselective ligands can promote beneficial effects in vivo while simultaneously antagonizing deleterious ones. But along with opportunity comes added complexity and new challenges for drug discovery. If ligands can be biased, then ligand classification becomes assay dependent, and more nuanced screening approaches are needed to capture ligand efficacy across several dimensions of signaling. Moreover, because the signaling repertoire of biased ligands differs from that of the native agonist, unpredicted responses may arise in vivo as these unbalanced signals propagate. For any given GPCR target, establishing a framework relating in vitro efficacy to in vivo biologic response is crucial to biased drug discovery. This review discusses approaches to describing ligand efficacy in vitro, translating ligand bias into biologic response, and developing a systemslevel understanding of biased agonism in vivo, with the overall goal of overcoming current barriers to developing biased GPCR therapeutics. C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Maudsley, Stuart] Univ Antwerp, Translat Neurobiol Grp, VIB Dept Mol Genet, Lab Neurogenet Inst Born Bunge, Antwerp, Belgium. [Bohn, Laura M.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. [Bohn, Laura M.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816CSB,MSC624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM095497]; National Institute of Diabetes, Digestive, and Kidney Diseases [R01-DK055524]; Intramural Research Program of the National Institute on Aging; National Institute on Drug Abuse [R01-DA031927, R01-DA033073, P01-DA009158, R01-DA038964]; Research Service of the Charleston, SC Veterans Affairs Medical Center FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM095497], the National Institute of Diabetes, Digestive, and Kidney Diseases [Grant R01-DK055524], the Intramural Research Program of the National Institute on Aging, the National Institute on Drug Abuse [Grants R01-DA031927, R01-DA033073, P01-DA009158, and R01-DA038964], and the Research Service of the Charleston, SC Veterans Affairs Medical Center. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 118 TC 33 Z9 33 U1 7 U2 35 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2015 VL 88 IS 3 BP 579 EP 588 DI 10.1124/mol.115.099630 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP8JI UT WOS:000360139400006 PM 26134495 ER PT J AU Voytek, B Kayser, AS Badre, D Fegen, D Chang, EF Crone, NE Parvizi, J Knight, RT D'Esposito, M AF Voytek, Bradley Kayser, Andrew S. Badre, David Fegen, David Chang, Edward F. Crone, Nathan E. Parvizi, Josef Knight, Robert T. D'Esposito, Mark TI Oscillatory dynamics coordinating human frontal networks in support of goal maintenance SO NATURE NEUROSCIENCE LA English DT Article ID HUMAN PREFRONTAL CORTEX; SHORT-TERM-MEMORY; COGNITIVE CONTROL; THETA RHYTHM; PHASE; FREQUENCY; COMMUNICATION; MECHANISM; BEHAVIOR; POWER AB Humans have a capacity for hierarchical cognitive control-the ability to simultaneously control immediate actions while holding more abstract goals in mind. Neuropsychological and neuroimaging evidence suggests that hierarchical cognitive control emerges from a frontal architecture whereby prefrontal cortex coordinates neural activity in the motor cortices when abstract rules are needed to govern motor outcomes. We utilized the improved temporal resolution of human intracranial electrocorticography to investigate the mechanisms by which frontal cortical oscillatory networks communicate in support of hierarchical cognitive control. Responding according to progressively more abstract rules resulted in greater frontal network theta phase encoding (4-8 Hz) and increased prefrontal local neuronal population activity (high gamma amplitude, 80-150 Hz), which predicts trial-by-trial response times. Theta phase encoding coupled with high gamma amplitude during inter-regional information encoding, suggesting that inter-regional phase encoding is a mechanism for the dynamic instantiation of complex cognitive functions by frontal cortical subnetworks. C1 [Voytek, Bradley; Fegen, David; Knight, Robert T.; D'Esposito, Mark] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Kayser, Andrew S.; D'Esposito, Mark] US Dept Vet Affairs, Div Neurol, Martinez, CA USA. [Kayser, Andrew S.] Univ Calif San Francisco, Ctr Integrat Neurosci, Dept Neurol, San Francisco, CA 94143 USA. [Badre, David] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Badre, David] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Chang, Edward F.] Univ Calif San Francisco, Dept Neurol Surg, Ctr Integrat Neurosci, San Francisco, CA USA. [Chang, Edward F.] Univ Calif San Francisco, Dept Physiol, Ctr Integrat Neurosci, San Francisco, CA USA. [Crone, Nathan E.] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. [Parvizi, Josef] Stanford Univ, SHICEP, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Knight, Robert T.; D'Esposito, Mark] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Voytek, B (reprint author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. EM bradley.voytek@gmail.com RI Voytek, Bradley/K-3305-2016 OI Voytek, Bradley/0000-0003-1640-2525 FU US National Institutes of Health (NIH) Institutional Research and Academic Career Development Award; Society for Neuroscience Scholars Program; US National Institutes of Health Institutional Research and Academic Career Development Award [GM081266]; Department of Veterans Affairs; National Eye Institute; National Institute of Neurological Disorders and Stroke [NS065046, NS065120, NS40596, NS07839601, NS21135]; Nielsen Corporation; National Institute of Mental Health [MH063901] FX We thank A. Flinker, J. Hoffman and A. Shestyuk for assistance with data collection, and C. Hamame, T. Lee and B. Postle for useful comments and suggestions. B.V. is funded by a US National Institutes of Health (NIH) Institutional Research and Academic Career Development Award and the Society for Neuroscience Scholars Program. B.V. is funded by a US National Institutes of Health Institutional Research and Academic Career Development Award (GM081266) and the Society for Neuroscience Scholars Program. A.S.K. is funded by the Department of Veterans Affairs and the National Eye Institute. D.B., E.F.C., N.E.C., J.P. and R.T.K. are funded by the National Institute of Neurological Disorders and Stroke (NS065046, NS065120, NS40596, NS07839601, NS21135). R.T.K. is funded by the Nielsen Corporation. M.D. is funded by the Department of Veterans Affairs and the National Institute of Mental Health (MH063901). NR 55 TC 18 Z9 18 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2015 VL 18 IS 9 BP 1318 EP + DI 10.1038/nn.4071 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CQ0NI UT WOS:000360292600022 PM 26214371 ER PT J AU Humar, M Yun, SH AF Humar, Matjaz Yun, Seok Hyun TI Intracellular microlasers SO NATURE PHOTONICS LA English DT Article ID LABEL-FREE; OPTICAL MICROCAVITIES; LASERS; PROBES AB Optical microresonators(1), which confine light within a small cavity, are widely exploited for various applications ranging from the realization of lasers(2) and nonlinear devices(3-5) to biochemical and optomechanical sensing(6-11). Here we use microresonators and suitable optical gain materials inside biological cells to demonstrate various optical functions in vitro including lasing. We explore two distinct types of microresonator-soft and hard-that support whispering-gallery modes. Soft droplets formed by injecting oil or using natural lipid droplets support intracellular laser action. The laser spectra from oil-droplet microlasers can chart cytoplasmic internal stress (similar to 500 pN mu m(-2)) and its dynamic fluctuations at a sensitivity of 20 pN mu m(-2) (20 Pa). In a second form, whispering-gallery modes within phagocytized polystyrene beads of different sizes enable individual tagging of thousands of cells easily and, in principle, a much larger number by multiplexing with different dyes. C1 [Humar, Matjaz; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Humar, Matjaz] J Stefan Inst, Condensed Matter Dept, SI-1000 Ljubljana, Slovenia. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Humar, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu RI Humar, Matjaz/I-8862-2012 OI Humar, Matjaz/0000-0003-3338-6723 FU US National Science Foundation (NSF) [ECCS-1101947, EEC-1358296, ECCS-1505569]; National Institutes of Health [P41 EB015903]; Marie Curie International Outgoing Fellowship within 7th European Community Framework Programme [627274]; NSF [ECS-0335765] FX This research was supported in part by the US National Science Foundation (NSF; ECCS-1101947, EEC-1358296, ECCS-1505569) and the National Institutes of Health (P41 EB015903). M.H. was supported in part by the Marie Curie International Outgoing Fellowship no. 627274 within the 7th European Community Framework Programme. The authors thank J. Zhao and Wellman Centre Photopathology Core for technical support. Part of this work was performed at the Centre for Nanoscale Systems (CNS) at Harvard University, which is a member of the National Nanotechnology Infrastructure Network (NNIN) and supported by the NSF under award no. ECS-0335765. NR 30 TC 34 Z9 34 U1 15 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-4885 EI 1749-4893 J9 NAT PHOTONICS JI Nat. Photonics PD SEP PY 2015 VL 9 IS 9 BP 572 EP + DI 10.1038/NPHOTON.2015.129 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA CQ1VN UT WOS:000360388400009 PM 26417383 ER PT J AU Kamer, KJ Mootha, VK AF Kamer, Kimberli J. Mootha, Vamsi K. TI The molecular era of the mitochondrial calcium uniporter SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID RAT KIDNEY MITOCHONDRIA; PANCREATIC BETA-CELLS; CA2+ UPTAKE; ESSENTIAL COMPONENT; ENDOPLASMIC-RETICULUM; SKELETAL-MUSCLE; INNER MEMBRANE; RUTHENIUM RED; MICE LACKING; MCU AB The mitochondrial calcium uniporter is an evolutionarily conserved calcium channel, and its biophysical properties and relevance to cell death, bioenergetics and signalling have been investigated for decades. However, the genes encoding this channel have only recently been discovered, opening up a new 'molecular era' in the study of its biology. We now know that the uniporter is not a single protein but rather a macromolecular complex consisting of pore-forming and regulatory subunits. We review recent studies that harnessed the power of molecular biology and genetics to characterize the mechanism of action of the uniporter, its evolution and its contribution to physiology and human disease. C1 [Kamer, Kimberli J.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Kamer, Kimberli J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Kamer, Kimberli J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Mootha, Vamsi K.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. [Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St 6th Floor, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu NR 72 TC 33 Z9 33 U1 8 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD SEP PY 2015 VL 16 IS 9 BP 545 EP 553 DI 10.1038/nrm4039 PG 9 WC Cell Biology SC Cell Biology GA CQ1FG UT WOS:000360342100007 PM 26285678 ER PT J AU Javitt, DC Sweet, RA AF Javitt, Daniel C. Sweet, Robert A. TI Auditory dysfunction in schizophrenia: integrating clinical and basic features SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SUPERIOR TEMPORAL GYRUS; TRANSCRANIAL MAGNETIC STIMULATION; MISMATCH NEGATIVITY GENERATION; NMDA-RECEPTOR ANTAGONIST; VOXEL-BASED MORPHOMETRY; STEADY-STATE RESPONSES; GRAY-MATTER VOLUME; VERBAL HALLUCINATIONS; PLANUM TEMPORALE; CORTICAL DYSFUNCTION AB Schizophrenia is a complex neuropsychiatric disorder that is associated with persistent psychosocial disability in affected individuals. Although studies of schizophrenia have traditionally focused on deficits in higher-order processes such as working memory and executive function, there is an increasing realization that, in this disorder, deficits can be found throughout the cortex and are manifest even at the level of early sensory processing. These deficits are highly amenable to translational investigation and represent potential novel targets for clinical intervention. Deficits, moreover, have been linked to specific structural abnormalities in post-mortem auditory cortex tissue from individuals with schizophrenia, providing unique insights into underlying pathophysiological mechanisms. C1 [Javitt, Daniel C.] Columbia Univ Coll Phys & Surg, Dept Psychiat & Neurosci, Div Expt Therapeut, New York, NY 10032 USA. [Javitt, Daniel C.] Nathan S Kline Inst, Program Cognit Neurosci & Schizophrenia, Orangeburg, NY 10962 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Res Off, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15240 USA. RP Javitt, DC (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat & Neurosci, Div Expt Therapeut, 1051 Riverside Dr,Unit 21, New York, NY 10032 USA. EM dcj2113@cumc.columbia.edu FU NIMH NIH HHS [P50 MH103204, R01 MH049334, R01 MH071533] NR 167 TC 21 Z9 21 U1 4 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD SEP PY 2015 VL 16 IS 9 BP 535 EP 550 DI 10.1038/nrn4002 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CP9CU UT WOS:000360192100008 PM 26289573 ER PT J AU Makris, A Yeung, K Lim, SM Sunderland, N Heffernan, S Thompson, JF Illiopoulos, J Killingsworth, MC Yong, J Xu, B Ogle, RF Thandhani, R Karumanchi, SA Hennessy, A AF Makris, A. Yeung, K. Lim, S. M. Sunderland, N. Heffernan, S. Thompson, J. F. Illiopoulos, J. Killingsworth, M. C. Yong, J. Xu, B. Ogle, R. F. Thandhani, R. Karumanchi, S. A. Hennessy, A. TI PLACENTAL GROWTH FACTOR REDUCES BLOOD PRESSURE IN EXPERIMENTAL PREECLAMPSIA SO NEPHROLOGY LA English DT Meeting Abstract C1 [Makris, A.; Yeung, K.; Lim, S. M.; Illiopoulos, J.; Killingsworth, M. C.; Yong, J.; Xu, B.; Hennessy, A.] Univ Western Sydney, Liverpool, NSW, Australia. [Makris, A.; Yeung, K.; Lim, S. M.; Illiopoulos, J.; Killingsworth, M. C.; Yong, J.; Xu, B.; Hennessy, A.] Ingham Inst, Liverpool, NSW, Australia. [Makris, A.] Univ New S Wales, Liverpool, NSW, Australia. [Sunderland, N.; Heffernan, S.; Thompson, J. F.; Ogle, R. F.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Thandhani, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karumanchi, S. A.] Beth Israel Deacon, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 EI 1440-1797 J9 NEPHROLOGY JI Nephrology PD SEP PY 2015 VL 20 SU 3 SI SI MA 010 BP 18 EP 19 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CP9LY UT WOS:000360217000011 ER PT J AU Schuster, RM Crane, NA Mermelstein, R Gonzalez, R AF Schuster, Randi M. Crane, Natania A. Mermelstein, Robin Gonzalez, Raul TI Tobacco May Mask Poorer Episodic Memory Among Young Adult Cannabis Users SO NEUROPSYCHOLOGY LA English DT Article DE cannabis; nicotine; episodic memory; young adults; neurocognition ID LONG-TERM POTENTIATION; ADOLESCENT MARIJUANA USERS; NEUROPSYCHOLOGICAL IMPAIRMENT; NICOTINE; RECEPTORS; BEHAVIOR; PERFORMANCE; EXPOSURE; RATS; HIPPOCAMPAL AB Objective: Co-occurring cannabis and tobacco use has become increasingly prevalent among young adults, but it is not clear how tobacco use may alter the neurocognitive profile typically observed among cannabis users. Although there is substantial evidence citing cannabis and tobacco's individual effect on episodic memory and related brain structures, few studies have examined the effect of combined cannabis and tobacco use on memory. Method: This investigation examined relationships between amount of past year cannabis and tobacco use on 4 different indices of episodic memory among a sample of young adults who identified cannabis as their drug of choice. Results: Results indicated that more cannabis use was linked with poorer initial acquisition, total learning, and delayed recall on the Hopkins Verbal Learning Test-Revised, but only among cannabis users who sporadically smoked cigarettes in the past year. Conversely, the amount of past year cannabis use was not associated with episodic memory performance among individuals who more consistently smoked cigarettes in the past year. These differences could not be explained by several relevant potential confounds. Conclusions: These findings provide important insight into a potential mechanism (i.e., attenuation of cognitive decrements) that might reinforce use of both substances and hamper cessation attempts among cannabis users who also smoke cigarettes. Ongoing and future research will help to better understand how co-use of cannabis and tobacco affects memory during acute intoxication and abstinence and the stability of these associations over time. C1 [Schuster, Randi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Crane, Natania A.; Mermelstein, Robin] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Crane, Natania A.; Mermelstein, Robin] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60680 USA. [Gonzalez, Raul] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Gonzalez, Raul] Florida Int Univ, Ctr Children & Families, Miami, FL 33199 USA. RP Schuster, RM (reprint author), 60 Staniford St,Room 124, Boston, MA 02114 USA. EM Rschuster@mgh.harvard.edu FU National Institute on Drug Abuse (NIDA) [K23 DA023560, R01 DA031176, R01 DA033156]; National Institute on Mental Health (NIMH) [T32MH067631]; National Cancer Institute (NCI) [P01CA098262] FX This publication was made possible by the National Institute on Drug Abuse (NIDA; K23 DA023560, R01 DA031176, and R01 DA033156, Principal Investigator: Raul Gonzalez); the National Institute on Mental Health (NIMH; T32MH067631, to Natania A. Crane); and the National Cancer Institute (NCI; P01CA098262, Principal Investigator: Robin Mermelstein). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDA, NCI, or the National Institutes of Health. The authors declare no conflicts of interest. NR 44 TC 5 Z9 5 U1 4 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD SEP PY 2015 VL 29 IS 5 BP 759 EP 766 DI 10.1037/neu0000173 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA CQ1UR UT WOS:000360385900011 PM 25558879 ER PT J AU Rosa, NM Deason, RG Budson, AE Gutchess, AH AF Rosa, Nicole M. Deason, Rebecca G. Budson, Andrew E. Gutchess, Angela H. TI Self-Referencing and False Memory in Mild Cognitive Impairment Due to Alzheimer's Disease SO NEUROPSYCHOLOGY LA English DT Article DE MCI-AD; self-reference; false memory; response bias ID OLDER-ADULTS; GIST MEMORY; RECOGNITION; DEMENTIA; YOUNG AB Objective: The present study explored the role of self-referencing on false alarm rates among people with mild cognitive impairment suggestive of the early signs of the Alzheimer's disease pathophysiologic process (MCI-AD). Given that people with MCI-AD demonstrate higher rates of false alarms and that false alarms have been shown to increase for self-relevant information, it was predicted that people with MCI-AD would experience a disproportionate increase in memory errors for highly self-related information. Method: Patients with a diagnosis of MCI-AD (n = 23) and healthy control participants (n = 27) rated words for self-descriptiveness or commonness and completed a surprise recognition test. Results: Contrary to expectations, results indicated that people with MCI-AD were at no greater risk for false alarms than were control participants as a function of self-descriptiveness, relative to a control condition. Despite the MCI-ADs' greater bias to say "yes" in the self condition, increasing self-descriptiveness did not lead to higher false alarm rates and did not impair performance in the self condition relative to commonness judgments. Conclusions: Therefore, although people with MCI-AD may be more susceptible to memory errors, they are at no greater risk of self-related errors than healthy control participants. C1 [Rosa, Nicole M.; Gutchess, Angela H.] Brandeis Univ, Dept Psychol, Waltham, MA 02254 USA. [Rosa, Nicole M.] Worcester State Univ, Dept Psychol, Worcester, MA 01602 USA. [Deason, Rebecca G.; Budson, Andrew E.