FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Martinez, ME Kearney, DJ Simpson, T Felleman, BI Bernardi, N Sayre, G AF Martinez, Michelle E. Kearney, David J. Simpson, Tracy Felleman, Benjamin I. Bernardi, Nicole Sayre, George TI Challenges to Enrollment and Participation in Mindfulness-Based Stress Reduction Among Veterans: A Qualitative Study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDERS; COGNITIVE THERAPY; CHRONIC PAIN; OF-LIFE; OEF/OIF VETERANS; MENTAL-HEALTH; CARE-SYSTEM; MEDITATION; DEPRESSION AB Background: Mindfulness-Based Stress Reduction (MBSR) is associated with reduced depressive symptoms, quality of life improvements, behavioral activation, and increased acceptance among veterans. This study was conducted to increase the reach and impact of a veterans' MBSR program by identifying barriers to enrollment and participation to inform modifications in program delivery. Objective: Verify or challenge suspected barriers, and identify previously unrecognized barriers, to enrollment and participation in MBSR among veterans. Design: A retrospective qualitative analysis of semistructured interviews. Setting/location: VA Puget Sound Health Care System (Seattle, WA). Subjects: 68 interviewed, and 48 coded and analyzed before reaching saturation. Approach: Content analysis of semistructured interviews. Results: Of the participants who enrolled, most (78%) completed the program and described MBSR positively. Veterans identified insufficient or inaccurate information, scheduling issues, and an aversion to groups as barriers to enrollment. Participants who discontinued the program cited logistics (e.g., scheduling and medical issues), negative reactions to instructors or group members, difficulty understanding the MBSR practice purposes, and struggling to find time for the practices as barriers to completion. Other challenges (cohort dynamics, teacher impact on group structure and focus, instructor lack of military service, and physical and psychological challenges) did not impede participation; we interpreted these as growth-facilitating challenges. Common conditions among veterans (chronic pain, posttraumatic stress disorder, and depression) were not described as barriers to enrollment or completion. Conclusions: Women-only MBSR groups and tele-health MBSR groups could improve accessibility to MBSR for veterans by addressing barriers such as commute anxiety, time restrictions, and an aversion to mixed gender groups among women. Educating MBSR teachers about veteran culture and health challenges faced by veterans, adding psychoeducation materials that relate mindfulness practice to conditions common among veterans, and improving visual aids for mindful movement exercises in the workbook could better accommodate veterans who participate in MBSR. C1 [Martinez, Michelle E.; Felleman, Benjamin I.; Bernardi, Nicole; Sayre, George] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kearney, David J.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Simpson, Tracy] VA Puget Sound Hlth Care Syst, Dept Mental Hlth, Seattle, WA USA. [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Simpson, Tracy] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Sayre, George] Univ Washington, Sch Med, Dept Hlth Serv, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI, 1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@VA.gov FU VA Puget Sound Office of Patient Centered Care & Cultural Transformation (OPCCCT) FX We would like to thank and acknowledge Emily Hu, MS, and Victoria Sanborn, MSW, for their contributions to this project. The study was funded by the VA Puget Sound Office of Patient Centered Care & Cultural Transformation (OPCC&CT). NR 57 TC 0 Z9 0 U1 3 U2 15 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUL 1 PY 2015 VL 21 IS 7 BP 409 EP 421 DI 10.1089/acm.2014.0324 PG 13 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CU9RM UT WOS:000363882600006 PM 26133205 ER PT J AU Iezzoni, LI Kurtz, SG Rao, SR AF Iezzoni, Lisa I. Kurtz, Stephen G. Rao, Sowmya R. TI Trends in Mammography Over Time for Women With and Without Chronic Disability SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PREVENTIVE SERVICES; MOBILITY IMPAIRMENTS; PHYSICAL-DISABILITIES; BREAST-CANCER; ACCESS; BARRIERS; RECEIPT; LEVEL; CARE AB Background: Women with disabilities often receive mammograms at lower rates than do nondisabled women, although this disparity varies by disability type and severity. Given the implementation of disability civil rights laws in the early 1990s, we examined whether disability disparities in mammogram use have diminished over time. Methods: We analyzed National Health Interview Survey responses of civilian, noninstitutionalized United States female residents 50 to 74 years old from selected years between 1998 and 2010. We identified seven chronic disability types using self-reported functional impairments, activity/participation limitations, and expected duration. We conducted bivariable and multivariable logistic regression analyses examining associations of self-reported mammogram use within the previous two years with sociodemographic factors and disability. Results: Most chronic disability rates rose over time. The most common disability was movement difficulties, with rates increasing from 35.6% (1998) to 39.8% (2010). Mammogram rates for all women remained relatively stable over time, ranging from 72% to 75%. Bivariable analyses generally found statistically significantly lower mammogram rates for women with disability versus nondisabled women. Over time, disparities grew significantly between women with any basic action difficulty or complex activity limitation and nondisabled women (p<0.01). In multivariable logistic analyses, having any difficulty with basic actions was significantly associated with lower adjusted odds of mammography; for example, adjusted odds [95% confidence interval]=0.5 [0.3-0.8], p=0.006, in the model involving movement disability. Conclusions: Little has changed since 1998 in mammogram rates for women with versus without disabilities. Women with certain disabilities continue to experience disparities in mammography testing. C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Kurtz, Stephen G.; 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. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu FU National Cancer Institute [5 R01 CA160286-02] FX This work was funded by the National Cancer Institute, 5 R01 CA160286-02. NR 29 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 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD JUL 1 PY 2015 VL 24 IS 7 BP 593 EP 601 DI 10.1089/jwh.2014.5181 PG 9 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 CU9WH UT WOS:000363896900011 PM 26083235 ER PT J AU Luckett, R Pena, N Vitonis, A Bernstein, MR Feldman, S AF Luckett, Rebecca Pena, Nancy Vitonis, Allison Bernstein, Marilyn R. Feldman, Sarah TI Effect of Patient Navigator Program on No-Show Rates at an Academic Referral Colposcopy Clinic SO JOURNAL OF WOMENS HEALTH LA English DT Article ID INCOME MINORITY WOMEN; CERVICAL-CANCER; FOLLOW-UP; CONTROLLED-TRIAL; CARE; DISPARITIES; ADHERENCE; IMPACT; BREAST; INTERVENTIONS AB Background: Patient navigators have been used successfully to guide vulnerable patients through barriers to cancer care and reduce disparities in cancer outcomes. This study evaluated the effect of a patient navigator program on no-show rates at a tertiary care referral colposcopy center and explored factors associated with missed appointments. Methods: No-show rates prior and subsequent to implementation of the intervention were compared by chi-square test. We compared patient demographic, lifestyle, and diagnostic characteristics between patients who had ever and never missed appointments. We described patient-reported barriers to care. Results: Of 4,199 women evaluated in our clinic from January 2006 to December 2013, 2,441 (58%) had at least one missed appointment. African American, Hispanic, and publicly insured women tended to miss appointments more frequently than did white and privately insured women (p<0.0001). Patients who missed appointments tended to have more abnormal cytology (p<0.0001), cervical pathology (p=0.007), and vulvar pathology (p=0.001). No-show rates declined from 49.7% to 29.5% after implementation of the patient navigator program (p<0.0001). We found that 45% of patient no-shows were anticipated or a result of patient misunderstanding and could be mediated with targeted education by the patient navigator. Conclusions: Patient navigator programs at referral centers reduce no-show rates, thus improving patient follow-up, which may reduce disparities in cervical cancer screening and treatment. C1 [Luckett, Rebecca; Vitonis, Allison; Feldman, Sarah] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Pena, Nancy; Bernstein, Marilyn R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Gynecol Oncol, Boston, MA 02115 USA. RP Luckett, R (reprint author), 75 Francis St, Boston, MA 02115 USA. EM rluckett@partners.org NR 33 TC 5 Z9 5 U1 1 U2 3 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 JUL 1 PY 2015 VL 24 IS 7 BP 608 EP 615 DI 10.1089/jwh.2014.5111 PG 8 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 CU9WH UT WOS:000363896900013 PM 26173000 ER PT J AU Brauner, E Holmes, BJ Krane, JF Nishino, M Zurakowski, D Hennessey, JV Faquin, WC Parangi, S AF Brauner, Eran Holmes, Brittany J. Krane, Jeffrey F. Nishino, Michiya Zurakowski, David Hennessey, James V. Faquin, William C. Parangi, Sareh TI Performance of the Afirma Gene Expression Classifier in Hurthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules SO THYROID LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CLINICAL-EXPERIENCE; CYTOLOGY; CARCINOMAS; CANCER; NEOPLASMS; BENIGN; DIAGNOSIS; IMPACT AB Background: The recently introduced Afirma gene expression classifier (AGEC) provides binary results (benign or suspicious) to guide management of cytologically indeterminate thyroid nodules. The AGEC is intended to reduce unnecessary surgeries for benign nodules, and management algorithms favor surgery for suspicious results. Limited data are available on the performance of this test for Hurthle cell nodules (HCNs). This study hypothesized that a predominance of Hurthle cells leads to an increased rate of suspicious AGEC results with a potential for overtreatment, despite a relatively low risk of malignancy. Methods: The pathology databases from three tertiary care facilities were queried from 2010 to 2014 for fine-needle aspirates (FNAs) diagnosed as suspicious for Hurthle cell neoplasm (SHCN) or atypia of undetermined significance/follicular lesion of undetermined significance concerning for Hurthle cell neoplasm (AFHCN). Cytology diagnoses were rendered internally prior to AGEC testing. The patient demographics, FNA diagnosis, AGEC result, surgical procedure, and pathologic outcomes were recorded. Results: The cohort consisted of 134 patients with HCNs. Prior to AGEC availability, 62 patients underwent surgery: 81% (50/62) of patients had surgery, and 34% (17/50) of the resected index nodules were malignant. After introduction of the AGEC, 72 patients underwent AGEC testing: 65% (47/72) of patients had surgery, and 13% (6/46) of the resected nodules were malignant. Thirty-two percent (23/72) of patients had a benign AGEC result and did not undergo surgery, and 4% (3/72) had surgery despite a benign AGEC result with benign final pathology, whereas 63% (45/72) of patients had suspicious AGEC results, with 96% of these patients (43/45) undergoing surgery, and 14% (6/43) of these index nodules were malignant. Conclusions: While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly. C1 [Brauner, Eran; Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Holmes, Brittany J.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nishino, Michiya] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Zurakowski, David] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Zurakowski, David] Boston Childrens Hosp, Dept Anesthesia, Boston, MA USA. [Hennessey, James V.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org FU Clair and Emanuel G. Rosenblatt Fund; American Healthcare Professionals and Friends for Medicine in Israel (APF) FX Eran Brauner is sponsored by a grant from the Clair and Emanuel G. Rosenblatt Fund and American Healthcare Professionals and Friends for Medicine in Israel (APF). This work was presented in abstract format at the United States and Canadian Academy of Pathology 2015 Annual Meeting in Boston, MA. NR 31 TC 16 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JUL 1 PY 2015 VL 25 IS 7 BP 789 EP 796 DI 10.1089/thy.2015.0049 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU9TB UT WOS:000363887000007 PM 25962906 ER PT J AU Marcos, S Alejandre, N Lamela, J Dorronsoro, C Kochevar, IE AF Marcos, Susana Alejandre, Nicolas Lamela, Jorge Dorronsoro, Carlos Kochevar, Irene E. TI Toward New Engagement Paradigms For Intraocular Lenses: Light-Initiated Bonding of Capsular Bag to Lens Materials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE A-IOLs; lens capsule; photobonding; physiological optics ID CROSS-LINKING; PHOTOCHEMICAL KERATODESMOS; CORNEAL INCISIONS; ROSE-BENGAL; TISSUE; ACCOMMODATION; FORCE; EYES AB PURPOSE. Successful intraocular lens procedures, that is, implantation of accommodating intraocular lenses (A-IOL), require firm engagement of the IOL haptics to the capsular bag. We evaluated the use of photochemical bonding to engage IOL materials to the capsular bag. METHODS. Freshly enucleated eyes of New Zealand rabbits were used in two types of photobonding experiments using Rose Bengal (RB) photoinitiation and green light (532-nm) irradiation. First, RB-stained capsular bag strips were photobonded ex vivo to IOL polymer [poly(2-hydroxyethyl methacrylate) pHEMA] strips in an atmosphere of air and of nitrogen. Second, IOLs were implanted intracapsularly and photobonded intraocularly. Irradiation times were between 30 and 180 seconds, and laser irradiance was between 0.25 and 0.65 W/cm(2). The strength of the bonding was tested using a custom-developed uniaxial extensiometry system and the breakage load (the load that caused breakage per bonded area) was calculated. RESULTS. The breakage load of ex vivo capsule-pHEMA bonds increased exponentially with irradiation time, using 0.45 W/cm(2). In air, the average breakage load across all conditions was 1 g/mm(2) and 1.6 times lower than that in a nitrogen atmosphere. Intraocularly, RB-stained IOLs were strongly photobonded to the capsule bag with breakage loads > 0.8 g/mm(2). CONCLUSIONS. Breakage of the photobonded linkage between IOL material and capsular bag required loads substantially greater than the maximum force of ciliary muscle, suggesting that this technology may introduce a new paradigm for engagement of A-IOLs. The bonding produced in air was stronger than that in nitrogen atmosphere, suggesting that oxygen is involved in the chemical mechanism for photobonding. C1 [Marcos, Susana; Alejandre, Nicolas; Lamela, Jorge; Dorronsoro, Carlos] CSIC, Inst Opt, Madrid 28006, Spain. [Alejandre, Nicolas] Fdn Jimenez Diaz, E-28040 Madrid, Spain. [Kochevar, Irene E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kochevar, Irene E.] Harvard Univ, Sch Med, Boston, MA USA. RP Lamela, J (reprint author), CSIC, Inst Opt, C Serrano 121, Madrid 28006, Spain. EM jorge.lamela82@gmail.com RI Dorronsoro, Carlos/A-2297-2011 NR 27 TC 2 Z9 2 U1 1 U2 9 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2015 VL 56 IS 8 BP 4249 EP 4256 DI 10.1167/iovs.15-17070 PG 8 WC Ophthalmology SC Ophthalmology GA CT5WV UT WOS:000362882700009 PM 26161986 ER PT J AU Ghafoori, E Kabir, MM Cao, J Shvilkin, A Tereshchenko, LG AF Ghafoori, Elyar Kabir, Muammar M. Cao, Jian Shvilkin, Alexei Tereshchenko, Larisa G. TI Construction of intracardiac vectorcardiogram from implantable cardioverter-defibrillator intracardiac electrograms SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Implantable cardioverter defibrillator; Vectorcardiography; Intracardiac electrogram ID VENTRICULAR TACHYARRHYTHMIAS AB We constructed an intracardiac vectorcardiogram from 3 configurations of intracardiac cardiovertor defibrilator (ICD) electrograms (EGMs). Six distinctive 3 lead combinations were selected out of five leads: can to right ventricular coil (RVC); RVC to superior vena cava coil (SVC); atrial lead tip (A-tip) to right ventricular (RV)-ring; can to RV-ring; RV-tip to RVC, in a patient with dual chamber ICD. Surface spatial QRS-T angle (119.8 degrees) was similar to intracardiac spatial QRS-T angle derived from ICD EGMs combination A (101.3 degrees), B (96.1 degrees), C (92.8 degrees), D (95.2), E (99.0), F (96.2) and median (101.5). Future validation of the novel method is needed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ghafoori, Elyar; Kabir, Muammar M.; Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Cao, Jian] Medtronic Inc, Minneapolis, MN USA. [Shvilkin, Alexei] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02115 USA. RP Tereshchenko, LG (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Shvilkin, Alexei/0000-0003-3662-9938; Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institute of Health [1R01HL118277] FX This research was supported in part by the National Institute of Health #1R01HL118277 (LGT). NR 9 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD JUL-AUG PY 2015 VL 48 IS 4 BP 669 EP 671 DI 10.1016/j.jelectrocard.2015.05.008 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU3OG UT WOS:000363434100028 PM 25987408 ER PT J AU Brown, RT Miao, YH Mitchell, SL Bharel, M Patel, M Ard, KL Grande, LJ Blazey-Martin, D Floru, D Steinman, MA AF Brown, Rebecca T. Miao, Yinghui Mitchell, Susan L. Bharel, Monica Patel, Mitkumar Ard, Kevin L. Grande, Laura J. Blazey-Martin, Deborah Floru, Daniella Steinman, Michael A. TI Health Outcomes of Obtaining Housing Among Older Homeless Adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; MINI-MENTAL-STATE; POPULATION; INDEX; INTERVENTIONS; INDIVIDUALS; VALIDATION; DEPRESSION; IMPROVE; ILLNESS AB Objectives. We determined the impact of obtaining housing on geriatric conditions and acute care utilization among older homeless adults. Methods. We conducted a 12-month prospective cohort study of 250 older homeless adults recruited from shelters in Boston, Massachusetts, between January and June 2010. We determined housing status at follow-up, determined number of emergency department visits and hospitalizations over 12 months, and examined 4 measures of geriatric conditions at baseline and 12 months. Using multivariable regression models, we evaluated the association between obtaining housing and our outcomes of interest. Results. At 12-month follow-up, 41% of participants had obtained housing. Compared with participants who remained homeless, those with housing had fewer depressive symptoms. Other measures of health status did not differ by housing status. Participants who obtained housing had a lower rate of acute care use, with an adjusted annualized rate of acute care visits of 2.5 per year among participants who obtained housing and 5.3 per year among participants who remained homeless. Conclusions. Older homeless adults who obtained housing experienced improved depressive symptoms and reduced acute care utilization compared with those who remained homeless. C1 [Brown, Rebecca T.; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Miao, Yinghui] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Bharel, Monica] Boston Hlth Care Homeless Program, Boston, MA USA. [Ard, Kevin L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Patel, Mitkumar] St Elizabeths Med Ctr, Dept Med, Boston, MA USA. [Grande, Laura J.] Vet Affairs Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Blazey-Martin, Deborah] Tufts Med Ctr, Dept Med, Boston, MA USA. [Floru, Daniella] Lemuel Shattuck Hosp, Div Geriatr Med, Boston, MA USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 4150 Clement St,UCSF Box VA-181G, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU National Institute on Aging [K23 AG045290, P30 AG044281, K24 AG033640]; National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Science Institute [KL2 TR000143]; National Institute on Aging; American Federation for Aging Research [1K23 AG030999] FX R. T. Brown was supported by the National Institute on Aging (K23 AG045290 and P30 AG044281) and by the National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Science Institute (KL2 TR000143). S. L. Mitchell was supported by the National Institute on Aging (K24 AG033640). M. A. Steinman was supported by the National Institute on Aging and the American Federation for Aging Research (1K23 AG030999). NR 43 TC 2 Z9 2 U1 4 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2015 VL 105 IS 7 BP 1482 EP 1488 DI 10.2105/AJPH.2014.302539 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT6FX UT WOS:000362909400038 PM 25973822 ER PT J AU De Maria, G AF De Maria, Gayle TI Multiple types of resistance to new lung cancer drug identified SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP De Maria, G (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TEKNOSCIENZE PUBL PI MILANO PA VIALE BRIANZA 22, 20127 MILANO, ITALY SN 0392-839X EI 1973-8250 J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD JUL-AUG PY 2015 VL 33 IS 4 BP 52 EP 52 PG 1 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA CT7AN UT WOS:000362965500012 ER PT J AU Najmi, LA Aukrust, I Flannick, J Molnes, J Burtt, N Molven, A Johansson, S Bjorkhaug, L Altshuler, D Njolstad, P AF Najmi, L. A. Aukrust, I. Flannick, J. Molnes, J. Burtt, N. Molven, A. Johansson, S. Bjorkhaug, L. Altshuler, D. Njolstad, P. TI Functional investigations of the monogenic diabetes gene HNF1A identify rare variants as risk factors for type 2 diabetes in a general population SO FEBS JOURNAL LA English DT Meeting Abstract CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS) - The Biochemical Basis of Life CY JUL 04-09, 2015 CL Berlin, GERMANY SP Federat European Biochemical Soc C1 [Najmi, L. A.; Njolstad, P.] Univ Bergen, Clin Sci, Bergen, Norway. [Najmi, L. A.; Aukrust, I.; Johansson, S.] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Najmi, L. A.; Bjorkhaug, L.] Univ Bergen, Biomed, Bergen, Norway. [Aukrust, I.; Molnes, J.] Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway. [Flannick, J.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Flannick, J.] MIT, Cambridge, MA 02139 USA. [Molnes, J.; Njolstad, P.