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Deason, Rebecca G.] Texas State Univ, Dept Psychol, San Marcos, TX 78666 USA. RP Rosa, NM (reprint author), Worcester State Univ, Dept Psychol, 486 Chandler St, Worcester, MA 01602 USA. EM nrosa@comcast.net FU National Institute on Aging [R01 AG025815, P30 AG13846]; Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award; Psychology Department at Brandeis University FX This research was supported by National Institute on Aging grants R01 AG025815 (AEB) and P30 AG13846 (AEB), by Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award (RGD), and by the Psychology Department at Brandeis University (NMR). This material is also the result of work supported with resources and the use of facilities at the VA Boston Healthcare System. NR 31 TC 2 Z9 2 U1 2 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD SEP PY 2015 VL 29 IS 5 BP 799 EP 805 DI 10.1037/neu0000186 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA CQ1UR UT WOS:000360385900016 PM 25689510 ER PT J AU Roberts-Toler, C O'Neill, BT Cypess, AM AF Roberts-Toler, Carla O'Neill, Brian T. Cypess, Aaron M. TI Diet-induced obesity causes insulin resistance in mouse brown adipose tissue SO OBESITY LA English DT Article ID INFLAMMATION; ADIPOCYTES; HUMANS; RAT AB ObjectiveDiet-induced obesity (DIO) causes several pathophysiological changes in adipose tissue. Increased inflammation reduces white adipose tissue (WAT) insulin sensitivity and contributes to the development of diabetes. However, little is known about how DIO alters the function of brown adipose tissue (BAT), an organ that consumes calories by 3-adrenergic receptor (AR)-mediated thermogenesis and helps regulate energy balance. MethodsTo test the effects of DIO on BAT, we fed 6-week-old C57BL/6 mice either a normal chow diet (NCD) or a high-fat diet (HFD). After 16 additional weeks, we measured body fat, WAT, and BAT mRNA expression, glucose tolerance, and rates of glucose uptake in response to insulin and the 3-AR agonist mirabegron. ResultsCompared with NCD, HFD increased body fat and impaired glucose tolerance. Both WAT and BAT had higher mRNA levels of markers of inflammation, including TNF and F4/80. Insulin signaling in BAT and WAT was reduced, with decreased Akt phosphorylation. Diet-normalized BAT glucose uptake rates were lower in response to mirabegron. ConclusionsThese results support a model in which DIO leads to BAT inflammation and insulin resistance, leading to a broader impairment of BAT function. C1 [Roberts-Toler, Carla; O'Neill, Brian T.; Cypess, Aaron M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [Cypess, Aaron M.] NIDDK, Translat Physiol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Cypess, AM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. EM aaron.cypess@nih.gov FU National Institutes of Health (NIH) [K23 DK081604, K08 DK100543]; Joslin DRC; National Center for Research Resources (NCRR) [UL1RR025758]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This work was supported by National Institutes of Health (NIH) grants K23 DK081604 (A.M.C.), K08 DK100543 (B.T.O.), Joslin DRC, the Clinical Translational Science Award UL1RR025758 to Harvard University and BIDMC from the National Center for Research Resources (NCRR), and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDDK, NCRR, or the NIH. NR 19 TC 19 Z9 19 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1765 EP 1770 DI 10.1002/oby.21134 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100008 PM 26242777 ER PT J AU Masheb, RM Lutes, LD Kim, HM Holleman, RG Goodrich, DE Janney, CA Kirsh, S Higgins, DM Richardson, CR Damschroder, LJ AF Masheb, Robin M. Lutes, Lesley D. Kim, Hyungjin Myra Holleman, Robert G. Goodrich, David E. Janney, Carol A. Kirsh, Susan Higgins, Diana M. Richardson, Caroline R. Damschroder, Laura J. TI Weight loss outcomes in patients with pain SO OBESITY LA English DT Article ID QUALITY-OF-LIFE; KNEE OSTEOARTHRITIS; MANAGEMENT PROGRAM; OBESE ADULTS; VETERANS; TRIAL; COMORBIDITY; PREVALENCE; DESIGN AB ObjectiveTo determine whether the presence or severity of pain is predictive of suboptimal weight loss outcomes in behavioral weight management programs. MethodsThis is a secondary data analysis comparing weight loss among participants with overweight/obesity who participated in a 12-month randomized controlled trial. Of the 481 participants randomized, 394 (81.9%) had available pain data and were categorized by Pain Type (back pain, arthritis pain, both, or neither) and Pain Severity (no pain, moderate pain, or severe pain). Dietary and physical activity outcomes were also explored. ResultsHigh rates of moderate and severe (80.2%), and back and arthritis (72.6%), pain were observed. Linear mixed models showed significant differences in % weight loss among Pain Severity, but not Pain Type, groups. Patients with severe pain lost significantly less weight (-0.1 kg, 95% CI=-1.5, -1.2) compared to those with either moderate or no pain (-1.9 kg, 95% CI=-2.5, -1.3; -2.1 kg, 95% CI=-3.3, -1.0, respectively). Patients with arthritis pain lost a significant amount of weight despite only minor improvements in walking distance. ConclusionsPain severity, but not pain type, is predictive of suboptimal weight loss outcomes. C1 [Masheb, Robin M.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Masheb, Robin M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Lutes, Lesley D.] E Carolina Univ, Dept Psychol, Greenville, NC 27858 USA. [Kim, Hyungjin Myra; Holleman, Robert G.; Goodrich, David E.; Janney, Carol A.; Richardson, Caroline R.; Damschroder, Laura J.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Kirsh, Susan] VA Cent Off, Off Primary Care, Washington, DC USA. [Kirsh, Susan] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Higgins, Diana M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Higgins, Diana M.] VA Boston Healthcare Syst, Boston, MA USA. [Richardson, Caroline R.] Univ Michigan, Sch Med, Dept Family Med, Ann Arbor, MI USA. RP Masheb, RM (reprint author), VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. EM robin.masheb@yale.edu OI Higgins, Diana/0000-0002-6885-266X; Damschroder, Laura/0000-0002-3657-8459; Goodrich, David/0000-0003-3232-2189 FU Department of Veterans Affairs, Health Services Research and Development Service [IBB 09-034] FX This research was supported by grant IBB 09-034 from the Department of Veterans Affairs, Health Services Research and Development Service. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 34 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1778 EP 1784 DI 10.1002/oby.21160 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100010 PM 26237112 ER PT J AU Delahanty, LM Dalton, KM Porneala, B Chang, YC Goldman, VM Levy, D Nathan, DM Wexler, DJ AF Delahanty, Linda M. Dalton, Kristen M. Porneala, Bianca Chang, Yuchiao Goldman, Valerie M. Levy, Douglas Nathan, David M. Wexler, Deborah J. TI Improving diabetes outcomes through lifestyle change - A randomized controlled trial SO OBESITY LA English DT Article ID LOOK-AHEAD TRIAL; QUALITY-OF-LIFE; OBESE ADULTS; RISK-FACTORS; INTERVENTION; WEIGHT; HEALTH; IMPACT; INDIVIDUALS; PREVENTION AB ObjectiveTo compare a diabetes group lifestyle intervention (GLI) with dietitian referral for medical nutrition therapy (RD) for weight loss in the usual care setting. MethodsRandomized clinical trial was conducted with 57 primary care patients with type 2 diabetes and body mass index (BMI) >25 kg/m(2) who received either a dietitian-led 19-week GLI adapted from the Look AHEAD study or RD. Outcome measures include 6-month and 1-year weight loss, changes in medications, glycemic control, cardiac risk factors, and cost analysis. ResultsPatients were mean age 61, 59% male, and 32% non-white, and they weighed 97 kg with mean HbA1c 8.2%. At 6 months, 46% of GLI vs. 21% of RD lost 5% body weight (P=0.04), with mean weight loss 6.6 (SD 7.0) kg with GLI and 2.1 (3.5) kg in RD (P=0.004). HbA1c improved by 0.70 (1.13) vs. 0.39 (1.51) in GLI vs. RD (P=0.4), respectively, and 82% vs. 38% stopped or reduced diabetes medications (P<0.001). Weight loss remained significantly greater in GLI compared to RD at 1 year. GLI program cost was $578 per participant. ConclusionsAn affordable GLI achieved significantly more weight loss and medication reduction than RD in primary care patients with type 2 diabetes. C1 [Delahanty, Linda M.; Dalton, Kristen M.; Goldman, Valerie M.; Nathan, David M.; Wexler, Deborah J.] Massachusetts Gen Hosp, Dept Med, Ctr Diabet, Boston, MA 02114 USA. [Delahanty, Linda M.; Chang, Yuchiao; Levy, Douglas; Nathan, David M.; Wexler, Deborah J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Porneala, Bianca; Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Levy, Douglas] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Diabet, Boston, MA 02114 USA. EM ldelahanty@partners.org FU Massachusetts General Hospital Clinical Innovation Award FX Massachusetts General Hospital Clinical Innovation Award. NR 19 TC 2 Z9 2 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1792 EP 1799 DI 10.1002/oby.21172 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100012 PM 26260043 ER PT J AU Cirnigliaro, CM LaFountaine, MF Dengel, DR Bosch, TA Emmons, RR Kirshblum, SC Sauer, S Asselin, P Spungen, AM Bauman, WA AF Cirnigliaro, Christopher M. LaFountaine, Michael F. Dengel, Donald R. Bosch, Tyler A. Emmons, Racine R. Kirshblum, Steven C. Sauer, Sue Asselin, Pierre Spungen, Ann M. Bauman, William A. TI Visceral adiposity in persons with chronic spinal cord injury determined by dual energy X-Ray absorptiometry SO OBESITY LA English DT Article ID BODY-FAT DISTRIBUTION; WAIST CIRCUMFERENCE; INSULIN SENSITIVITY; ABDOMINAL ADIPOSITY; COMPUTED-TOMOGRAPHY; WEIGHT-LOSS; OBESITY; MEN; INDIVIDUALS; TISSUE AB ObjectiveTo determine visceral adipose tissue (VAT) volume (VAT(vol)) by dual energy X-ray absorptiometry (DXA) in spinal cord injured (SCI) and able-bodied (AB) participants and to explore the relationships between VAT(vol) and routine anthropometric measures. MethodsSixty-three subjects with SCI and 126 healthy male AB controls were stratified as low risk [LR: waist circumference (WC)<102 cm] and moderate to high risk (MHR: WC102 cm) for identification of risk for cardiometabolic disease: AB-LR, SCI-LR, AB-MHR, and SCI-MHR. Anthropometrics and standard body composition measurements by DXA with analysis to derive VAT(vol) were performed. ResultsComparison of the four subgroups demonstrated the highest subcutaneous adipose tissue volume (SAT(vol)) in the AB-MHR group (P<0.01), and the highest VAT(vol) in the SCI-MHR group (P<0.01). Furthermore, when compared to the AB group, participants with SCI had a 27% increase in VAT(vol) for every centimeter increase in WC and a 20% increase in VAT(vol) for every unit increase in BMI. ConclusionsBecause cutoff values for the routine surrogate measures of adiposity underestimate visceral adiposity in persons with SCI, the risk of adverse metabolic consequences would also be underestimated, which necessitates adjustment of the these cutoff values or, preferably, to perform its direct measurement. C1 [Cirnigliaro, Christopher M.; LaFountaine, Michael F.; Asselin, Pierre; Spungen, Ann M.; Bauman, William A.] Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs Rehabil Res & Dev Serv, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [LaFountaine, Michael F.] Seton Hall Univ, Inst Adv Study Rehabil & Sports Sci, Sch Hlth & Med Sci, S Orange, NJ 07079 USA. [LaFountaine, Michael F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA. [Dengel, Donald R.; Bosch, Tyler A.] Univ Minnesota, Sch Kinesiol, Minneapolis, MN USA. [Emmons, Racine R.] William Patterson Univ, Dept Kinesiol, Wayne, NJ USA. [Kirshblum, Steven C.; Sauer, Sue] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers State Univ, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07102 USA. [Spungen, Ann M.; Bauman, William A.] James J Peters Vet Affairs Med Ctr, Med Serv, Bronx, NY USA. [Spungen, Ann M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med & Rehabil Med, New York, NY 10029 USA. RP Cirnigliaro, CM (reprint author), Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs Rehabil Res & Dev Serv, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. EM christopher.cirnigliaro@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [B4162C]; James J. Peters Veterans Affairs Medical Center FX Veterans Affairs Rehabilitation Research and Development Service (#B4162C) and the James J. Peters Veterans Affairs Medical Center. NR 37 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1811 EP 1817 DI 10.1002/oby.21194 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100014 PM 26239944 ER PT J AU Milman, T Kao, AA Chu, D Gorski, M Steiner, A Simon, CZ Shih, C Aldave, AJ Eagle, RC Jakobiec, FA Udell, I AF Milman, Tatyana Kao, Andrew A. Chu, David Gorski, Matthew Steiner, Annie Simon, Carrie Zaslow Shih, Carolyn Aldave, Anthony J. Eagle, Ralph C., Jr. Jakobiec, Frederick A. Udell, Ira TI Paraproteinemic Keratopathy The Expanding Diversity of Clinical and Pathologic Manifestations SO OPHTHALMOLOGY LA English DT Article ID IMMUNOTACTOID GLOMERULOPATHY; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA; DEPOSITS; GLOMERULONEPHRITIS AB Purpose: To describe 7 patients with paraproteinemic keratopathy and to highlight the clinical and pathologic diversity of this rare entity and the importance of timely, systemic evaluation. Design: Retrospective, multicenter collaborative case series. Participants: Seven patients with paraproteinemic keratopathy. Methods: Clinical and pathologic records were reviewed to identify patients with well-documented corneal immunoglobulin deposits. Detailed ophthalmologic and medical histories were assembled. In 6 patients, corneal tissue was evaluated histochemically and immunohistochemically; in selected cases, corneal tissue was evaluated by in situ hybridization and ultrastructurally. Main Outcome Measures: Visual acuity and anterior segment examination at presentation and follow-up; local therapy; systemic diagnosis and management; and histopathologic, immunohistochemical, in situ hybridization, and ultrastructural findings. Results: Seven patients were identified with corneal immunoglobulin deposition. In addition to previously reported crystalline, nummular, patch-like, and lattice-like corneal opacities, prominent corneal vascularization was present in 2 patients mimicking interstitial keratitis and limbal stem cell deficiency. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenstrom macroglobulinemia. Corneal findings were the first manifestation of systemic disease in 4 patients, and the diagnosis was not suspected in 3 of these patients. Pathologic evaluation of biopsied corneal and conjunctival tissues demonstrated immunoglobulin deposits. Previously unreported ultrastructural patterns in the cornea were noted: large scroll-like immunotactoid deposits, immune complex-like deposits, and randomly arranged fibrils morphologically intermediate between amyloid and immunotactoid deposits. Surgical intervention to improve vision was performed in 4 patients, with recurrence of deposits in 3 patients. Three patients underwent systemic therapy with diminution of the deposits and improvement in vision in 1 patient. Conclusions: The clinical and pathologic expressions of corneal immunoglobulin deposits are protean and present a diagnostic challenge. Early recognition of this rare entity is important to address the potentially serious associated systemic disease. (C) 2015 by the American Academy of Ophthalmology. C1 [Milman, Tatyana; Kao, Andrew A.] New York Eye & Ear Infirm Mt Sinai, Dept Ophthalmol, New York, NY 10003 USA. [Milman, Tatyana; Kao, Andrew A.] New York Eye & Ear Infirm Mt Sinai, Dept Pathol, New York, NY 10003 USA. [Chu, David] Metropolitan Eye Res & Surg Inst, Palisades Pk, NJ USA. [Gorski, Matthew; Steiner, Annie; Simon, Carrie Zaslow; Shih, Carolyn; Udell, Ira] North Shore Long Isl Jewish Hlth Syst, Dept Ophthalmol, Manhasset, NY USA. [Aldave, Anthony J.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Eagle, Ralph C., Jr.] Thomas Jefferson Univ, Wills Eye Hosp, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Eagle, Ralph C., Jr.] Thomas Jefferson Univ, Wills Eye Hosp, Dept Pathol, Philadelphia, PA 19107 USA. [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Eye Pathol, Boston, MA 02114 USA. RP Milman, T (reprint author), New York Eye & Ear Infirm Mt Sinai, Dept Ophthalmol, 310 East 14th St, New York, NY 10003 USA. EM tatyana.milman@gmail.com NR 12 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2015 VL 122 IS 9 BP 1748 EP 1756 DI 10.1016/j.ophtha.2015.05.029 PG 9 WC Ophthalmology SC Ophthalmology GA CP8BU UT WOS:000360116900012 PM 26118999 ER PT J AU Comander, J Weigel-DiFranco, C Sandberg, MA Berson, EL AF Comander, Jason Weigel-DiFranco, Carol Sandberg, Michael A. Berson, Eliot L. TI Visual Function in Carriers of X-Linked Retinitis Pigmentosa SO OPHTHALMOLOGY LA English DT Article ID RPGR GENE; DISEASE COURSE; EXON ORF15; MUTATIONS; RP2; CHROMOSOME; ELECTRORETINOGRAM AB Purpose: To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). Design: Case series. Participants: Two hundred seventy-six XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34; median follow-up, 16 years; follow-up range, 3-37 years). Half of the carriers were from RPGR-or RP2-genotyped families. Methods: Retrospective medical records review. Main Outcome Measures: Visual acuities, visual field areas, final dark adaptation thresholds, and full-field electroretinography (ERG) responses to 0.5-Hz and 30-Hz flashes. Results: In genotyped families, 40% of carriers showed a baseline abnormality on at least 1 of 3 psychophysical tests. There was a wide range of function among carriers. For example, 3 of 121 (2%) genotyped carriers were legally blind because of poor visual acuity, some as young as 35 years. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30-Hz flashes was approximately 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs. 7.4%/year, respectively). Among obligate carriers with affected fathers, sons, or both, 53 of 55 (96%) had abnormal baseline ERG results. Some carriers who initially had completely normal fundi in both eyes went on to experience moderately decreased vision, although not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared with those in exons 1-14, had worse final dark adaptation thresholds and lower 0.5-Hz and 30-Hz ERG amplitudes. Conclusions: Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1 through 14 mutations. Because XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, these observations were consistent with the Lyon hypothesis of random X-inactivation. (C) 2015 by the American Academy of Ophthalmology. C1 [Comander, Jason; Weigel-DiFranco, Carol; Sandberg, Michael A.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Comander, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St,Room 501B, Boston, MA 02114 USA. EM jason_comander@meei.harvard.edu FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [K12 EY16335]; Research to Prevent Blindness, Inc., New York, New York; Foundation Fighting Blindness, Owings Mills, MD FX Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: K12 EY16335 [J.C.]); Research to Prevent Blindness, Inc., New York, New York (Career Development Award [J.C.]); and the Foundation Fighting Blindness, Owings Mills, MD (Center Grant [E.L.B.]). The funding organizations had no role in the design or conduct of this research. NR 36 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2015 VL 122 IS 9 BP 1899 EP 1906 DI 10.1016/j.ophtha.2015.05.039 PG 8 WC Ophthalmology SC Ophthalmology GA CP8BU UT WOS:000360116900032 PM 26143542 ER PT J AU Moore, TM Scott, JC Reise, SP Port, AM Jackson, CT Ruparel, K Savitt, AP Gur, RE Gur, RC AF Moore, Tyler M. Scott, J. Cobb Reise, Steven P. Port, Allison M. Jackson, Chad T. Ruparel, Kosha Savitt, Adam P. Gur, Raquel E. Gur, Ruben C. TI Development of an Abbreviated Form of the Penn Line Orientation Test Using Large Samples and Computerized Adaptive Test Simulation SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE psychometrics; Penn Computerized Neurocognitive Battery; item response theory; computerized adaptive testing; line orientation test ID ITEM RESPONSE THEORY; CEREBRAL BLOOD-FLOW; NEUROCOGNITIVE BATTERY; SEX-DIFFERENCES; SCHIZOPHRENIA; JUDGMENT; PERFORMANCE; ENDOPHENOTYPES; INTERNET; QUESTIONNAIRES AB Visuospatial processing is a commonly assessed neurocognitive domain with deficits linked to dysfunction in right posterior regions of the brain. With the growth of large-scale clinical research studies, there is an increased need for efficient and scalable assessments of neurocognition, including visuospatial processing. The purpose of the current study was to use a novel method that combines item response theory (IRT) and computerized adaptive testing (CAT) approaches to create an abbreviated form of the computerized Penn Line Orientation Test (PLOT). The 24-item PLOT was administered to 8,498 youths (aged 8-21 years) as part of the Philadelphia Neurodevelopmental Cohort study and, by Web-based data collection, in an independent sample of 4,593 adults from Great Britain as part of a TV documentary. IRT-based CAT simulations were used to select the best PLOT items for an abbreviated form by performing separate simulations in each group and choosing only items that were selected as useful (i.e., high item discrimination and in the appropriate difficulty range) in at least 1 of the simulations. Fifteen items were chosen for the final, short form of the PLOT, indicating substantial agreement among the models in how they evaluated each item's usefulness. Moreover, this abbreviated version performed comparably to the full version in tests of sensitivity to age and sex effects. This abbreviated version of the PLOT cuts administration time by 50% without detectable loss of information, which points to its feasibility for large-scale clinical and genomic studies. C1 [Moore, Tyler M.; Scott, J. Cobb; Port, Allison M.; Jackson, Chad T.; Ruparel, Kosha; Savitt, Adam P.; Gur, Raquel E.; Gur, Ruben C.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Scott, J. Cobb; Gur, Ruben C.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA. [Reise, Steven P.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Gur, RC (reprint author), Univ Penn, Brain Behav Lab, Perelman Sch Med, 3400 Spruce St,10th Floor Gates Pavil, Philadelphia, PA 19104 USA. EM gur@upenn.edu FU National Institute of Mental Health [MH089983, MH019112, MH096891]; Department of Veterans Affairs [1IK2CX000772] FX This work was supported by National Institute of Mental Health grants MH089983, MH019112, and MH096891. J. Cobb Scott's contribution was supported by Department of Veterans Affairs Career Development Award 1IK2CX000772. NR 46 TC 2 Z9 2 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 SEP PY 2015 VL 27 IS 3 BP 955 EP 964 DI 10.1037/pas0000102 PG 10 WC Psychology, Clinical SC Psychology GA CQ1UX UT WOS:000360386700023 PM 25822834 ER PT J AU Chandregowda, A Arbel, Y Lucchio, S Manasterski, C Donchin, E AF Chandregowda, Adithya Arbel, Yael Lucchio, Samantha Manasterski, Christine Donchin, Emanuel TI DETECTING ERRORS IN OTHERS' SPEECH: AN ERP INVESTIGATION SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 30-OCT 04, 2015 CL Seattle, WA SP Soc Psychophysiol Res DE speech errors; error-related negativity; P300 C1 [Chandregowda, Adithya; Lucchio, Samantha; Manasterski, Christine; Donchin, Emanuel] Univ S Florida, Tampa, FL 33620 USA. [Arbel, Yael] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2015 VL 52 SU 1 SI SI MA 4-90 BP S122 EP S122 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CQ2PS UT WOS:000360444100522 ER PT J AU Hazlett, EA Blair, NJ Fernandez, NG New, AS Goodman, M AF Hazlett, Erin A. Blair, Nicholas J. Fernandez, Nicolas G. New, Antonia S. Goodman, Marianne TI GENDER DIFFERENCES IN AFFECTIVE STARTLE MODULATION AND EMOTION REGULATION IN BORDERLINE PERSONALITY DISORDER SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 30-OCT 04, 2015 CL Seattle, WA SP Soc Psychophysiol Res DE startle; borderline personality disorder; emotion regulation C1 Icahn Sch Med Mt Sinai, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2015 VL 52 SU 1 SI SI MA 3-82 BP S94 EP S94 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CQ2PS UT WOS:000360444100404 ER PT J AU Lake, JI Infantolino, ZP Spielberg, JM Crocker, LD Yee, CM Heller, W Miller, GA AF Lake, Jessica I. Infantolino, Zachary P. Spielberg, Jeffrey M. Crocker, Laura D. Yee, Cindy M. Heller, Wendy Miller, Gregory A. TI INTOLERANCE OF UNCERTAINTY MODULATES PERFORMANCE AND NEURAL ACTIVITY DURING THE ANTICIPATION OF PUNISHMENT SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 30-OCT 04, 2015 CL Seattle, WA SP Soc Psychophysiol Res DE uncertainty; punishment; anticipation C1 [Lake, Jessica I.; Yee, Cindy M.; Miller, Gregory A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Infantolino, Zachary P.] Univ Delaware, Newark, DE 19716 USA. [Spielberg, Jeffrey M.