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Burtt, N.] Univ Cambridge, Broad Inst Harvard, Cambridge, MA USA. [Burtt, N.] Univ Cambridge, MIT, Cambridge, MA USA. [Molven, A.] Univ Bergen, Med Clin, Bergen, Norway. [Molven, A.] Haukeland Hosp, Pathol, N-5021 Bergen, Norway. [Altshuler, D.] Harvard Univ, Sch Med, Genet, Boston, MA USA. [Altshuler, D.] Massachusetts Gen Hosp, Mol Biol, 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 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD JUL PY 2015 VL 282 SU 1 SI SI MA P03-035 BP 79 EP 79 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT1PC UT WOS:000362570601081 ER PT J AU Marti, AP Coelho, ALD do Rosario, AC Pardo, JR Gonzalez, PFM Bautista, DH AF Perez Marti, A. De Sousa Coelho, A. L. Carrilho do Rosario, A. Relat Pardo, J. Marrero Gonzalez, P. F. Haro Bautista, D. TI FGF21 is down regulated by fasting in mice under leucine deficient diet SO FEBS JOURNAL LA English DT Meeting Abstract CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS) - The Biochemical Basis of Life CY JUL 04-09, 2015 CL Berlin, GERMANY SP Federat European Biochemical Soc C1 [Perez Marti, A.; De Sousa Coelho, A. L.; Carrilho do Rosario, A.; Relat Pardo, J.; Marrero Gonzalez, P. F.; Haro Bautista, D.] Univ Barcelona, Biochem & Mol Biol Pharm, Barcelona, Spain. [De Sousa Coelho, A. L.] Joslin Diabet Ctr, Med, Boston, MA 02215 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 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD JUL PY 2015 VL 282 SU 1 SI SI MA P03-067 BP 88 EP 88 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT1PC UT WOS:000362570601112 ER PT J AU Sieverdes, JC Nemeth, LS Magwood, GS Baliga, PK Chavin, KD Brunner-Jackson, B Patel, SK Ruggiero, KJ Treiber, FA AF Sieverdes, John Christopher Nemeth, Lynne S. Magwood, Gayenell S. Baliga, Prabhakar K. Chavin, Kenneth D. Brunner-Jackson, Brenda Patel, Sachin K. Ruggiero, Kenneth J. Treiber, Frank A. TI Patient-Centered mHealth Living Donor Transplant Education Program for African Americans: Development and Analysis SO JMIR RESEARCH PROTOCOLS LA English DT Article DE kidney transplantation; living donors; mobile apps; qualitative research; telemedicine ID SELF-DETERMINATION THEORY; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; INTRINSIC MOTIVATION; HEALTH-CARE; INTERVENTION; CANDIDATES; RECIPIENTS AB Background: There is a critical need to expand the pool of available kidneys for African Americans who are on the transplant wait-list due to the disproportionally lower availability of deceased donor kidneys compared with other races/ethnic groups. Encouraging living donation is one method to fill this need. Incorporating mHealth strategies may be a way to deliver educational and supportive services to African American transplant-eligible patients and improve reach to those living in remote areas or unable to attend traditional group-session-based programs. Before program development, it is essential to perform formative research with target populations to determine acceptability and cultivate a patient-centered and culturally relevant approach to be used for program development. Objective: The objectives of this study were to investigate African American kidney transplant recipients' and kidney donors'/potential donors' attitudes and perceptions toward mobile technology and its viability in an mHealth program aimed at educating patients about the process of living kidney donation. Methods: Using frameworks from the technology acceptance model and self-determination theory, 9 focus groups (n=57) were administered to African Americans at a southeastern medical center, which included deceased/living donor kidney recipients and living donors/potential donors. After a demonstration of a tablet-based video education session and explanation of a group-based videoconferencing session, focus groups examined members' perceptions about how educational messages should be presented on topics pertaining to the process of living kidney donation and the transplantation. Questionnaires were administered on technology use and perceptions of the potential program communication platform. Transcripts were coded and themes were examined using NVivo 10 software. Results: Qualitative findings found 5 major themes common among all participants. These included the following: (1) strong support for mobile technology use; (2) different media formats were preferred; (3) willingness to engage in video chats, but face-to-face interaction sometimes preferred; (4) media needs to be user friendly; (5) high prevalence of technology access. Our results show that recipients were willing to spend more time on education than the donors group, they wanted to build conversation skills to approach others, and preferred getting information from many sources, whereas the donor group wanted to hear from other living donors. The questionnaires revealed 85% or more of the sample scored 4+ on a 5-point Liken scale, which indicates high degree of interest to use the proposed program, belief that other mHealth technologies would help with adherence to medical regimens, and doctors would make regimen adjustments quicker. In addition, high utilization of mobile technology was reported; 71.9% of the participants had a mobile phone and 43.9% had a tablet. Conclusions: Our study supports the use of an mHealth education platform for African Americans to learn about living donation. However, potential recipients and potential donors have differing needs, and therefore, programs should be tailored to each target audience. C1 [Sieverdes, John Christopher; Brunner-Jackson, Brenda; Patel, Sachin K.; Ruggiero, Kenneth J.; Treiber, Frank A.] Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC 29425 USA. [Nemeth, Lynne S.; Magwood, Gayenell S.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Baliga, Prabhakar K.; Chavin, Kenneth D.] Med Univ S Carolina, Coll Med, Dept Surg, Div Transplant Surg, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Psychiat Inst, Charleston, SC USA. [Treiber, Frank A.] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. RP Treiber, FA (reprint author), Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, 99 Jonathan Lucas St,MSC 160, Charleston, SC 29425 USA. EM treiberf@musc.edu RI Emchi, Karma/Q-1952-2016; OI Brunner-Jackson, Brenda/0000-0002-1518-758X; Magwood, Gayenell/0000-0002-2451-4888; Nemeth, Lynne/0000-0001-8691-1400 FU NCATS NIH HHS [UL1 TR000062]; NIDDK NIH HHS [R01 DK098777] NR 44 TC 1 Z9 1 U1 2 U2 6 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD JUL-SEP PY 2015 VL 4 IS 3 AR UNSP e84 DI 10.2196/resprot.3715 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CT3TR UT WOS:000362730300019 PM 26265532 ER PT J AU Sweeney, C AF Sweeney, C. TI NEW INSIGHTS IN GCT SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT ANZUP Annual Scientific Meeting, Redefining Personalised Medicine CY JUL 12-14, 2015 CL Sydney, AUSTRALIA C1 [Sweeney, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD JUL PY 2015 VL 11 SU 2 SI SI MA 7 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA CT4WL UT WOS:000362808000008 ER PT J AU Sweeney, C AF Sweeney, C. TI IMMEDIATE DOCETAXEL IN METASTATIC PROSTATE CANCER SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT ANZUP Annual Scientific Meeting, Redefining Personalised Medicine CY JUL 12-14, 2015 CL Sydney, AUSTRALIA C1 [Sweeney, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD JUL PY 2015 VL 11 SU 2 SI SI MA 6 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA CT4WL UT WOS:000362808000007 ER PT J AU Sweeney, C AF Sweeney, C. TI PRECISION MEDICINE IN PROSTATE CANCER: HOW CLOSE ARE WE? SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT ANZUP Annual Scientific Meeting, Redefining Personalised Medicine CY JUL 12-14, 2015 CL Sydney, AUSTRALIA C1 [Sweeney, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD JUL PY 2015 VL 11 SU 2 SI SI MA 1 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA CT4WL UT WOS:000362808000002 ER PT J AU Morgans, AK van Bommel, ACM Stowell, C Abrahm, JL Basch, E Bekelman, JE Berry, DL Bossi, A Davis, ID de Reijke, TM Denis, LJ Evans, SM Fleshner, NE George, DJ Kiefert, J Lin, DW Matthew, AG McDermott, R Payne, H Roos, IAG Schrag, D Steuber, T Tombal, B van Basten, J van der Hoeven, JJM Penson, D AF Morgans, A. K. van Bommel, A. C. M. Stowell, C. Abrahm, J. L. Basch, E. Bekelman, J. E. Berry, D. L. Bossi, A. Davis, I. D. de Reijke, T. M. Denis, L. J. Evans, S. M. Fleshner, N. E. George, D. J. Kiefert, J. Lin, D. W. Matthew, A. G. McDermott, R. Payne, H. Roos, I. A. G. Schrag, D. Steuber, T. Tombal, B. van Basten, J. van der Hoeven, J. J. M. Penson, D. TI DEVELOPMENT OF A STANDARDIZED SET OF PATIENT-CENTERED OUTCOMES FOR ADVANCED PROSTATE CANCER: AN INTERNATIONAL EFFORT FOR A UNIFIED APPROACH SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT ANZUP Annual Scientific Meeting, Redefining Personalised Medicine CY JUL 12-14, 2015 CL Sydney, AUSTRALIA C1 [Morgans, A. K.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [van Bommel, A. C. M.; Stowell, C.] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [van Bommel, A. C. M.] Dutch Inst Clin Auditing, Leiden, Netherlands. [Stowell, C.] Monash Univ, Box Hill, Vic, Australia. [Stowell, C.] Eastern Hlth, Box Hill, Vic, Australia. [Abrahm, J. L.; Berry, D. L.; Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Basch, E.] Univ N Carolina, Chapel Hill, NC USA. [Bekelman, J. E.] Univ Penn, Philadelphia, PA 19104 USA. [Bossi, A.] Gustave Roussy Canc Inst, Villejuif, France. [Davis, I. D.] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic 3004, Australia. [Davis, I. D.] Eastern Hlth, Dept Canc Serv, Box Hill, Vic, Australia. [de Reijke, T. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Denis, L. J.] Oncol Ctr Antwerp, Antwerp, Belgium. [Denis, L. J.] US TOO Belgium, Antwerp, Belgium. [Evans, S. M.] Monash Univ, Melbourne, Vic 3004, Australia. [Fleshner, N. E.; Matthew, A. G.] Univ Toronto, Toronto, ON, Canada. [George, D. J.] Duke Univ, Med Ctr, Durham, NC USA. [Kiefert, J.] US TOO Int, Des Plaines, IL USA. [Lin, D. W.] Univ Washington, Seattle, WA 98195 USA. [McDermott, R.] St Vincents Univ Hosp, Dublin 4, Ireland. [Payne, H.] Univ Coll London Hosp, London, England. [Roos, I. A. G.] Canc Act Victoria, Melbourne, Vic, Australia. [Steuber, T.] Univ Hamburg Hosp, Hamburg, Germany. [Tombal, B.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. [van Basten, J.] Canisius Wilhelmina Hosp, Nijmegen, Netherlands. [van der Hoeven, J. J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Penson, D.] VA Tennessee Valley Geriatr Res Educ, Nashville, TN USA. [Penson, D.] Clin Ctr GRECC, Nashville, TN USA. [Penson, D.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 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 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD JUL PY 2015 VL 11 SU 2 SI SI MA 23 BP 29 EP 29 PG 1 WC Oncology SC Oncology GA CT4WL UT WOS:000362808000024 ER PT J AU Shore, N Smith, MR Lipton, A Brown, JE Oudard, S Carducci, M Saad, F Damiao, R Zhu, L Warner, D Fizazi, K AF Shore, N. Smith, M. R. Lipton, A. Brown, J. E. Oudard, S. Carducci, M. Saad, F. Damiao, R. Zhu, L. Warner, D. Fizazi, K. TI BONE TURNOVER MARKER LEVELS AND OUTCOMES IN MEN WITH PROSTATE CANCER AND BONE METASTASES TREATED WITH BONE ANTIRESORPTIVE AGENTS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT ANZUP Annual Scientific Meeting, Redefining Personalised Medicine CY JUL 12-14, 2015 CL Sydney, AUSTRALIA C1 [Shore, N.] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lipton, A.] Penn State Univ, Milton S Hershey Med Ctr, Hersbey, PA USA. [Brown, J. E.] Univ Sheffield, Weston Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England. [Oudard, S.] Georges Pompidou Hosp, Paris, France. [Carducci, M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Saad, F.] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Damiao, R.] Univ Pedro Ernesto, Rio De Janeiro, Brazil. [Zhu, L.; Warner, D.] Amgen Inc, Thousand Oaks, CA USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD JUL PY 2015 VL 11 SU 2 SI SI MA 120 BP 40 EP 41 PG 2 WC Oncology SC Oncology GA CT4WL UT WOS:000362808000052 ER PT J AU Pulliam, L Gupta, A AF Pulliam, Lynn Gupta, Archana TI Modulation of Cellular Function Through Immune-Activated Exosomes SO DNA AND CELL BIOLOGY LA English DT Review ID EXTRACELLULAR VESICLES; DENDRITIC CELLS; T-CELLS; MICROVESICLES; MACROPHAGES; MICRORNAS; MIR-155; INDUCTION; PHENOTYPE; MIGRATION AB Extracellular vesicles classified as exosomes, microvesicles, or apoptotic bodies based on size are shed from most cells under normal as well as pathological conditions. They are released into the surrounding milieu, including plasma, urine, saliva, and tissues. Exosomes are highly enriched in microRNAs (miRs), which function in recipient cells by regulating posttranscriptional processing of targeted genes. Interaction of a miR with its mRNA target typically results in suppression of its gene expression. Peripheral inflammatory conditions can modulate miR expression in immune cells such as circulating monocytes that can influence their migration and differentiation. Changes within monocyte-derived macrophage miR expression can influence exosome content and further affect end-organ target cells. C1 [Pulliam, Lynn] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Lab Med, San Francisco, CA 94121 USA. [Pulliam, Lynn] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Gupta, Archana] Syst Biosci SBI, Mountain View, CA USA. RP Pulliam, L (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Lab Med, 4150 Clement St, San Francisco, CA 94121 USA. EM lynn.pulliam@ucsf.edu FU NIH [MH085538, MH096673] FX The experiments from the authors in this article were funded by the NIH to LP (MH085538, MH096673). NR 40 TC 4 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL 1 PY 2015 VL 34 IS 7 BP 459 EP 463 DI 10.1089/dna.2015.2884 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA CT0SJ UT WOS:000362506500001 PM 25945690 ER PT J AU Danford, DA Martin, AB Danford, CJ Kaul, S Marshall, AM Kutty, S AF Danford, David A. Martin, Ameeta B. Danford, Christopher J. Kaul, Sheetal Marshall, Amanda M. Kutty, Shelby TI Clinical Implications of a Multivariate Stratification Model for the Estimation of Prognosis in Ventricular Septal Defect SO JOURNAL OF PEDIATRICS LA English DT Article ID CONGENITAL HEART-DISEASE; SPONTANEOUS CLOSURE; NATURAL-HISTORY; SURGICAL CLOSURE; SEX DIFFERENCE; PREDICTORS; MORTALITY; STENOSIS; CHILDREN; SURVIVAL AB Objectives To derive and validate a multivariate stratification model for prediction of survival free from intervention (SFFI) in ventricular septal defect (VSD). A secondary aim is for this model to serve as proof of concept for derivation of a more general congenital heart disease prognostic model, of which the VSD model will be the first component. Study design For 12 years, 2334 subjects with congenital heart disease were prospectively and consecutively enrolled. Of these, 675 had VSD and form the derivation cohort. One hundred seven other subjects with VSD followed in another practice formed the validation cohort. The derivation cohort was serially stratified based on clinical and demographic features correlating with SFFI. Results Six strata were defined, the most favorable predicting nearly 100% SFFI at 10 years, and the least favorable, a high likelihood of event within weeks. Strata with best SFFI had many subjects with nearly normal physiology, muscular VSD location, or prior intervention. In the validation cohort, the relation between predicted and actual SFFI at 6 months, 1 year, 2 years, and 5 years follow-up had areas under the receiver operating characteristic curves 0.800 or greater. Conclusions A prediction model for SFFI in VSD has been derived and validated. It has potential for clinical application to the benefit of patients and families, medical trainees, and practicing physicians. C1 [Danford, David A.; Kaul, Sheetal; Marshall, Amanda M.; Kutty, Shelby] Univ Nebraska Med Ctr, Coll Med, Childrens Hosp & Med Ctr, Omaha, NE 68198 USA. [Martin, Ameeta B.] St Elizabeth Hosp, Dept Cardiol, Lincoln, NE USA. [Danford, Christopher J.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Kutty, S (reprint author), Univ Nebraska Med Ctr, 8200 Dodge St, Omaha, NE 68198 USA. EM skutty@unmc.edu OI KUTTY, SHELBY/0000-0001-9428-0979 NR 36 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 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2015 VL 167 IS 1 BP 103 EP U468 DI 10.1016/j.jpeds.2015.04.005 PG 7 WC Pediatrics SC Pediatrics GA CS9ZS UT WOS:000362453900026 PM 25935817 ER PT J AU Hoen, AG Li, J Moulton, LA O'Toole, GA Housman, ML Koestler, DC Guill, MF Moore, JH Hibberd, PL Morrison, HG Sogin, ML Karagas, MR Madan, JC AF Hoen, Anne G. Li, Jing Moulton, Lisa A. O'Toole, George A. Housman, Molly L. Koestler, Devin C. Guill, Margaret F. Moore, Jason H. Hibberd, Patricia L. Morrison, Hilary G. Sogin, Mitchell L. Karagas, Margaret R. Madan, Juliette C. TI Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis SO JOURNAL OF PEDIATRICS LA English DT Article ID PULMONARY EXACERBATIONS; OROPHARYNGEAL CULTURES; YOUNG-CHILDREN; PSEUDOMONAS-AERUGINOSA; INTESTINAL MICROBIOTA; BACTERIAL COMMUNITIES; INFLAMMATORY DISEASE; IMMUNE-SYSTEM; DELIVERY MODE; INFANTS AB Objective To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes. Study design A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis, and principal components analysis. Results Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts, and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health. Conclusions Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed. C1 [Hoen, Anne G.; Li, Jing; Moore, Jason H.] Dartmouth Coll, Geisel Sch Med Dartmouth, Inst Quantitat Biomed Sci, Computat Genet Lab, Hanover, NH 03755 USA. [Hoen, Anne G.; Karagas, Margaret R.] Dartmouth Coll, Geisel Sch Med Dartmouth, Dept Epidemiol, Hanover, NH 03755 USA. [Moulton, Lisa A.; Guill, Margaret F.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Div Allergy & Pediat Pulmonol, Lebanon, NH 03766 USA. [O'Toole, George A.; Housman, Molly L.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH USA. [Koestler, Devin C.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Morrison, Hilary G.; Sogin, Mitchell L.] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Madan, Juliette C.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Div Neonatol, Lebanon, NH 03766 USA. RP Madan, JC (reprint author), Childrens Hosp Dartmouth, Dept Pediat, Div Neonatol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Juliette.C.Madan@Dartmouth.Edu OI Morrison, Hilary/0000-0003-0281-326X FU Cystic Fibrosis Foundation; Harry Shwachman Career Development Award; Joshua Burnett Career Development Award through the Hitchcock Foundation; Geisel School of Medicine at Dartmouth Department of Pediatrics; Neukom Institute; Cystic Fibrosis Foundation Research Development Program [STAN-TO07R0]; National Institutes of Health [K01LM011985, R01AI59694, R37AI83256-06, 4UH3DK083993, K24AT003683, P20GM104410, P01ES022832]; Environmental Protection Agency [RD-83459901] FX Supported by the Cystic Fibrosis Foundation and the Harry Shwachman Career Development Award, The Joshua Burnett Career Development Award through the Hitchcock Foundation, the Geisel School of Medicine at Dartmouth Department of Pediatrics (to J.M.), the Neukom Institute (to G.O. and J.M.), the Cystic Fibrosis Foundation Research Development Program (STAN-TO07R0 [to G.O.]) the National Institutes of Health (K01LM011985 [to A.H.], R01AI59694 [J.M.], R37AI83256-06 [G.O.], 4UH3DK083993 [M.S. and H.M.], K24AT003683 [to P.H.], P20GM104410 [to A.H., M.K., J.M.], P01ES022832 [to M.K.]), and Environmental Protection Agency (RD-83459901 [to M.K.]). NR 78 TC 22 Z9 22 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2015 VL 167 IS 1 BP 138 EP U520 DI 10.1016/j.jpeds.2015.02.049 PG 13 WC Pediatrics SC Pediatrics GA CS9ZS UT WOS:000362453900033 PM 25818499 ER PT J AU O'Donnell, K Mansbach, JM LoVecchio, F Cheng, J Piedra, PA Clark, S Sullivan, AF Camargo, CA AF O'Donnell, Katherine Mansbach, Jonathan M. LoVecchio, Frank Cheng, John Piedra, Pedro A. Clark, Sunday Sullivan, Ashley F. Camargo, Carlos A., Jr. CA Multictr Airway Res Collaboration MARC-30 Investigator TI Use of Cough and Cold Medications in Severe Bronchiolitis before and after a Health Advisory Warning against Their Use SO JOURNAL OF PEDIATRICS LA English DT Article ID PROSPECTIVE MULTICENTER AB We compared the use of cough and cold medications in 2 multicenter studies of young children hospitalized with bronchiolitis before and after the 2008 Food and Drug Administration cough and cold medications advisory. Although cough and cold medication use decreased after the advisory, nearly 20% of children age 12-23.9 months with severe bronchiolitis received cough and cold medications. C1 [O'Donnell, Katherine; Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Div Gen Pediat,Boston Childrens Hosp, Boston, MA USA. [LoVecchio, Frank] Maricopa Cty Gen Hosp, Dept Emergency Med, Phoenix, AZ USA. [Cheng, John] Childrens Healthcare Atlanta Egleston, Dept Pediat Emergency Med, Atlanta, GA USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP O'Donnell, K (reprint author), Boston Childrens Hosp, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM katherine.odonnell2@childrens.harvard.edu FU Thrasher Research Fund; Merck; National Institutes of Health [U01 AI-67693, K23 AI-77801] FX MARC-25 was supported by the Thrasher Research Fund and an unrestricted data analysis grant from Merck. MARC-30 was supported by the National Institutes of Health (U01 AI-67693 and K23 AI-77801). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. J.M. and P.P. served as consultants for Regeneron. The other authors declare no conflicts of interest. NR 8 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2015 VL 167 IS 1 BP 196 EP U296 DI 10.1016/j.jpeds.2015.03.037 PG 5 WC Pediatrics SC Pediatrics GA CS9ZS UT WOS:000362453900044 PM 25888349 ER PT J AU Wyvekens, N Topkar, VV Khayter, C Joung, JK Tsai, SQ AF Wyvekens, Nicolas Topkar, Ved V. Khayter, Cyd Joung, J. Keith Tsai, Shengdar Q. TI Dimeric CRISPR RNA-Guided FokI-dCas9 Nucleases Directed by Truncated gRNAs for Highly Specific Genome Editing SO HUMAN GENE THERAPY LA English DT Article ID CAS NUCLEASES; DNA CLEAVAGE; TARGET; ENDONUCLEASE; IDENTIFICATION; NICKASES; CELLS AB Monomeric clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) nucleases have been widely adopted for simple and robust targeted genome editing but also have the potential to induce high-frequency off-target mutations. In principle, two orthogonal strategies for reducing off-target cleavage, truncated guide RNAs (tru-gRNAs) and dimerization-dependent RNA-guided FokI-dCas9 nucleases (RFNs), could be combined as tru-RFNs to further improve genome editing specificity. Here we identify a robust tru-RFN architecture that shows high activity in human cancer cell lines and embryonic stem cells. Additionally, we demonstrate that tru-gRNAs reduce the undesirable mutagenic effects of monomeric FokI-dCas9. Tru-RFNs combine the advantages of two orthogonal strategies for improving the specificity of CRISPR/Cas nucleases and therefore provide a highly specific platform for performing genome editing. C1 [Wyvekens, Nicolas; Topkar, Ved V.; Khayter, Cyd; Joung, J. Keith; Tsai, Shengdar Q.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Wyvekens, Nicolas; Topkar, Ved V.; Khayter, Cyd; Joung, J. Keith; Tsai, Shengdar Q.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Wyvekens, Nicolas; Topkar, Ved V.; Khayter, Cyd; Joung, J. Keith; Tsai, Shengdar Q.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Joung, J. Keith; Tsai, Shengdar Q.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tsai, SQ (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149,13th St,6th Floor, Charlestown, MA 02129 USA. EM jjoung@mgh.harvard.edu; stsai4@mgh.harvard.edu FU National Institutes of Health (NIH) [DP1 GM105378]; NIH [P50 HG005550, R01 AR063070, F32 GM105189]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award FX This work was funded by a National Institutes of Health (NIH) Director's Pioneer Award (DP1 GM105378), NIH P50 HG005550, NIH R01 AR063070, and the Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. S.Q.T. was supported by NIH F32 GM105189. NR 26 TC 32 Z9 36 U1 4 U2 29 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 1 PY 2015 VL 26 IS 7 BP 425 EP 431 DI 10.1089/hum.2015.084 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CS4YT UT WOS:000362083000005 PM 26068112 ER PT J AU Holden, TR Smith, MA Bartels, CM Campbell, TC Yu, MG Kind, AJH AF Holden, Timothy R. Smith, Maureen A. Bartels, Christie M. Campbell, Toby C. Yu, Menggang Kind, Amy J. H. TI Hospice Enrollment, Local Hospice Utilization Patterns, and Rehospitalization in Medicare Patients SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; HEALTH-CARE; PATIENTS PREFERENCES; REGIONAL-VARIATIONS; MENTAL-HEALTH; LAST YEAR; END; CANCER; DEATH; QUALITY AB Background: Rehospitalizations are prevalent and associated with decreased quality of life. Although hospice has been advocated to reduce rehospitalizations, it is not known how area-level hospice utilization patterns affect rehospitalization risk. Objectives: The study objective was to examine the association between hospice enrollment, local hospice utilization patterns, and 30-day rehospitalization in Medicare patients. Methods: With a retrospective cohort design, 1,997,506 hospitalizations were assessed between 2005 and 2009 from a 5% national sample of Medicare beneficiaries. Local hospice utilization was defined using tertiles representing the percentage of all deaths occurring in hospice within each Hospital Service Area (HSA). Cox proportional hazard models were used to assess the relationship between 30-day rehospitalization, hospice enrollment, and local hospice utilization, adjusting for patient sociodemographics, medical history, and hospital characteristics. Results: Rates of patients dying in hospice were 27% in the lowest hospice utilization tertile, 41% in the middle tertile, and 53% in the highest tertile. Patients enrolled in hospice had lower rates of 30-day rehospitalization than those not enrolled (2.2% versus 18.8%; adjusted hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.118-0.131). Patients residing in areas of low hospice utilization were at greater rehospitalization risk than those residing in areas of high utilization (19.1% versus 17.5%; HR, 1.05; 95% CI, 1.04-1.06), which persisted beyond that accounted for by individual hospice enrollment. Conclusions: Area-level hospice utilization is inversely proportional to rehospitalization rates. This relationship is not fully explained by direct hospice enrollment, and may reflect a spillover effect of the benefits of hospice extending to nonenrollees. C1 [Holden, Timothy R.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53705 USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI 53705 USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53705 USA. [Bartels, Christie M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Rheumatol, Madison, WI 53705 USA. [Campbell, Toby C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Hematol Oncol & Palliat Care Med Div, Madison, WI 53705 USA. [Yu, Menggang] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Geriatr, Madison, WI 53705 USA. [Kind, Amy J. H.] US Dept Vet Affairs, William S Middleton Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Kind, AJH (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Geriatr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ajk@medicine.wisc.edu FU National Institutes of Health (NIH) T32 Training Grant [5T32HS000083-15]; University of Wisconsin (UW) Health Innovation Program; National Institute on Aging Beeson Career Development Award - National Institute on Aging [K23AG034551]; American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases Mentored Patient-Oriented Research Career Development Award [K23 AR062381]; UW Health Innovation Program; Clinical and Translational Science Award (CTSA) program through National Center for Advancing Translational Sciences (NCATS) [1UL1RR025011]; UW School of Medicine and Public Health from The Wisconsin Partnership Program; National Center for Advancing Translational Sciences (NCATS) [9U54TR000021] FX Thank you to Katie Ronk for data management and variable creation, Jacquelyn Mirr for manuscript preparation, and to Bill Buckingham for map creation. Funding for this project was provided by National Institutes of Health (NIH) T32 Training Grant 5T32HS000083-15 and the University of Wisconsin (UW) Health Innovation Program. Dr. Kind is supported by a National Institute on Aging Beeson Career Development Award (K23AG034551, PI Kind), funded by National Institute on Aging, The American Federation for Aging Research, The John A. Hartford Foundation, The Atlantic Philanthropies, and The Starr Foundation. Dr. Christie Bartels is supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Mentored Patient-Oriented Research Career Development Award K23 AR062381. Further support was provided by the UW Health Innovation Program and the Clinical and Translational Science Award (CTSA) program, previously through the National Center for Research Resources (NCRR) grant 1UL1RR025011, and now by the National Center for Advancing Translational Sciences (NCATS), grant 9U54TR000021. Additional funding for this project was provided by the UW School of Medicine and Public Health from The Wisconsin Partnership Program. NR 47 TC 1 Z9 1 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL 1 PY 2015 VL 18 IS 7 BP 601 EP 612 DI 10.1089/jpm.2014.0395 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CS2EM UT WOS:000361880600007 PM 25879990 ER PT J AU Vargas, M Servillo, G Pelosi, P Kacmarek, RM AF Vargas, Maria Servillo, Giuseppe Pelosi, Paolo Kacmarek, Robert M. TI Are New Devices for Percutaneous Dilatational Tracheostomy Really Needed? Yes SO RESPIRATORY CARE LA English DT Letter ID LUMEN ENDOTRACHEAL-TUBE; ULTRASOUND; TIME C1 [Vargas, Maria; Servillo, Giuseppe] Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy. [Pelosi, Paolo] Univ Genoa, Dept Surg Sci & Integrated Diagnost, Ist Ricovero & Cura Carattere Sci, Azienda Osped,Univ San Martino IST, Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Dept Resp Care, Boston, MA 02114 USA. RP Vargas, M (reprint author), Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy. RI Vargas, Maria/H-6876-2014; Servillo, Giuseppe/M-9132-2016 OI Vargas, Maria/0000-0001-7652-970X; Servillo, Giuseppe/0000-0002-4618-3434 NR 9 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD JUL PY 2015 VL 60 IS 7 BP E133 EP E133 DI 10.4187/respcare.04232 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CS7MC UT WOS:000362266700008 PM 26113571 ER PT J AU Friedlander, AH El Saden, SM Hazboun, RC Chang, TI Wong, WK Garrett, NR AF Friedlander, A. H. El Saden, S. M. Hazboun, R. C. Chang, T. I. Wong, W. K. Garrett, N. R. TI Detection of carotid artery calcification on the panoramic images of post-menopausal females is significantly associated with severe abdominal aortic calcification: a risk indicator of future adverse vascular events SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE atherosclerosis; panoramic radiography; carotid arteries; abdominal aorta; abdominal radiography ID ATHEROSCLEROSIS; STROKE; RADIOGRAPHS; PROGRESSION; FRAMINGHAM; ROTTERDAM; ATHEROMA; DEPOSITS; DISEASE AB Objectives: Outcome studies among post-menopausal females with calcified carotid artery plaque (CCAP) on their panoramic images have not been previously undertaken. We sought to compare the extent of abdominal aortic calcification (AAC) on lateral lumbar spine radiographs (LLSRs), among groups of females with (CCAP+) and without (CCAP) carotid lesions on their panoramic images. "Severe" levels of AAC have previously been validated as a risk indicator of future adverse cardiovascular events. Methods: This cross-sectional case control study included a "CCAP+ group" consisting of females more than 50 years of age having the carotid lesion diagnosed by their dentists and an atherogenic risk factor (age, body mass index, hypertension, diabetes and dyslipidaemia)matched "CCAP- group". A physician radiologist, using the Framingham index, evaluated the LLSRs for the magnitude of AAC. Summary statistics for key variables were computed and conditional logistic regression techniques were considered. Results: Members of the CCAP+ group were significantly (p = 0.038) more likely to demonstrate "severe" levels of AAC on their LLSRs than members of the CCAP group. Conclusions: This is the first published study demonstrating that CCAP on panoramic images of post-menopausal females is significantly associated with "severe" levels of AACs on LLSRs independent of traditional risk factors. Given that these levels of AAC are a validated risk indicator of future myocardial infarction and stroke, dentists must evaluate the panoramic images of post-menopausal females for the presence of CCAP. Patients with carotid atheromas should be referred to their physicians for further evaluation given the systemic implications. C1 [Friedlander, A. H.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Grad Med Educ, Los Angeles, CA 90095 USA. [Friedlander, A. H.; Chang, T. I.] Univ Calif Los Angeles, Sch Dent, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA. [El Saden, S. M.] Vet Affairs Greater Los Angeles Healthcare Syst, Imaging Serv, Los Angeles, CA USA. [El Saden, S. M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Hazboun, R. C.; Chang, T. I.] Vet Affairs Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Div, Dent Serv, Los Angeles, CA USA. [Wong, W. K.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Garrett, N. R.] Univ Calif Los Angeles, Sch Dent, Deans Off, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Grad Med Educ, Los Angeles, CA 90095 USA. EM arthur.friedlander@va.gov FU National Center for Research Resources, National Institutes of Health [CO6 RR-14529-01] FX Elements of this investigation were conducted in a facility constructed with support from Research Facilities Improvement Program grant number CO6 RR-14529-01 from the National Center for Research Resources, National Institutes of Health. NR 27 TC 1 Z9 2 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X EI 1476-542X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD JUL PY 2015 VL 44 IS 7 AR 20150094 DI 10.1259/dmfr.20150094 PG 7 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA CR9AI UT WOS:000361645200006 PM 25945511 ER PT J AU Luke, B Stern, JE Kotelchuck, M Declercq, ER Hornstein, MD Gopal, D Hoang, L Diop, H AF Luke, Barbara Stern, Judy E. Kotelchuck, Milton Declercq, Eugene R. Hornstein, Mark D. Gopal, Daksha Hoang, Lan Diop, Hafsatou TI Adverse pregnancy outcomes after in vitro fertilization: effect of number of embryos transferred and plurality at conception SO FERTILITY AND STERILITY LA English DT Article DE Assisted reproductive technology; embryos transferred; fetal heartbeats; birth outcomes ID ASSISTED-REPRODUCTIVE-TECHNOLOGY; LOW-BIRTH-WEIGHT; EARLY FETAL LOSSES; PERINATAL OUTCOMES; MASSACHUSETTS OUTCOMES; MULTIPLE BIRTHS; TWIN PREGNANCY; DATABASE; GESTATION; SINGLETON AB Objective: To evaluate risks for adverse pregnancy outcomes by number of embryos transferred (ET) and fetal heartbeats (FHB) in assisted reproductive technology-conceived singleton live births. Design: Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2008 among women who were treated and gave birth in Massachusetts. Setting: Not applicable. Patient(s): Assisted reproductive technology data on 6,073 births between 2004 and 2008 were linked to vital records and hospital data. Likelihood of ET >= vs. 1-2, FHB > 1 vs. 1, and risks of preterm birth (PTB, < 37 weeks' gestation), low birth weight (LBW, < 2,500 g), and small-for-gestational-age birth weight (SGA, < 10th percentile) with FHB > 1 were modeled with binary logistic regression using a backward-stepping algorithm, and presented as adjusted odds ratios (95% confidence intervals). Intervention(s): None. Main Outcome Measure(s): ET >= 3, FHB > 1, PTB, LBW, and SGA. Result(s): Higher ET was significantly more likely with older maternal age, intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and thawed embryos. The likelihood of FHB > 1 with >= 3 ET vs. 1-2 ET was 2.04 (1.68-2.48). Risks of PTB and LBW with FHB > 1 were 1.63 (1.27-2.09) and 1.81 (1.36-2.39), respectively; the risk of SGA was not significant. Nulliparity was associated with higher risks of PTB (1.34 [1.12-1.59]), LBW (1.48 [1.20-1.83]), and SGA (2.17 [1.69-2.78]). Conclusion(s): Number of embryos transferred was strongly associated with FHBs, with twice the risk of FHB > 1 with >= 3 ET vs. 1-2 ET. Increasing FHBs were associated with significantly greater risks for PTB and LBW outcomes. (C)2015 by American Society for Reproductive Medicine. C1 [Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA. [Stern, Judy E.] Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. [Declercq, Eugene R.; Gopal, Daksha; Hoang, Lan] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Hornstein, Mark D.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Hornstein, Mark D.] Harvard Univ, Sch Med, Boston, MA USA. [Diop, Hafsatou] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Luke, B (reprint author), Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, 965 Fee Rd,East Fee Hall,Room 628, E Lansing, MI 48824 USA. EM lukeb@msu.edu FU Society for Assisted Reproductive Technology; National Institutes of Health; American Society for Reproductive Medicine; National Institutes of Health [R01HD0672700, R01HD0645950]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD064595, R01 HD067270] FX B.L. reports personal fees from the Society for Assisted Reproductive Technology. J.E.S. received grants from the National Institutes of Health and the American Society for Reproductive Medicine. M.K. received grants from the National Institutes of Health (R01HD0672700 and R01HD0645950). M.D.H. is on the medical advisory board of WINFertility and receives author royalties from UpToDate. E.R.D. has nothing to disclose. D.G. has nothing to disclose. L.H. has nothing to disclose. H.D. has nothing to disclose.; The project described was supported by grants R01HD064595 and R01 HD067270 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. NR 43 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2015 VL 104 IS 1 BP 79 EP 86 DI 10.1016/j.fertnstert.2015.04.006 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CS1RF UT WOS:000361844700017 PM 25956368 ER PT J AU Childress, KJ Lawson, AK Ghant, MS Mendoza, G Cardozo, ER Confino, E Marsh, EE AF Childress, Krista J. Lawson, Angela K. Ghant, Marissa S. Mendoza, Gricelda Cardozo, Eden R. Confino, Edmond Marsh, Erica E. TI First contact: the intersection of demographics, knowledge, and appraisal of treatment at the initial infertility visit SO FERTILITY AND STERILITY LA English DT Article DE Anxiety; appraisal; infertility; knowledge; treatment ID FERTILITY TREATMENT; WOMENS KNOWLEDGE; CHILDBEARING; TECHNOLOGY; AWARENESS; DISCONTINUE; ADJUSTMENT; ATTITUDES; STUDENTS; REASONS AB Objective: To determine the impact of the initial infertility visit on treatment-related knowledge, patient anxiety, and appraisals of treatment. Design: Prospective survey. Setting: Academic medical center. Patient(s): Two hundred thirty-four English-speaking women aged 18-50 years attending their first infertility visit. Intervention(s): Participants completed a survey assessing health literacy, knowledge, anxiety, and appraisals of the treatment process before and after their infertility visit. Main Outcome Measure(s): Knowledge of infertility and treatment and anxiety and appraisal scores. Result(s): Most participants were white and earned >$ 100,000/year and had at least a college education. Baseline knowledge of reproductive anatomy, assisted reproductive technology (ART), and fertility factors was modest but improved after the initial visit. Factors associated with higher knowledge included higher education and income, white or Asian ethnicity, and English as a primary language. Patient appraisals of treatment represented by the positive (Challenge) and negative (Threat and Loss) subscale scores on the Appraisal of Life Events (ALE) scale changed over time Negative appraisals of treatment and anxiety scores decreased and positive appraisals of treatment increased after the initial visit. Lower knowledge was associated with higher positive appraisal scores; lower health literacy was associated with higher anxiety and appraisal scores (positive and negative) after the visit. Black women had higher Challenge scores compared with white and Asian women. Hispanic women had higher anxiety scores than non-Hispanic women. Conclusion(s): Infertility patients have modest baseline knowledge of fertility and infertility treatment. The initial infertility visit can improve this knowledge and decrease both negative appraisals of treatment and anxiety levels. Differences in knowledge and appraisal were seen across ethnic groups and other demographic variables. Physicians should individualize patient counseling to improve patients' knowledge and provide realistic treatment expectations while also reducing patient anxiety. (C) 2015 by American Society for Reproductive Medicine. C1 [Childress, Krista J.; Lawson, Angela K.; Ghant, Marissa S.; Mendoza, Gricelda; Confino, Edmond; Marsh, Erica E.] Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Cardozo, Eden R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Boston, MA 02114 USA. RP Marsh, EE (reprint author), Northwestern Univ, Feinberg Sch Med, 676 N St Clair,Suite 1845, Chicago, IL 60611 USA. EM erica-marsh@northwestern.edu FU National Institutes of Health [P01HD57877]; Feinberg School of Medicine, Northwestern University; Northwestern Memorial Hospital; Robert Wood Johnson Foundation; NIH Women's Reproductive Health Research Scholar Program at Northwestern [K12HD050121] FX Supported by the National Institutes of Health (grant P01HD57877) (to E.E.M.), the Feinberg School of Medicine, Northwestern University, Northwestern Memorial Hospital, Robert Wood Johnson Foundation, grant (to E.E.M.), and NIH K12HD050121 Women's Reproductive Health Research Scholar Program at Northwestern (to E.E.M.). NR 37 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2015 VL 104 IS 1 BP 180 EP 187 DI 10.1016/j.fertnstert.2015.04.002 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CS1RF UT WOS:000361844700031 PM 26003271 ER PT J AU Cole, PD Finkelstein, Y Stevenson, KE Blonquist, TM Vijayanathan, V Silverman, LB Neuberg, DS Sallan, SE Robaey, P Waber, DP AF Cole, Peter D. Finkelstein, Yaron Stevenson, Kristen E. Blonquist, Traci M. Vijayanathan, Veena Silverman, Lewis B. Neuberg, Donna S. Sallan, Stephen E. Robaey, Philippe Waber, Deborah P. TI Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSORTIUM PROTOCOL 00-01; FARBER CANCER INSTITUTE; DANA-FARBER; NEUROPSYCHOLOGICAL OUTCOMES; METHOTREXATE NEUROTOXICITY; INTRATHECAL METHOTREXATE; NEUROCOGNITIVE OUTCOMES; CEREBROSPINAL-FLUID; STANDARD RISK; CHILDREN AB Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) exhibit increased rates of neurocognitive deficits. This study was conducted to test whether interpatient variability in neurocognitive outcomes can be explained by polymorphisms in candidate genes conferring susceptibility to neurocognitive decline. Methods Neurocognitive testing was conducted in 350 pediatric leukemia survivors, treated on Dana-Farber Cancer Institute ALL Consortium Protocols 95-01 or 00-01. Genomic DNA was isolated from bone marrow collected at remission. Candidate polymorphisms were selected on the basis of prior literature, targeting genes related to drug metabolism, oxidative damage, altered neurotransmission, neuroinflammation, and folate physiology. Single nucleotide polymorphisms were detected using either a customized multiplexed Sequenom MassARRAY assay or polymerase chain reaction-based allelic discrimination assays. Multivariable logistic regression models were used to estimate the effects of genotype on neurocognitive outcomes, adjusted for the effects of demographic and treatment variables. False-discovery rate correction was made for multiple hypothesis testing, indicated as a Q value. Results Inferior cognitive or behavioral outcomes were associated with polymorphisms in three genes related to oxidative stress and/or neuroinflammation: NOS3 (IQ, Q = 0.008; Vocabulary Q = 0.011; Matrix Reasoning Q = 0.008), SLCO2A1 (IQ Q = 0.043; Digit Span Q = 0.006; Block Design Q = 0.076), and COMT (Behavioral Assessment System for Children-2 Attention Q = 0.080; and Hyperactivity Q = 0.084). Survivors homozygous for NOS3 894T, with at least one SLCO2A1 variant G allele or with at least one GSTP1 variant allele, had lower mean estimated IQ scores than those without these genotypes. Conclusion These data are consistent with the hypothesis that oxidative damage contributes to chemotherapy-associated neurocognitive decline among children with leukemia. C1 [Cole, Peter D.; Vijayanathan, Veena] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Finkelstein, Yaron] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Robaey, Philippe] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Stevenson, Kristen E.; Blonquist, Traci M.