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Crocker, Laura D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Heller, Wendy] Univ Illinois, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2015 VL 52 SU 1 SI SI MA 1-3 BP S23 EP S23 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CQ2PS UT WOS:000360444100109 ER PT J AU Sheerin, CM Konig, A Eonta, AM Vrana, SR AF Sheerin, Christina M. Konig, Andrea Eonta, Alison M. Vrana, Scott R. TI CHANGE IN RESPIRATORY SINUS ARRHYTHMIA OVER TIME DURING AN EXPRESSIVE WRITING TASK SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 30-OCT 04, 2015 CL Seattle, WA SP Soc Psychophysiol Res DE heart rate variability; expressive writing C1 [Sheerin, Christina M.] Richmond VAMC, Richmond, VA USA. [Sheerin, Christina M.; Vrana, Scott R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Konig, Andrea] Bon Secours St Marys Hosp Richmond Hlth Syst, Richmond, VA USA. [Eonta, Alison M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2015 VL 52 SU 1 SI SI MA 4-13 BP S104 EP S104 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CQ2PS UT WOS:000360444100445 ER PT J AU Rosenfeld, EA Marx, J Terry, MA Stall, R Pallatino, C Miller, E AF Rosenfeld, Elian A. Marx, John Terry, Martha A. Stall, Ron Pallatino, Chelsea Miller, Elizabeth TI Healthcare providers' perspectives on expedited partner therapy for chlamydia: a qualitative study SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; US PHYSICIANS; NOTIFICATION; GONORRHEA; PRACTITIONERS; ATTITUDES; TRIAL; STD; UK AB Objectives Expedited partner therapy (EPT) effectively reduces rates of reinfection with chlamydia and increases the number of partners treated for the infection. Healthcare provider (HCP) provision of EPT is low. The objective of this qualitative study was to understand HCP views and opinions regarding the use of EPT in a state where EPT is permissible but underused. Methods Using a purposive sampling strategy to include diverse HCPs who treat young women at risk for chlamydia, 23 semistructured, in-depth interviews were conducted between October and December 2013. The interviews included questions about knowledge, attitudes, experiences with, and barriers and facilitators regarding the use of EPT. Results Many respondents report using EPT and believe the practice is beneficial for their patients. Most providers were unaware of their colleagues' practices and had limited knowledge regarding institutional policies around EPT. HCPs noted a variety of barriers, such as fear of liability, confusion around the legal status of EPT and not being able to counsel patients' partners that make routine use of this practice a challenge. Facilitators of EPT include speaking on the phone with patients' partners and establishing legislation enabling EPT. Conclusions This is the first study to qualitatively examine HCPs' perspectives on EPT in the USA. Barriers to EPT, including concerns about counselling patients' partners and the legal status of EPT, can be overcome. EPT recommendations could include the use of phone calls as part of their guidelines. Changing EPT legislation at the state level in the USA is an important factor to facilitate EPT use. C1 [Rosenfeld, Elian A.] VA Pittsburgh Healthcare Syst, VA Womens Hlth, Pittsburgh, PA 15240 USA. [Marx, John; Terry, Martha A.; Stall, Ron; Pallatino, Chelsea] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Miller, Elizabeth] Univ Pittsburgh, Childrens Hosp Pittsburgh UPMC, Div Adolescent Med, Pittsburgh, PA USA. RP Rosenfeld, EA (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C 151C Bldg 30, Pittsburgh, PA 15240 USA. EM elian.rosenfeld@va.gov FU University of Pittsburgh FX The Myrna Silverman Award and William Green Award from the University of Pittsburgh. NR 25 TC 3 Z9 3 U1 4 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 EI 1472-3263 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD SEP PY 2015 VL 91 IS 6 BP 407 EP 411 DI 10.1136/sextrans-2014-051873 PG 5 WC Infectious Diseases SC Infectious Diseases GA CP9BZ UT WOS:000360190000008 PM 25792537 ER PT J AU Keddem, S Barg, FK Glanz, K Jackson, T Green, S George, M AF Keddem, Shimrit Barg, Frances K. Glanz, Karen Jackson, Tara Green, Sarah George, Maureen TI Mapping the urban asthma experience: Using qualitative GIS to understand contextual factors affecting asthma control SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Asthma control; Disparities; Geographic information systems; Semi-structured interviews ID NEW-YORK-CITY; GEOGRAPHIC INFORMATION-SYSTEMS; PHYSICAL-ACTIVITY; CHILDHOOD ASTHMA; AIR-POLLUTION; MIXED METHODS; HEALTH; OBESITY; DISPARITIES; COMMUNITY AB Asthma is complex and connected to a number of factors including access to healthcare, crime and violence, and environmental triggers. A mixed method approach was used to examine the experiences of urban people with asthma in controlling their asthma symptoms. The study started with an initial phase of qualitative interviews in West Philadelphia, a primarily poor African American community. Data from qualitative, semi-structured interviews indicated that stress, environmental irritants, and environmental allergens were the most salient triggers of asthma. Based on the interviews, the team identified six neighborhood factors to map including crime, housing vacancy, illegal dumping, tree canopy and parks. These map layers were combined into a final composite map. These combined methodologies contextualized respondents' perceptions in the framework of the actual community and built environment which tells a more complete story about their experience with asthma. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Keddem, Shimrit] Univ Penn, Perelman Sch Med, Dept Gen Internal Med, Philadelphia, PA 19104 USA. [Keddem, Shimrit] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Perelman Sch Med, Mixed Methods Res Lab, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Perelman Sch Med, Dept Family Med, Philadelphia, PA 19104 USA. [Glanz, Karen; George, Maureen] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Glanz, Karen; Green, Sarah] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jackson, Tara] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Cartog Modeling Lab, Philadelphia, PA 19104 USA. RP Keddem, S (reprint author), Philadelphia VA Med Ctr, CEPACT, 4100 Chester Ave,Ste 203, Philadelphia, PA 19104 USA. EM Shimrit.keddem@uphs.upenn.edu NR 52 TC 3 Z9 3 U1 6 U2 42 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 SEP PY 2015 VL 140 BP 9 EP 17 DI 10.1016/j.socscimed.2015.06.039 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CP9ZE UT WOS:000360253600002 PM 26184704 ER PT J AU Macintosh, PW Jakobiec, FA Stagner, AM Gilani, S Fay, A AF Macintosh, Peter W. Jakobiec, Frederick A. Stagner, Anna M. Gilani, Sapideh Fay, Aaron TI High grade neuroendocrine neoplasm of the antrum and orbit SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE neuroendocrine carcinoma; esthesioneuroblastoma; sinonasal carcinoma; immunohistochemistry; sinusitis; orbital tumor; orbit ID SMALL-CELL-CARCINOMA; PARANASAL SINUSES; NASAL CAVITY; SINONASAL MALIGNANCIES; LUNG-CANCER; ESTHESIONEUROBLASTOMA; TUMOR; ACTINOMYCOSIS; DIFFERENTIATION; NEUROBLASTOMA AB Neuroendocrine malignancies tumors characterized by the production of dense-core secretory granules are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. (C) 2015 Elsevier Inc. All rights reserved. C1 [Macintosh, Peter W.; Jakobiec, Frederick A.; Stagner, Anna M.; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Macintosh, Peter W.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast & Reconstruct Surg, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Gilani, Sapideh] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 38 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 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 2015 VL 60 IS 5 BP 486 EP 494 DI 10.1016/j.survophthal.2015.03.002 PG 9 WC Ophthalmology SC Ophthalmology GA CQ0YU UT WOS:000360325300007 PM 26077631 ER PT J AU Tran, NH Cavalcante, LL Lubner, SJ Mulkerin, DL LoConte, NK Clipson, L Matkowskyj, KA Deming, DA AF Tran, Nguyen H. Cavalcante, Ludmila L. Lubner, Sam J. Mulkerin, Daniel L. LoConte, Noelle K. Clipson, Linda Matkowskyj, Kristina A. Deming, Dustin A. TI Precision medicine in colorectal cancer: the molecular profile alters treatment strategies SO THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY LA English DT Review DE BRAF; cetuximab; KRAS; NRAS; panitumumab; PIK3CA ID KRAS WILD-TYPE; 1ST-LINE TREATMENT; ANTIBODY THERAPY; RANDOMIZED-TRIAL; RAS MUTATIONS; COLON CANCERS; POOR SURVIVAL; PIK3CA GENE; CETUXIMAB; FLUOROURACIL AB When considering treatment options for patients with metastatic colorectal cancer (mCRC), molecular profiling has become a pivotal component in guiding clinical decisions. FOLFOX and FOLFIRI (fluorouracuil, leucovorin plus oxaliplatin or ininotecan, respectively) are the standard base regimens used for the treatment of mCRC. Biologic agents, such as the epidermal growth factor receptor (EGFR) targeted therapies, cetuximab and panitumumab and the vascular endothelial growth factor monoclonal antibody, bevacizumab, are safe and effective in the first-line setting. The most efficacious use of these agents in terms of timing and selection of the right patient population continues to be debated. Here we review multiple investigations into the effectiveness of treatment options as a function of the mutations present in colon cancers. Early studies have reported that KRAS mutations at exon 2 predict resistance to EGFR targeted therapies. More recently the data have expanded to include KRAS mutations at exons 3 and 4 and NRAS mutations at exons 2, 3 and 4 as well as other biomarkers including BRAF and PIK3CA, leading to the evolution of the treatment of mCRC to a more precision-based approach. As our understanding of relevant biomarkers increases, and data from both molecular profiling and treatment response become more readily available, treatment options will become more precise and their outcomes more effective. C1 [Tran, Nguyen H.; Cavalcante, Ludmila L.; Lubner, Sam J.; Mulkerin, Daniel L.; LoConte, Noelle K.; Deming, Dustin A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Hematol & Oncol, Madison, WI 53792 USA. [Cavalcante, Ludmila L.; Lubner, Sam J.; Mulkerin, Daniel L.; LoConte, Noelle K.; Matkowskyj, Kristina A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA. [Clipson, Linda] Univ Wisconsin, Dept Oncol, Madison, WI 53792 USA. [Matkowskyj, Kristina A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Matkowskyj, Kristina A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Deming, DA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Hematol & Oncol, 600 Highland Ave,K6-544, Madison, WI 53792 USA. EM ddeming@medicine.wisc.edu FU National Institutes of Health (Core Grant, University of Wisconsin Carbone Cancer Center) [P30 CA014520] FX This work was supported by the National Institutes of Health (P30 CA014520, Core Grant, University of Wisconsin Carbone Cancer Center). NR 43 TC 14 Z9 14 U1 0 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1758-8340 EI 1758-8359 J9 THER ADV MED ONCOL JI Ther. Adv. Med. Oncol. PD SEP PY 2015 VL 7 IS 5 BP 252 EP 262 DI 10.1177/1758834015591952 PG 11 WC Oncology SC Oncology GA CQ0KK UT WOS:000360283800002 PM 26327923 ER PT J AU Connolly, JJ Glessner, JT Kao, C Elia, J Hakonarson, H AF Connolly, J. J. Glessner, J. T. Kao, C. Elia, J. Hakonarson, H. TI Attention-Deficit Hyperactivity Disorder and PharmacotherapyPast, Present, and Future: A Review of the Changing Landscape of Drug Therapy SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Review DE ADHD; pharmacotherapy; pharmacology; drug; medication; adverse events ID COGNITION ENHANCER NS-105; METABOTROPIC GLUTAMATE RECEPTORS; ADENYLATE-CYCLASE ACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER; PREFRONTAL CORTEX; STIMULANT MEDICATION; CLINICAL-RESPONSE; FOLLOW-UP; ADHD AB Attention-deficit hyperactivity disorder (ADHD) is the most common neurobiological disorder in children. Efficacy of pharmacotherapy in treating ADHD symptoms has generally been considerable with at least three-fourths of individuals benefiting from pharmacotherapy, typically in the form of stimulants. In this review, we begin by briefly reviewing the history of pharmacotherapy in relation to ADHD, before focusing (primarily) on the state of the field on themes such as biophysiology, pharmacokinetics, and pharmacogenomics. We conclude with a summary of emerging clinical and research studies, particularly the potential role for precision therapy in matching ADHD patients and drug types. C1 [Connolly, J. J.; Kao, C.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Glessner, J. T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Glessner, J. T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Elia, J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Elia, J.] Thomas Jefferson Univ, Dept Psychiat, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Elia, J.] Thomas Jefferson Univ, Dept Pediat, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Elia, J.] Univ Penn, Al Dupont Hosp Children, Philadelphia, PA 19104 USA. [Hakonarson, H.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, 3615 Civ Ctr Blvd,Abramson Bldg 1216E, Philadelphia, PA 19104 USA. EM Hakonarson@email.chop.edu FU NHGRI as part of Electronic Medical Record and Genomics (eMERGE) Network [U01HG006830]; Institutional Development Fund from Children's Hospital of Philadelphia FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Support for this work was provided by the NHGRI as part of Electronic Medical Record and Genomics (eMERGE) Network to The Children's Hospital of Philadelphia (U01HG006830), and by Institutional Development Fund grant from The Children's Hospital of Philadelphia. NR 80 TC 3 Z9 3 U1 9 U2 36 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD SEP PY 2015 VL 49 IS 5 BP 632 EP 642 DI 10.1177/2168479015599811 PG 11 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA CQ2FG UT WOS:000360414200004 PM 26366330 ER PT J AU Wang, YT Mohammed, SD Farmer, AD Wang, D Zarate, N Hobson, AR Hellstrom, PM Semler, JR Kuo, B Rao, SS Hasler, WL Camilleri, M Scott, SM AF Wang, Y. T. Mohammed, S. D. Farmer, A. D. Wang, D. Zarate, N. Hobson, A. R. Hellstrom, P. M. Semler, J. R. Kuo, B. Rao, S. S. Hasler, W. L. Camilleri, M. Scott, S. M. TI Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID WHOLE GUT TRANSIT; SMALL-BOWEL TRANSIT; COLONIC TRANSIT; RADIOTELEMETRY DEVICE; CHRONIC CONSTIPATION; INTESTINAL TRANSIT; CLINICAL-PRACTICE; BREATH TEST; TIME; SCINTIGRAPHY AB BackgroundThe wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AimTo investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. MethodsRegional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. ResultsFor GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52min, P=0.0063) and colonic transit time (CTT; longer with protocol 2: median 140min, P=0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17min, P=0.0307), and also longer CTT by (104min, P=0.0285) and whole gut transit time by (263min, P=0.0077). Increasing age was associated with shorter small bowel transit time (P=0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. ConclusionsRegional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research. C1 [Wang, Y. T.; Mohammed, S. D.; Farmer, A. D.; Scott, S. M.] Queen Mary Univ, Blizard Inst Cell & Mol Sci, Neurogastroenterol Grp, GI Physiol Unit, London, England. [Farmer, A. D.] Royal Stoke Univ Hosp, Univ Hosp North Midlands, Stoke On Trent, Staffs, England. [Wang, D.] Univ Liverpool, Liverpool Sch Trop Med, Biostat Unit, Dept Clin Sci, Liverpool L3 5QA, Merseyside, England. [Zarate, N.] Univ Coll London Hosp, Dept Gastroenterol, London, England. [Hobson, A. R.] Funct Gut Clin, London, England. [Hellstrom, P. M.] Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden. [Semler, J. R.] Medtronic, Minneapolis, MN USA. [Kuo, B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02115 USA. [Rao, S. S.] Georgia Hlth Sci Univ, Med Coll Georgia, Sect Gastroenterol & Hepatol, Augusta, GA USA. [Hasler, W. L.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA. [Camilleri, M.] Mayo Clin, Div Gastroenterol & Hepatol, CENTER, Rochester, MN USA. RP Scott, SM (reprint author), Wingate Inst Neurogastroenterol, 26 Ashfield St, London E1 2AJ, England. EM m.scott@qmul.ac.uk FU SmartPill Corporation FX Declaration of funding interests: The healthy control research was supported by a grant from the SmartPill Corporation. NR 56 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2015 VL 42 IS 6 BP 761 EP 772 DI 10.1111/apt.13329 PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA CP4MJ UT WOS:000359855900011 PM 26223837 ER PT J AU Pollack, SF Geffrey, AL Thiele, EA Shah, U AF Pollack, Sarah F. Geffrey, Alexandra L. Thiele, Elizabeth A. Shah, Uzma TI Primary Intestinal Lymphangiectasia Treated With Rapamycin in a Child With Tuberous Sclerosis Complex (TSC) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE primary intestinal lymphangiectasia (PIL); tuberous sclerosis complex (TSC); rapamycin; mTOR ID LYMPHANGIOLEIOMYOMATOSIS; LYMPHEDEMA; SIROLIMUS; SEVERITY; EFFICACY; DISEASE AB Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF-C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies. (C) 2015 Wiley Periodicals, Inc. C1 [Pollack, Sarah F.; Geffrey, Alexandra L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. [Shah, Uzma] Massachusetts Gen Hosp, Dept Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. RP Shah, U (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol Hepatol & Nutr, 55 Fruit St, Boston, MA 02114 USA. EM ushah@mgh.harvard.edu FU Herscot Center for Tuberous Sclerosis Complex FX Thank you to the Herscot Center for Tuberous Sclerosis Complex for supporting this study. NR 16 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 2209 EP 2212 DI 10.1002/ajmg.a.37148 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700034 PM 25943403 ER PT J AU Williams, RM Turner, AP Green, M Norvell, DC Henderson, AW Hakimi, KN Blake, DJ Czerniecki, JM AF Williams, Rhonda M. Turner, Aaron P. Green, Monica Norvell, Daniel C. Henderson, Alison W. Hakimi, Kevin N. Blake, Donna Jo Czerniecki, Joseph M. TI Relationship Between Cognition and Functional Outcomes After Dysvascular Lower Extremity Amputation A Prospective Study SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article ID LOWER-LIMB AMPUTATION; FOLLOW-UP; DISABILITY; AMPUTEES; QUESTIONNAIRE; PREDICT; PROSTHESIS; ADJUSTMENT; HANDICAP; VALIDITY AB Objective The aim of this study was to examine associations between a cognitive screen and four neuropsychologic tests administered at both 6 wks and 4 mos after amputation and five functional outcomes measured 12 mos after lower extremity amputation. Design This study includes a prospective cohort from four medical centers. Participants were primarily male Veterans experiencing their first lower extremity amputation as a result of complications of diabetes mellitus or peripheral arterial disease. Of those eligible, 87 (64%) enrolled; 75 (86%) were retained at 12 mos. Measures included demographic/health information, four neuropsychologic measures, the Locomotor Capability Index-5, the Gronigen Activity Restriction Scale, prosthetic use, community participation, and social integration. Results Better performance on the Short Portable Mental Status Questionnaire at 4 mos was associated with greater 12-mo mobility and social integration. Better attention and working memory abilities 6 wks after amputation were associated with increased 12-mo prosthetic wear; and at 4 mos after amputation, with greater 12-mo mobility. Better verbal memory at 6 wks was associated with greater 12-mo social integration and community participation as well as increased prosthetic wear. Conclusions These findings highlight the potential value in including a brief, formal cognitive assessment in addition to a general mental status screen. Specific domains of cognitive function are differentially associated with functional outcomes and may inform amputation rehabilitation decisions. C1 [Williams, Rhonda M.; Turner, Aaron P.; Green, Monica; Henderson, Alison W.; Hakimi, Kevin N.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Williams, Rhonda M.; Turner, Aaron P.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. [Blake, Donna Jo] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Blake, Donna Jo] Univ Colorado, Denver, CO 80202 USA. RP Williams, RM (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. OI Turner, Aaron/0000-0001-6897-8003 FU United States Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [A41241, B4927W] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (Merit Review A41241 Joseph Czerniecki, principal investigator, and Career Development Award B4927W Aaron P. Turner, principal investigator). Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 38 TC 1 Z9 1 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2015 VL 94 IS 9 BP 707 EP 717 DI 10.1097/PHM.0000000000000235 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CP5PI UT WOS:000359935400005 PM 25357146 ER PT J AU Thorpe, JM Thorpe, CT Schulz, R Van Houtven, CH Schleiden, L AF Thorpe, Joshua M. Thorpe, Carolyn T. Schulz, Richard Van Houtven, Courtney H. Schleiden, Loren TI Informal Caregiver Disability and Access to Preventive Care in Care Recipients SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID EXPENDITURE PANEL SURVEY; HEALTH-CARE; FAMILY CAREGIVERS; OLDER-ADULTS; PSYCHOLOGICAL DISTRESS; MEDICATION ADHERENCE; ELDERLY PATIENTS; RISK-FACTOR; SERVICES; DEMENTIA AB Introduction: Many informal caregivers of dependent midlife and older adults suffer from their own functional limitations. The impact of caregiver functional limitations on care recipient receipt of preventive services is unknown. The purpose of this study is to examine the association between caregiver functional limitations and decreased access to recommended preventive services in dependent care recipients. Methods: Dependent adults (those receiving assistance with activities of daily living or instrumental activities of daily living) and their primary informal caregiver were identified from pooled alternate years (2000-2008) of the nationally representative Medical Expenditure Panel Survey (data analyzed February-October 2014). The impact of caregiver limitations (cognitive, mobility, sensory, emotional health) on care recipient's receipt of up to seven different preventive services was assessed via survey-weighted linear and logistic regression. Results: Of the 5-year weighted estimate of 14.2 million caregiver-care recipient dyads, 38.0% of caregivers reported at least one functional limitation. The percentage of recommended preventive services received by care recipients was significantly lower if the caregiver had cognitive, mobility, or emotional health limitations. Each type of caregiver functional limitation was negatively associated with at least four different preventive services. Conclusions: Informal caregivers burdened by their own functional impairments may face challenges in facilitating access to preventive care in dependent midlife and older adults. Policies and interventions designed to prevent or mitigate the impact of caregiver functional impairments are critical to the success of community-based models of care for dependent adults. (C) 2015 American Journal of Preventive Medicine C1 [Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15261 USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.; Schleiden, Loren] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Schulz, Richard] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Schulz, Richard] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15261 USA. [Van Houtven, Courtney H.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Van Houtven, Courtney H.] Duke Univ, Med Ctr, Sch Med, Div Gen Internal Med, Durham, NC 27710 USA. RP Thorpe, JM (reprint author), Univ Pittsburgh, Sch Pharm, 916 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM jmthorpe@pitt.edu FU National Institute of Nursing Research (NINR) [1R01 NR014434] FX R. Schulz received funding support from a National Institute of Nursing Research (NINR) R01 on tailored technology interventions among caregivers of Alzheimer disease patients (1R01 NR014434). The NINR had no role in the study design, analysis, interpretation of data, writing of the manuscript, or the decision to submit for publication. NR 47 TC 0 Z9 0 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2015 VL 49 IS 3 BP 370 EP 379 DI 10.1016/j.amepre.2015.02.003 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CP5VX UT WOS:000359954200005 PM 26091932 ER PT J AU Karimkhani, C Boyers, LN Schilling, LM Dellavalle, RP AF Karimkhani, Chante Boyers, Lindsay N. Schilling, Lisa M. Dellavalle, Robert P. TI The Surgeon General Should Say That Indoor Ultraviolet Radiation Tanning Causes Skin Cancer SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID METAANALYSIS; ASSOCIATION C1 [Karimkhani, Chante] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Schilling, Lisa M.] Univ Colorado, Dept Med, Aurora, CO USA. [Dellavalle, Robert P.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO USA. [Dellavalle, Robert P.] US Dept Vet Affairs, Dermatol Serv, Eastern Colorado Hlth Care Syst, Denver, CO USA. RP Dellavalle, RP (reprint author), Dept Vet Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu NR 10 TC 2 Z9 2 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2015 VL 49 IS 3 BP 437 EP 440 DI 10.1016/j.amepre.2015.02.006 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CP5VX UT WOS:000359954200015 PM 25863587 ER PT J AU Soulez, G Bloomgarden, DC Rofsky, NM Smith, MP Abujudeh, HH Morgan, DE Lichtenstein, RJ Schiebler, ML Wippold, FJ Russo, C Kuhn, MJ Mennitt, KW Maki, JH Stolpen, A Liou, J Semelka, RC Kirchin, MA Shen, NY Pirovano, G Spinazzi, A AF Soulez, Gilles Bloomgarden, Daniel C. Rofsky, Neil M. Smith, Martin P. Abujudeh, Hani H. Morgan, Desiree E. Lichtenstein, Richard J. Schiebler, Mark L. Wippold, Franz J., II Russo, Craig Kuhn, Matthew J. Mennitt, Kevin W. Maki, Jeffrey H. Stolpen, Alan Liou, Johnson Semelka, Richard C. Kirchin, Miles A. Shen, Ningyan Pirovano, Gianpaolo Spinazzi, Alberto TI Prospective Cohort Study of Nephrogenic Systemic Fibrosis in Patients With Stage 3-5 Chronic Kidney Disease Undergoing MRI With Injected Gadobenate Dimeglumine or Gadoteridol SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE gadobenate dimeglumine; gadoteridol; nephrogenic systemic fibrosis; prospective studies ID GLOMERULAR-FILTRATION-RATE; RESONANCE CONTRAST AGENTS; CHRONIC-RENAL-FAILURE; GADOLINIUM; RISK; DIALYSIS; SAFETY; PHARMACOKINETICS; INSUFFICIENCY; HEMODIALYSIS AB OBJECTIVE. The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderateto- severe impairment of kidney function who had not previously been exposed to gadolinium- based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND METHODS. Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [ eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years. RESULTS. For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C. CONCLUSION. To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF. C1 [Soulez, Gilles] Hop Notre Dame de Bon Secours, Ctr Hosp Univ Montreal, Montreal, PQ H2L 4K8, Canada. [Bloomgarden, Daniel C.] Milwaukee Radiologists Ltd, St Lukes Med Ctr, Milwaukee, WI USA. [Rofsky, Neil M.; Smith, Martin P.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Morgan, Desiree E.] Univ Alabama Birmingham, Sch Med, Dept Radiol, Birmingham, AL 35233 USA. [Lichtenstein, Richard J.] Sarasota Mem Hosp, Dept Radiol, Sarasota, FL USA. [Schiebler, Mark L.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Wippold, Franz J., II] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Russo, Craig] Clin Radiologists SC, Springfield, IL USA. [Kuhn, Matthew J.] St Johns Hosp, Dept Radiol, Springfield, IL USA. [Mennitt, Kevin W.] Weill Cornell Med Coll, Diagnost Radiol, New York, NY USA. [Maki, Jeffrey H.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Stolpen, Alan] Univ Iowa Hosp & Clin, Dept Radiol, Iowa City, IA 52242 USA. [Liou, Johnson] Radiol Associates Atlanta, Atlanta, GA USA. [Semelka, Richard C.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. [Kirchin, Miles A.] Bracco Imaging SpA, Global Med & Regulatory Affairs, I-20134 Milan, Italy. [Shen, Ningyan; Pirovano, Gianpaolo; Spinazzi, Alberto] Bracco Diagnost Inc, Global Med & Regulatory Affairs, Monroe Township, NJ USA. RP Kirchin, MA (reprint author), Bracco Imaging SpA, Global Med & Regulatory Affairs, Via Caduti Marcinelle 13, I-20134 Milan, Italy. EM miles.kirchin@bracco.com NR 51 TC 12 Z9 14 U1 0 U2 7 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 SEP PY 2015 VL 205 IS 3 BP 469 EP 478 DI 10.2214/AJR.14.14268 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP6KW UT WOS:000359997100026 PM 26295633 ER PT J AU Keraliya, AR Krajewski, KM Giardino, AA Tirumani, SH Shinagare, AB Ramaiya, NH Jagannathan, JP AF Keraliya, Abhishek R. Krajewski, Katherine M. Giardino, Angela A. Tirumani, Sree Harsha Shinagare, Atul B. Ramaiya, Nikhil H. Jagannathan, Jyothi P. TI Imaging of Nervous System Involvement in Hematologic Malignancies: What Radiologists Need to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CNS; hematologic malignancies; lymphoma; MRI ID PRIMARY CNS LYMPHOMA; LANGERHANS CELL HISTIOCYTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; DISSEMINATED NECROTIZING LEUKOENCEPHALOPATHY; LYMPHOPROLIFERATIVE DISORDER; DIABETES-INSIPIDUS; RESPONSE CRITERIA; CEREBRAL LYMPHOMA; AIDS PATIENTS; MRI FEATURES AB OBJECTIVE. The purpose of this article is to provide a comprehensive review of the imaging features of neurologic involvement in hematologic malignancies. CONCLUSION. Neurologic involvement can be seen in lymphoma, leukemia, post-transplant lymphoproliferative disorder (PTLD), plasma cell neoplasms, and histiocytic and dendritic neoplasms. Imaging, MRI in particular, plays an important role in the workup of these patients. Familiarity with the imaging features of nervous system involvement in hematologic malignancies can help radiologists suggest the diagnosis and guide management. C1 [Keraliya, Abhishek R.; Krajewski, Katherine M.; Giardino, Angela A.; Tirumani, Sree Harsha; Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Keraliya, Abhishek R.; Krajewski, Katherine M.; Giardino, Angela A.; Tirumani, Sree Harsha; Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Keraliya, AR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM akeraliya@partners.org FU Radiological Society of North America research grant FX A. B. Shinagare was awarded a Radiological Society of North America research grant starting in July 2014. NR 75 TC 2 Z9 2 U1 1 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2015 VL 205 IS 3 BP 604 EP 617 DI 10.2214/AJR.14.14092 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP6KW UT WOS:000359997100043 PM 26295649 ER PT J AU Eschenauer, GA Nguyen, MH Clancy, CJ AF Eschenauer, Gregory A. Nguyen, Minh-Hong Clancy, Cornelius J. TI Is Fluconazole or an Echinocandin the Agent of Choice for Candidemia SO ANNALS OF PHARMACOTHERAPY LA English DT Review DE fluconazole; echinocandin; candidemia; Candida; candidiasis ID CRITICALLY-ILL PATIENTS; BLOOD-STREAM INFECTION; INVASIVE CANDIDIASIS; ANTIFUNGAL AGENTS; RISK-FACTORS; ANIDULAFUNGIN; MORTALITY; GLABRATA; OUTCOMES; THERAPY AB Objective: Candidemia is among the most common nosocomial bloodstream infections and is associated with high mortality, increased length of hospital stay, and significant economic burden. The introduction of the echinocandins in the 2000s has expanded the armamentarium against Candida spp and provides therapeutic options that are effective, safe, and tolerable. Although the Infectious Diseases Society of America favors echinocandins as treatment for candidemia in selected settings (at least as initial therapy), there remain divergent opinions about whether an echinocandin or fluconazole is the preferred agent for candidemia, and clinical practice guidelines are in flux. In this review, the currently available laboratory and clinical data are summarized and critically evaluated. Data Sources: A MEDLINE search of the English language literature was performed using the search terms echinocandin, fluconazole, and candidemia. References of review articles and guidelines were also screened for inclusion. Study Selection and Data Extraction: Studies whose primary goal was to compare echinocandins with fluconazole were evaluated as well as studies that differentiated pharmacological and pharmacokinetic properties between agents. Data Synthesis: It is clear that echinocandins and fluconazole each have roles in the management of candidemia. Specific recommendations are provided that will hopefully optimize outcomes in candidemia while incorporating stewardship concepts of cost-effectiveness and limiting the emergence of resistance. Conclusions: Despite the advantages brought by the echinocandins and fluconazole, outcomes among patients with candidemia remain suboptimal. Improved treatment of candidennia may ultimately be achieved by optimizing the use of antifungal agents rather than the development of new drugs. C1 [Eschenauer, Gregory A.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Nguyen, Minh-Hong; Clancy, Cornelius J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Eschenauer, GA (reprint author), Univ Michigan, Coll Pharm, Dept Clin Social & Adm Sci, Dept Pharm, 1500 East Med Ctr, Ann Arbor, MI 48109 USA. EM gregorye@med.umich.edu NR 45 TC 3 Z9 4 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 2015 VL 49 IS 9 BP 1068 EP 1074 DI 10.1177/1060028015590838 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP6XN UT WOS:000360031600013 PM 26104051 ER PT J AU Abtahian, F Waldo, S Jang, IK AF Abtahian, Farhad Waldo, Stephen Jang, Ik-Kyung TI Comparison of heparin and bivalirudin in patients undergoing percutaneous coronary intervention without use of glycoprotein IIb/IIIa inhibitors SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE anticoagulation; bleeding ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN; CLINICAL-OUTCOMES; PRIMARY PCI; HIGH-RISK; IMPACT; TRIAL; COMPLICATIONS; ANGIOPLASTY AB ObjectivesThe primary objective of this study is the compare the association between bleeding and the use unfractionated heparin (UFH) versus bivalirudin during percutaneous coronary intervention (PCI). BackgroundIn patients undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in the absence of glycoprotein IIb/IIIa inhibitors is not well defined.Methods: Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single institution between 2007 and 2014 were included (n=6,143). Propensity score matching was used to adjust for baseline characteristics yielding 2,984 well matched patients (1,492 in each group). The primary endpoint was major non-coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding Academic Consortium type 3 or 5. Secondary outcomes included combined major and minor bleeding, in-hospital death, periprocedural myocardial infarction, and recurrent ischemia requiring urgent revascularization (repeat PCI). ResultsIn the propensity matched cohort, there was no difference in major bleeding between UFH and bivalirudin monotherapy (1.8% versus 2.4%, P=0.305). Combined major and minor bleeding was also similar between the two groups (4.3% versus 4.3%, P=1.0). Likewise, no differences were observed between the bivalirudin and UFH groups in terms of in-hospital death (0.4% versus 0.5%, P=0.592), periprocedural myocardial infarction (1.5% versus 2.0%, P=0.332) and repeat PCI (0.7% versus 0.8%, P=0.669). ConclusionAmong patients undergoing PCI, there was no significant difference in rate of bleeding between bivalirudin and heparin monotherapy in a real-world setting. (c) 2015 Wiley Periodicals, Inc. C1 [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 25 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2015 VL 86 IS 3 BP 390 EP 396 DI 10.1002/ccd.25911 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP3VU UT WOS:000359811600013 PM 25753749 ER PT J AU Ain, DL Jang, IK AF Ain, David L. Jang, Ik-Kyung TI Natural history of coronary atherosclerosis: did contemporary medical therapy change the course? SO CORONARY ARTERY DISEASE LA English DT Editorial Material ID OPTICAL COHERENCE TOMOGRAPHY; RUPTURED CULPRIT PLAQUE; VULNERABLE PLAQUE; INTRAVASCULAR ULTRASOUND; RISK-ASSESSMENT; ARTERY-DISEASE; EVENTS C1 [Ain, David L.; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2015 VL 26 IS 6 BP 463 EP 465 DI 10.1097/MCA.0000000000000279 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP4LS UT WOS:000359853900001 PM 26217890 ER PT J AU Cordoba-Chacon, J Majumdar, N List, EO Diaz-Ruiz, A Frank, SJ Manzano, A Bartrons, R Puchowicz, M Kopchick, JJ Kineman, RD AF Cordoba-Chacon, Jose Majumdar, Neena List, Edward O. Diaz-Ruiz, Alberto Frank, Stuart J. Manzano, Anna Bartrons, Ramon Puchowicz, Michelle Kopchick, John J. Kineman, Rhonda D. TI Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice SO DIABETES LA English DT Article ID NONALCOHOLIC FATTY LIVER; BODY-COMPOSITION; GH DEFICIENCY; TRIGLYCERIDE SYNTHESIS; RECEPTOR ANTAGONIST; ENDOGENOUS GH; IGF-I; INSULIN; DISEASE; STEATOSIS AB Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. C1 [Cordoba-Chacon, Jose; Majumdar, Neena; Kineman, Rhonda D.] Jesse Brown VA Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. [Cordoba-Chacon, Jose; Majumdar, Neena; Kineman, Rhonda D.] Univ Illinois, Coll Med, Div Endocrinol Diabet & Metab, Dept Med, Chicago, IL USA. [List, Edward O.; Kopchick, John J.] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. [List, Edward O.] Ohio Univ, Heritage Coll Osteopath Med, Dept Special Med, Athens, OH 45701 USA. [Diaz-Ruiz, Alberto] NIA, NIH, Translat Gerontol Branch, Expt Gerontol Sect, Baltimore, MD 21224 USA. [Frank, Stuart J.] Univ Alabama Birmingham, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Endocrinol Sect Med Serv, Birmingham, AL USA. [Manzano, Anna; Bartrons, Ramon] Univ Barcelona, Dept Physiol Sci, Barcelona, Spain. [Puchowicz, Michelle] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH USA. [Kopchick, John J.] Ohio Univ, Heritage Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. RP Kineman, RD (reprint author), Jesse Brown VA Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. EM kineman@uic.edu RI Kineman, Rhonda/H-2221-2011 OI Kineman, Rhonda/0000-0001-7322-1152 FU Endocrine Society/Genentech, Inc.; Endocrine Scholars Award in Growth Hormone Research; Intramural Research Program of the National Institutes of Health; National Institute on Aging; Institute de Salud Carlos III (Madrid, Spain) [PI13-00096]; Mouse Metabolic Phenotyping Center of Case Western Reserve University grant [U24 DK76174]; State of Ohio's Eminent Scholar Program; National Institutes of Health [P01AG031736, R01DK088133]; U.S. Department of Veterans Affairs, Office of Research and Development Merit Award [BX001114] FX This work was supported by an Endocrine Society/Genentech, Inc. Endocrine Scholars Award in Growth Hormone Research (to J.C.-C.); Intramural Research Program of the National Institutes of Health, National Institute on Aging (to A.D.-R.); Institute de Salud Carlos III (Madrid, Spain) grant PI13-00096 (to R.B.); Mouse Metabolic Phenotyping Center of Case Western Reserve University grant U24 DK76174 (to M.P.); State of Ohio's Eminent Scholar Program, which includes a gift by Milton and Lawrence Goll, and National Institutes of Health grant P01AG031736 (to J.J.K.); U.S. Department of Veterans Affairs, Office of Research and Development Merit Award BX001114; and National Institutes of Health grant R01DK088133 (to R.D.K.). NR 61 TC 6 Z9 6 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3093 EP 3103 DI 10.2337/db15-0370 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300008 PM 26015548 ER PT J AU Huang, T Zheng, Y Qi, QB Xu, M Ley, SH Li, YP Kang, JH Wiggs, J Pasquale, LR Chan, AT Rimm, EB Hunter, DJ Manson, AE WillettL, WC Hul, FB Qi, L AF Huang, Tao Zheng, Yan Qi, Qibin Xu, Min Ley, Sylvia H. Li, Yanping Kang, Jae H. Wiggs, Janey Pasquale, Louis R. Chan, Andrew T. Rimm, Eric B. Hunter, David J. Manson, Ann E. WillettL, Walter C. Hul, Frank B. Qi, Lu TI DNA Methylation Variants at HIF3A Locus, B-Vitamin Intake, and Long-term Weight Change: Gene-Diet Interactions in Two US Cohorts SO DIABETES LA English DT Article ID GENOME-WIDE ANALYSIS; BODY-MASS INDEX; FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; MENDELIAN RANDOMIZATION; ENVIRONMENT INTERACTION; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; FOLIC-ACID; OBESITY AB The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation-associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B-2 and B-12 intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B-2 intake and -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B-12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B-2, vitamin B-12, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity. C1 [Huang, Tao; Zheng, Yan; Ley, Sylvia H.; Li, Yanping; Rimm, Eric B.; Hunter, David J.; WillettL, Walter C.; Hul, Frank B.; Qi, Lu] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02163 USA. [Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Xu, Min] Shanghai Jiao Tong Univ, Sch Med, Shanghai Clin Ctr Endocrine & Metab Dis, Shanghai 200030, Peoples R China. [Xu, Min] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Endocrine & Metab Dis, Ruijin Hosp, Shanghai 200030, Peoples R China. [Kang, Jae H.; Pasquale, Louis R.; Rimm, Eric B.; Manson, Ann E.; WillettL, Walter C.; Hul, Frank B.; Qi, Lu] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Kang, Jae H.; Pasquale, Louis R.; Rimm, Eric B.; Manson, Ann E.; WillettL, Walter C.; Hul, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA. [Wiggs, Janey; Pasquale, Louis R.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Rimm, Eric B.; Hunter, David J.; Manson, Ann E.; WillettL, Walter C.; Hul, Frank B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Manson, Ann E.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Manson, Ann E.] Harvard Univ, Sch Med, Boston, MA USA. RP Qi, L (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02163 USA. EM nhlqi@channing.harvard.edu FU National Institutes of Health [HL-126024, DK-100383, DK-091718, HL-071981, HL-073168, CA-87969, CA-49449, CA-055075, HL-34594, HL-088521, U01-HG-004399, DK-080140, P30-DK-46200, U01-CA-137088, U54-CA-155626, DK-58845, DK-098311, U01-HG-004728, EY-015473, CA-134958, DK-70756, DK-46200]; Arthur Ashley Williams Foundation; Glaucoma Center of Excellence; American Heart Association Scientist Development Grant [0730094N] FX This study was supported by grants HL-126024, DK-100383, DK-091718, HL-071981, HL-073168, CA-87969, CA-49449, CA-055075, HL-34594, HL-088521, U01-HG-004399, DK-080140, P30-DK-46200, U01-CA-137088, U54-CA-155626, DK-58845, DK-098311, U01-HG-004728, EY-015473, CA-134958, DK-70756, and DK-46200 from the National Institutes of Health. L.R.P. is supported by the Arthur Ashley Williams Foundation and a Harvard Medical School Ophthalmology Scholar Award from the Glaucoma Center of Excellence. A.T.C. is a Damon Runyon Clinical Investigator. L.Q. is a recipient of an American Heart Association Scientist Development Grant (0730094N). NR 56 TC 10 Z9 11 U1 1 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3146 EP 3154 DI 10.2337/db15-0264 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300013 PM 26001398 ER PT J AU Pezzolesi, MG Satake, E McDonnell, KP Major, M Smiles, AM Krolewski, AS AF Pezzolesi, Marcus G. Satake, Eiichiro McDonnell, Kevin P. Major, Melissa Smiles, Adam M. Krolewski, Andrzej S. TI Circulating TGF-beta 1-Regulated miRNAs and the Risk of Rapid Progression to ESRD in Type 1 Diabetes SO DIABETES LA English DT Article ID GROWTH-FACTOR-BETA; PROMOTES RENAL FIBROSIS; GLOMERULAR MESANGIAL CELLS; COLLAGEN EXPRESSION; NEPHROPATHY; MICRORNA; MIR-21; DISEASE; TARGET; PLASMA AB We investigated whether circulating TGF-beta 1-regulated miRNAs detectable in plasma are associated with the risk of rapid progression to end-stage renal disease (ESRD) in a cohort of proteinuric patients with type 1 diabetes (T1D) and normal eGFR. Plasma specimens obtained at entry to the study were examined in two prospective subgroups that were followed for 7-20 years (rapid progressors and nonprogressors), as well as a reference panel of normoalbuminuric T1D patients. Of the five miRNAs examined in this study, let-7c-5p and miR-29a-3p were significantly associated with protection against rapid progression and let-7b-5p and miR-21-5p were significantly associated with the increased risk of ESRD. In logistic analysis, controlling for HbA(1c) and other covariates, let-7c-5p and miR-29a-3p were associated with more than a 50% reduction in the risk of rapid progression (P <= 0.001), while let-7b-5p and miR-21-5p were associated with a >2.5-fold increase in the risk of ESRD (P <= 0.005). This study is the first prospective study to demonstrate that circulating TGF-beta 1-regulated miRNAs are deregulated early in T1D patients who are at risk for rapid progression to ESRD. C1 [Pezzolesi, Marcus G.; Satake, Eiichiro; McDonnell, Kevin P.; Major, Melissa; Smiles, Adam M.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Pezzolesi, Marcus G.; Satake, Eiichiro; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu RI deng, qiongxia/A-3206-2017 FU National Institutes of Health [DK-090125, 25034-40/U24-DK-076169, DK-14526, P30-DK-036836]; JDRF [17-2013-8, 17-2013-311]; Sunstar Foundation FX The authors acknowledge grant support from the National Institutes of Health (DK-090125 and 25034-40/U24-DK-076169 to M.G.P., DK-14526 to ASK., and P30-DK-036836 to the Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center), the JDRF (17-2013-8 and 17-2013-311 to ASK.), and the Sunstar Foundation (Hiroo Kaneda Scholarship to ES.). NR 50 TC 12 Z9 12 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3285 EP 3293 DI 10.2337/db15-0116 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300027 PM 25931475 ER PT J AU Katz, ML Volkening, LK Dougher, CE Laffel, LMB AF Katz, M. L. Volkening, L. K. Dougher, C. E. Laffel, L. M. B. TI Validation of the Diabetes Family Impact Scale: a new measure of diabetes-specific family impact SO DIABETIC MEDICINE LA English DT Article ID EMOTIONAL DISTRESS; TYPE-1; CHILDREN; PARENTS; MOTHERS; BURDEN; PERSPECTIVES; FATHERS AB AimsTo develop and validate the Diabetes Family Impact Scale, a scale to measure the impact of diabetes on families. MethodsThe Diabetes Family Impact Scale was developed by an iterative process, with input from multidisciplinary diabetes providers and parents of children with Type 1 diabetes. The psychometric properties of the Diabetes Family Impact Scale were assessed in parents of children with Type 1 diabetes. This assessment included internal consistency, convergent validity and exploratory factor analysis. ResultsParents (n=148) of children (meansd age 12.93.3years) with Type 1 diabetes (meansd duration 6.23.6years) completed the 15-item Diabetes Family Impact Scale. After eliminating one item, the 14-item measure demonstrated good internal consistency (Cronbach's = 0.84). Correlations between the Diabetes Family Impact Scale and measures of parent diabetes burden (r=0.48, P<0.0001), stressful life events (r=0.28, P=0.0007), and child's quality of life (r=-0.52 and -0.54, P<0.0001 for generic and diabetes-specific quality of life, respectively) supported the convergent validity of the instrument. Factor analysis identified four factors corresponding to the four survey domains (school, work, finances and family well-being). ConclusionsThe Diabetes Family Impact Scale measures diabetes-specific family impacts with good internal consistency and convergent validity and may be a useful tool in clinical and research settings. C1 [Katz, M. L.; Volkening, L. K.; Dougher, C. E.; Laffel, L. M. B.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Katz, M. L.; Laffel, L. M. B.] Joslin Diabet Ctr, Adolescent & Young Adult Sect, Pediat, Boston, MA 02215 USA. RP Katz, ML (reprint author), Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. EM michelle.katz@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [K12DK094721, P30DK036836, T32DK007260]; American Diabetes Association through the FSU Research Foundation; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; Eleanor Chesterman Beatson Fund FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers K12DK094721, P30DK036836, and T32DK007260; an American Diabetes Association subaward through the FSU Research Foundation; the Katherine Adler Astrove Youth Education Fund; the Maria Griffin Drury Pediatric Fund; and the Eleanor Chesterman Beatson Fund. NR 21 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2015 VL 32 IS 9 BP 1227 EP 1231 DI 10.1111/dme.12689 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP4LK UT WOS:000359853000016 PM 25655562 ER PT J AU Mehta, SN Nansel, TR Volkening, LK Butler, DA Haynie, DL Laffel, LMB AF Mehta, S. N. Nansel, T. R. Volkening, L. K. Butler, D. A. Haynie, D. L. Laffel, L. M. B. TI Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire SO DIABETIC MEDICINE LA English DT Article ID GLYCEMIC CONTROL; SELF-MANAGEMENT; STRUCTURED INTERVIEW; YOUNG-PEOPLE; ADOLESCENTS; YOUTH; CHILDHOOD; CARE; ASSOCIATIONS; INVOLVEMENT AB AimsTo evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. MethodsA total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8-18years) had Type 1 diabetes for 1year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. ResultsThe children (49% female) had a mean sd (range) age 13.32.9 (8-18) years and their meansd HbA1c was 7115mmol/mol (8.6 +/- 1.4%). Internal consistency was good for parents (=0.83) and children (=0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient=0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient=0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r=-0.41, P<0.0001; children: r=-0.27, P<0.0001). Psychometrics were stronger in the children aged 13years compared with those aged <13years, but were acceptable in both age groups. Mean +/- sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n=181) than in children receiving multiple daily injections (n=92) according to parent (75.9 +/- 11.8 vs. 70.5 +/- 15.5; P=0.004) and child report (72.2 +/- 12.1 vs. 67.6 +/- 13.9; P=0.006). ConclusionsThe Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8-18years who are receiving either multiple daily injections or insulin pump therapy. C1 [Mehta, S. N.; Volkening, L. K.; Butler, D. A.; Laffel, L. M. B.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Adolescent & Young Adult Sect, Pediat, Boston, MA 02215 USA. [Nansel, T. R.; Haynie, D. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, Bethesda, MD USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Genet & Epidemiol Sect, Adolescent & Young Adult Sect, Pediat, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN26720070 3434C]; Joslin Diabetes Center's Diabetes and Endocrinology Research Center [NIH P30DK036836] FX This research was supported by the intramural research programme of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN26720070 3434C and the Joslin Diabetes Center's Diabetes and Endocrinology Research Center (NIH P30DK036836). NR 27 TC 4 Z9 4 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2015 VL 32 IS 9 BP 1232 EP 1238 DI 10.1111/dme.12682 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP4LK UT WOS:000359853000017 PM 26280463 ER PT J AU Akiba, Y Kaji, I Kaunitz, JD AF Akiba, Yasutada Kaji, Izumi Kaunitz, Jonathan D. TI Short-Chain Fatty Acid Chemosensing and Transport in the Duodenal Epithelium SO DIGESTIVE DISEASES AND SCIENCES LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2015 VL 60 IS 9 BP 2552 EP 2553 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LC UT WOS:000359997700022 ER PT J AU Kaji, I Akiba, Y Kaunitz, JD AF Kaji, Izumi Akiba, Yasutada Kaunitz, Jonathan D. TI Luminal 5-HT Induces Colonic Anion Secretion in Rats: Segmental Differences and an Inhibitory Effect of Submucosal Nitric Oxide SO DIGESTIVE DISEASES AND SCIENCES LA English DT Meeting Abstract C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2015 VL 60 IS 9 BP 2552 EP 2552 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LC UT WOS:000359997700020 ER PT J AU Beste, LA Harp, BK Blais, RK Evans, GA Zickmund, SL AF Beste, Lauren A. Harp, Bonnie K. Blais, Rebecca K. Evans, Ginger A. Zickmund, Susan L. TI Primary Care Providers Report Challenges to Cirrhosis Management and Specialty Care Coordination SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Primary care health; Specialty care; Chronic liver disease; Attitudes ID QUALITY-OF-CARE; HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; COMMUNICATION; SURVEILLANCE; PHYSICIANS; SERVICES; OUTCOMES; DISEASE AB Two-thirds of patients with cirrhosis do not receive guideline-concordant liver care. Cirrhosis patients are less likely to receive recommended care when followed exclusively by primary care providers (PCPs), as opposed to specialty co-management. Little is known about how to optimize cirrhosis care delivered by PCPs. We conducted a qualitative analysis to explore PCPs' attitudes and self-reported roles in caring for patients with cirrhosis. We recruited PCPs from seven Veterans Affairs facilities in the Pacific Northwest via in-service trainings and direct email from March to October 2012 (n = 24). Trained staff administered structured telephone interviews covering: (1) general attitudes; (2) roles and practices; and (3) barriers and facilitators to cirrhosis management. Two trained, independent coders reviewed each interview transcript and thematically coded responses. Three overarching themes emerged in PCPs' perceptions of cirrhosis patients: the often overwhelming complexity of comorbid medical, psychiatric, and substance issues; the importance of patient self-management; and challenges surrounding specialty care involvement and co-management of cirrhosis. While PCPs felt they brought important skills to bear, such as empathy and care coordination, they strongly preferred to defer major cirrhosis management decisions to specialists. The most commonly reported barriers to care included patient behaviors, access issues, and conflicts with specialists. PCPs perceive Veterans with cirrhosis as having significant medical and psychosocial challenges. PCPs tend not to see their role as directing cirrhosis-related management decisions. Educational efforts directed at PCPs must foster PCP empowerment and improve comfort with managing cirrhosis. C1 [Beste, Lauren A.; Evans, Ginger A.] VA Puget Sound Hlth Care Syst, Primary Care Serv, Seattle, WA 98108 USA. [Beste, Lauren A.; Harp, Bonnie K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.; Evans, Ginger A.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Blais, Rebecca K.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Blais, Rebecca K.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Zickmund, Susan L.] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Zickmund, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Zickmund, Susan L.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. RP Beste, LA (reprint author), VA Puget Sound Hlth Care Syst, Primary Care Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Lauren.Beste@va.gov FU VA National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens FX 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. Portions of this work were presented at The Liver Meeting (November 5, 2013), the annual meeting of the American Association for the Study of Liver Disease. This material is the result of work supported by resources from the VA Puget Sound Health Care System (Seattle, Washington). Funding was provided by the VA National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens. NR 25 TC 2 Z9 2 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2015 VL 60 IS 9 BP 2628 EP 2635 DI 10.1007/s10620-015-3592-1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LC UT WOS:000359997700070 PM 25732712 ER PT J AU Kesler, CT Pereira, ER Cui, CH Nelson, GM Masuck, DJ Baish, JW Padera, TP AF Kesler, Cristina T. Pereira, Ethel R. Cui, Cheryl H. Nelson, Gregory M. Masuck, David J. Baish, James W. Padera, Timothy P. TI Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation SO FASEB JOURNAL LA English DT Article DE endothelial; TIE2; lymphangiography; 2-photon microscopy ID ENDOTHELIAL GROWTH-FACTOR; INTERSTITIAL FLUID PRESSURE; VEGF-D PROMOTES; FACTOR-C; BREAST-CANCER; IN-VIVO; TUMOR LYMPHANGIOGENESIS; CELL-CELL; ANGIOGENESIS; METASTASIS AB The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)expressing tumors increased to 123 and 135 mu m, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (similar to 60 mu m). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability. C1 [Kesler, Cristina T.; Pereira, Ethel R.; Cui, Cheryl H.; Masuck, David J.; Padera, Timothy P.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin Steele Lab Tumor Biol, Boston, MA 02114 USA. [Nelson, Gregory M.] Brigham Young Univ, Harold B Lee Lib, Provo, UT 84602 USA. [Baish, James W.] Bucknell Univ, Dept Biomed Engn, Lewisburg, PA 17837 USA. RP Padera, TP (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM tpadera@steele.mgh.harvard.edu RI Nelson, Gregory/H-6315-2011; OI Nelson, Gregory/0000-0002-8382-910X; Pereira, Ethel/0000-0003-0562-4536; Padera, Timothy/0000-0002-3453-9384 FU U.S. National Institutes of Health (NIH) National Cancer Institute (NCI) Grant [R00CA137167]; NIH Office of the Director Grant [DP2OD008780]; NCI Federal Share/Massachusetts General Hospital Proton Beam Income Grant [C06 CA059267] FX This work was funded by U.S. National Institutes of Health (NIH) National Cancer Institute (NCI) Grant R00CA137167 (to T.P.P.), NIH Office of the Director Grant DP2OD008780 (to T.P.P.), and NCI Federal Share/Massachusetts General Hospital Proton Beam Income Grant C06 CA059267 (to T.P.P.). The authors thank Dr. Dai Fukumura, Dr. Jay Loeffler, Dr. Rakesh Jain, Dr. Vikash Chuahan, Julia Kahn, Anna Khachatryan, and members of the Edwin L. Steele Laboratories for support, technical assistance, and helpful discussions. NR 39 TC 2 Z9 2 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD SEP PY 2015 VL 29 IS 9 BP 3668 EP 3677 DI 10.1096/fj.14-268920 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CP5IU UT WOS:000359915600006 PM 25977256 ER PT J AU Smith, MJ Cobia, DJ Reilly, JL Gilman, JM Roberts, AG Alpert, KI Wang, L Breiter, HC Csernansky, JG AF Smith, Matthew J. Cobia, Derin J. Reilly, James L. Gilman, Jodi M. Roberts, Andrea G. Alpert, Kathryn I. Wang, Lei Breiter, Hans C. Csernansky, John G. TI Cannabis-Related Episodic Memory Deficits and Hippocampal Morphological Differences in Healthy Individuals and Schizophrenia Subjects SO HIPPOCAMPUS LA English DT Article DE hippocampus; Marijuana; neuroimaging; morphology; shape analysis ID NONPSYCHOTIC SIBLINGS; LONGITUDINAL MRI; GRAY-MATTER; BRAIN; ASYMMETRY; VOLUME; USERS; ABNORMALITIES; AMYGDALA; SHAPE AB Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis. (c) 2015 Wiley Periodicals, Inc. C1 [Smith, Matthew J.; Cobia, Derin J.; Reilly, James L.; Roberts, Andrea G.; Alpert, Kathryn I.; Wang, Lei; Breiter, Hans C.; Csernansky, John G.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Smith, Matthew J.; Cobia, Derin J.; Reilly, James L.; Roberts, Andrea G.; Breiter, Hans C.] Warren Wright Adolescent Ctr, Chicago, IL USA. [Wang, Lei] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Gilman, Jodi M.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. RP Smith, MJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, 710 N Lake Shore Dr,13th Floor Abbott Hall, Chicago, IL 60611 USA. EM matthewsmith@northwestern.edu OI Smith, Matthew/0000-0002-0079-1477; Cobia, Derin/0000-0003-2339-958X FU National Institute of Mental Health [R01 MH056584, P50 MH071616]; National Institute on Drug Abuse [DA026002, DA026104, DA027804] FX Grant sponsor: National Institute of Mental Health; Grant number: R01 MH056584 and P50 MH071616; Grant sponsor: National Institute on Drug Abuse; Grant number: DA026002, DA026104, DA027804. L.W., H.C.B., and J.G.C. (senior authors) contributed equally to this work. NR 48 TC 5 Z9 5 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD SEP PY 2015 VL 25 IS 9 BP 1042 EP 1051 DI 10.1002/hipo.22427 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CP7JK UT WOS:000360063000006 PM 25760303 ER PT J AU Hong, TS Moughan, J Garofalo, MC Bendell, J Berger, AC Oldenburg, NBE Anne, PR Perera, F Lee, RJ Jabbour, SK Nowlan, A DeNittis, A Crane, C AF Hong, Theodore S. Moughan, Jennifer Garofalo, Michael C. Bendell, Johanna Berger, Adam C. Oldenburg, Nicklas B. E. Anne, Pramila Rani Perera, Francisco Lee, R. Jeffrey Jabbour, Salma K. Nowlan, Adam DeNittis, Albert Crane, Christopher TI NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID DOSE-VOLUME RELATIONSHIP; SMALL-BOWEL; III TRIAL; RADIOTHERAPY; CHEMORADIOTHERAPY; IRRADIATION; TOXICITY; 5-FLUOROURACIL; CHEMOTHERAPY; REDUCTION AB Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade >= 2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hong, Theodore S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moughan, Jennifer] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Garofalo, Michael C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Bendell, Johanna] Sarah Cannon Res Inst, Nashville, TN USA. [Berger, Adam C.; Anne, Pramila Rani] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Oldenburg, Nicklas B. E.] North Main Radiat Oncol, Providence, RI USA. [Perera, Francisco] London Reg Canc Program Western Ontario, London, ON, Canada. [Lee, R. Jeffrey] Intermt Med Ctr, Salt Lake City, UT USA. [Jabbour, Salma K.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Nowlan, Adam] Piedmont Hosp, Atlanta, GA USA. [DeNittis, Albert] Main Line Community Clin Oncol Program, Wynnewood, PA USA. [Crane, Christopher] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 3, Boston, MA 02114 USA. EM tshong1@mgh.harvard.edu FU National Cancer Institute [U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803] FX Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and U24CA180803 from the National Cancer Institute. NR 24 TC 14 Z9 16 U1 0 U2 1 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 SEP 1 PY 2015 VL 93 IS 1 BP 29 EP 36 DI 10.1016/j.ijrobp.2015.05.005 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CP3AV UT WOS:000359750100008 PM 26163334 ER PT J AU Chandra, RA Taghian, AG AF Chandra, Ravi A. Taghian, Alphonse G. TI Regional lymph node radiation and lymphedema Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID BREAST-CANCER; THERAPY; IRRADIATION; RISK C1 [Chandra, Ravi A.] Harvard Radiat Oncol Program, Boston, MA 02215 USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chandra, RA (reprint author), Harvard Radiat Oncol Program, Boston, MA 02215 USA. NR 9 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2015 VL 93 IS 1 BP 215 EP 216 DI 10.1016/j.ijrobp.2015.03.023 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CP3AV UT WOS:000359750100037 PM 26279043 ER PT J AU Arvold, ND Tanguturi, SK Alexander, BM AF Arvold, Nils D. Tanguturi, Shyam K. Alexander, Brian M. TI Radiation as a foundation for glioblastoma therapy in elderly patients Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID PHASE-3 TRIAL; TEMOZOLOMIDE; RADIOTHERAPY; OLDER C1 [Arvold, Nils D.; Alexander, Brian M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02163 USA. [Tanguturi, Shyam K.] Harvard Radiat Oncol Program, Boston, MA USA. RP Arvold, ND (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02163 USA. NR 5 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2015 VL 93 IS 1 BP 218 EP 219 DI 10.1016/j.ijrobp.2015.05.007 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CP3AV UT WOS:000359750100041 PM 26279047 ER PT J AU Barclay, L Yeargin, T Langley, C Kanwar, N Selvarangan, R Bryant, PW Beenhouwer, D Matthews-Greer, J Vinje, J AF Barclay, L. Yeargin, T. Langley, C. Kanwar, N. Selvarangan, R. Bryant, P. W. Beenhouwer, D. Matthews-Greer, J. Vinje, J. TI Multicenter evaluation of RIDA Gene Norovirus GI/GII assay for the detection of norovirus from stool specimens SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract C1 [Barclay, L.; Yeargin, T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Langley, C.; Vinje, J.] CDC, Div Viral Dis, Atlanta, GA 30333 USA. [Kanwar, N.; Selvarangan, R.