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Silverman, Lewis B.; Sallan, Stephen E.] Harvard Univ, DFCI, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Waber, Deborah P.] Harvard Univ, DFCI, Sch Med, Boston, MA 02115 USA. RP Cole, PD (reprint author), Albert Einstein Coll Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM Peter.Cole@Einstein.YU.edu FU NCI NIH HHS [P30 CA013330, P01 CA068484]; NICHD NIH HHS [IH P30 HD18655, P30 HD018655] NR 49 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2015 VL 33 IS 19 BP 2205 EP U117 DI 10.1200/JCO.2014.59.0273 PG 9 WC Oncology SC Oncology GA CR8UV UT WOS:000361630500013 PM 25987702 ER PT J AU Cohen, LS Viguera, AC McInerney, KA Kwiatkowski, MA Murphy, SK Lemon, EL Hernandez-Diaz, S AF Cohen, Lee S. Viguera, Adele C. McInerney, Kathryn A. Kwiatkowski, Molly A. Murphy, Shannon K. Lemon, Elizabeth L. Hernandez-Diaz, Sonia TI Establishment of the National Pregnancy Registry for Atypical Antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID EXPOSED PREGNANCIES; DRUGS; PREVALENCE; EXPERIENCE; LACTATION; INFANTS; SAFETY AB Objective: Atypical antipsychotics are widely used by reproductive-age women to treat a spectrum of psychiatric illnesses. Despite widespread use of this class of agents in women of childbearing potential, reproductive safety data across these medicines remain limited. The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) at Massachusetts General Hospital was established in 2008 to address this knowledge gap. Method: Data are prospectively collected from pregnant women, ages 18-45 years, using 3 phone interviews conducted at the following times: (1) proximate to the time of enrollment, (2) 7 months' gestation, and (3) 2-3 months postpartum. Subjects include pregnant women with histories of fetal exposure to second-generation antipsychotics and a comparison group of nonexposed pregnant women. Medical record release authorization is obtained for obstetric, labor and delivery, and newborn pediatric (up to 6 months of age) records. Information regarding the presence of major malformations is abstracted from the medical records along with other data regarding neonatal and maternal health outcomes. Identified cases of congenital malformations are sent to a dysmorphologist blinded to drug exposure for final adjudication. Results: As of May 2014, 428 subjects have enrolled in the NPRAA. Efforts continue to increase enrollment for the purpose of enhancing the capacity to define risk estimates of in utero exposure to atypical antipsychotics. Conclusions: The NPRAA gathers prospective data regarding risk for critical outcomes following use of atypical antipsychotics during pregnancy. The NPRAA offers a systematic way to collect reproductive safety information that informs the care of women who use these agents to sustain psychiatric well-being. C1 [Cohen, Lee S.; Viguera, Adele C.; McInerney, Kathryn A.; Kwiatkowski, Molly A.; Murphy, Shannon K.; Lemon, Elizabeth L.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Viguera, Adele C.] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. [McInerney, Kathryn A.; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Cohen, LS (reprint author), 185 Cambridge St,Ste 2000, Boston, MA 02114 USA. EM lcohen2@mgh.harvard.edu FU AstraZeneca (Wilmington, Delaware); Bristol-Myers Squibb/Otsuka (Hopewell, New Jersey); Ortho-McNeil-Janssen Pharmaceuticals, Inc (Raritan, New Jersey); Pfizer, Inc (New York, NY); Sunovion Pharmaceuticals, Inc (Fort Lee, New Jersey) FX The National Pregnancy Registry for Atypical Antipsychotics has received funding from AstraZeneca (Wilmington, Delaware; 2009-2014); Bristol-Myers Squibb/Otsuka (Hopewell, New Jersey; 2008-present); Ortho-McNeil-Janssen Pharmaceuticals, Inc (Raritan, New Jersey; 2009-2014); Pfizer, Inc (New York, NY; 2009-2011); and Sunovion Pharmaceuticals, Inc (Fort Lee, New Jersey; 2011-present). NR 28 TC 6 Z9 6 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2015 VL 76 IS 7 BP 986 EP 989 DI 10.4088/JCP.14br09418 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CR7MU UT WOS:000361535200030 PM 25939066 ER PT J AU Biederman, J AF Biederman, Joseph TI Further Evidence for Robust Familiality of Pediatric Bipolar I Disorder: Results From a Very Large Controlled Family Study of Pediatric Bipolar I Disorder and a Meta-Analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. EM jbiederman@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2015 VL 76 IS 7 BP E891 EP E892 DI 10.4088/JCP.14lcx09028 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CR7MU UT WOS:000361535200009 PM 26231018 ER PT J AU Hamner, MB AF Hamner, Mark B. TI Smoking Cessation in Homeless Veterans SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID TOBACCO; SMOKERS C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM mark.hamner@va.gov NR 8 TC 0 Z9 0 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2015 VL 76 IS 7 BP E911 EP E912 DI 10.4088/JCP.14com09726 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CR7MU UT WOS:000361535200019 PM 26231027 ER PT J AU Purohit, MP Zafonte, RD Sherman, LM Davis, RB Giwerc, MY Shenton, ME Yeh, GY AF Purohit, Maulik P. Zafonte, Ross D. Sherman, Laura M. Davis, Roger B. Giwerc, Michelle Y. Shenton, Martha E. Yeh, Gloria Y. TI Neuropsychiatric Symptoms and Expenditure on Complementary and Alternative Medicine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMMON NEUROLOGICAL CONDITIONS; MIND-BODY THERAPIES; STRESS REDUCTION; DEPRESSION; TRIAL; ADULTS; MEDITATION; MIGRAINE; ANXIETY; PAIN AB Objective: Neuropsychiatric symptoms affect 37% of US adults. These symptoms are often refractory to standard therapies, and patients may consequently opt for complementary and alternative medicine therapies (CAM). We sought to determine the demand for CAM by those with neuropsychiatric symptoms compared to those without neuropsychiatric symptoms as measured by out-of-pocket expenditure. Method: We compared CAM expenditure between US adults with and without neuropsychiatric symptoms (n = 23,393) using the 2007 National Health Interview Survey. Symptoms included depression, anxiety, insomnia, attention deficits, headaches, excessive sleepiness, and memory loss. CAM was defined per guidelines from the National Institutes of Health as mind-body therapies, biological therapies, manipulation therapies, or alternative medical systems. Expenditure on CAM by those without neuropsychiatric symptoms was compared to those with neuropsychiatric symptoms. Results: Of the adults surveyed, 37% had >= 1 neuropsychiatric symptom and spent $14.8 billion out-of-pocket on CAM. Those with >= 1 neuropsychiatric symptom were more likely than those without neuropsychiatric symptoms to spend on CAM (27.4% vs 20.3%, P < .001). Likelihood to spend on CAM increased with number of symptoms (27.2% with >= 3 symptoms, P < .001). After adjustment was made for confounders using logistic regression, those with >= 1 neuropsychiatric symptom remained more likely to spend on CAM (odds ratio [OR] = 1.34; 95% CI, 1.22-1.48), and the likelihood increased to 1.55 (95% CI, 1.34-1.79) for >= 3 symptoms. Anxiety (OR = 1.40 [95% CI, 1.22-1.60]) and excessive sleepiness (OR = 1.36 [95% CI, 1.21-1.54]) were the most closely associated with CAM expenditure. Conclusions: Those with >= 1 neuropsychiatric symptom had disproportionately higher demand for CAM than those without symptoms. Research regarding safety, efficacy, and cost-effectiveness of CAM is limited; therefore, future research should evaluate these issues given the tremendous demand for these treatments. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Purohit, Maulik P.; Zafonte, Ross D.; Sherman, Laura M.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp Network, Boston, MA USA. [Purohit, Maulik P.; Zafonte, Ross D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Purohit, Maulik P.; Davis, Roger B.; Yeh, Gloria Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Purohit, Maulik P.; Zafonte, Ross D.; Giwerc, Michelle Y.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Purohit, Maulik P.] Ft Belvoir Community Hosp, Intrepid Spirit One, Natl Intrepid Ctr Excellence NICoE, Ft Belvoir, VA USA. [Purohit, Maulik P.] Def Vet Brain Injury Ctr, Ft Belvoir, VA USA. RP Purohit, MP (reprint author), Spaulding Rehabil Hosp Network, 300 First Ave, Charlestown, MA 02129 USA. EM maulik.p.purohit.civ@mail.mil FU institutional National Research Service award from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) [T32AT000051]; Investigator Award [5R24HD065688-02]; National Institute of Disability and Research; Department of Defense; Mid-Career investigator award [K24AT000589]; Harvard Catalyst (NIH) [UL1 RR 025758] FX Dr Purohit was supported by an institutional National Research Service award #T32AT000051 from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH). Dr Zafonte was supported by an Investigator Award 5R24HD065688-02, the National Institute of Disability and Research, and the Department of Defense. Dr Davis was supported by a Mid-Career investigator award K24AT000589 and by Harvard Catalyst (NIH award #UL1 RR 025758) NR 33 TC 2 Z9 2 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2015 VL 76 IS 7 BP E870 EP E876 DI 10.4088/JCP.13m08682 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CR7MU UT WOS:000361535200005 PM 26231014 ER PT J AU Herr, DJ Aune, SE Menick, DR AF Herr, Daniel J. Aune, Sverre E. Menick, Donald R. TI Induction and Assessment of Ischemia-reperfusion Injury in Langendorff-perfused Rat Hearts SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 101; Ischemia reperfusion; isolated heart; cardiac preconditioning; infarct staining; histone deacetylase; cardiac function ID INHIBITION; PROTECTION; MYOCARDIUM; MECHANISM; STRESS AB The biochemical events surrounding ischemia reperfusion injury in the acute setting are of great importance to furthering novel treatment options for myocardial infarction and cardiac complications of thoracic surgery. The ability of certain drugs to precondition the myocardium against ischemia reperfusion injury has led to multiple clinical trials, with little success. The isolated heart model allows acute observation of the functional effects of ischemia reperfusion injury in real time, including the effects of various pharmacological interventions administered at any time-point before or within the ischemia-reperfusion injury window. Since brief periods of ischemia can precondition the heart against ischemic injury, in situ aortic cannulation is performed to allow for functional assessment of non-preconditioned myocardium. A saline filled balloon is placed into the left ventricle to allow for real-time measurement of pressure generation. Ischemic injury is simulated by the cessation of perfusion buffer flow, followed by reperfusion. The duration of both ischemia and reperfusion can be modulated to examine biochemical events at any given time-point. Although the Langendorff isolated heart model does not allow for the consideration of systemic events affecting ischemia and reperfusion, it is an excellent model for the examination of acute functional and biochemical events within the window of ischemia reperfusion injury as well as the effect of pharmacological intervention on cardiac pre-and postconditioning. The goal of this protocol is to demonstrate how to perform in situ aortic cannulation and heart excision followed by ischemia/reperfusion injury in the Langendorff model. C1 [Herr, Daniel J.; Aune, Sverre E.; Menick, Donald R.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med Cardiol, Charleston, SC 29403 USA. [Menick, Donald R.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Menick, DR (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med Cardiol, Charleston, SC 29403 USA. EM menickd@musc.edu OI Herr, Daniel/0000-0002-5593-4965 FU South Carolina Clinical & Translational Research (SCTR) Institute; Medical University of South Carolina, NIH/NCATS [UL1 TR000062]; VA merit award [BX002327-01]; NIH/NCATS [TL1 TR000061]; NIH [T32 GM008716, T32 HL07260] FX This publication was supported by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, NIH/NCATS Grant Number UL1 TR000062. Further support was provided by VA merit award BX002327-01 to DRM. DJH was supported by NIH/NCATS Grant Number TL1 TR000061 and by NIH Grant Number T32 GM008716. SEA was supported by NIH Grant Number T32 HL07260. NR 18 TC 1 Z9 1 U1 0 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2015 IS 101 AR e52908 DI 10.3791/52908 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7ND UT WOS:000361536200039 PM 26274877 ER PT J AU Nguyen, PL Shin, H Yousefi, K Thompson, DJ Hornberger, J Hyatt, AS Badani, KK Morgan, TM Feng, FY AF Nguyen, Paul L. Shin, Heesun Yousefi, Kasra Thompson, Darby J. Hornberger, John Hyatt, Andrew S. Badani, Ketan K. Morgan, Todd M. Feng, Felix Y. TI Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists SO UROLOGY LA English DT Article ID PROSTATE-CANCER; RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; PHYSICIAN SPECIALTY; THERAPY; TRIAL AB OBJECTIVE To evaluate how a genomic classifier (GC) that predicts the risk of metastasis after prostatectomy would impact adjuvant treatment recommendations made by radiation oncologists and urologists. The 2 specialties often disagree about postprostatectomy adjuvant treatment recommendations. MATERIALS AND METHODS Twenty-six radiation oncologists and 20 urologists with genitourinary oncology expertise reviewed de-identified clinical results from 11 patients after radical prostatectomy and made adjuvant treatment recommendations. The same cases were later randomized and reassigned, and treatment recommendations were made using the clinical information and GC test results together. RESULTS Using clinical information alone, observation was recommended in 42% of decisions made by urologists vs 23% by radiation oncologists (P < .0001). The GC test results altered 35% and 45% of treatment recommendations made by radiation oncologists and urologists, respectively. Multivariate analysis showed GC risk was the strongest factor influencing treatment recommendations by both specialties, with an adjusted odds ratio of 4.17 (95% confidence interval [CI], 2.26-7.70) and 6.51 (95% CI, 4.29-9.88) for radiation oncologists and urologists, respectively. GC results indicating high metastatic risk resulted in intensification of treatment, whereas low metastatic risk resulted in less aggressive recommendations. The GC results increased interdisciplinary agreement in treatment recommendations, as the odds of a recommendation for adjuvant treatment by urologists vs radiation oncologists increased from 0.27 (95% CI, 0.17-0.44) to 0.46 (95% CI, 0.29-0.75) after results of the GC test were available. CONCLUSION The GC test significantly influenced adjuvant postprostatectomy treatment recommendations, reduced disagreement between radiation oncologists and urologists, and has the potential to enhance personalization of postprostatectomy care. (C) 2015 Elsevier Inc. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. GenomeDx Biosci, Vancouver, BC, Canada. EMMES Canada, Burnaby, BC, Canada. Cedar Associates, Menlo Pk, CA USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Columbia Univ, Med Ctr, Dept Urol, New York, NY USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Radiat Oncol, Ann Arbor, MI 48109 USA. RP Nguyen, PL (reprint author), Dana Farber Brigham & Womens Canc Ctr, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU GenomeDx Biosciences; National Research Council Canada Industrial Research Assistance Program [765817]; Prostate Cancer Foundation; Fitz's Cancer Warriors FX This study was supported by GenomeDx Biosciences and the National Research Council Canada Industrial Research Assistance Program (grant no. 765817). Partial support was also provided by the Prostate Cancer Foundation, David and Cynthia Chapin, Fitz's Cancer Warriors, Frank and Anne Simons, and a grant from an anonymous family foundation. NR 17 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JUL PY 2015 VL 86 IS 1 BP 35 EP 40 DI 10.1016/j.urology.2015.04.004 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CS2LP UT WOS:000361902700011 PM 26142578 ER PT J AU Beatty, AL Ku, IA Bibbins-Domingo, K Christenson, RH DeFilippi, CR Ganz, P Ix, JH Lloyd-Jones, D Omland, T Sabatine, MS Schiller, NB Shlipak, MG Skali, H Takeuchi, M Vittinghoff, E Whooley, MA AF Beatty, Alexis L. Ku, Ivy A. Bibbins-Domingo, Kirsten Christenson, Robert H. DeFilippi, Christopher R. Ganz, Peter Ix, Joachim H. Lloyd-Jones, Donald Omland, Torbjorn Sabatine, Marc S. Schiller, Nelson B. Shlipak, Michael G. Skali, Hicham Takeuchi, Madoka Vittinghoff, Eric Whooley, Mary A. TI Traditional Risk Factors Versus Biomarkers for Prediction of Secondary Events in Patients With Stable Coronary Heart Disease: From the Heart and Soul Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE coronary disease; epidemiology; prevention; risk prediction ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; TROPONIN-T ASSAY; ARTERY-DISEASE; CARDIOVASCULAR RISK; NATRIURETIC-PEPTIDE; MYOCARDIAL-INFARCTION; MULTIPLE BIOMARKERS; ATRIAL-FIBRILLATION; WORKING GROUP AB Background-Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD. Methods and Results-We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin: creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort. Conclusions-Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD. C1 [Beatty, Alexis L.; Ku, Ivy A.; Bibbins-Domingo, Kirsten; Ganz, Peter; Schiller, Nelson B.; Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bibbins-Domingo, Kirsten; Shlipak, Michael G.; Vittinghoff, Eric; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Beatty, Alexis L.] VA Puget Sound Hlth Care Syst, Cardiol Sect, Seattle, WA 98108 USA. [Beatty, Alexis L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Ku, Ivy A.; Bibbins-Domingo, Kirsten; Ganz, Peter] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Ku, Ivy A.; Takeuchi, Madoka] Kaiser Permanente Med Ctr, Dept Cardiol, San Francisco, CA USA. [Christenson, Robert H.] Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. [DeFilippi, Christopher R.] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Lloyd-Jones, Donald] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald] Northwestern Univ, Bluhm Cardiovasc Inst, Feinberg Sch Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Omland, Torbjorn] Akershus Univ Hosp, Div Med, Lorenskog, Norway. [Omland, Torbjorn] Univ Oslo, Lorenskog, Norway. [Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, Boston, MA 02115 USA. [Sabatine, Marc S.; Skali, Hicham] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med, Boston, MA 02115 USA. [Shlipak, Michael G.; Whooley, Mary A.] Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Beatty, AL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111, Seattle, WA 98108 USA. EM beattya@uw.edu FU National Heart, Lung, and Blood Institute [F32 HL110518, F32 HL097461, R01 HL079235, N01HC65149, R01 HL094390]; National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000143]; Sha Family Fellowship in Cardiovascular Research; Department of Veterans Affairs; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; Knoll Pharmaceuticals; Abbott Laboratories; Roche Diagnostics FX Dr Beatty was supported by the National Heart, Lung, and Blood Institute (F32 HL110518) and the National Center for Advancing Translational Sciences of the National Institutes of Health (KL2 TR000143). Dr Ku was supported by the National Heart, Lung, and Blood Institute (F32 HL097461) and the Sha Family Fellowship in Cardiovascular Research. The Heart and Soul Study was supported by the Department of Veterans Affairs; the National Heart, Lung, and Blood Institute (R01 HL079235); the American Federation for Aging Research; the Robert Wood Johnson Foundation; and the Ischemia Research and Education Foundation. The PEACE trial was supported by a contract (N01HC65149) from the National Heart, Lung, and Blood Institute and by Knoll Pharmaceuticals and Abbott Laboratories. Dr Sabatine and measurement of hs-CRP in PEACE was supported by the National Heart, Lung, and Blood Institute (R01 HL094390). Roche Diagnostics provided support for NT-proBNP and troponin T testing in both cohorts. The funding organizations had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 48 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUL PY 2015 VL 4 IS 7 AR e001646 DI 10.1161/JAHA.114.001646 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR6WR UT WOS:000361489400006 ER PT J AU Lin, CB Cox, M Olson, DM Britz, GW Constable, M Fonarow, GC Schwamm, L Peterson, ED Shah, BR AF Lin, Cheryl B. Cox, Margueritte Olson, DaiWai M. Britz, Gavin W. Constable, Mark Fonarow, Gregg C. Schwamm, Lee Peterson, Eric D. Shah, Bimal R. TI Perception Versus Actual Performance in Timely Tissue Plasminogen Activation Administration in the Management of Acute Ischemic Stroke SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE hospital perception; quality improvement; quality of care; stroke; thrombolytics ID QUALITY-OF-CARE; GUIDELINES PROGRAM; ASSOCIATION; OUTCOMES; ATTACK; IMPROVEMENT AB Background-Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA "door-to-needle" (DTN) time within 60 minutes and how DTN rates compare across different hospitals. Methods and Results-DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and low DTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN <= 60 minutes among treated patients (10.6% versus 16.6%, P=0.002). Conclusions-Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care. C1 [Lin, Cheryl B.] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA. [Cox, Margueritte] Duke Clin Res Inst, Durham, NC 27705 USA. [Olson, DaiWai M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Britz, Gavin W.; Constable, Mark; Peterson, Eric D.; Shah, Bimal R.] Duke Univ, Med Ctr, Durham, NC USA. [Fonarow, Gregg C.] Ronald Reagan Univ Calif Los Angeles, Med Ctr, Los Angeles, CA USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shah, BR (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM Bimal.shah@duke.edu FU Agency for Healthcare Research and Quality [U18HS016964] FX This project was supported by cooperative agreement number U18HS016964 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. NR 20 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUL PY 2015 VL 4 IS 7 AR e001298 DI 10.1161/JAHA.114.001298 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR6WR UT WOS:000361489400004 ER PT J AU Lin, XC Zhang, X Guo, JJ Roberts, CK McKenzie, S Wu, WC Liu, SM Song, YQ AF Lin, Xiaochen Zhang, Xi Guo, Jianjun Roberts, Christian K. McKenzie, Steve Wu, Wen-Chih Liu, Simin Song, Yiqing TI Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE biomarker; cardiometabolic health; cardiovascular disease prevention; exercise training ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; HIGH-INTENSITY EXERCISE; IMPROVED INSULIN SENSITIVITY; OBESE POSTMENOPAUSAL WOMEN; MODERATE AEROBIC EXERCISE; RESTING METABOLIC-RATE; MIDDLE-AGED ADULTS AB Background-Guidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta-analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease. Methods and Results-Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random-effects meta-analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment-insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin-18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more. Conclusions-This meta-analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions. C1 [Lin, Xiaochen; Wu, Wen-Chih; Liu, Simin] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02903 USA. [Wu, Wen-Chih; Liu, Simin] Brown Univ, Alpert Med Sch, Dept Med, Div Cardiol, Providence, RI 02903 USA. [Wu, Wen-Chih; Liu, Simin] Brown Univ, Alpert Med Sch, Dept Med, Vet Affairs Med Ctr, Providence, RI 02903 USA. [Zhang, Xi; Song, Yiqing] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA. [Guo, Jianjun] China Inst Sport Sci, Ctr Youth Sport Res & Dev, Beijing, Peoples R China. [Roberts, Christian K.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [McKenzie, Steve] Indiana Univ Purdue Univ, Dept Kinesiol, Ctr Phys Act Wellness & Prevent, Indianapolis, IN 46202 USA. [Liu, Simin] Rhode Isl Hosp, Dept Med, Div Endocrinol, Providence, RI 02903 USA. RP Liu, SM (reprint author), Brown Univ, Dept Epidemiol & Med, 121 South Main St, Providence, RI 02903 USA. EM Simin_liu@brown.edu; yiqsong@iu.edu RI Lin, Xiaochen/P-6460-2015 FU Indiana University Health-Indiana University School of Medicine Strategic Research Initiative Grant; National Institutes of Health (NIH) [R01DK09406, P50HL105188]; Brown University FX The study was supported by the Indiana University Health-Indiana University School of Medicine Strategic Research Initiative Grant (Zhang and Song), R01DK09406 (Roberts) and P50HL105188 (Roberts) from the National Institutes of Health (NIH), and Brown University. The NIH, Brown University, or Indiana University had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 217 TC 22 Z9 22 U1 9 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUL PY 2015 VL 4 IS 7 AR e002014 DI 10.1161/JAHA.115.002014 PG 28 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR6WR UT WOS:000361489400031 ER PT J AU Sosnovik, DE AF Sosnovik, David E. TI Seeing What We Build-The Need for New Imaging Techniques in Myocardial Regeneration SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Editorial Material ID MESENCHYMAL STEM-CELLS; IN-VIVO; INFARCTED MYOCARDIUM; THERAPY; SURVIVAL; HEART; MODEL C1 [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Boston, MA USA. RP Sosnovik, DE (reprint author), Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUL PY 2015 VL 4 IS 7 AR e002306 DI 10.1161/JAHA.115.002306 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR6WR UT WOS:000361489400042 ER PT J AU Stern, TA AF Stern, Theodore A. TI This issue: Geriatric Psychopharmacology SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Stern, Theodore A.] Harvard Univ, Sch Med, Psychiat Field Psychosomat Med, Cambridge, MA 02138 USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stern, Theodore A.] Avery D Weisman Psychiat Consultat Serv, New York, NY USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Off Clin Careers, Boston, MA 02114 USA. [Stern, Theodore A.] Acad Psychosomat Med, New York, NY USA. RP Stern, TA (reprint author), Harvard Univ, Sch Med, Psychiat Field Psychosomat Med, Cambridge, MA 02138 USA. EM TStern@Partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 2015 VL 45 IS 7 BP 333 EP 334 DI 10.3928/00485713-20150626-03 PG 2 WC Psychiatry SC Psychiatry GA CR6OV UT WOS:000361467900003 ER PT J AU Carlo, AD Alpert, JE AF Carlo, Andrew D. Alpert, Jonathan E. TI Geriatric Psychopharmacology: Pharmacokinetic and Pharmacodynamic Considerations SO PSYCHIATRIC ANNALS LA English DT Article ID ADVERSE DRUG-REACTIONS; LIVER-MICROSOMES; ELDERLY-PATIENTS; AGE; METABOLISM; RISK AB Older adults represent the fastest growing demographic in both developing and developed countries. Understanding pharmacokinetic and pharmacodynamic principles relevant to psychopharmacology in geriatric patients is increasingly important to optimize psychiatric treatment. This review discusses the four pharmacokinetic processes (absorption, distribution, metabolism, and excretion) with regard to age-related changes. These include a generally slower rate of absorption, increases in the ratio of adipose to lean body mass and volume of distribution of medications, reductions in phase I metabolism, and decreases in renal function. In addition, this review discusses pharmacodynamic factors relevant to pharmacotherapy in older age, such as changes in receptor density and homeostatic and regulatory mechanisms. Geriatric psychopharmacology will benefit from an expanding evidence base as research on pharmacokinetics and pharmacodynamics increasingly includes older individuals. C1 [Carlo, Andrew D.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Psychiat Clin Serv, Boston, MA 02114 USA. [Alpert, Jonathan E.] Harvard Univ, Sch Med, Depress Clin & Res Program, Cambridge, MA 02138 USA. [Alpert, Jonathan E.] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. [Alpert, Jonathan E.] Harvard Univ, Sch Med, Field Depress Studies, Cambridge, MA 02138 USA. RP Carlo, AD (reprint author), Massachusetts Gen Hosp, Wang ACC 812,15 Parkman St, Boston, MA 02114 USA. EM acarlo@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 30 TC 0 Z9 0 U1 0 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 2015 VL 45 IS 7 BP 336 EP 341 DI 10.3928/00485713-20150626-04 PG 6 WC Psychiatry SC Psychiatry GA CR6OV UT WOS:000361467900004 ER PT J AU McCall, C Winkelman, JW AF McCall, Catherine Winkelman, John W. TI The Use of Hypnotics to Treat Sleep Problems in the Elderly SO PSYCHIATRIC ANNALS LA English DT Article ID CHRONIC PRIMARY INSOMNIA; OLDER-ADULTS; OUTPATIENT TRIAL; METAANALYSIS; RAMELTEON; EFFICACY; SAFETY; DEPRESSION; DISORDERS; MORTALITY AB Sleep problems are common in the elderly, with a prevalence of close to 50% in those older than age 65 years. Older adults may suffer from disturbances of sleep that are related to medical problems, to psychiatric illness, to primary sleep disorders, to use or withdrawal from drugs/medications, and/or to poor sleep habits. Loss of sleep in older adults is associated with significant morbidity, low quality of life, and mortality. When approaching the diagnosis and management of sleep disorders in elderly patients, it is important to evaluate and treat comorbid conditions. Pharmacologic treatments for sleep, although increasingly common, present significant challenges due to age-related changes in drug metabolism and clearance, side effects, and drug-drug interactions. When possible, it is preferable to manage sleep problems with nonpharmacologic approaches. This review discusses current pharmacologic and nonpharmacologic treatments for sleep problems in the elderly. C1 [McCall, Catherine] Brigham & Womens Hosp, Harvard Longwood Psychiat Residency Training Prog, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [McCall, Catherine; Winkelman, John W.] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. [Winkelman, John W.] Massachusetts Gen Hosp, Dept Psychiat, Sleep Disorders Clin Res Program, Boston, MA 02114 USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,9th Floor, Boston, MA 02114 USA. EM jwwinkelman@partners.org FU UCB Pharma; Xenopart; INSYS Therapeutics; Merck Co.; Flex Pharma FX Disclosure: John W. Winkelman has received consulting fees from UCB Pharma, Xenopart, INSYS Therapeutics, Merck & Co., and Flex Pharma; has performed contracted research for Purdue, Xenopart, UCB Pharma, and Neurometrix; and has provided expert testimony for Canter Colburn. The remaining author has no relevant financial relationships to disclose. NR 31 TC 0 Z9 0 U1 2 U2 7 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 2015 VL 45 IS 7 BP 342 EP 347 DI 10.3928/00485713-20150626-05 PG 6 WC Psychiatry SC Psychiatry GA CR6OV UT WOS:000361467900005 ER PT J AU Rothenberg, KG Wiechers, IR AF Rothenberg, Kasia Gustaw Wiechers, Ilse R. TI Antipsychotics for Neuropsychiatric Symptoms of Dementia-Safety and Efficacy in the Context of Informed Consent SO PSYCHIATRIC ANNALS LA English DT Article ID SEVERE ALZHEIMERS-DISEASE; PLACEBO-CONTROLLED TRIALS; POPULATION-BASED COHORT; ATYPICAL ANTIPSYCHOTICS; ADVERSE OUTCOMES; CATIE-AD; DRUGS; RISK; METAANALYSIS; MEDICATIONS AB Appropriate use of antipsychotic medications in older adults with dementia can be challenging due to several important safety concerns. This article reviews the risks and benefits of using antipsychotic medications in the treatment of patients with neuropsychiatric symptoms of dementia through the framework of an informed-consent conversation. Informed-consent discussions help provide patients, surrogate decision-makers, and caregivers with the essential data necessary to make informed treatment choices. C1 [Rothenberg, Kasia Gustaw] Yale Univ, Sch Med, Geriatr Psychiat, New Haven, CT 06520 USA. [Wiechers, Ilse R.] Northeast Program Evaluat Ctr, West Haven, CT USA. [Wiechers, Ilse R.] US Dept Vet Affairs, Psychotrop Drug Safety Initiat, Off Mental Hlth Operat, Washington, DC USA. [Wiechers, Ilse R.] Yale Univ, Sch Med, Psychiat, New Haven, CT 06520 USA. RP Wiechers, IR (reprint author), VA Connecticut Healthcare Syst, NEPEC 182,950 Campbell Ave, West Haven, CT 06516 USA. EM Ilse.Wiechers@va.gov NR 33 TC 0 Z9 0 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 2015 VL 45 IS 7 BP 348 EP 353 DI 10.3928/00485713-20150626-06 PG 6 WC Psychiatry SC Psychiatry GA CR6OV UT WOS:000361467900006 ER PT J AU Atri, A Stern, TA AF Atri, Alireza Stern, Theodore A. TI Psychopharmacologic Agents to Enhance Cognition in Alzheimer's Disease SO PSYCHIATRIC ANNALS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PATIENTS RECEIVING DONEPEZIL; CHOLINESTERASE-INHIBITORS; MEMANTINE TREATMENT; DOUBLE-BLIND; OPEN-LABEL; COMBINATION THERAPY; MODERATELY-SEVERE; VITAMIN-E; GALANTAMINE TREATMENT AB Cognitive dysfunction in people with Alzheimer's disease (AD) significantly affects their interactions, independence, behavior, health, wellness, and quality of life; care providers also experience quality of life issues as a result. This review summarizes clinical data on agents associated with cognitive enhancement in AD, particularly the currently approved anti-AD medications including the acetyl cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) and the N-methyl-d-aspartate antagonist, memantine. Initiation and maintenance of stage-appropriate monotherapy or combination therapy with a ChEI and memantine provides the best pharmacologic approach to stem the expected inexorable course of cognitive decline. Discontinuation of agents that impair cognition and treatment of comorbid conditions (eg, sleep disorders, dehydration, depression, anxiety, pain, as well as metabolic, hormone, and vitamin derangements) may also improve cognition. The preponderance of evidence regarding ChEIs, memantine, and vitamin E strongly supports modest, but clinically relevant, "disease-course modifying" effects of cognitive enhancement (eg, improvement, stabilization, or shifting of the trajectory of cognitive or functional decline) in patients who receive appropriate and persistent treatment. C1 [Atri, Alireza] Ray Dolby Brain Hlth Ctr, Res & Educ, San Francisco, CA 94114 USA. [Atri, Alireza] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Atri, Alireza] Massachusetts Gen Hosp, Neurol, Memory Disorders Unit, Dept Neurol, Boston, MA 02114 USA. [Atri, Alireza] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Psychiat Field Psychosomat Med Consultat, Cambridge, MA 02138 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Off Clin Careers, Boston, MA 02114 USA. RP Atri, A (reprint author), Ray Dolby Brain Hlth Ctr, CPMC Davies Campus,45 Castro St,Suite 220, San Francisco, CA 94114 USA. EM atria@cpmcri.org FU Actavis/Forest Laboratories; Merck Co.; Lundbeck; Academy of Psychosomatic Medicine FX Disclosure: Alireza Atri discloses royalties received from Oxford University Press; consulting fees received from Actavis/Forest Laboratories, Merck & Co., and Lundbeck; and an institutional research contract from Lundbeck. Theodore A. Stern discloses a salary received from the Academy of Psychosomatic Medicine and royalties received from Elsevier and Massachusetts General Hospital. NR 103 TC 0 Z9 0 U1 1 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 2015 VL 45 IS 7 BP 354 EP 367 DI 10.3928/00485713-20150626-07 PG 14 WC Psychiatry SC Psychiatry GA CR6OV UT WOS:000361467900007 ER PT J AU Novak, M Winkelman, JW Unruh, M AF Novak, Marta Winkelman, John W. Unruh, Mark TI Restless Legs Syndrome in Patients With Chronic Kidney Disease SO SEMINARS IN NEPHROLOGY LA English DT Review DE Chronic kidney disease; dialysis; kidney transplantation; quality of life; restless legs syndrome; sleep ID PLACEBO-CONTROLLED TRIAL; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; AMINOMETHYL)-1-CYCLOHEXANE ACETIC-ACID; PERIODIC LIMB MOVEMENTS; DOUBLE-BLIND; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; GABAPENTIN ENACARBIL; SLEEP DISORDERS AB Symptoms of restless legs syndrome (RLS) are common in patients with chronic kidney disease (CKD) on dialysis; symptoms of RLS are estimated to affect up to 25% of patients on dialysis when the international RLS diagnostic criteria are applied. RLS is a neurologic disorder with a circadian rhythmicity characterized by an overwhelming urge to move the legs during rest, which can be relieved temporarily by movement. RLS has been associated with an increase in sleep disturbance, higher cardiovascular morbidity, decreased quality of life, and an increased risk of death in patients with CKD. Although the exact pathophysiology of RLS is unknown, it is thought to involve an imbalance in iron metabolism and dopamine neurotransmission in the brain. The symptoms of moderate to severe RLS can be treated with several pharmacologic agents; however, data specific to patients on dialysis with RLS are lacking. The purpose of this article is to examine the relationship between, and complications of, RLS and CKD both in dialysis and nondialysis patients, and discuss the treatment options for patients on dialysis with RLS. (C) 2015 Published by Elsevier Inc. C1 [Novak, Marta] Univ Toronto, Dept Psychiat, Univ Hlth Network, Toronto, ON, Canada. [Novak, Marta] Semmelweis Univ, Inst Behav Sci, H-1085 Budapest, Hungary. [Winkelman, John W.] Massachusetts Gen Hosp, Dept Psychiat, Sleep Disorders Clin Res Program, Boston, MA 02114 USA. [Unruh, Mark] Univ New Mexico, Sch Med, Div Nephrol, Albuquerque, NM 87131 USA. RP Novak, M (reprint author), Univ Hlth Network, Dept Psychiat, 200 Elizabeth St,EN8-212A, Toronto, ON M5G 2C4, Canada. EM marta.novak@uhn.ca FU UCB Pharma FX Supported by UCB Pharma. The content of this article reflects the opinions and clinical experience of the authors only. UCB Pharma was offered the opportunity to comment on this article; changes resulting from the comments were made on the basis of scientific and editorial merit. NR 98 TC 4 Z9 4 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JUL PY 2015 VL 35 IS 4 BP 347 EP 358 DI 10.1016/j.semnephrol.2015.06.006 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CR5ZA UT WOS:000361421700006 PM 26355253 ER PT J AU Coulter, RWS Kenst, KS Bowen, DJ Scout AF Coulter, Robert W. S. Kenst, Karey S. Bowen, Deborah J. Scout TI CONTINUED DISPARITIES IN LESBIAN, GAY, AND BISEXUAL RESEARCH FUNDING AT NIH RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Coulter, Robert W. S.] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Kenst, Karey S.] Massachusetts Gen Hosp, Dispar Solut Ctr, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Bowen, Deborah J.] Univ Washington, Dept Bioeth & Humanities, Sch Publ Hlth, Seattle, WA USA. [Scout] CenterLink Community LGBT Ctr, Network LGBT Hlth Equ, Ft Lauderdale, FL USA. RP Coulter, RWS (reprint author), Univ Pittsburgh, Dept Behav & Community Hlth Sci, Grad Sch Publ Hlth, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM robert.ws.coulter@gmail.com OI Coulter, Robert/0000-0001-8350-0075 FU NIDA NIH HHS [F31 DA037647] NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2015 VL 105 SU 3 BP E2 EP E3 DI 10.2105/AJPH.2014.302316 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ9LH UT WOS:000360935700002 PM 25905847 ER PT J AU Bharel, M Santiago, ER Forgione, SN Leon, CK Weinreb, L AF Bharel, Monica Santiago, Emely R. Forgione, Sanju Nembang Leon, Casey K. Weinreb, Linda TI Eliminating Health Disparities: Innovative Methods to Improve Cervical Cancer Screening in a Medically Underserved Population SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HOMELESS WOMEN; LOS-ANGELES; BEHAVIORS; ADULTS; NEEDS; CARE; RISK AB Homeless women have disproportionately lower rates of cervical cancer screening and higher rates of cervical cancer. In 2008, only 19% of the homeless women seen by Boston Health Care for the Homeless Program (BHCHP) were screened for cervical cancer. To improve screening, BHCHP implemented a 6-part intervention that incorporates point-of-care service, multidisciplinary screening, improved health maintenance forms, population management, process improvement, and increased provider and patient education. This resulted in a significant increase in cervical cancer screening, from 19% in 2008 to 50% in 2013. When compared with national and local cervical cancer screening trends, BHCHP surpassed improvement rates seen in other vulnerable populations. Simple and innovative interventions proved to be the most effective and practical methods of improving screening. C1 [Bharel, Monica; Santiago, Emely R.; Forgione, Sanju Nembang; Leon, Casey K.] Boston Hlth Care Homeless Program, Boston, MA USA. [Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bharel, Monica] Boston Med Ctr, Boston, MA USA. [Weinreb, Linda] Univ Massachusetts, Med Ctr, Dept Family Med, Boston, MA 02125 USA. RP Leon, CK (reprint author), 780 Albany St, Boston, MA 02446 USA. EM cleon@bhchp.org NR 14 TC 1 Z9 1 U1 2 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2015 VL 105 SU 3 BP S438 EP S442 DI 10.2105/AJPH.2014.302417 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ9LH UT WOS:000360935700023 PM 25905832 ER PT J AU McCarthy, AM Yang, JN Armstrong, K AF McCarthy, Anne Marie Yang, Jianing Armstrong, Katrina TI Increasing Disparities in Breast Cancer Mortality From 1979 to 2010 for US Black Women Aged 20 to 49 Years SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ETHNIC-DIFFERENCES; MAMMOGRAPHY USE; YOUNG-WOMEN; SURVIVAL; POPULATION; SUBTYPES; HEALTH; WHITE; RATES; RACE AB Racial disparities in breast cancer mortality persist, and young Black women have higher disease incidence compared with White women. We compared trends in breast cancer mortality for young Black and White women with mortality trends for other common diseases from 1979 to 2010. In contrast to other cancers, ischemic heart disease, and stroke, the breast cancer mortality disparity has widened over the past 30 years, suggesting that unique aspects of disease biology, prevention, and treatment may explain persistent racial differences for young women. C1 [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Anne Marie; Armstrong, Katrina] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Jianing] Univ Penn, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,940F, Boston, MA 02114 USA. EM amccarthy8@partners.org FU National Institutes of Health/National Cancer Institute [1U54CA163313] FX This work was supported by the National Institutes of Health/National Cancer Institute (grant 1U54CA163313: Population-Based Research Optimizing Screening Through Personalized Regimens). NR 25 TC 7 Z9 7 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2015 VL 105 SU 3 BP S446 EP S448 DI 10.2105/AJPH.2014.302297 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ9LH UT WOS:000360935700025 PM 25905842 ER PT J AU Gros, DF AF Gros, Daniel F. TI Design challenges in transdiagnostic psychotherapy research: Comparing Transdiagnostic Behavior Therapy (TBT) to existing evidence-based psychotherapy in veterans with affective disorders SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Transdiagnostic; Comorbidity; RDoC; Psychotherapy; Transdiagnostic Behavior Therapy; TBT ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; RESEARCH DOMAIN CRITERIA; PRIMARY-CARE; CLINICAL-TRIALS; PSYCHOMETRIC PROPERTIES; ACTIVATION TREATMENTS; SYMPTOM OVERLAP; MOOD DISORDERS; PANIC DISORDER AB Background: To address the limitations of disorder-specific approaches, newer transdiagnostic approaches to psychotherapy have been developed to provide a single treatment that is capable of addressing several, related disorders. However, the recruitment of multiple diagnoses presents many challenges to the traditional design of psychotherapy randomized controlled trials (RCTs). Objective: The goal of the manuscript is to present the challenges and rationale for designing a RCT for transdiagnostic treatment to inform and aid in the development of future investigations. Methods: A recently funded and ongoing RCT for Transdiagnostic Behavior Therapy (TBT) is used as an example to discuss the related design challenges. The TBT study involves the recruitment of 96 veteran participants with any of the following eight principal diagnoses: posttraumatic stress disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, generalized anxiety disorder, specific phobia, major depressive disorder, or persistent depressive disorder. Within the TBT study, participants will complete a semi-structured diagnostic interview and a series of transdiagnostic self-report measures to determine eligibility and assess baseline symptomatology. Qualifying participants will be randomized to TBT or control psychotherapy. Additional assessments will be completed at post-treatment and 6-month follow-up. Conclusions: Due to the transdiagnostic nature of the sample, adjustments to the recruitment and randomization procedures, selection of measures, selection of control psychotherapy, and analysis plan were required. These adjustments have implications to future trials on transdiagnostic psychotherapy protocols as well as future research in line with the transdiagnostic focus of the National Institute of Mental Health's Research Domain Criteria (RDoC) funding strategy. Published by Elsevier Inc. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Department of Veterans Affairs Clinical Sciences Research and Development Career Development Award [CX000845] FX This study is supported by Department of Veterans Affairs Clinical Sciences Research and Development Career Development Award CX000845 (PI: Gros). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government There are no conflicts of interest to disclose. NR 45 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 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2015 VL 43 BP 114 EP 119 DI 10.1016/j.cct.2015.05.011 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CQ7HI UT WOS:000360773200015 PM 26003434 ER PT J AU Staehr-Rye, AK Eikermann, M AF Staehr-Rye, Anne K. Eikermann, Matthias TI Eliminate postoperative respiratory complications: preoperative screening opens the door to clinical pathways that individualise perioperative treatment SO EUROPEAN JOURNAL OF ANAESTHESIOLOGY LA English DT Editorial Material ID NEUROMUSCULAR BLOCKING-AGENTS; NATIONWIDE INPATIENT SAMPLE; PULMONARY COMPLICATIONS; ABDOMINAL-SURGERY; OUTCOMES; SCORE; VENTILATION; VALIDATION; COHORT; RISK C1 [Staehr-Rye, Anne K.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Staehr-Rye, Anne K.] Univ Copenhagen, Herlev Hosp, Dept Anaesthesiol, DK-2730 Herlev, Denmark. [Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Eikermann, Matthias] Univ Duisburg Essen, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org NR 15 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0265-0215 EI 1365-2346 J9 EUR J ANAESTH JI Eur. J. Anaesth. PD JUL PY 2015 VL 32 IS 7 BP 455 EP 457 DI 10.1097/EJA.0000000000000210 PG 3 WC Anesthesiology SC Anesthesiology GA CQ8BO UT WOS:000360831300002 PM 26389546 ER PT J AU Ding, SA Simonson, DC Wewalka, M Halperin, F Foster, K Goebel-Fabbri, A Hamdy, O Clancy, K Lautz, D Vernon, A Goldfine, AB AF Ding, Su-Ann Simonson, Donald C. Wewalka, Marlene Halperin, Florencia Foster, Kathleen Goebel-Fabbri, Ann Hamdy, Osama Clancy, Kerri Lautz, David Vernon, Ashley Goldfine, Allison B. TI Adjustable Gastric Band Surgery or Medical Management in Patients With Type 2 Diabetes: A Randomized Clinical Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BARIATRIC SURGERY; BYPASS-SURGERY; OBESE-PATIENTS; LIFE-STYLE; FOLLOW-UP; MELLITUS; WEIGHT; REDUCTION; MORTALITY; THERAPY AB Context: Recommendations for surgical, compared with lifestyle and pharmacologically based, approaches for type 2 diabetes (T2D) management remain controversial. Objective: The objective was to compare laparoscopic adjustable gastric band (LAGB) to an intensive medical diabetes and weight management (IMWM) program for T2D. Design: This was designed as a prospective, randomized clinical trial. Setting: The setting was two Harvard Medical School-affiliated academic institutions. Interventions and Participants: A 12-month randomized trial comparing LAGB (n = 23) vs IMWM (n = 22) in persons aged 21-65 years with body mass index of 30-45 kg/m(2), T2D diagnosed more than 1 year earlier, and glycated hemoglobin (HbA(1c)) >= 6.5% on antihyperglycemic medication(s). Main Outcome Measure: The proportion meeting the prespecified primary glycemic endpoint, defined as HbA(1c) < 6.5% and fasting glucose < 7.0 mmol/L at 12 months, on or off medication. Results: After randomization, five participants did not undergo the surgical intervention. Of the 40 initiating intervention (22 males/18 females; age, 51 +/- 10 y; bodymassindex, 36.5 +/- 3.7kg/m(2); diabetes duration, 9 +/- 5 y; HbA(1c), 8.2 +/- 1.2%; 40% on insulin), the proportion meeting the primary glycemic endpoint was achieved in 33% of the LAGB patients and 23% of the IMWM patients (P = .457). HbA(1c) reduction was similar between groups at both 3 and 12 months (-1.2 +/- 0.3 vs -1.0 +/- 0.3%; P = .496). Weight loss was similar at 3 months but greater 12 months after LAGB (-13.5 +/- 1.7 vs -8.5 +/- 1.6 kg; P = .027). Systolic blood pressure reduction was greater after IMWM than LAGB, whereas changes in diastolic blood pressure, lipids, fitness, and cardiovascular risk scores were similar between groups. Patient-reported health status, assessed using the Short Form-36, Impact of Weight on Quality of Life, and Problem Areas in Diabetes, all improved similarly between groups. Conclusions: LAGB and a multidisciplinary IMWM program have similar 1-year benefits on diabetes control, cardiometabolic risk, and patient satisfaction, which should be considered in the context of other factors, such as personal preference, when selecting treatment options with obese T2D patients. Longer duration studies are important to understand emergent differences. C1 [Ding, Su-Ann; Simonson, Donald C.; Wewalka, Marlene; Halperin, Florencia; Goebel-Fabbri, Ann; Hamdy, Osama; Lautz, David; Vernon, Ashley; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ding, Su-Ann; Wewalka, Marlene; Halperin, Florencia; Foster, Kathleen; Goebel-Fabbri, Ann; Hamdy, Osama; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Simonson, Donald C.; Halperin, Florencia; Clancy, Kerri; Lautz, David; Vernon, Ashley; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Goldfine, AB (reprint author), One Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [RC1-DK086918, R56-DK095451, P30-DK03836]; Patient-Centered Outcomes Research Institute [CE-1304-6756]; Marietta Blau Grant from the Osterreichischer Austausdienst [ICM-2010-02797]; Herbert Graetz Fund; Joslin Clinical Research Center FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (RC1-DK086918, R56-DK095451, and P30-DK03836), Patient-Centered Outcomes Research Institute (CE-1304-6756), the Marietta Blau Grant ICM-2010-02797 from the Osterreichischer Austausdienst, and the Herbert Graetz Fund. Covidien provided funds for surgical costs of participants randomized to surgery with BMI < 35 kg/m2. Lifescan, a Division of Johnson & Johnson, provided home glucose monitoring supplies. Nestle Nutrition Inc provided Boost. Novo Nordisk provided FDA-approved medications to be administered according to label. We also acknowledge support from the Joslin Clinical Research Center and thank its philanthropic donors. No funding source had a role in trial design, conduct, data analysis, or manuscript preparation. NR 39 TC 18 Z9 18 U1 2 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2015 VL 100 IS 7 BP 2546 EP 2556 DI 10.1210/jc.2015-1443 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8EZ UT WOS:000360840600024 PM 25909333 ER PT J AU Tsai, JN Zhu, YL Foley, K Lee, H Burnett-Bowie, SA Neer, RM Leder, BZ AF Tsai, Joy N. Zhu, Yuli Foley, Katelyn Lee, Hang Burnett-Bowie, Sherri-Ann Neer, Robert M. Leder, Benjamin Z. TI Comparative Resistance to Teriparatide-Induced Bone Resorption With Denosumab or Alendronate SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; OSTEOPOROSIS; ACTIVATION; MEN; PTH AB Context: In postmenopausal osteoporotic women, denosumab fully inhibits teriparatide-induced bone resorption at approved doses. This property of denosumab is distinct from that of alendronate and likely contributes to the efficacy of combination denosumab and teriparatide therapy. Whether denosumab fully inhibits bone resorption when challenged by a higher dose of teriparatide is unknown. Objective: We aimed to define the comparative ability of denosumab and alendronate to block the acute proresorptive effects of high-dose teriparatide. Design, Setting, and Participants: In this randomized controlled trial, bone resorption (serum C-telopeptide [CTX]) wasmeasured in 25 postmenopausal women prior to and 4 hours after a single 40-mu g sc teriparatide injection. Subjects then received either a single injection of denosumab 60 mg or oral alendronate 70 mg weekly for 8 weeks. After 8 weeks, serum CTX was again measured before and 4 hours after a teriparatide a 40-mu g injection. Outcomes: The primary outcome was the between-group difference in the teriparatide-induced change in CTX from baseline to week 8. Results: At baseline, 40 mu g of teriparatide induced similar 4-hour increases in mean CTX in both groups (alendronate 47% +/- 14%, denosumab 46% +/- 16%). After 8 weeks, teriparatide was still able to stimulate bone resorption in women treated with alendronate (mean CTX increase of 43% +/- 29%) but not in women treated with denosumab (-7% (+/-) 11%; P < .001 for between group comparison). Conclusions: Denosumab, but not alendronate, fully inhibits the ability of high-dose teriparatide to increase bone resorption acutely. These results suggest that combining denosumab with a more potent anabolic stimulus may result in greater separation between bone resorption and formation and hence greater increases in bone mass. C1 [Tsai, Joy N.; Zhu, Yuli; Foley, Katelyn; Burnett-Bowie, Sherri-Ann; Neer, Robert M.; Leder, Benjamin Z.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Tsai, JN (reprint author), 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM jntsai@mgh.harvard.edu FU National Center for Advancing Translational Science [1UL1TR001102-01, 8 UL1 TR000170-05]; Amgen Inc FX This work was supported by Amgen Inc and by Grants 1UL1TR001102-01 and 8 UL1 TR000170-05 to the Harvard Clinical and Translational Science Center from the National Center for Advancing Translational Science. NR 20 TC 4 Z9 4 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2015 VL 100 IS 7 BP 2718 EP 2723 DI 10.1210/jc.2015-1541 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8EZ UT WOS:000360840600044 PM 25933031 ER PT J AU Linnemann, AK Neuman, JC Battiola, TJ Wisinski, JA Kimple, ME Davis, DB AF Linnemann, Amelia K. Neuman, Joshua C. Battiola, Therese J. Wisinski, Jaclyn A. Kimple, Michelle E. Davis, Dawn Belt TI Glucagon-Like Peptide-1 Regulates Cholecystokinin Production in beta-Cells to Protect From Apoptosis SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FAT-FED MICE; INSULIN-SECRETION; PANCREATIC-ISLETS; RECEPTOR; GLP-1; GENE; MASS; TRANSCRIPTION; ACTIVATION; HORMONES AB Cholecystokinin (CCK) is a classic gut hormone that is also expressed in the pancreatic islet, where it is highly up-regulated with obesity. Loss of CCK results in increased beta-cell apoptosis in obese mice. Similarly, islet alpha-cells produce increased amounts of another gut peptide, glucagon-like peptide 1 (GLP-1), in response to cytokine and nutrient stimulation. GLP-1 also protects beta-cells from apoptosis via cAMP-mediated mechanisms. Therefore, we hypothesized that the activation of islet-derived CCK and GLP-1 may be linked. We show here that both human and mouse islets secrete active GLP-1 as a function of body mass index/obesity. Furthermore, GLP-1 can rapidly stimulate beta-cell CCK production and secretion through direct targeting by the cAMP-modulated transcription factor, cAMP response element binding protein (CREB). We find that cAMP-mediated signaling is required for Cck expression, but CCK regulation by cAMP does not require stimulatory levels of glucose or insulin secretion. We also show that CREB directly targets the Cck promoter in islets from obese (Leptin(ob/ob)) mice. Finally, we demonstrate that the ability of GLP-1 to protect beta-cells from cytokine-induced apoptosis is partially dependent on CCK receptor signaling. Taken together, our work suggests that in obesity, active GLP-1 produced in the islet stimulates CCK production and secretion in a paracrine manner via cAMP and CREB. This intraislet incretin loop may be one mechanism whereby GLP-1 protects beta-cells from apoptosis. C1 [Linnemann, Amelia K.; Battiola, Therese J.; Wisinski, Jaclyn A.; Kimple, Michelle E.; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53705 USA. [Neuman, Joshua C.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Davis, DB (reprint author), Univ Wisconsin, 4147 MFCB,MC5148,1685 Highland Ave, Madison, WI 53705 USA. EM dbd@medicine.wisc.edu FU National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases (NIH-NIDDK) [1K01DK102492]; National Institute on Aging [5T32AG000213]; NIH-NIDDK [1RO1DK102598, DK083442]; United States Department of Veterans Affairs [1101BX001880]; University of Wisconsin; Wisconsin Partnership Program FX This work was supported by the National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases (NIH-NIDDK) Grant 1K01DK102492 (to A.K.L.); the National Institute on Aging Grant 5T32AG000213 (to J.C.N.); the NIH-NIDDK Grant 1RO1DK102598 (to M.E.K.); and the NIH-NIDDK Grant DK083442, the United States Department of Veterans Affairs Grant 1101BX001880, the University of Wisconsin, and the Wisconsin Partnership Program (D.B.D.). NR 37 TC 6 Z9 6 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2015 VL 29 IS 7 BP 978 EP 987 DI 10.1210/me.2015-1030 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CR0DH UT WOS:000360987900004 PM 25984632 ER PT J AU Wen, PY AF Wen, Patrick Y. TI Controversies in neuro-oncology: role of whole-brain radiation therapy in the treatment of newly diagnosed brain metastases SO NEURO-ONCOLOGY LA English DT Editorial Material ID TRIAL C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. EM patrick_wen@dfci.harvard.edu NR 5 TC 0 Z9 1 U1 0 U2 3 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 JUL PY 2015 VL 17 IS 7 BP 915 EP 915 DI 10.1093/neuonc/nov102 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR0BM UT WOS:000360983200003 PM 26092876 ER PT J AU Ayata, C Lauritzen, M AF Ayata, Cenk Lauritzen, Martin TI SPREADING DEPRESSION, SPREADING DEPOLARIZATIONS, AND THE CEREBRAL VASCULATURE SO PHYSIOLOGICAL REVIEWS LA English DT Review ID CORTICAL BLOOD-FLOW; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; METHYL-D-ASPARTATE; FAMILIAL HEMIPLEGIC MIGRAINE; MITOCHONDRIAL PERMEABILITY TRANSITION; ANEURYSMAL SUBARACHNOID HEMORRHAGE; NEAR-INFRARED SPECTROSCOPY; OXIDATION-REDUCTION STATE; PIAL ARTERIOLAR DILATION AB Spreading depression (SD) is a transient wave of near-complete neuronal and glial depolarization associated with massive transmembrane ionic and water shifts. It is evolutionarily conserved in the central nervous systems of a wide variety of species from locust to human. The depolarization spreads slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity, such as action potentials and synaptic transmission. Seventy years after its discovery by Leao, the mechanisms of SD and its profound metabolic and hemodynamic effects are still debated. What we did learn of consequence, however, is that SD plays a central role in the pathophysiology of a number of diseases including migraine, ischemic stroke, intracranial hemorrhage, and traumatic brain injury. An intriguing overlap among them is that they are all neurovascular disorders. Therefore, the interplay between neurons and vascular elements is critical for our understanding of the impact of this homeostatic breakdown in patients. The challenges of translating experimental data into human pathophysiology notwithstanding, this review provides a detailed account of bidirectional interactions between brain parenchyma and the cerebral vasculature during SD and puts this in the context of neurovascular diseases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol & Stroke Serv,Neurovasc Res Lab, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurosci Intens Care Unit, Boston, MA USA. Univ Copenhagen, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. Univ Copenhagen, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark. Glostrup Cty Hosp, Dept Clin Neurophysiol, Glostrup, Denmark. RP Ayata, C (reprint author), 149 13th St,Rm 6403, Charlestown, MA 02129 USA. EM cayata@partners.org; mlaurit@sund.ku.dk FU National Institutes of Health [NS061505, NS055104, NS35611]; Fondation Leducq; Heitman Foundation; Ellison Foundation; Lundbeck Foundation; NOVO-Nordisk Foundation; Nordea Foundation for the Center for Healthy Aging; Foundation Leducq; Danish Medical Research Council FX C. Ayata was supported by the National Institutes of Health Grants NS061505, NS055104, and NS35611; Fondation Leducq; The Heitman Foundation; and The Ellison Foundation. M. Lauritzen was supported by the Lundbeck Foundation, the NOVO-Nordisk Foundation, the Nordea Foundation for the Center for Healthy Aging, Foundation Leducq, and the Danish Medical Research Council. NR 532 TC 29 Z9 30 U1 1 U2 17 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 EI 1522-1210 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 2015 VL 95 IS 3 BP 953 EP 993 DI 10.1152/physrev.00027.2014 PG 41 WC Physiology SC Physiology GA CQ9HV UT WOS:000360925500007 PM 26133935 ER PT J AU Mitchell, JC Dick, MB Wood, AE Tapp, AM Ziegler, R AF Mitchell, Joel C. Dick, Malcolm B. Wood, Amanda E. Tapp, Andre M. Ziegler, Raphael TI The Utility of the Dementia Severity Rating Scale in Differentiating Mild Cognitive Impairment and Alzheimer Disease From Controls SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia assessment; mild cognitive impairment; Alzheimer disease; screening; Dementia Severity Rating Scale ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; DEPRESSION; CARE; RECOMMENDATIONS; INDIVIDUALS; PERFORMANCE; PREVALENCE; COMMUNITY AB The current study investigated the utility of the Dementia Severity Rating Scale (DSRS) total score to identify individuals at the earliest stage of impairment (ie, mild cognitive impairment/MCI). In addition, the authors sought to investigate how well the measure correlates with an expanded battery of cognitive tests and other measures of functional abilities. Of the 320 participants included in this study, 85 were normal controls, 96 had single-domain or multiple-domain amnestic MCI, and 139 had possible or probable Alzheimer disease (AD). Each participant underwent a thorough cognitive, neurological, and physical examination. Results from this study indicated that the DSRS total scores differed significantly between the 3 groups (P<0.001) and accurately identified 81% of the control group, 60% of the MCI group, and 78% of the AD group in a post hoc discriminant analysis. When combined with a brief cognitive measure (ie, Consortium to Establish a Registry for Alzheimer's Disease Word List 5 min recall test), the DSRS accurately identified 98% of the control group, 76% of the MCI group, and 82% of the AD group. Implications for clinical practice and proposed areas of future research are discussed. C1 [Mitchell, Joel C.; Wood, Amanda E.; Tapp, Andre M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Mitchell, Joel C.; Wood, Amanda E.; Tapp, Andre M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dick, Malcolm B.; Ziegler, Raphael] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA. RP Mitchell, JC (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM joel.mitchell@va.gov FU National Institute on Aging (NIA) [P50 AG16573] FX Supported by the National Institute on Aging (NIA) (grant number P50 AG16573 to the University of California at Irvine, Alzheimer's Disease Research Center). NR 39 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2015 VL 29 IS 3 BP 222 EP 228 DI 10.1097/WAD.0000000000000057 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA CQ5PX UT WOS:000360658900007 PM 25187220 ER PT J AU Bledsoe, JR Shinagare, SA Deshpande, V AF Bledsoe, Jacob R. Shinagare, Shweta A. Deshpande, Vikram TI Difficult Diagnostic Problems in Pancreatobiliary Neoplasia SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ACINAR-CELL-CARCINOMA; INTRADUCTAL TUBULOPAPILLARY NEOPLASMS; ONCOCYTIC PAPILLARY NEOPLASM; FROZEN-SECTION DIAGNOSIS; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; DIFFERENTIAL-DIAGNOSIS; CHRONIC-PANCREATITIS; GROOVE PANCREATITIS; MUCINOUS NEOPLASMS AB Context.-Many common diagnostic dilemmas are encountered in pancreatobiliary pathology, frequently resulting in uncertainty on behalf of the pathologist and referral for a second opinion. Objectives.-To review 4 common diagnostic dilemmas encountered in the practice of pancreatobiliary pathology: (1) pancreatic ductal adenocarcinoma versus chronic pancreatitis; (2) pancreatic ductal carcinoma versus adenocarcinomas arising in the ampulla and intrapancreatic common bile duct; (3) the distinction of uncommon intraductal neoplasms-intraductal oncocytic papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal acinar cell carcinoma; and (4) intrahepatic cholangiocarcinoma versus metastatic carcinoma. Data Sources.-A review of pertinent literature, along with the authors' personal experience, based on institutional and consultation materials. Conclusions.-Important diagnostic features for a few challenging problems in pancreatobiliary pathology are reviewed. Careful study of the microscopic features along with awareness of differential diagnoses and diagnostic pitfalls generally allows distinction of these entities. We also highlight established and novel ancillary studies that help to arrive at an accurate diagnosis. C1 [Bledsoe, Jacob R.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shinagare, Shweta A.