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Bryant, P. W.] Wadsworth Ctr, Albany, NY USA. [Beenhouwer, D.] VA Greater LA Healthcare Syst, Los Angeles, CA USA. [Matthews-Greer, J.] Michigan Dept Community Hlth, Bur Labs, Lansing, MI USA. NR 0 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 EI 1873-5967 J9 J CLIN VIROL JI J. Clin. Virol. PD SEP PY 2015 VL 70 SU 1 MA 1692 BP S60 EP S61 DI 10.1016/j.jcv.2015.07.143 PG 2 WC Virology SC Virology GA CP7QI UT WOS:000360082500134 ER PT J AU Ryskina, KL Dine, CJ Kim, EJ Bishop, TF Epstein, AJ AF Ryskina, Kira L. Dine, C. Jessica Kim, Esther J. Bishop, Tara F. Epstein, Andrew J. TI Effect of Attending Practice Style on Generic Medication Prescribing by Residents in the Clinic Setting: An Observational Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Medical education; Graduate; Practice variation; Health care costs; Drugs; Medical culture ID TOP 5 LISTS; CARE; RESPONSIBILITY; ATORVASTATIN; SIMVASTATIN; PRAVASTATIN; COMPETENCE; PHYSICIANS AB Despite increased emphasis on cost-consciousness in graduate medical training, there is little empirical evidence of the role of attending physician supervision on resident practice in this area. To study whether the prescribing practices of attendings influence residents' prescribing of brand-name statin medications in the ambulatory clinic setting. A retrospective study of statin prescriptions by residents at two internal medicine residency programs, using electronic medical record data from July 2007 through November 2011. We estimated multivariable hierarchical logistic regression models to assess the independent effect of the supervising attending's rate of brand-name prescribing in the preceding quarter on the likelihood of a resident prescribing a brand-name statin. The sample included 342 residents and 58 attendings, accounting for 10,151 initial statin prescriptions, including 3,942 by residents. Brand-name statins were prescribed in about one-fourth of encounters. After adjusting for patient-, physician-, and practice-level factors, the supervising attendings' brand-name prescribing rate in the quarter preceding the encounter was positively associated with a postgraduate year (PGY)-1 resident's prescribing a brand-name statin, but not for PGY-2 or PGY-3 residents. For PGY-1 residents, the adjusted probability of a resident prescribing a brand-name statin ranged from 22.6 % (95 % CI 17.3-28.0 %, p < 0.001) for residents supervised by an attending who prescribed < 20 % brand-name statins in the previous quarter to 41.6 % (95 % CI 24.6-58.5 %, p < 0.001) for residents supervised by an attending who prescribed at least 80 % brand-name statins in the previous quarter. A higher PGY level was associated with brand-name prescribing (aOR 2.07, 95 % CI 1.28-3.35, p = 0.003 for PGY-2; aOR 2.15, 95 % CI 1.31-3.55, p = 0.003 for PGY-3, vs. PGY-1). Supervising attendings' prescribing of brand-name medications may have a significant influence on PGY-1 residents' prescribing of brand-name medications, but not on prescribing by more senior residents. C1 [Ryskina, Kira L.; Kim, Esther J.; Epstein, Andrew J.] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ryskina, Kira L.; Dine, C. Jessica; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Dine, C. Jessica] Univ Penn, Div Pulm & Crit Care, Philadelphia, PA 19104 USA. [Bishop, Tara F.] Weill Cornell Med Coll, Div Hlth Outcomes & Effectiveness, Dept Publ Hlth, New York, NY USA. [Bishop, Tara F.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Epstein, Andrew J.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Ryskina, KL (reprint author), Univ Penn, Div Gen Internal Med, Perelman Sch Med, 13-30B4 13th Floor Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ryskina@mail.med.upenn.edu FU Ruth L. Kirschstein National Research Service Award (NRSA) [T32-HP10026] FX Dr. Ryskina is supported by the Ruth L. Kirschstein National Research Service Award (NRSA) T32-HP10026. This study received no external funding. NR 20 TC 4 Z9 4 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2015 VL 30 IS 9 BP 1286 EP 1293 DI 10.1007/s11606-015-3323-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CP5PC UT WOS:000359934600013 PM 26173522 ER PT J AU Patel, MS Reed, DA Smith, C Arora, VM AF Patel, Mitesh S. Reed, Darcy A. Smith, Cynthia Arora, Vineet M. TI Role-Modeling Cost-Conscious Care-A National Evaluation of Perceptions of Faculty at Teaching Hospitals in the United States SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cost-conscious care; high-value; role-modeling; resident; program director; residency program; teaching hospitals; faculty; medical education ID MEDICAL-EDUCATION; PHYSICIANS; RESIDENTS; IMPACT AB Little is known about how well faculty at teaching hospitals role-model behaviors consistent with cost-conscious care. We aimed to evaluate whether residents and program directors report that faculty at their program consistently role-model cost-conscious care, and whether the presence of a formal residency curriculum in cost-conscious care impacted responses. Cost-conscious care surveys were administered to internal medicine residents during the 2012 Internal Medicine In-Training Examination and to program directors during the 2012 Association of Program Directors in Internal Medicine Annual Survey. Respondents stated whether or not they agreed that faculty in their program consistently role-model cost-conscious care. To evaluate a more comprehensive assessment of faculty behaviors, resident responses were matched with those of the director of their residency program. A multivariate logistic regression model was fit to the outcome variable, to identify predictors of responses that faculty do consistently role-model cost-conscious care from residency program, resident, and program director characteristics. Responses from 12,623 residents (58.4 % of total sample) and 253 program directors (68.4 %) from internal medicine residency programs in the United States were included. The primary outcome measure was responses to questionnaires on faculty role-modeling cost-conscious care. Among all responses in the final sample, 6,816 (54.0 %) residents and 121 (47.8 %) program directors reported that faculty in their program consistently role-model cost-conscious care. Among paired responses of residents and their program director, the proportion that both reported that faculty do consistently role-modeled cost-conscious care was 23.0 % for programs with a formal residency curriculum in cost-conscious care, 26.3 % for programs working on a curriculum, and 23.7 % for programs without a curriculum. In the adjusted model, the presence of a formal curriculum in cost-conscious care did not have a significant impact on survey responses (odds ratio [OR], 1.04; 95 % Confidence Interval [CI], 0.52-2.06; p value [p] = 0.91). Responses from residents and program directors indicate that faculty at US teaching hospitals were not consistently role-modeling cost-conscious care. The presence of a formal residency curriculum in cost-conscious care did not impact responses. Future efforts should focus on placing more emphasis on faculty development and on combining curricular improvements with institutional interventions to adapt the training environment. C1 [Patel, Mitesh S.] Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Patel, Mitesh S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Reed, Darcy A.] Mayo Clin, Div Primary Care Internal Med, Rochester, MN USA. [Smith, Cynthia] Amer Coll Physicians, Philadelphia, PA USA. [Arora, Vineet M.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. RP Patel, MS (reprint author), Univ Penn, Med & Hlth Care Management, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu OI Arora, Vineet/0000-0002-4745-7599 FU Department of Veteran Affairs; Robert Wood Johnson Foundation FX Dr. Patel was supported in part by the Department of Veteran Affairs and the Robert Wood Johnson Foundation. The funding sources 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. NR 32 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2015 VL 30 IS 9 BP 1294 EP 1298 DI 10.1007/s11606-015-3242-5 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CP5PC UT WOS:000359934600014 PM 26173514 ER PT J AU Chikarmane, SA Gombos, EC Jagadeesan, J Raut, C Jagannathan, JP AF Chikarmane, Sona A. Gombos, Eva C. Jagadeesan, Jayender Raut, Chandrajit Jagannathan, Jyothi P. TI MRI findings of radiation-associated angiosarcoma of the breast (RAS) SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE breast magnetic resonance imaging; angiosarcoma; radiation-associated ID CUTANEOUS ANGIOSARCOMA; SECONDARY ANGIOSARCOMA; IMAGING FINDINGS; RADIOTHERAPY; DIAGNOSIS; THERAPY; CANCER; RISK AB PurposeTo describe the magnetic resonance imaging (MRI) characteristics of radiation-associated breast angiosarcomas (RAS). Materials and MethodsIn this Institutional Review board (IRB)-approved retrospective study, 57 women were diagnosed with pathologically confirmed RAS during the study period (January 1999 to May 2013). Seventeen women underwent pretreatment breast MRI (prior to surgical resection or chemotherapy), of which 16 studies were available for review. Imaging features, including all available mammograms, ultrasounds, and breast MRIs, of these patients were evaluated by two radiologists independently and correlated with clinical management and outcomes. ResultsThe median age of patients at original breast cancer diagnosis was 69.3 years (range 42-84 years), with average time from initial radiation therapy to diagnosis of RAS of 7.3 years (range 5.1-9.5 years). Nine women had mammograms (9/16, 56%) and six had breast ultrasound (US) (6/16, 38%) prior to MRI, which demonstrated nonsuspicious findings in 5/9 mammograms and 3/6 ultrasounds. Four patients had distinct intraparenchymal masses on mammogram and MRI. MRI findings included diffuse T-2 high signal skin thickening (16/16, 100%). Nearly half (7/16, 44%) of patients had T-2 low signal intensity lesions; all lesions rapidly enhanced on postcontrast T-1-weighted imaging. All women underwent surgical resection, with 8/16 (50%) receiving neoadjuvant chemotherapy. Four women died during the study period. ConclusionClinical, mammographic, and sonographic findings of RAS are nonspecific and may be occult on conventional breast imaging; MRI findings of RAS include rapidly enhancing dermal and intraparenchymal lesions, some of which are low signal on T-2 weighted imaging. J. Magn. Reson. Imaging 2015;42:763-770. C1 [Chikarmane, Sona A.; Gombos, Eva C.; Jagadeesan, Jayender] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Gombos, Eva C.; Jagannathan, Jyothi P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Imaging,Dana Farber Canc Inst, Boston, MA 02115 USA. [Raut, Chandrajit] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Sarcoma & Bone Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chikarmane, SA (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM schikarmane@partners.org FU NCRR NIH HHS [P41 RR019703]; NIBIB NIH HHS [P41 EB015898] NR 17 TC 4 Z9 4 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2015 VL 42 IS 3 BP 763 EP 770 DI 10.1002/jmri.24822 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP5CN UT WOS:000359899000024 PM 25504856 ER PT J AU Schmidt, F Boltze, J Jager, C Hofmann, S Willems, N Seeger, J Hartig, W Stolzing, A AF Schmidt, Franziska Boltze, Johannes Jager, Carsten Hofmann, Sarah Willems, Nicole Seeger, Johannes Hartig, Wolfgang Stolzing, Alexandra TI Detection and Quantification of beta-Amyloid, Pyroglutamyl A beta, and Tau in Aged Canines SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; DIFFUSE PLAQUES; SENILE PLAQUES; LIFE-SPAN; DOGS; BRAIN; NEURONS; DEPOSITION; PATHOLOGY AB Canine cognitive dysfunction syndrome is an age-associated disorder that resembles many aspects of human Alzheimer disease. The characterization of canine cognitive dysfunction syndrome has been restricted to selected laboratory dogs and mongrels, thereby limiting our knowledge of potential breed-related and age-related differences. We examined the brains of 24 dogs from various breeds. The frontal cortex, hippocampus, and entorhinal cortex were investigated. Deposits of beta-amyloid (A beta) and tau were analyzed phenotypically and quantified stereologically. In all dogs aged 10 years or older, plaques containing pyroglutamyl A beta and A beta(8-17) were detected. Within the ventral hippocampus, significantly more pyroglutamyl A beta plaques were deposited in small and medium dogs than in large dogs. Hyperphosphorylated tau with formation of neurofibrillary tangles was observed in 3 animals aged 13 to 15 years. This study provides the first investigation of pyroglutamyl A beta in comparison with total A beta (as shown by A beta(8-17) immunoreactivity) in dogs of different breeds, sizes, and ages. Our results indicate that canine cognitive dysfunction syndrome is relatively common among aged canines, thereby emphasizing the relevance of such populations to translational Alzheimer disease research. C1 [Schmidt, Franziska; Boltze, Johannes; Stolzing, Alexandra] Fraunhofer Res Inst Marine Biotechnol, D-23562 Lubeck, Germany. [Boltze, Johannes] Univ Leipzig, Fraunhofer Res Inst Marine Biotechnol, D-04109 Leipzig, Germany. [Schmidt, Franziska; Seeger, Johannes] Univ Leipzig, Inst Anat Histol & Embryol, Fac Vet Med, D-04109 Leipzig, Germany. [Boltze, Johannes; Stolzing, Alexandra] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany. [Jager, Carsten; Hofmann, Sarah; Hartig, Wolfgang] Univ Leipzig, Paul Flechsig Inst Brain Res, D-04109 Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Neuroscience Res Ctr, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Charlestown, MA USA. [Willems, Nicole] Univ Utrecht, Fac Vet Med, Univ Clin Compan Anim, Utrecht, Netherlands. [Stolzing, Alexandra] Univ Loughborough, Wolfson Sch, Ctr Biol Engn, Loughborough, Leics, England. RP Boltze, J (reprint author), Fraunhofer Res Inst Marine Biotechnol, Monkhofer Weg 239a, D-23562 Lubeck, Germany. EM johannes.boltze@emb.fraunhofer.de RI Stolzing, Alexandra/O-7815-2016 OI Stolzing, Alexandra/0000-0002-2975-5736 NR 50 TC 5 Z9 5 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2015 VL 74 IS 9 BP 912 EP 923 DI 10.1097/NEN.0000000000000230 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CP8KP UT WOS:000360142900006 PM 26247394 ER PT J AU Choi, BD Fecci, PE Sampson, JH AF Choi, Bryan D. Fecci, Peter E. Sampson, John H. TI Not everything that matters can be measured and not everything that can be measured matters SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 [Choi, Bryan D.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Choi, Bryan D.] Harvard Univ, Sch Med, Boston, MA USA. [Fecci, Peter E.; Sampson, John H.] Duke Univ, Med Ctr, Div Neurosurg, Duke Brain Tumor lmmunotherapy Program,Dept Surg, Durham, NC 27710 USA. [Sampson, John H.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. [Sampson, John H.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Sampson, John H.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. RP Choi, BD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2015 VL 123 IS 3 BP 543 EP 544 DI 10.3171/2015.2.JNS142977 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CP6VZ UT WOS:000360027600001 PM 26115465 ER PT J AU Friedlander, AH Chang, TI Hazboun, RC Garrett, NR AF Friedlander, Arthur H. Chang, Tina I. Hazboun, Renna C. Garrett, Neal R. TI High C-Terminal Cross-Linking Telopeptide Levels Are Associated With a Minimal Risk of Osteonecrosis of the Jaws in Patients Taking Oral Bisphosphonates and Having Exodontia SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OSTEOPOROSIS; CTX; PREVENTION; POSITION; THERAPY; WOMEN; SERUM AB Purpose: The clinical significance of bone turnover marker C-terminal cross-linking telopeptide (CTX) levels less than 150 pg/mL among recipients of oral bisphosphonate (OBP) medications who develop osteonecrosis of the jaws (MRONJ) after exodontia is unclear. We searched the published data to determine the prevalence of such levels and the association, if any, with development of MRONJ. Materials and Methods: A systematic review of published studies in the PubMed database was undertaken to ascertain the prevalence of preoperative, fasting CTX levels less than 150 pg/mL among recipients of OBP scheduled for exodontia and to determine whether such levels are associated with the development of postoperative MRONJ. The data were aggregated and analyzed to provide the sensitivity, specificity, and positive and negative predictive values of the association between low CTX levels and the development of MRONJ. Results: Two studies were chosen for review. The first, with an enrollment of 21 patients, reported that 10 (48%) patients had a preoperative CTX level less than 150 pg/mL and that after exodontia, none developed MRONJ. The second study, with an enrollment of 950 patients, reported that approximately 282 (30%) had a preoperative CTX level less than 150 pg/mL. All the patients with depressed CTX levels were offered a "drug holiday''; however, only 101 accepted the offer. Of the remaining 181 patients, 4 developed MRONJ. The aggregated study data have demonstrated that 30% of patients evidence CTX levels less than 150 pg/mL and that the sensitivity and specificity of these levels in association with the development of MRONJ was 100% and 80.7%, respectively. The positive predictive value was 2.09% and the negative predictive value was 100%. Conclusion: The published data suggest that approximately one third of patients exposed to OBP will evidence depressed CTX levels and that only a very small minority (similar to 2%) will develop postexodontia MRONJ. Prudence would suggest that patients scheduled for exodontia and receiving OBPs should be informed about the strengths and weaknesses of the CTX test and that it should be offered during the consent process. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons C1 [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Ronald Reagan Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA. Ronald Reagan Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA. [Friedlander, Arthur H.; Chang, Tina I.] Univ Calif Los Angeles, Sch Dent, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA. [Chang, Tina I.] Vet Affairs Greater Los Angeles Healthcare Syst, Inpatient Oral & Maxillofacial Surg, Los Angeles, CA 90073 USA. [Hazboun, Renna C.] Vet Affairs Greater Los Angeles Healthcare Syst, Dent Serv, Oral & Maxillofacial Surg Sect, Los Angeles, CA 90073 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Educ, Los Angeles, CA 90024 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Weintraub Ctr Reconstruct Biotechnol, Adv Prosthodont, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 25 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2015 VL 73 IS 9 BP 1735 EP 1740 DI 10.1016/j.joms.2015.03.015 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CP6SG UT WOS:000360017800018 PM 25863230 ER PT J AU Pace, CG Hwang, KG Papadaki, ME Troulis, MJ AF Pace, Christopher G. Hwang, Kyung-Gyun Papadaki, Maria E. Troulis, Maria J. TI Sialadenitis Without Sialolithiasis Treated by Sialendoscopy SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CHRONIC RECURRENT PAROTITIS; CHRONIC OBSTRUCTIVE PAROTITIS; SALIVARY DUCT DISORDERS; MANAGEMENT; SIALOGRAPHY; DIAGNOSIS; STENOSIS; SIALODOCHOPLASTY; STRICTURE AB Purpose: The aim of the present study was to evaluate the effectiveness of interventional sialendoscopy in the management of non-stone obstructive sialadenitis. Patients and Methods: In the present retrospective study, we assessed the treatment outcomes of 51 patients (34 women and 17 men) who had been diagnosed with sialadenitis without salivary duct stones. The included patients had an obstructive duct condition coupled with recurrent episodes of swelling or pain in a major salivary gland. The patients who had a sialolith detected during the sialendoscopic procedure or by preoperative imaging were excluded from the present study. The outcomes assessment was based on successful removal of the obstructive etiology during the endoscopic procedure and the absence of clinical symptoms after 6 months. The involved glands included 16 submandibular glands and 35 parotid glands. Results: The sialendoscopic navigation was successful in 43 of 51 patients (84%). Of the 43 patients, 37 (86%) were free of symptoms from the obstructive gland after the endoscopic procedure. Of the 6 patients who were still symptomatic after the procedure, 5 had involvement of the parotid gland. Finally, 1 of the original 37 symptom-free patients developed recurrent symptoms and denied additional treatment, resulting in 36 of 43 patients (84%) remaining asymptomatic 6 months after endoscopic navigation. Conclusion: The outcomes of the present study suggest that interventional sialendoscopy can provide symptomatic improvement in most subjects. Clinicians should consider sialendoscopy as a useful and minimally invasive procedure to treat sialadenitis without sialolithiasis. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Pace, Christopher G.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Pace, Christopher G.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hwang, Kyung-Gyun] Hanyang Univ, Coll Med, Dept Dent, Div Oral & Maxillofacial Surg, Seoul 133791, South Korea. [Papadaki, Maria E.] Univ Hosp Heraklio, Iraklion, Greece. [Troulis, Maria J.] Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. [Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Residency Training Program, Boston, MA 02114 USA. RP Pace, CG (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Suite 1201,55 Fruit St, Boston, MA 02114 USA. EM cgpace@mgh.harvard.edu NR 22 TC 2 Z9 2 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2015 VL 73 IS 9 BP 1748 EP 1752 DI 10.1016/j.joms.2015.03.012 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CP6SG UT WOS:000360017800020 PM 25863231 ER PT J AU Jacobson, IG Donoho, CJ Crum-Cianflone, NF Maguen, S AF Jacobson, Isabel G. Donoho, Carrie J. Crum-Cianflone, Nancy F. Maguen, Shira TI Longitudinal assessment of gender differences in the development of PTSD among US military personnel deployed in support of the operations in Iraq and Afghanistan SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE PTSD; Gender; Military; Combat; Sexual assault ID POSTTRAUMATIC-STRESS-DISORDER; MILLENNIUM COHORT; COMBAT DEPLOYMENT; MENTAL-HEALTH; FUNCTIONAL HEALTH; PRIMARY-CARE; PRIME-MD; PREVALENCE; VALIDATION; EXPOSURES AB Divergent findings from previous research examining gender differences in the development of post-traumatic stress disorder (PTSD) among US military members deployed to the operations in Iraq or Afghanistan (recent operations) prompted this study utilizing a matching approach to examine whether risk for new-onset PTSD and PTSD severity scores differed by gender. US military members from the Millennium Cohort Study deployed in support of the recent operations were followed for approximately 7 years from baseline through 2 follow-up periods between 2001 and 2008. Propensity score matching was used to match 1 male to each female using demographic, military, and behavioral factors including baseline sexual assault. Analyses were stratified by combat experience defined as reporting at least one of five exposures during follow-up. Outcome measures included a positive screen for PTSD and severity scores measured by the PTSD Patient Checklist Civilian Version. Discrete-time survival analysis quantified the association between gender and incident PTSD. Among 4684 matched subjects (2342 women and men), 6.7% of women and 6.1% of men developed PTSD during follow-up. Results showed no significant gender differences for the likelihood of developing PTSD or for PTSD severity scores among women and men who reported combat experience and among those who did not. This study is the first of its kind to match a large population of male and female service members on important baseline characteristics including sexual assault. Findings suggest that while combat deployed personnel develop PTSD, women do not have a significantly different risk for developing PTSD than men after experiencing combat. Published by Elsevier Ltd. C1 [Jacobson, Isabel G.; Donoho, Carrie J.; Crum-Cianflone, Nancy F.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. [Donoho, Carrie J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Crum-Cianflone, Nancy F.] Naval Med Ctr San Diego, San Diego, CA USA. [Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA USA. [Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Donoho, CJ (reprint author), Naval Hlth Res Ctr, Deployment Hlth Res Dept, 140 Sylvester Rd, San Diego, CA 92106 USA. EM carrie.j.donoho.mil@mail.mil FU Military Operational Medicine Research Program of the US Army Medical Research and Materiel Command, Fort Detrick, Maryland FX Funding/support: The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the US Army Medical Research and Materiel Command, Fort Detrick, Maryland. The funding organization had no role in the design and conduct of the study; collection, analysis, or preparation of data; or preparation, review or approval of the manuscript. NR 36 TC 4 Z9 4 U1 3 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 30 EP 36 DI 10.1016/j.jpsychires.2015.05.015 PG 7 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100005 PM 26228397 ER PT J AU Maguen, S Madden, E Cohen, BE Bertenthal, D Neylan, TC Seal, KH AF Maguen, Shira Madden, Erin Cohen, Beth E. Bertenthal, Daniel Neylan, Thomas C. Seal, Karen H. TI Suicide risk in Iraq and Afghanistan veterans with mental health problems in VA care SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Suicide; Suicidal ideation; Mental health; Veteran; Veterans health ID POSTTRAUMATIC-STRESS-DISORDER; SERVICEMEMBERS ARMY STARRS; VIETNAM VETERANS; WARNING SIGNS; IDEATION; MILITARY; PREVALENCE; PTSD; RESILIENCE; DEPRESSION AB Suicide rates among U.S. military personnel and veterans are a public health concern, and those with mental health conditions are at particular risk. We examined demographic, military, temporal, and diagnostic associations with suicidality in veterans. We conducted a population-based, retrospective cohort study of all Iraq and Afghanistan war veterans who screened positive for posttraumatic stress disorder (PTSD) and/or depression, received a suicide risk assessment, and endorsed hopelessness about the present or future after their last deployment and between January 1, 2010 and June 29, 2014 (N = 45,741). We used bivariate and multivariate logistic regression analyses to examine variables associated with having endorsed suicidal thoughts and a plan. Multiple factors were associated with suicidality outcomes, including longer time from last deployment to screening (proxy for time to seeking VA care), an alcohol use disorder diagnosis, further distance from VA (rurality), and being active duty during military service. Hispanic veterans were at decreased risk of having suicidal ideation and a plan, compared to their white counterparts. In high-risk veterans, some of the strongest associations with suicidality were with modifiable risk factors, including time to VA care and alcohol use disorder diagnoses. Promising avenues for suicide prevention efforts can include early engagement/intervention strategies with a focus on amelioration of high-risk drinking. Published by Elsevier Ltd. C1 [Maguen, Shira; Madden, Erin; Cohen, Beth E.; Bertenthal, Daniel; Neylan, Thomas C.; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Cohen, Beth E.; Neylan, Thomas C.; Seal, Karen H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bertenthal, Daniel; Neylan, Thomas C.] Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov; Erin.Madden@va.gov; Beth.Cohen@va.gov; Daniel.Bertenthal@va.gov; Thomas.Neylan@va.gov; Karen.Seal@va.gov FU Department of Defense [W81XWH-11-2-0189]; Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC) FX This research was supported by Department of Defense Award Grant (W81XWH-11-2-0189) and the Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC). The authors would like to thank Julie Dinh for her assistance with this manuscript. NR 37 TC 1 Z9 1 U1 9 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 120 EP 124 DI 10.1016/j.jpsychires.2015.06.013 PG 5 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100019 PM 26228410 ER PT J AU Targum, SD Wedel, PC Fava, M AF Targum, Steven D. Wedel, Pamela C. Fava, Maurizio TI Changes in cognitive symptoms after a buspirone-melatonin combination treatment for Major Depressive Disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Cognition; Depression; Anti-depressant treatment; CPFQ ID RESIDUAL SYMPTOMS; ANTIDEPRESSANT TREATMENT; NEUROGENESIS; INVENTORY; DEFICITS; SR AB Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepressant treatment response using the patient self-rated Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) during a 6-week, double-blind trial of a combination antidepressant treatment (buspirone 15 mg with melatonin-SR 3 mg) versus buspirone (15 mg) monotherapy versus placebo in MDD patients with acute depressive episodes. The CPFQ includes distinct cognitive and physical functioning dimension subscales. Treatment response was determined using the Inventory of Depressive Symptomatology (IDSc30). Treatment responders improved significantly more on the total CPFQ than non-responders (p < 0.0001) regardless of treatment assignment. The cognitive dimension of the CPFQ score favored the combination treatment over the other two groups (ANCOVA: p = 0.050). Among the treatment non-responders, the effect size for the CPFQ cognitive dimension was 0.603 favoring the combination treatment over the over two groups and 0.113 for the CPFQ physical dimension. These preliminary findings suggest that a combination of buspirone with melatonin may benefit cognitive function distinct from mood symptoms and that some aspects of cognition may be specific targets for treatment within a population of patients with MDD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Targum, Steven D.] Clintara LLC, Boston, MA USA. [Wedel, Pamela C.] BrainCells Inc, San Diego, CA USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Targum, SD (reprint author), 11 Beacon St,Suite 600, Boston, MA 02108 USA. EM sdtargum@yahoo.com; scoutwedel@yahoo.com; mfava@mgh.harvard.edu FU BrainCells Inc (San Diego, California) FX Partial support for this research came from BrainCells Inc (San Diego, California) who funded the clinical trial that used the MGH-CPFQ. NR 26 TC 3 Z9 3 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 392 EP 396 DI 10.1016/j.jpsychires.2015.04.024 PG 5 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100054 PM 26025562 ER PT J AU Ehrlich, S Geisler, D Ritschel, F King, JA Seidel, M Boehm, I Breier, M Clas, S Weiss, J Marxen, M Smolka, MN Roessner, V Kroemer, NB AF Ehrlich, Stefan Geisler, Daniel Ritschel, Franziska King, Joseph A. Seidel, Maria Boehm, Ilka Breier, Marion Clas, Sabine Weiss, Jessika Marxen, Michael Smolka, Michael N. Roessner, Veit Kroemer, Nils B. TI Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID ALTERED INSULA RESPONSE; EATING-DISORDERS; PREFRONTAL CORTEX; WORKING-MEMORY; WOMEN; FLEXIBILITY; INHIBITION; STIMULI; FOOD; PSYCHOPATHOLOGY AB Background Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives. Methods This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC). Results We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding. Limitations The results we obtained using monetary stimuli might not generalize to other forms of reward. Conclusion Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral-frontal brain circuitry in recovered patients suggests an elevated degree of self-regulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom-up and top-down processes may be a trait marker of the disorder. C1 [Ehrlich, Stefan; Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Seidel, Maria; Boehm, Ilka; Breier, Marion; Clas, Sabine; Weiss, Jessika; Roessner, Veit] Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Dept Child & Adolescent Psychiat,Translat Dev Neu, Dresden, Germany. [Ehrlich, Stefan; Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Seidel, Maria; Boehm, Ilka; Breier, Marion; Clas, Sabine; Weiss, Jessika; Roessner, Veit] Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Res Ctr, Dresden, Germany. [Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Marxen, Michael; Smolka, Michael N.; Kroemer, Nils B.] Tech Univ Dresden, Dept Psychiat, Dresden, Germany. [Marxen, Michael; Smolka, Michael N.; Kroemer, Nils B.] Tech Univ Dresden, Neuroimaging Ctr, Dresden, Germany. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Dept Child & Adolescent Psychiat,Translat Dev Neu, Fetscherstr 74, Dresden, Germany. EM Stefan.Ehrlich@uniklinikum-dresden.de FU Deutsche Forschungsgemeinschaft [EH 367/5-1, SM 80/5-2, SFB 940/1]; Swiss Anorexia Nervosa Foundation FX This work was supported by the Deutsche Forschungsgemeinschaft (EH 367/5-1, SM 80/5-2 and SFB 940/1) and the Swiss Anorexia Nervosa Foundation. The authors thank the numerous medical students and other interns for their assistance with participant recruitment and data collection, Franziska Wuttig for support with the connectivity analysis, and all participants for their time and cooperation. NR 60 TC 13 Z9 13 U1 7 U2 28 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 EI 1488-2434 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2015 VL 40 IS 5 BP 307 EP 315 DI 10.1503/jpn.140249 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CP5PT UT WOS:000359936600001 PM 26107161 ER PT J AU Drijkoningen, T van Weel, V Eberlin, KR Cetrulo, CL AF Drijkoningen, Tessa van Weel, Vincent Eberlin, Kyle R. Cetrulo, Curtis L., Jr. TI Eptifibatide Salvage of Arterial Anastomotic Thrombosis in Lower Extremity Free Flap Reconstruction: A Case Report SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Letter ID FRACTURES; TRIAL C1 [Drijkoningen, Tessa; Eberlin, Kyle R.; Cetrulo, Curtis L., Jr.] Harvard Univ, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [van Weel, Vincent] Meander Med Ctr, Dept Surg, Amersfoort, Netherlands. RP Drijkoningen, T (reprint author), Wang Ambulatory Care Ctr 435,55 Fruit St, Boston, MA 02114 USA. EM tdrijkoningen@mgh.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD SEP PY 2015 VL 31 IS 7 BP 544 EP 546 DI 10.1055/s-0035-1555011 PG 3 WC Surgery SC Surgery GA CP4VS UT WOS:000359881300010 PM 26115546 ER PT J AU Yeh, DD Park, YS AF Yeh, D. Dante Park, Yoon Soo TI Improving Learning Efficiency of Factual Knowledge in Medical Education SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE medical education; testing effect; distributive practice; feedback; smartphones ID LONG-TERM RETENTION; RANDOMIZED CONTROLLED-TRIAL; DISTRIBUTED PRACTICE; SPACED-EDUCATION; EXPANDING RETRIEVAL; LATER MEMORY; FEEDBACK; STUDENTS; TESTS; CLASSROOM AB OBJECTIVE: The purpose of this review is to synthesize recent literature relating to factual knowledge acquisition and retention and to explore its applications to medical education. RESULTS: Distributing, or spacing, practice is superior to massed practice (i.e. cramming). Testing, compared to re-study, produces better learning and knowledge retention, especially if tested as retrieval format (short answer) rather than recognition format (multiple choice). Feedback is important to solidify the testing effect. CONCLUSIONS: Learning basic factual knowledge is often overlooked and under-appreciated in medical education. Implications for applying these concepts to smartphones are discussed; smartphones are owned by the majority of medical trainees and can be used to deploy evidence-based educational methods to greatly enhance learning of factual knowledge. (C) 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Yeh, D. Dante] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Park, Yoon Soo] Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL USA. RP Yeh, DD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St 810, Boston, MA 02114 USA. EM Dyeh2@mgh.harvard.edu NR 65 TC 1 Z9 1 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD SEP-OCT PY 2015 VL 72 IS 5 BP 882 EP 889 DI 10.1016/j.jsurg.2015.03.012 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA CP4ZE UT WOS:000359890300019 PM 25920573 ER PT J AU Chee, YE Newman, LR Loewenstein, JI Kloek, CE AF Chee, Yewlin E. Newman, Lori R. Loewenstein, John I. Kloek, Carolyn E. TI Improving the Teaching Skills of Residents in a Surgical Training Program: Results of the Pilot Year of a Curricular Initiative in an Ophthalmology Residency Program SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE resident-as-teacher; resident education; surgical education; procedural teaching ID COGNITIVE TASK-ANALYSIS; MEDICAL-EDUCATION; PROCEDURAL SKILLS AB OBJECTIVE: To design and implement a teaching skills curriculum that addressed the needs of an ophthalmology residency training program, to assess the effect of the curriculum, and to present important lessons learned. DESIGN: A teaching skills curriculum was designed for the Harvard Medical School (HMS) Residency Training Program in Ophthalmology. Results of a needs assessment survey were used to guide curriculum objectives. Overall, 3 teaching workshops were conducted between October 2012 and March 2013 that addressed areas of need, including procedural teaching. A postcurriculum survey was used to assess the effect of the curriculum. SETTING: Massachusetts Eye and Ear Infirmary, a tertiary care institution in Boston, MA. PARTICIPANTS: Overall, 24 residents in the HMS Residency Training Program in Ophthalmology were included. RESULTS: The needs assessment survey demonstrated that although most residents anticipated that teaching would be important in their future career, only one-third had prior formal training in teaching. All residents reported they found the teaching workshops to be either very or extremely useful. All residents reported they would like further training in teaching, with most residents requesting additional training in best procedural teaching practices for future sessions. CONCLUSIONS: The pilot year of the resident-as-teacher curriculum for the HMS Residency Training Program in Ophthalmology demonstrated a need for this curriculum and was perceived as beneficial by the residents, who reported increased comfort in their teaching skills after attending the workshops. (C) 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Chee, Yewlin E.; Loewenstein, John I.; Kloek, Carolyn E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. [Newman, Lori R.] Harvard Univ, Sch Med, Shapiro Inst Med Educ & Res, Boston, MA USA. [Newman, Lori R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Chee, YE (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM yewlin_chee@meei.harvard.edu NR 28 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD SEP-OCT PY 2015 VL 72 IS 5 BP 890 EP 897 DI 10.1076/j.jsurg.2015.03.002 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA CP4ZE UT WOS:000359890300020 PM 25921191 ER PT J AU Allard, CB Meyer, CP Gandaglia, G Chang, SL Chun, FKH Gelpi-Hammerschmidt, F Hanske, J Kibel, AS Preston, MA Trinh, QD AF Allard, Christopher B. Meyer, Christian P. Gandaglia, Giorgio Chang, Steven L. Chun, Felix K. H. Gelpi-Hammerschmidt, Francisco Hanske, Julian Kibel, Adam S. Preston, Mark A. Quoc-Dien Trinh TI The Effect of Resident Involvement on Perioperative Outcomes in Transurethral Urologic Surgeries SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE surgical education; bladder cancer; benign prostatic hyperplasia; complications ID OPERATING-ROOM; BLADDER-TUMOR; RESECTION; IMPACT; PROSTATE; PROGRAM; COMPLICATIONS; HOSPITALS; EDUCATION AB OBJECTIVE: To conduct the first study of intra- and postoperative outcomes related to intraoperative resident involvement in transurethral resection procedures for benign prostatic hyperplasia and bladder cancer in a large, multi-institutional database. DESIGN: Relying on the American College of Surgeons National Surgical Quality Improvement Program Participant User Files (2005-2012), we abstracted all cases of endoscopic prostate surgery (EPS) for benign prostatic hyperplasia and transurethral resection of bladder tumors (TURBTs). Multivariable logistic regression models were constructed to assess the effect of trainee involvement (postgraduate year [PGY] 1-2: junior, PGY 3-4: senior, PGY 5: chief or fellow) vs attending only on operative time and length of hospital stay, as well as 30-day complication, reoperation, and readmission rates. RESULTS: In all, 5093 EPS and 3059 TURBTs for a total of 8152 transurethral resection procedures were performed during the study period for which data on resident involvement were available. In multivariable analyses, resident involvement in EPS or TURBT was associated with increased odds of prolonged operative times and hospital readmissions in 30 days independent of resident level of training. Resident involvement was not associated with overall complications or reoperation rates. CONCLUSIONS: Resident involvement in lower urinary tract surgeries is associated with increased readmissions. Strategies to optimize resident teaching of these common urologic procedures in order to minimize possible risks to patients should be explored. (C) 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Allard, Christopher B.; Meyer, Christian P.; Chang, Steven L.; Gelpi-Hammerschmidt, Francisco; Kibel, Adam S.; Preston, Mark A.; Quoc-Dien Trinh] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Allard, Christopher B.; Gelpi-Hammerschmidt, Francisco] Massachusetts Gen Hosp, Div Urol, Boston, MA 02114 USA. [Meyer, Christian P.; Chun, Felix K. H.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Gandaglia, Giorgio] IRCCS Osped San Raffaele, Div Oncol, Unit Urol, Milan, Italy. [Hanske, Julian] Harvard Univ, Sch Med, Ctr Surg & Publ Hlth, Boston, MA USA. [Hanske, Julian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. [Hanske, Julian] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. RP Allard, CB (reprint author), Massachusetts Gen Hosp, Div Urol, 55 Fruit St, Boston, MA 02114 USA. EM callard@mgh.harvard.edu RI Chun, Felix/M-4652-2015 OI Chun, Felix/0000-0001-8486-9536 FU Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital; Vattikuti Urology Institute FX Quoc-Dien Trinh is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital and by an unrestricted educational grant from the Vattikuti Urology Institute. NR 32 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD SEP-OCT PY 2015 VL 72 IS 5 BP 1018 EP 1025 DI 10.1016/j.jsurg.2015.04.012 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA CP4ZE UT WOS:000359890300038 PM 26003818 ER PT J AU Cauley, CE Pitman, MB Zhou, JH Perkins, J Kuleman, B Liss, AS Fernandez-del Castillo, C Warshaw, AL Lillemoe, KD Thayer, SP AF Cauley, Christy E. Pitman, Martha B. Zhou, Jiahua Perkins, James Kuleman, Birte Liss, Andrew S. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Lillemoe, Keith D. Thayer, Sarah P. TI Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and Pathologic Findings SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID BREAST-CANCER PATIENTS; TUMOR-CELLS; PROGNOSTIC VALUE; ADENOCARCINOMA; METAANALYSIS; METASTASIS; DIAGNOSIS AB BACKGROUND: Circulating epithelial cell (CEC) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, premalignant, and malignant pancreatic lesions using a size-selective filtration device. STUDY DESIGN: Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathologic data and clinical outcomes of these patients were obtained from medical records during a 1-year follow-up period. RESULTS: Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. Circulating epithelial cells were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions (p = 0.41). In addition, CEC findings in pancreatic ductal adenocarcinoma patients were not associated with poor prognosis. CONCLUSIONS: Although CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is neither diagnostic of malignancy nor prognostic for patients with pancreatic ductal adenocarcinoma. (C) 2015 by the American College of Surgeons C1 [Cauley, Christy E.; Zhou, Jiahua; Perkins, James; Kuleman, Birte; Liss, Andrew S.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pitman, Martha B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cauley, Christy E.; Zhou, Jiahua; Perkins, James; Kuleman, Birte; Liss, Andrew S.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Lillemoe, Keith D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Warshaw Inst Pancreat Canc Res, Boston, MA USA. [Thayer, Sarah P.] Univ Nebraska Med Ctr, Div Surg Oncol, Dept Surg, Omaha, NE USA. RP Cauley, CE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 159 Hancock St 2, Cambridge, MA 02139 USA. EM ccauley@partners.org FU NIH [R01CA169086, R25CA092203] FX Dr Thayer was supported by NIH grant R01CA169086, and Dr Cauley was supported by NIH grant R25CA092203. NR 31 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2015 VL 221 IS 3 BP 699 EP 707 DI 10.1016/j.jamcollsurg.2015.05.014 PG 9 WC Surgery SC Surgery GA CP7UK UT WOS:000360093800009 PM 26209458 ER PT J AU Ceppa, EP Pitt, HA Nakeeb, A Schmidt, CM Zyromski, NJ House, MG Kilbane, EM George-Minkner, AN Brand, B Lillemoe, KD AF Ceppa, Eugene P. Pitt, Henry A. Nakeeb, Attila Schmidt, C. Max Zyromski, Nicholas J. House, Michael G. Kilbane, E. Molly George-Minkner, Alisha N. Brand, Beth Lillemoe, Keith D. TI Reducing Readmissions after Pancreatectomy: Limiting Complications and Coordinating the Care Continuum SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SINGLE-INSTITUTION EXPERIENCE; SURGICAL SITE INFECTIONS; HEPATOPANCREATOBILIARY SURGERY; 1423 PANCREATICODUODENECTOMIES; RISK-FACTORS; ACS-NSQIP; RESECTION; CANCER; VOLUME; HOSPITALIZATION AB BACKGROUND: Recent analyses of gastrointestinal operations document that complications are a key driver of readmissions. Pancreatectomy is a high outlier with respect to readmission. This analysis sought to determine if a multifactorial approach could reduce readmissions after pancreatectomy. STUDY DESIGN: From 2007 to 2012, the number of patients readmitted by 30 days after pancreaticoduodenectomy, and distal and total pancreatectomy was measured. Steps to decrease readmissions were implemented independently at 1-year intervals; these efforts included strategies to reduce complications, creation of a Readmissions Team with a "discharge coach," increased use of home health, preferred relationships with post-acute care facilities, and the adoption of "Project RED" (Re-Engineered Discharge). The ACS NSQIP was used to track 30-day outcomes for all pancreatic resections. The University HealthSystem Consortium was used to determine length of stay index. RESULTS: Over 5 years, 1,163 patients underwent proximal (66%), distal (32%), or total pancreatectomy (2%). The observed 30-day mortality was 2.9% for the study period, and the length of stay index (observed/expected days) was 1.10. Neither varied significantly over time. However, 30-day morbidity decreased from 57% to 46%, and proportion of patients with 30-day all-cause readmissions decreased from 23.0% to 11.5% (p = 0.001). CONCLUSIONS: All-cause 30-day readmissions after pancreatectomy decreased without increasing length of stay. Efforts by surgeons to decrease complications and an increased emphasis on coordination of care may be useful for reducing readmissions. (C) 2015 by the American College of Surgeons C1 [Ceppa, Eugene P.; Nakeeb, Attila; Schmidt, C. Max; Zyromski, Nicholas J.; House, Michael G.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Kilbane, E. Molly; George-Minkner, Alisha N.] Indiana Univ Hlth, Dept Nursing, Indianapolis, IN USA. [Brand, Beth] Indiana Univ Hlth, Clin Decis Support, Indianapolis, IN USA. [Pitt, Henry A.] Temple Univ, Sch Med, Dept Surg, Philadelphia, PA 19140 USA. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pitt, HA (reprint author), Temple Univ, Sch Med, Dept Surg, 3509 N Broad St, Philadelphia, PA 19140 USA. EM Henry.pitt@tuhs.temple.edu NR 28 TC 4 Z9 4 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2015 VL 221 IS 3 BP 708 EP 716 DI 10.1016/j.jamcollsurg.2015.05.012 PG 9 WC Surgery SC Surgery GA CP7UK UT WOS:000360093800010 PM 26228016 ER PT J AU Rajaram, R Chung, JW Cohen, ME Dahlke, AR Yang, AD Meeks, JJ Ko, CY Tarpley, JL Hoyt, DB Bilimoria, KY AF Rajaram, Ravi Chung, Jeanette W. Cohen, Mark E. Dahlke, Allison R. Yang, Anthony D. Meeks, Joshua J. Ko, Clifford Y. Tarpley, John L. Hoyt, David B. Bilimoria, Karl Y. TI Association of the 2011 ACGME Resident Duty Hour Reform with Postoperative Patient Outcomes in Surgical Specialties SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID INSTITUTE-OF-MEDICINE; HOURS ENHANCING SLEEP; ACCREDITATION COUNCIL; WORKING HOURS; SURGERY; QUALITY; SAFETY; MORTALITY; RESTRICTIONS; EDUCATION AB BACKGROUND: The 2011 ACGME resident duty hour reform implemented additional restrictions to existing duty hour policies. Our objective was to determine the association between this reform and patient outcomes among several surgical specialties. STUDY DESIGN: Patients from 5 surgical specialties (neurosurgery, obstetrics/gynecology, orthopaedic surgery, urology, and vascular surgery) were identified from the American College of Surgeons NSQIP. Data from 1 year before and 2 years after the reform was implemented were obtained for teaching and nonteaching hospitals. Hospital teaching status was defined based on the percentage of operations with a resident present intraoperatively. Difference-in-differences models were developed separately for each specialty and adjusted for patient demographics, comorbidities, procedural case-mix, and time trends. The association between duty hour reform and a composite measure of death or serious morbidity within 30 days of surgery was estimated for each specialty. RESULTS: The unadjusted rate of death or serious morbidity decreased during the study period in both teaching and nonteaching hospitals for all surgical specialties. In multivariable analyses, there were no significant associations between duty hour reform and the composite outcomes of death or serious morbidity in the 2 years post-reform for any surgical specialty evaluated (neurosurgery: odds ratio [OR] = 0.90; 95% CI, 0.75-1.08; p = 0.26; obstetrics/gynecology: OR = 0.96; 95% CI, 0.71-1.30; p = 0.80; orthopaedic surgery: OR = 0.95; 95% CI, 0.74-1.22; p = 0.70; urology: OR = 1.16; 95% CI, 0.89-1.51; p = 0.26; vascular surgery: OR = 1.07; 95% CI, 0.93-1.22; p = 0.35). CONCLUSIONS: Implementation of the 2011 ACGME resident duty hour reform was not associated with a significant change in patient outcomes for several surgical specialties in the 2 years after reform. (C) 2015 by the American College of Surgeons C1 [Rajaram, Ravi; Cohen, Mark E.; Ko, Clifford Y.; Hoyt, David B.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Yang, Anthony D.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, SOQIC, Dept Surg, Chicago, IL 60611 USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Yang, Anthony D.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Inst Publ Hlth & Med, Chicago, IL 60611 USA. [Meeks, Joshua J.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tarpley, John L.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA. RP Rajaram, R (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM rrajaram@facs.org FU Agency for Healthcare Research and Quality [T32HS000078]; American College of Surgeons Clinical Scholars in Residence Program; Merck FX Dr Rajaram is supported by the Agency for Healthcare Research and Quality #T32HS000078, the American College of Surgeons Clinical Scholars in Residence Program, and an unrestricted educational grant from Merck. The sponsors had no part in the design and conduct of the study; analysis and interpretation of the data; and preparation or approval of the manuscript. The sponsors had no access to the data and did not perform any of the analyses. NR 38 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2015 VL 221 IS 3 BP 748 EP 757 DI 10.1016/j.jamcollsurg.2015.06.010 PG 10 WC Surgery SC Surgery GA CP7UK UT WOS:000360093800014 PM 26228013 ER PT J AU Lott, ME Slocomb, JE Gao, ZH Gabbay, RA Quillen, D Gardner, TW Bettermann, K AF Lott, Mary E. Slocomb, Julia E. Gao, Zhaohui Gabbay, Robert A. Quillen, David Gardner, Thomas W. Bettermann, Kerstin TI Impaired coronary and retinal vasomotor function to hyperoxia in Individuals with Type 2 diabetes SO MICROVASCULAR RESEARCH LA English DT Article DE Coronary reactivity; Retinal reactivity; Diabetes; Vasoconstriction; Hyperoxia ID VASCULAR SMOOTH-MUSCLE; BLOOD-FLOW; VITAMIN-C; ATHEROSCLEROSIS RISK; ARTERY-DISEASE; HEART-DISEASE; ENDOTHELIAL FUNCTION; ARTERIOLAR DIAMETER; SUPPLEMENTAL OXYGEN; SYSTEMIC HYPEROXIA AB Purpose: Adults with diabetes are at a high risk of developing coronary heart disease. The purpose of this study was to assess coronary artery vascular function non-invasively in individuals with and without Type 2 diabetes and to compare these coronary responses to another microvascular bed (i.e. retina). We hypothesized that individuals with diabetes would have impaired coronary reactivity and that these impairments would be associated with impairments in retinal reactivity. Methods: Coronary blood velocity (Transthoracic Doppler Echocardiography) and retinal diameters (Dynamic Vessel Analyzer) were measured continuously during five minutes of breathing 100% oxygen (i.e. hyperoxia) in 15 persons with Type 2 diabetes and 15 age-matched control subjects. Using fundus photographs, retinal vascular calibers were also measured (central retinal arteriole and venule equivalents). Results: Individuals with diabetes compared to controls had impaired coronary (-2.34 +/- 16.64% vs. -14.27 +/- 10.58%, P = 0.03) and retinal (arteriole: -0.04 +/- 3.34% vs. -3.65 +/- 5.07%, P = 0.03; venule: -1.65 +/- 3.68% vs. -5.23 +/- 5.47%, P = 0.05) vasoconstrictor responses to hyperoxia, and smaller central arteriole-venule equivalent ratios (0.83 +/- 0.07 vs. 0.90 +/- 0.07, P = 0.014). Coronary reactivity was associated with central retinal arteriole equivalents (r = -0.516, P = 0.005) and retinal venular reactivity (r = 0.387, P = 0.034). Conclusion: Diabetes impairs coronary and retinal microvascular function to hyperoxia. Impaired vasoconstrictor responses may be part of a systemic diabetic vasculopathy, which may contribute to adverse cardiovascular events in individuals with diabetes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lott, Mary E.; Gao, Zhaohui] Penn State Hershey Med Ctr, Inst Heart & Vasc, Hershey, PA 17033 USA. [Slocomb, Julia E.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Gabbay, Robert A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02116 USA. [Quillen, David] Penn State Hershey Med Ctr, Dept Ophthalmol, Hershey, PA 17033 USA. [Gardner, Thomas W.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48105 USA. [Bettermann, Kerstin] Penn State Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. RP Lott, ME (reprint author), Milton S Hershey Med Ctr, Penn State Heart & Vasc Inst, Campus Box H047,500 Univ Dr, Hershey, PA 17033 USA. EM mlott@hmc.psu.edu OI Gardner, Thomas/0000-0002-5112-5810 FU Pennsylvania Tobacco Settlement Funds [4100042746]; Penn State Diabetes and Obesity Institute Equipment Grant; Pennsylvania Lions Sight Conservation and Eye Research Foundation; Jack and Nancy Turner Professorship at Penn State; A. Alfred Taubman Medical Research Institute at the University of Michigan; Research to Prevent Blindness Physician-Scientist Award; National Institutes of Health [EY20582, DK094292]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000127] FX We would like to thank Bruce Smith, Vikram Shivkumar, Michael Herr, Surju Patel, Cheryl Blaha and Jessica Mast for their help with the study. We would like to thank Allen Kunselman in the Department for Public Health Sciences for his assistance with power and sample size calculations. We would like to thank the individuals who participated in the studies, as well as the nursing staff of the Clinical Research Center. Support was provided by a grant from Pennsylvania Tobacco Settlement Funds (4100042746). The DVA was partially funded by the Penn State Diabetes and Obesity Institute Equipment Grant and the Pennsylvania Lions Sight Conservation and Eye Research Foundation and the Jack and Nancy Turner Professorship at Penn State supported Dr. Gardner. Dr. Gardner is currently supported by the A. Alfred Taubman Medical Research Institute at the University of Michigan, a Research to Prevent Blindness Physician-Scientist Award and National Institutes of Health EY20582 and DK094292. The studies were performed in Penn State's Clinical Research Center, which was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000127. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. There are no conflicts of interest. NR 68 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 EI 1095-9319 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 2015 VL 101 BP 1 EP 7 DI 10.1016/j.mvr.2015.05.002 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP6WI UT WOS:000360028500001 PM 26002545 ER PT J AU Hu, ZM Qi, HX Zhang, RX Zhang, K Shi, ZM Chang, YN Chen, LF Esmaeili, M Baniahmad, A Hong, W AF Hu, Zhimei Qi, Haixia Zhang, Ruixue Zhang, Kun Shi, Zhemin Chang, Yanan Chen, Linfeng Esmaeili, Mohsen Baniahmad, Aria Hong, Wei TI Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer cells by promoting the degradation of the androgen receptor SO MOLECULAR MEDICINE REPORTS LA English DT Article DE docosahexaenoic acid; prostate cancer; androgen receptor ID POLYUNSATURATED FATTY-ACIDS; MAMMARY TUMORIGENESIS; RISK; PROGRESSION; DIET; OMEGA-3-FATTY-ACIDS; PROLIFERATION; EXPRESSION; THERAPY; INDEPENDENCE AB Epidemiological and preclinical data have demonstrated the preventative effects of omega-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), on prostate cancer. However, there are inconsistencies in these previous studies and the underlying mechanisms remain to be elucidated. In the present study, the androgen receptor (AR), which is a transcription factor involved in cell proliferation and prostate carcinogenesis, was identified as a target of DHA. It was revealed that DHA inhibited hormone-dependent growth of LNCaP prostate cancer cells. Reverse transcription-quantitative polymerase chain reaction analysis revealed that treatment with DHA caused no alteration in the transcribed mRNA expression levels of the AR gene. However, immunoblotting revealed that this treatment reduces the protein expression level of the AR. The androgen-induced genes were subsequently repressed by treatment with DHA. It was demonstrated that DHA exhibits no effect on the translation process of the AR, however, it promotes the proteasome-mediated degradation of the AR. Therefore, the present study provided a novel mechanism by which DHA exhibits an inhibitory effect on growth of prostate cancer cells. C1 [Hu, Zhimei; Qi, Haixia; Zhang, Ruixue; Zhang, Kun; Shi, Zhemin; Chang, Yanan; Hong, Wei] Tianjin Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Tianjin 300070, Peoples R China. [Chen, Linfeng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Esmaeili, Mohsen; Baniahmad, Aria] Jena Univ Hosp, Inst Human Genet, D-07740 Jena, Germany. RP Hong, W (reprint author), Tianjin Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, 22 Qixiangtai Road, Tianjin 300070, Peoples R China. EM aria.baniahmad@med.uni-jena.de; hongwei@tijmu.edu.cn FU Tianjin Municipal Science and Technology Commission [12JCZDJC21600]; National Natural Science Foundation of China [81271203]; German Academic Exchange Service DAAD; German Cancer Aid FX This study was supported by the Tianjin Municipal Science and Technology Commission (grant no. 12JCZDJC21600 to Dr Wei Hong), the National Natural Science Foundation of China (grant no. 81271203 to Dr Wei Hong), the German Academic Exchange Service DAAD (to Mr. Mohsen Esmaeili) and the German Cancer Aid (to Professor Aria Baniahmad) The authors would like to thank Dr David Fisher for critically reading the manuscript. NR 33 TC 0 Z9 0 U1 0 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1791-2997 EI 1791-3004 J9 MOL MED REP JI Mol. Med. Rep. PD SEP PY 2015 VL 12 IS 3 BP 3769 EP 3774 DI 10.3892/mmr.2015.3813 PG 6 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA CP5OW UT WOS:000359933900077 PM 25997493 ER PT J AU Paganoni, S Hyman, T Shui, A Allred, P Harms, M Liu, JX Maragakis, N Schoenfeld, D Yu, H Atassi, N Cudkowicz, M Miller, TM AF Paganoni, Sabrina Hyman, Theodore Shui, Amy Allred, Peggy Harms, Matthew Liu, Jingxia Maragakis, Nicholas Schoenfeld, David Yu, Hong Atassi, Nazem Cudkowicz, Merit Miller, Timothy M. TI Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis SO MUSCLE & NERVE LA English DT Article DE ALS; BMI; diabetes; prognosis; survival ID BODY-MASS INDEX; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RISK; ALS; FAT; DYSLIPIDEMIA; METABOLISM; PREDICTOR; DISEASE AB Introduction: The aim of this study was to determine whether a history of pre-morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS). Methods: The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from 6 clinical trials. Results: Survival did not differ by diabetes status (log-rank test, P=0.98), but did differ by body mass index (BMI) (log-rank test, P=0.008). In multivariate analysis, there was no significant association between diabetes and survival (P=0.18), but the risk of reaching a survival endpoint decreased by 4% for each unit increase in baseline BMI (HR 0.96, 95% CI 0.94-0.99, P=0.001). DM2 was less prevalent among ALS clinical trial participants than predicted. Conclusions: A history of pre-morbid DM2 is not an independent prognostic factor in ALS clinical trial databases. The low DM2 prevalence rate should be examined in a large, prospective study to determine whether DM2 affects ALS risk. Muscle Nerve 52:339-343, 2015 C1 [Paganoni, Sabrina; Yu, Hong; Atassi, Nazem; Cudkowicz, Merit] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA USA. [Paganoni, Sabrina] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Paganoni, Sabrina] VA Healthcare Syst, Boston, MA USA. [Hyman, Theodore; Allred, Peggy; Harms, Matthew; Liu, Jingxia; Miller, Timothy M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Shui, Amy; Schoenfeld, David] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Maragakis, Nicholas] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Miller, TM (reprint author), Washington Univ, Sch Med, Dept Neurol, 115 Biotech Bldg,Box 8111,660 South Euclid St, St Louis, MO 63110 USA. EM millert@neuro.wustl.edu FU NIH [R01NS078398, U01NS084970, U01NS049640] FX This study was supported by NIH (grants R01NS078398 and U01NS084970 to T.M.M. Salary support for statistical analysis was provided by NIH (U01NS049640). NR 30 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2015 VL 52 IS 3 BP 339 EP 343 DI 10.1002/mus.24688 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CP1XT UT WOS:000359671800004 PM 25900666 ER PT J AU Reeves, RK Li, HY Jost, S Blass, E Li, HL Schafer, JL Varner, V Manickam, C Eslamizar, L Altfeld, M von Andrian, UH Barouch, DH AF Reeves, R. Keith Li, Haiying Jost, Stephanie Blass, Eryn Li, Hualin Schafer, Jamie L. Varner, Valerie Manickam, Cordelia Eslamizar, Leila Altfeld, Marcus von Andrian, Ulrich H. Barouch, Dan H. TI Antigen-specific NK cell memory in rhesus macaques SO NATURE IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; SIMIAN IMMUNODEFICIENCY VIRUS; CONTROLLER PATIENTS; ADAPTIVE IMMUNITY; HIV-1 INFECTION; LYMPHOID-CELLS; CUTTING EDGE; T-CELLS; ACTIVATION; RESPONSES AB Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exists in primates. We found that splenic and hepatic NK cells from SHIVSF162p3-infected and SIVmac251-infected macaques specifically lysed Gag- and Env-pulsed dendritic cells in an NKG2-dependent fashion, in contrast to NK cells from uninfected macaques. Moreover, splenic and hepatic NK cells from Ad26-vaccinated macaques efficiently lysed antigen-matched but not antigen-mismatched targets 5 years after vaccination. These data demonstrate that robust, durable, antigen-specific NK cell memory can be induced in primates after both infection and vaccination, and this finding could be important for the development of vaccines against HIV-1 and other pathogens. C1 [Reeves, R. Keith; Li, Haiying; Blass, Eryn; Li, Hualin; Schafer, Jamie L.; Varner, Valerie; Manickam, Cordelia; Eslamizar, Leila; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Reeves, R. Keith; Li, Haiying] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. [Jost, Stephanie; Altfeld, Marcus; von Andrian, Ulrich H.; Barouch, Dan H.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA. [Altfeld, Marcus] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Reeves, RK (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. EM rreeves@bidmc.harvard.edu; dbarouch@bidmc.harvard.edu FU National Institutes of Health [AI078526, AI096040, AI095985, AI069259, AI111595, AI112521, AI067031, AI118468]; American Foundation for AIDS Research [108547-53-RGRL]; Harvard Center for AIDS Research [AI060354]; Ragon Institute of MGH, MIT and Harvard FX This work was supported by the National Institutes of Health (grants AI078526, AI096040 and AI095985 to D.H.B.; AI069259, AI111595 and AI112521 to U.H.v.A.; AI067031 to MA.; and AI118468 to R.K.R.), the American Foundation for AIDS Research (grant 108547-53-RGRL to R.K.R.), the Harvard Center for AIDS Research (grant AI060354 to R.K.R.) and the Ragon Institute of MGH, MIT and Harvard (S.J., M.A., D.H.B. and U.H.v.A.). NR 48 TC 33 Z9 34 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2015 VL 16 IS 9 BP 927 EP 932 DI 10.1038/ni.3227 PG 6 WC Immunology SC Immunology GA CP4UA UT WOS:000359876900010 PM 26193080 ER PT J AU Wittrup, A Lieberman, J AF Wittrup, Anders Lieberman, Judy TI Knocking down disease: a progress report on siRNA therapeutics SO NATURE REVIEWS GENETICS LA English DT Review ID SMALL INTERFERING RNAS; SILENCING IN-VIVO; ANTISENSE OLIGONUCLEOTIDES; CHEMICAL-MODIFICATION; LIPID NANOPARTICLES; NONHUMAN-PRIMATES; TARGETED DELIVERY; VIRUS-REPLICATION; SYSTEMIC DELIVERY; MAMMALIAN-CELLS AB Small interfering RNAs (siRNAs), which downregulate gene expression guided by sequence complementarity, can be used therapeutically to block the synthesis of disease-causing proteins. The main obstacle to siRNA drugs-their delivery into the target cell cytosol-has been overcome to allow suppression of liver gene expression. Here, we review the results of recent clinical trials of siRNA therapeutics, which show efficient and durable gene knockdown in the liver, with signs of promising clinical outcomes and little toxicity. We also discuss the barriers to more widespread applications that target tissues besides the liver and the most promising avenues to overcome them. C1 [Wittrup, Anders; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wittrup, Anders; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wittrup, Anders] Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, S-22185 Lund, Sweden. RP Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu FU Swedish Research Council; US National Institutes of Health (NIH) [CA139444] FX This work was supported by the Swedish Research Council (A.W.) and the US National Institutes of Health (NIH) grant CA139444 (to J.L.). NR 94 TC 73 Z9 75 U1 22 U2 106 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD SEP PY 2015 VL 16 IS 9 BP 543 EP 552 DI 10.1038/nrg3978 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CP5WD UT WOS:000359954900009 PM 26281785 ER EF