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 2-256,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 58 TC 6 Z9 6 U1 1 U2 1 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2015 VL 139 IS 7 BP 848 EP 857 DI 10.5858/arpa.2014-0205-RA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CQ5NX UT WOS:000360653200006 PM 26125425 ER PT J AU Laudadio, J McNeal, JL Boyd, SD Le, LP Lockwood, C McCloskey, CB Sharma, G Voelkerding, KV Haspel, RL AF Laudadio, Jennifer McNeal, Jeffrey L. Boyd, Scott D. Le, Long Phi Lockwood, Christina McCloskey, Cindy B. Sharma, Gaurav Voelkerding, Karl V. Haspel, Richard L. TI Design of a Genomics Curriculum Competencies for Practicing Pathologists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ESSENTIAL-NURSING-COMPETENCES; PERSONALIZED MEDICINE; GENETICS; ASSOCIATION; RESIDENTS; AGENDA; ERA AB Context.-The field of genomics is rapidly impacting medical care across specialties. To help guide test utilization and interpretation, pathologists must be knowledgeable about genomic techniques and their clinical utility. The technology allowing timely generation of genomic data is relatively new to patient care and the clinical laboratory, and therefore, many currently practicing pathologists have been trained without any molecular or genomics exposure. Furthermore, the exposure that current and recent trainees receive in this field remains inconsistent. Objective.-To assess pathologists' learning needs in genomics and to develop a curriculum to address these educational needs. Design.-A working group formed by the College of American Pathologists developed an initial list of genomics competencies (knowledge and skills statements) that a practicing pathologist needs to be successful. Experts in genomics were then surveyed to rate the importance of each competency. These data were used to create a final list of prioritized competencies. A subset of the working group defined subtopics and tasks for each competency. Appropriate delivery methods for the educational material were also proposed. Results.-A final list of 32 genomics competency statements was developed. A prioritized curriculum was created with designated subtopics and tasks associated with each competency. Conclusions.-We present a genomics curriculum designed as a first step toward providing practicing pathologists with the competencies needed to practice successfully. C1 [Laudadio, Jennifer] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [McNeal, Jeffrey L.] Coll Amer Pathologists, CAP Learning, Northfield, IL USA. [Boyd, Scott D.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Le, Long Phi] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Le, Long Phi] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lockwood, Christina] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [McCloskey, Cindy B.] Univ Oklahoma, Coll Med, Dept Pathol, Oklahoma City, OK 73190 USA. [Sharma, Gaurav] Henry Ford Hlth Syst, Dept Pathol & Lab Med, Detroit, MI USA. [Voelkerding, Karl V.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Voelkerding, Karl V.] ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Haspel, Richard L.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Haspel, RL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Yamins 309, Boston, MA 02215 USA. EM rhaspel@bidmc.harvard.edu NR 19 TC 1 Z9 1 U1 1 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2015 VL 139 IS 7 BP 894 EP 900 DI 10.5858/arpa.2014-0253-CP PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CQ5NX UT WOS:000360653200011 PM 26125429 ER PT J AU Keyt, H Faverio, P Restrepo, MI AF Keyt, H. Faverio, P. Restrepo, M. I. TI Selective digestive decontamination saves lives whilst preventing resistance Response SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Letter ID INTENSIVE-CARE-UNIT; TRACT; TRIAL; PNEUMONIA C1 [Keyt, H.; Restrepo, M. I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Keyt, H.; Restrepo, M. I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Faverio, P.] Univ Milano Bicocca, Dept Hlth Sci, San Gerardo Hosp, Resp Unit, Monza, Italy. RP Keyt, H (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD JUL PY 2015 VL 142 PG 2 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA CQ5NQ UT WOS:000360652400016 ER PT J AU Choi, S Taylor, KP Chatzigeorgiou, M Hu, ZT Schafer, WR Kaplan, JM AF Choi, Seungwon Taylor, Kelsey P. Chatzigeorgiou, Marios Hu, Zhitao Schafer, William R. Kaplan, Joshua M. TI Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release SO PLOS GENETICS LA English DT Article ID SLEEP-LIKE STATE; NEMATODE CAENORHABDITIS-ELEGANS; BEHAVIORAL QUIESCENCE; NERVOUS-SYSTEM; SOCIAL-BEHAVIOR; RECEPTOR; CIRCUIT; HOMOLOG; UNC-13; NMDA AB C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states. C1 [Choi, Seungwon; Taylor, Kelsey P.; Hu, Zhitao; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Choi, Seungwon; Taylor, Kelsey P.; Hu, Zhitao; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Choi, Seungwon; Taylor, Kelsey P.; Hu, Zhitao; Kaplan, Joshua M.] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Chatzigeorgiou, Marios; Schafer, William R.] MRC Lab Mol Biol, Div Cell Biol, Cambridge, England. RP Choi, S (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu OI Schafer, William/0000-0002-6676-8034 FU Kwanjeong Educational Foundation; NSF; [NIH DK80215]; [MRC MC-A022-5PB9] FX This work was supported by Predoctoral Fellowships from the Kwanjeong Educational Foundation (SC) and the NSF (KPT) (https://www.nsfgrfp.org), and by research grants to JMK (NIH DK80215) (grants.nih.gov) and WRS (MRC MC-A022-5PB9). (www.mrc.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 7 Z9 7 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2015 VL 11 IS 7 AR e1005359 DI 10.1371/journal.pgen.1005359 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA CQ5CZ UT WOS:000360622200029 PM 26154367 ER PT J AU Gao, L Li, DT Ma, K Zhang, WJ Xu, T Fu, C Jing, CB Jia, XE Wu, S Sun, X Dong, M Deng, M Chen, Y Zhu, WG Peng, JR Wan, FY Zhou, Y Zon, LI Pan, WJ AF Gao, Lei Li, Dantong Ma, Ke Zhang, Wenjuan Xu, Tao Fu, Cong Jing, Changbin Jia, Xiaoe Wu, Shuang Sun, Xin Dong, Mei Deng, Min Chen, Yi Zhu, Wenge Peng, Jinrong Wan, Fengyi Zhou, Yi Zon, Leonard I. Pan, Weijun TI TopBP1 Governs Hematopoietic Stem/Progenitor Cells Survival in Zebrafish Definitive Hematopoiesis SO PLOS GENETICS LA English DT Article ID DNA-DAMAGE RESPONSE; REPLICATION CHECKPOINT CONTROL; BONE-MARROW FAILURE; BLOOD STEM-CELLS; TRANSGENIC ZEBRAFISH; AORTIC ENDOTHELIUM; GENOME INTEGRITY; PROGENITOR CELLS; FANCONI-ANEMIA; ATR ACTIVATION AB In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutant(cas003) with nonsense mutation in topbp1 gene encoding topoisomerase II beta binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1(cas003) mutants manifest reduced number of HSPCs during definitive hematopoietic cell expansion, without affecting the formation and migration of HSPCs. Moreover, HSPCs in the caudal hematopoietic tissue (an equivalent of the fetal liver in mammals) in topbp1(cas003) mutant embryos are more sensitive to hydroxyurea (HU) treatment. Mechanistically, subcellular mislocalization of TopBP1(cas003) protein results in ATR/Chk1 activation failure and DNA damage accumulation in HSPCs, and eventually induces the p53-dependent apoptosis of HSPCs. Collectively, this study demonstrates a novel and vital role of TopBP1 in the maintenance of HSPCs genome integrity and survival during hematopoietic progenitor expansion. C1 [Gao, Lei; Li, Dantong; Ma, Ke; Zhang, Wenjuan; Xu, Tao; Fu, Cong; Jing, Changbin; Jia, Xiaoe; Wu, Shuang; Dong, Mei; Deng, Min; Pan, Weijun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China. [Gao, Lei; Li, Dantong; Ma, Ke; Zhang, Wenjuan; Xu, Tao; Fu, Cong; Jing, Changbin; Jia, Xiaoe; Wu, Shuang; Dong, Mei; Deng, Min; Pan, Weijun] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China. [Sun, Xin; Wan, Fengyi] Johns Hopkins Univ, Dept Biochem & Mol Biol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chen, Yi] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Hematol, State Key Lab Med Genom,RuiJin Hosp, Shanghai 200030, Peoples R China. [Zhu, Wenge] George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC USA. [Peng, Jinrong] Zhejiang Univ, Coll Anim Sci, Minist Educ, Key Lab Mol Anim Nutr, Hangzhou 310003, Zhejiang, Peoples R China. [Wan, Fengyi] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Wan, Fengyi] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Zhou, Yi; Zon, Leonard I.] Harvard Univ, Childrens Hosp, Stem Cell Program, Hematol Oncol Program,Sch Med, Boston, MA 02115 USA. [Zhou, Yi; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gao, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China. EM weijunpan@sibs.ac.cn OI Peng, Jinrong/0000-0002-0793-4848 FU National Natural Science Foundation of China [31371461, 31301209, 31301196]; Science and Technology Commission of Shanghai Municipality [13JC1406400]; National Thousand Talents Program for Distinguished Young Scholars FX This work was supported by the National Natural Science Foundation of China (31371461 to WP; 31301209 to CJ; 31301196 to MDo, http://www.nsfc.gov.cn/), the Science and Technology Commission of Shanghai Municipality (13JC1406400; WP, http://www.stcsm.gov.cn/), and the National Thousand Talents Program for Distinguished Young Scholars (WP, http://www.1000plan.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 87 TC 4 Z9 6 U1 3 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2015 VL 11 IS 7 AR e1005346 DI 10.1371/journal.pgen.1005346 PG 30 WC Genetics & Heredity SC Genetics & Heredity GA CQ5CZ UT WOS:000360622200022 PM 26131719 ER PT J AU Staller, K Barshop, K Ananthakrishnan, AN Kuo, B AF Staller, Kyle Barshop, Kenneth Ananthakrishnan, Ashwin N. Kuo, Braden TI Rectosigmoid Localization of Radiopaque Markers Does Not Correlate with Prolonged Balloon Expulsion in Chronic Constipation: Results from a Multicenter Cohort SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PELVIC FLOOR DYSSYNERGIA; COLONIC MOTILITY; IDIOPATHIC CONSTIPATION; TRANSIT CONSTIPATION; ANORECTAL MANOMETRY; CLINICAL-PRACTICE; CONTROLLED-TRIAL; BIOFEEDBACK; DISORDERS; REPRODUCIBILITY AB OBJECTIVES: Ingestion of radiopaque markers (ROMs) is a common means of assessing colonic transit time in chronic constipation. Because anorectal manometry (ARM) testing for pelvic floor dysfunction is mostly limited to academic centers, clinicians frequently use rectosigmoid accumulation of markers as a surrogate for pelvic floor dysfunction. We sought to determine whether rectosigmoid localization of markers on a ROM study correlated with measures of pelvic floor dysfunction by ARM and balloon expulsion testing. METHODS: We assembled a multicenter, retrospective cohort of patients diagnosed with chronic constipation who underwent both transit testing by ROM transit testing and ARM with balloon expulsion testing. We compared the proportion of patients with outlet obstruction by rectoanal pressure gradient or prolonged balloon expulsion stratified by marker location. RESULTS: There were 610 patients with both ROM testing and ARM with balloon expulsion testing. The mean age was 44 years and 526 were women (86%). Eighty-one (13%) patients had markers confined to the rectosigmoid area alone and were compared with 529 patients with markers elsewhere (51%) or no retained markers (49%). Of those with markers confined to the rectosigmoid colon, 48 (59%) had a prolonged balloon expulsion compared with 276 (52%) who did not have rectosigmoid markers (P = 0.28). The mean rectoanal gradient for patients with markers in the rectosigmoid colon was -29 +/- 46 mm Hg compared with -34 +/- 59 mm Hg for all others (P = 0.59). CONCLUSIONS: Among patients with chronic constipation undergoing ROM transit testing, there is no association between rectosigmoid location of markers and rectoanal gradient or prolonged balloon expulsion. C1 [Staller, Kyle; Ananthakrishnan, Ashwin N.; Kuo, Braden] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Staller, Kyle; Ananthakrishnan, Ashwin N.; Kuo, Braden] Harvard Univ, Sch Med, Boston, MA USA. [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Staller, K (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM kstaller@mgh.harvard.edu OI Staller, Kyle/0000-0003-4925-4290 FU National Institutes of Health [K23 DK097142] FX A.N.A. is supported by a grant from the National Institutes of Health (K23 DK097142). NR 24 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2015 VL 110 IS 7 BP 1049 EP 1055 DI 10.1038/ajg.2015.140 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP9FV UT WOS:000360200100017 PM 25964224 ER PT J AU Sonnenberg, A Genta, RM AF Sonnenberg, Amnon Genta, Robert M. TI Low Prevalence of Colon Polyps in Chronic Inflammatory Conditions of the Colon SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI; ESOPHAGEAL EOSINOPHILIA; MICROSCOPIC COLITIS; PATHOLOGY DATABASE; COLORECTAL-CANCER; RISK; DISORDERS; DISEASE AB OBJECTIVES: Previous studies have reported a low prevalence of colon polyps in patients with microscopic colitis. The aim of the study was to test whether such inverse associations applied to other inflammatory diseases of the colon. METHODS: In a case-control study among 130,204 patients undergoing colonoscopy for the work-up of diarrhea, we compared the prevalence of colon polyps in a case population of patients with inflammatory bowel disease (IBD), microscopic colitis, histologic signs of active colitis, diverticulitis, or ischemic colitis, and in a control population with normal colon mucosa. Case and control subjects were compared using odds ratios and their 95% confidence intervals adjusted for age and sex. RESULTS: In 11,176 patients with microscopic colitis, the prevalence of hyperplastic polyps, serrated adenomas, and tubular adenomas were all reduced: odds ratios= 0.46 (95% confidence intervals= 0.43-0.49), 0.24 (0.19-0.30), and 0.35 (0.33-0.38), respectively. In 4,435 patients with IBD, the corresponding values were: 0.18 (0.15-0.21), 0.24 (0.16-0.35), and 0.18 (0.15-0.21), respectively. In 6,501 patients with histologically active colitis, the corresponding values were: 0.58 (0.53-0.63), 0.57 (0.46-0.70), and 0.63 (0.58-0.68), respectively. No such consistent reduction in polyp prevalence was found in patients with diverticulitis or ischemic colitis. CONCLUSIONS: Chronic inflammatory conditions of the colon are associated with a decreased prevalence of colon polyps. 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, Dept Gastroenterol, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 14 TC 7 Z9 8 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2015 VL 110 IS 7 BP 1056 EP 1061 DI 10.1038/ajg.2015.130 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP9FV UT WOS:000360200100018 PM 25916222 ER PT J AU Buettner, C Davis, RB Phillips, RS Mittleman, MA AF Buettner, C. Davis, R. B. Phillips, R. S. Mittleman, M. A. TI COQ10 DOES NOT IMPROVE STATIN MYALGIA-A RANDOMIZED CONTROLLED TRIAL SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT 83rd Congress of the European-Atherosclerosis-Society (EAS) CY MAR 22-25, 2015 CL Glasgow, SCOTLAND SP European Atherosclerosis Soc C1 [Buettner, C.; Davis, R. B.; Phillips, R. S.] Harvard Univ, Sch Med, BIDMC, Med, Boston, MA USA. [Mittleman, M. A.] Harvard Univ, Sch Med, BIDMC, Cardiol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JUL PY 2015 VL 241 IS 1 MA EAS-0814 BP E206 EP E206 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WS UT WOS:000360100600677 ER PT J AU Buettner, C Morioka, T Lee, AJ Bertisch, S AF Buettner, C. Morioka, T. Lee, A. J. Bertisch, S. TI VITAMIN D STATUS MODIFIES THE ASSOCIATION BETWEEN STATIN USE AND MUSCULOSKELETAL PAIN: A POPULATION BASED STUDY SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT 83rd Congress of the European-Atherosclerosis-Society (EAS) CY MAR 22-25, 2015 CL Glasgow, SCOTLAND SP European Atherosclerosis Soc C1 [Buettner, C.; Bertisch, S.] Harvard Univ, Sch Med, Med, BIDMC, Boston, MA USA. [Morioka, T.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. [Lee, A. J.] Harvard Univ, Sch Med, BIDMC, Harvard Clin & Translat Sci Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2015 VL 241 IS 1 MA EAS-0821 BP E20 EP E20 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WS UT WOS:000360100600064 ER PT J AU Agrawal, S Agarwal, S Arnason, T Saini, S Belghitik, J AF Agrawal, Shefali Agarwal, Sheela Arnason, Thomas Saini, Sanjay Belghitik, Jacques TI Management of Hepatocellular Adenoma: Recent Advances SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Hepatocellular Adenoma; Malignant Transformation; Hemorrhage; Liver Resection; Conservative Management; Pregnancy ID FOCAL NODULAR HYPERPLASIA; LIVER-CELL ADENOMAS; MULTIPLE HEPATIC ADENOMAS; GLYCOGEN-STORAGE-DISEASE; PERCUTANEOUS RADIOFREQUENCY ABLATION; TRANSCATHETER ARTERIAL EMBOLIZATION; PORTOSYSTEMIC VENOUS SHUNT; SINGLE-CENTER EXPERIENCE; MALIGNANT-TRANSFORMATION; SUBTYPE CLASSIFICATION AB Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the 13-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-la-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of H CA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended. C1 [Agrawal, Shefali] Indraprastha Apollo Hosp, Dept Surg Oncol, Hepatobiliary & Pancreat Surg, New Delhi, India. [Agarwal, Sheela; Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Arnason, Thomas] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arnason, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Belghitik, Jacques] Univ Paris, Beaujon Hosp, Dept Hepatobiliary & Transplant Surg, F-92110 Clichy, France. RP Belghitik, J (reprint author), Univ Paris, Beaujon Hosp, Dept Hepatobiliary & Transplant Surg, 100 Blvd Gen Leclerc, F-92110 Clichy, France. EM jacques.belghiti@bjn.aphp.fr OI Agrawal, Shefali/0000-0002-2502-7651 NR 104 TC 3 Z9 4 U1 1 U2 2 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 JUL PY 2015 VL 13 IS 7 BP 1221 EP 1230 DI 10.1016/j.cgh.2014.05.023 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP7FY UT WOS:000360053800119 PM 24909909 ER PT J AU Wani, S Hall, M Keswani, RN Aslanian, HR Casey, B Burbridge, R Chak, A Chen, AM Cote, G Edmundowicz, SA Faulx, AL Hollander, TG Lee, LS Mullady, D Murad, F Muthusamy, VR Pfau, PR Scheiman, JM Tokar, J Wagh, MS Watson, R Early, D AF Wani, Sachin Hall, Matthew Keswani, Rajesh N. Aslanian, Harry R. Casey, Brenna Burbridge, Rebecca Chak, Amitabh Chen, Ann M. Cote, Gregory Edmundowicz, Steven A. Faulx, Ashley L. Hollander, Thomas G. Lee, Linda S. Mullady, Daniel Murad, Faris Muthusamy, V. Raman Pfau, Patrick R. Scheiman, James M. Tokar, Jeffrey Wagh, Mihir S. Watson, Rabindra Early, Dayna TI Variation in Aptitude of Trainees in Endoscopic Ultrasonography, Based on Cumulative Sum Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE RATE US Study; Training; Competency; Cumulative Sum Analysis ID AMERICAN SOCIETY; EUS; RECOMMENDATIONS; COMPETENCE; ULTRASOUND AB BACKGROUND & AIMS: Studies have reported substantial variation in the competency of advanced endoscopy trainees, indicating a need for more supervised training in endoscopic ultrasound (EUS). We used a standardized, validated, data collection tool to evaluate learning curves and measure competency in EUS among trainees at multiple centers. METHODS: In a prospective study performed at 15 centers, 17 trainees with no prior EUS experience were evaluated by experienced attending endosonographers at the 25th and then every 10th upper EUS examination, over a 12-month training period. A standardized data collection form was used (using a 5-point scoring system) to grade the EUS examination. Cumulative sum analysis was applied to produce a learning curve for each trainee; it tracked the overall performance based on median scores at different stations and also at each station. Competency was defined by a median score of 1, with acceptable and unacceptable failure rates of 10% and 20%, respectively. RESULTS: Twelve trainees were included in the final analysis. Each of the trainees performed 265 to 540 EUS examinations (total, 4257 examinations). There was a large amount of variation in their learning curves: 2 trainees crossed the threshold for acceptable performance (at cases 225 and 245), 2 trainees had a trend toward acceptable performance (after 289 and 355 cases) but required continued observation, and 8 trainees needed additional training and observation. Similar results were observed at individual stations. CONCLUSIONS: A specific case load does not ensure competency in EUS; 225 cases should be considered the minimum caseload for training because we found that no trainee achieved competency before this point. Ongoing training should be provided for trainees until competency is confirmed using objective measures. C1 [Wani, Sachin; Hall, Matthew] Univ Colorado, Anschutz Med Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA. [Keswani, Rajesh N.] Northwestern Univ, Div Gastroenterol & Hepatol, Chicago, IL 60611 USA. [Aslanian, Harry R.] Yale Univ, Div Gastroenterol & Hepatol, New Haven, CT USA. [Casey, Brenna; Lee, Linda S.] Massachusetts Gen Hosp, Div Gastroenterol & Hepatol, Boston, MA 02114 USA. [Casey, Brenna; Lee, Linda S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burbridge, Rebecca] Duke Univ, Div Gastroenterol & Hepatol, Durham, NC USA. [Chak, Amitabh; Faulx, Ashley L.] Univ Hosp Case Med Ctr, Div Gastroenterol & Hepatol, Cleveland, OH USA. [Chen, Ann M.] Stanford Univ, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Cote, Gregory] Indiana Univ Hosp, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Edmundowicz, Steven A.; Hollander, Thomas G.; Mullady, Daniel; Murad, Faris; Early, Dayna] Washington Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Muthusamy, V. Raman; Watson, Rabindra] Univ Calif Los Angeles, David Geffen Sch Med, Div Gastroenterol & Hepatol, Los Angeles, CA 90095 USA. [Pfau, Patrick R.] Univ Wisconsin, Sch Med, Div Gastroenterol & Hepatol, Madison, WI USA. [Scheiman, James M.] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. [Tokar, Jeffrey] Fox Chase Canc Ctr, Div Gastroenterol & Hepatol, Philadelphia, PA 19111 USA. [Wagh, Mihir S.] Univ Florida, Div Gastroenterol & Hepatol, Gainesville, FL USA. RP Wani, S (reprint author), Univ Colorado, Anschutz Med Ctr, Div Gastroenterol & Hepatol, Mail Stop F735,1635 Aurora Court,Room 2-031, Aurora, CO 80045 USA. EM sachinwani10@yahoo.com FU NCI NIH HHS [P50 CA150964, U54 CA163060] NR 13 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2015 VL 13 IS 7 BP 1318 EP + DI 10.1016/j.cgh.2014.11.008 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP7FY UT WOS:000360053800132 PM 25460557 ER PT J AU Allen, KF Gaier, ED Wiggs, JL AF Allen, Keri F. Gaier, Eric D. Wiggs, Janey L. TI Genetics of Primary Inherited Disorders of the Optic Nerve: Clinical Applications SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID OPEN-ANGLE GLAUCOMA; AXENFELD-RIEGER SYNDROME; NORMAL-TENSION GLAUCOMA; CONGENITAL GLAUCOMA; UNITED-STATES; MITOCHONDRIAL DISORDERS; CYP1B1 MUTATIONS; MOUSE MODEL; NEUROPATHY; SPECTRUM AB Inherited disorders of the optic nerve significantly impact vision in children and adults. The optic nerve disorders most commonly encountered clinically are glaucoma and primary optic neuropathy including Leber's hereditary optic neuropathy (LHON) and autosomal dominant or Kjer's optic atrophy. Current knowledge of the genetics of optic neuropathy and glaucoma makes it possible to test for mutations in disease-causing genes allowing for presymptomatic testing and risk assessment, and recent advances have revealed important disease mechanisms that may suggest potential therapeutic targets. In this perspective, we describe the current approaches and limitations to genetic testing for these disorders and provide an update on the development of gene-based therapies. C1 [Allen, Keri F.; Gaier, Eric D.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu FU NEI NIH HHS [P30 EY014104, R01 EY009847] NR 58 TC 5 Z9 5 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JUL PY 2015 VL 5 IS 7 AR a017277 DI 10.1101/cshperspect.a017277 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CQ1WU UT WOS:000360391700001 PM 26134840 ER PT J AU Stengel, A Karasawa, H Tache, Y AF Stengel, Andreas Karasawa, Hiroshi Tache, Yvette TI The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior SO HORMONES AND BEHAVIOR LA English DT Review DE Body weight; Brain-gut axis; Food intake; Hypothalamus; Satiation; Satiety; Somatostatin receptor; Stress; Water intake ID CENTRAL-NERVOUS-SYSTEM; CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED INHIBITION; FOOD-INTAKE; NEUROPEPTIDE-Y; GROWTH-HORMONE; RAT-BRAIN; MESSENGER-RNA; IN-VITRO; OREXINS HYPOCRETINS AB Somatostatin was discovered four decades ago as hypothalamic factor inhibiting growth hormone release. Subsequently, somatostatin was found to be widely distributed throughout the brain and to exert pleiotropic actions via interaction with five somatostatin receptors (sst(1-5)) that are also widely expressed throughout the brain. Interestingly, in contrast to the predominantly inhibitory actions of peripheral somatostatin, the activation of brain sst(2) signaling by intracerebroventricular injection of stable somatostatin agonists potently stimulates food intake and independently, drinking behavior in rodents. The orexigenic response involves downstream orexin-1, neuropeptide Y-1 and mu receptor signaling while the dipsogenic effect is mediated through the activation of the brain angiotensin 1 receptor. Brain sst2 activation is part of mechanisms underlying the stimulation of feeding and more prominently water intake in the dark phase and is able to counteract the anorexic response to visceral stressors. Published by Elsevier Inc. C1 [Stengel, Andreas] Charite Univ Med Berlin, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, Berlin, Germany. [Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth, Dept Med,Digest Dis Div, Los Angeles, CA 90024 USA. [Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA GLA Healthcare Syst, Ctr Neurobiol Stress, Cure Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIH Center [DK-41301]; German Research Foundation [STE 1765/3-1]; Charite University [UFF 88-226-168] FX This work was supported by NIH Center Grant DK-41301 (Animal Core), VA Research Career Scientist (Y.T.), German Research Foundation STE 1765/3-1 (A.S.) and Charite University Funding UFF 88-226-168 (A.S.). NR 111 TC 4 Z9 4 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD JUL PY 2015 VL 73 BP 15 EP 22 DI 10.1016/j.yhbeh.2015.05.009 PG 8 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA CP9YM UT WOS:000360251800003 PM 26026616 ER PT J AU Kalim, S Ortiz, G Trottier, CA Deferio, JJ Karumanchi, SA Thadhani, RI Berg, AH AF Kalim, Sahir Ortiz, Guillermo Trottier, Caitlin A. Deferio, Joseph J. Karumanchi, S. Ananth Thadhani, Ravi I. Berg, Anders H. TI The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in Maintenance Hemodialysis Patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID STAGE RENAL-DISEASE; KIDNEY-DISEASE; NUTRITION; MORTALITY; KINETICS; OUTCOMES; FAILURE; UREMIA AB Objective: Protein carbamylation is a urea-driven post-translational protein modification associated with mortality in dialysis patients. Free amino acids (AAs) are competitive inhibitors of protein carbamylation and animal studies suggest increasing AA concentrations reduces carbamylation burden. We hypothesized that AA therapy in maintenance hemodialysis patients would reduce carbamylation, carrying the potential to improve clinical outcomes. Design: Prospective pilot clinical trial (NCT1612429). Setting: The study was conducted from March 2013 to March 2014 in outpatient dialysis facilities in the Boston metropolitan area. Subjects and Intervention: We enrolled 23 consecutively consenting hemodialysis subjects, infusing the first 12 individuals with 250 cc of AAs 3 times per week postdialysis over 8 weeks. The remaining 11 subjects served as controls. Main Outcome Measure: Change in carbamylated albumin (C-Alb), a measure of total body carbamylation burden, between baseline and 8 weeks was the primary outcome. Results: The treated and control groups had similar clinical characteristics and similar baseline C-Alb levels (mean +/- SE 9.5 +/- 2.4 and 9.3 +/- 1.3 mmol/mol, respectively; P = .61). The treated arm showed a significant reduction in C-Alb compared with controls at 4 weeks (8.4% reduction in the treated arm vs. 4.3% increase in controls; P = .03) and the effect was greater by 8 weeks (15% reduction in the treated vs. 1% decrease in controls; P = .01). Conclusion: In this pilot study, AA therapy appeared safe and effective at reducing C-Alb levels in hemodialysis patients compared with no treatment. The impact of reduced protein carbamylation on clinical outcomes should be further investigated. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Kalim, Sahir; Ortiz, Guillermo; Trottier, Caitlin A.; Deferio, Joseph J.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Kalim, Sahir; Ortiz, Guillermo; Trottier, Caitlin A.; Deferio, Joseph J.; Karumanchi, S. Ananth; Thadhani, Ravi I.; Berg, Anders H.] Harvard Univ, Sch Med, Boston, MA USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Clin Chem, Boston, MA 02215 USA. RP Kalim, S (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM skalim@partners.org FU National Kidney Foundation; NIH [KL2TR001100, K24 DK094872, K08 HL121801] FX S.K. received support from the National Kidney Foundation Young Investigator award and NIH award KL2TR001100; R.T. receives support from NIH award K24 DK094872.; S.A.K. receives support from the Howard Hughes Medical Institute; A.H.B. received support from NIH award K08 HL121801. NR 26 TC 4 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2015 VL 25 IS 4 BP 388 EP 392 DI 10.1053/j.jrn.2015.01.019 PG 5 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA CQ0KA UT WOS:000360282800012 PM 25753604 ER PT J AU Delgado, C AF Delgado, Cynthia TI Characterization of Physical Activity and Sitting Time Among Patients on Hemodialysis Using a New Physical Activity Instrument (vol 25, pg 25, 2015) SO JOURNAL OF RENAL NUTRITION LA English DT Correction C1 [Delgado, Cynthia] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. RP Delgado, C (reprint author), San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2015 VL 25 IS 4 BP 397 EP 397 PG 1 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA CQ0KA UT WOS:000360282800016 ER PT J AU Fitzgerald, A Johnson, M Hirsch, J Rich, MA Fidler, R AF Fitzgerald, Abi Johnson, Meshell Hirsch, Jan Rich, Mary-Ann Fidler, Richard TI Inconsistent shock advisories for monomorphic VT and Torsade de Pointes - A prospective experimental study on AEDs and defibrillators SO RESUSCITATION LA English DT Article DE Defibrillation; Automated external defibrillator; AED; Ventricular arrhythmias; Ventricular tachycardia; Torsade de Pointes ID AMERICAN-HEART-ASSOCIATION; HOSPITAL CARDIAC-ARREST AB Background: Cardiovascular disease and sudden cardiac arrest are the leading causes of death in the United States. Early defibrillation is key to successful resuscitation for patients who experience shockable rhythms during a cardiac arrest. It is therefore vital that the shock advisory of AEDs (automated external defibrillators) or defibrillators in AED mode be reliable and appropriate. The goal of this study was to better understand the performance of multiple lay-rescuer and hospital professional defibrillators in AED mode in their analysis of ventricular arrhythmias. The measurable objectives of this study sought to quantify: 1. No shock advisory for sinus rhythms at any rate. 2. Recognition and shock advisory for ventricular fibrillation (VF). 3. Recognition and shock advisory for monomorphic ventricular tachycardia (VT). 4. Recognition and shock advisory for Torsades de Pointes (TdP). Methods: This is a prospective evaluation of two AEDs and four semi-automatic, hospital professional defibrillators. This study represents post-marketing evaluation of FDA approved devices. Each defibrillator was connected to multiple rhythm simulators and presented with simulated ECG waveforms 20 consecutive times at various rates when possible. Results: All four defibrillators and both AEDs tested consistently recognized normal sinus rhythm (NSR) from all rhythm sources, and did not recommend a shock for NSR at any rate (from 80 to 220 bpm). All four defibrillators and both AEDs recognized VF from all rhythm sources tested and recommended a shock 100% of the time. Variations were found in the shock advisory rates among defibrillators when testing simulated VT heart rates at or below 150 bpm. One AED tested did not consistently advise a shock for monomorphic VT or TdP at any tested rate. Conclusion: Lay-rescuer AEDs and professional hospital defibrillators tested in AED mode did not reliably recommend a shock for sustained monomorphic VT or TdP at certain rates, despite the fact that it is a critical component of the currently recommended treatment. These findings require further examination of the risk benefit analysis of shocking or not shocking rhythms such as TdP or pulseless VT. Published by Elsevier Ireland Ltd. C1 [Fitzgerald, Abi; Johnson, Meshell; Hirsch, Jan; Rich, Mary-Ann; Fidler, Richard] San Francisco VA Med Ctr, Simulat Lab, San Francisco, CA 94121 USA. RP Fitzgerald, A (reprint author), San Francisco VA Med Ctr, Simulat Lab, 4150 Clement St, San Francisco, CA 94121 USA. EM abirankin@gmail.com OI Rich, Mary-Ann/0000-0002-1660-9887 FU United States Department of Veterans Affairs, Biomedical Laboratory Research and Development Program [IK2 BX001707] FX Dr. M. Johnson is supported by Career Development Award #IK2 BX001707 from the United States Department of Veterans Affairs, Biomedical Laboratory Research and Development Program. This material is the result of work supported with resources and the use of facilities at the San Francisco VA Medical Center. NR 11 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 0300-9572 J9 RESUSCITATION JI Resuscitation PD JUL PY 2015 VL 92 BP 137 EP 140 DI 10.1016/j.resuscitation.2015.02.016 PG 4 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA CQ1JD UT WOS:000360352500035 PM 25724355 ER PT J AU Welling, M Chen, HH Munoz, J Musheev, MU Kester, L Junker, JP Mischerikow, N Arbab, M Kuijk, E Silberstein, L Kharchenko, PV Geens, M Niehrs, C van de Velde, H van Oudenaarden, A Heck, AJR Geijsen, N AF Welling, Maaike Chen, Hsu-Hsin Munoz, Javier Musheev, Michael U. Kester, Lennart Junker, Jan Philipp Mischerikow, Nikolai Arbab, Mandana Kuijk, Ewart Silberstein, Lev Kharchenko, Peter V. Geens, Mieke Niehrs, Christof van de Velde, Hilde van Oudenaarden, Alexander Heck, Albert J. R. Geijsen, Niels TI DAZL regulates Tet1 translation in murine embryonic stem cells SO EMBO REPORTS LA English DT Article DE 2i conditions; Dazl; DNA hydroxymethylation; naive pluripotency; TET1 ID GROUND-STATE PLURIPOTENCY; PRIMORDIAL GERM-CELLS; DNA DEMETHYLATION; SINGLE-CELL; NAIVE PLURIPOTENCY; SELF-RENEWAL; IN-VIVO; 5-METHYLCYTOSINE; DIFFERENTIATION; METHYLATION AB Embryonic stem cell (ESC) cultures display a heterogeneous gene expression profile, ranging from a pristine naive pluripotent state to a primed epiblast state. Addition of inhibitors of GSK3 and MEK (so-called 2i conditions) pushes ESC cultures toward a more homogeneous naive pluripotent state, but the molecular underpinnings of this naive transition are not completely understood. Here, we demonstrate that DAZL, an RNA-binding protein known to play a key role in germ-cell development, marks a subpopulation of ESCs that is actively transitioning toward naive pluripotency. Moreover, DAZL plays an essential role in the active reprogramming of cytosine methylation. We demonstrate that DAZL associates with mRNA of Tet1, a catalyst of 5-hydroxylation of methyl-cytosine, and enhances Tet1 mRNA translation. Overexpression of DAZL in heterogeneous ESC cultures results in elevated TET1 protein levels as well as increased global hydroxymethylation. Conversely, null mutation of Dazl severely stunts 2i-mediated TET1 induction and hydroxymethylation. Our results provide insight into the regulation of the acquisition of naive pluripotency and demonstrate that DAZL enhances TET1-mediated cytosine hydroxymethylation in ESCs that are actively reprogramming to a pluripotent ground state. C1 [Welling, Maaike; Kester, Lennart; Junker, Jan Philipp; Arbab, Mandana; Kuijk, Ewart; van Oudenaarden, Alexander; Geijsen, Niels] Hubrecht Inst KNAW, Utrecht, Netherlands. [Welling, Maaike; Kester, Lennart; Junker, Jan Philipp; Arbab, Mandana; Kuijk, Ewart; van Oudenaarden, Alexander; Geijsen, Niels] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Chen, Hsu-Hsin; Silberstein, Lev] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Chen, Hsu-Hsin; Silberstein, Lev] Harvard Stem Cell Inst, Cambridge, MA USA. [Munoz, Javier; Mischerikow, Nikolai; Heck, Albert J. R.] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands. [Munoz, Javier; Mischerikow, Nikolai; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. [Munoz, Javier; Mischerikow, Nikolai; Heck, Albert J. R.] Netherlands Prote Ctr, Utrecht, Netherlands. [Musheev, Michael U.; Niehrs, Christof] Inst Mol Biol, Mainz, Germany. [Kharchenko, Peter V.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Geens, Mieke; van de Velde, Hilde] Vrije Univ Brussel, Res Grp Reprod & Genet, Brussels, Belgium. [Niehrs, Christof] DKFZ ZMBH Alliance, Div Mol Embryol, Heidelberg, Germany. [Geijsen, Niels] Univ Utrecht, Fac Vet Med, Dept Compan Anim, Utrecht, Netherlands. RP Geijsen, N (reprint author), Hubrecht Inst KNAW, Utrecht, Netherlands. EM n.geijsen@hubrecht.eu RI Geens, Mieke/N-5576-2015; Munoz, Javier/I-4891-2012; Junker, Jan Philipp/A-9754-2010 OI Geens, Mieke/0000-0003-2849-1406; Munoz, Javier/0000-0003-3288-3496; Junker, Jan Philipp/0000-0002-2826-8290 FU Netherlands Proteomics Centre, embedded in the Netherlands Genomics Initiative; Netherlands Organization for Scientific Research (NWO) [91796323]; grant from the Netherlands Institute for Regenerative Medicine FX We thank Sarah Opitz for critically reading the manuscript, Nune Schelling for technical support, and Lucas Kaaij for help with statistical analysis. We also thank Laura Prickett-Rice and Kat Folz-Donahue at the HSCI FACS facility at Mass. General Hospital; Stefan van der Elst at the Hubrecht Institute FACS facility for help with cell sorting; Anko de Graaf of the Hubrecht Institute imaging facility; and David Egan of the Cell Screening facility at the UMCU. MW is supported by a grant from the Netherlands Institute for Regenerative Medicine. JM and AJRH acknowledge support by the Netherlands Proteomics Centre, embedded in the Netherlands Genomics Initiative. This work was funded in part by The Netherlands Organization for Scientific Research (NWO, project 91796323). NR 53 TC 4 Z9 4 U1 0 U2 5 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 JUL PY 2015 VL 16 IS 7 BP 791 EP 802 DI 10.15252/embr.201540538 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CL9VI UT WOS:000357325800006 PM 26077710 ER PT J AU Jain, RK Fukumura, D Duda, DG AF Jain, Rakesh K. Fukumura, Dai Duda, Dan G. TI Role of Tumor Microenvironment in Tumor Progression and Treatment Response: A 30 Years' Journey SO CANCER JOURNAL LA English DT Editorial Material C1 [Jain, Rakesh K.; Fukumura, Dai; Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Steele Labs, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [P01 CA080124, R01 CA115767, R01 CA159258] NR 7 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 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JUL-AUG PY 2015 VL 21 IS 4 BP 235 EP 236 DI 10.1097/PPO.0000000000000136 PG 2 WC Oncology SC Oncology GA CP3YY UT WOS:000359820200001 PM 26222072 ER PT J AU Batista, A Riedemann, L Vardam, T Jain, RK AF Batista, Ana Riedemann, Lars Vardam, Trupti Jain, Rakesh K. TI Targeting the Tumor Microenvironment to Enhance Pediatric Brain Cancer Treatment SO CANCER JOURNAL LA English DT Review DE Brain cancers; pediatric brain tumors; pediatric oncology; targeted stromal therapies; tumor microenvironment ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMAS; GLIOBLASTOMA PATIENTS; DENDRITIC CELLS; T-CELLS; BLOOD PERFUSION; DOSE-ESCALATION; IMMUNE CELLS AB Strategies targeting the microenvironment of pediatric brain cancers have the potential to improve the efficacy of standard and genome-based molecular therapeutics. These strategies also have the potential of helping resolve many of the challenges associated with developing new drugs and running clinical trials for relatively small pediatric brain tumor population. Disrupting vital paracrine and physical interactions between cancer cells and surrounding stroma, targeting and normalizing the abnormal tumor vasculature, and/or inducing antitumor immunity represent some of the most promising approaches. A comprehensive characterization of the pediatric brain tumor microenvironment's composition and function and its modulation by chemoradiation and molecularly targeted therapies is warranted to develop and effectively implement these approaches. C1 Massachusetts Gen Hosp, Edwin L Steele Labs, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Labs, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Riedemann, Lars/J-5725-2014 OI Riedemann, Lars/0000-0002-9510-1845 FU National Cancer Institute [P01 CA080124, R01 CA163815]; National Foundation for Cancer Research; Alex's Lemonade Stand Foundation FX The findings presented in this review were supported with grants from the National Cancer Institute (P01 CA080124, R01 CA163815), National Foundation for Cancer Research, and Alex's Lemonade Stand Foundation. NR 90 TC 1 Z9 1 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JUL-AUG PY 2015 VL 21 IS 4 BP 307 EP 313 DI 10.1097/PPO.0000000000000125 PG 7 WC Oncology SC Oncology GA CP3YY UT WOS:000359820200012 PM 26222083 ER PT J AU Gerstner, ER Emblem, KE Sorensen, GA AF Gerstner, Elizabeth R. Emblem, Kyrre E. Sorensen, Gregory A. TI Vascular Magnetic Resonance Imaging in Brain Tumors During Antiangiogenic Therapy-Are We There Yet? SO CANCER JOURNAL LA English DT Review DE Glioblastoma (GBM); MRI; tumor vascular ID CEREBRAL BLOOD-VOLUME; NEWLY-DIAGNOSED GLIOBLASTOMA; CONTRAST-ENHANCED MRI; HIGH-GRADE GLIOMA; CLINICAL-TRIALS; ANTIVASCULAR THERAPIES; RESPONSE ASSESSMENT; RADIATION NECROSIS; MALIGNANT GLIOMAS; ANGIOGENESIS AB Abnormal tumor vasculature is a potent mediator of treatment resistance because it results in heterogeneous perfusion, hypoxia, increased interstitial fluid pressure, and incomplete penetration of cytotoxic chemotherapies. Targeting this abnormal tumor vasculature is a promising therapeutic strategy, but results with antiangiogenic drugs in brain cancer have been mixed. Vasculature's response to treatment is a dynamic physiological process that can change rapidly throughout treatment, so it requires noninvasive techniques to serially monitor these changes in order to improve outcome. We review the role of vascular magnetic resonance imaging to measure tumor response to treatment and highlight opportunities and future avenues for expanding these promising techniques. C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gerstner, Elizabeth R.] Harvard Univ, Sch Med, Boston, MA USA. [Emblem, Kyrre E.] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Sorensen, Gregory A.] Siemens Healthcare, Malvern, PA USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM egerstner@mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012 OI Emblem, Kyrre/0000-0002-6580-9519 FU South Eastern Norway Regional Health Authority [2013069] FX Grant was provided by South Eastern Norway Regional Health Authority (grant 2013069) to K.E.E. NR 62 TC 0 Z9 1 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JUL-AUG PY 2015 VL 21 IS 4 BP 337 EP 342 DI 10.1097/PPO.0000000000000128 PG 6 WC Oncology SC Oncology GA CP3YY UT WOS:000359820200016 PM 26222087 ER PT J AU Paterson, NE Darby, WC Sandhu, PS AF Paterson, Neil E. Darby, W. Connor Sandhu, Preetpal S. TI N,N-Dimethyltryptamine-Induced Psychosis SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE DMT; Cannabis; hallucinogen; substance-induced psychosis; quetiapine ID PHARMACOKINETICS; AYAHUASCA; HUMANS; ABUSE AB Background: N,N-dimethyltryptamine (DMT) is a 5-hydroxytryptamine 2A and 1A receptor agonist that exhibits potent psychoactive properties in humans. Recreational use of this drug has increased precipitously and is likely to result in an increase in patients presenting with substance-induced psychoses. The present case provides an early example of substance-induced psychosis attributable to repeated use of DMT. Case: A 42-year-old white man, with no significant past psychiatric history, was brought to the emergency department by the police and was found to exhibit disinhibited behavior, elevated affect, disorganized thought process, and delusions of reference. Laboratory studies revealed elevated creatinine kinase level indicative of rhabdomyolysis. The patient endorsed recent and repeated use of DMT, as well as long-term Cannabis (marijuana) use. Over the course of the next 3 weeks, the patient was successfully treated with quetiapine for psychosis, divalproex sodium (Depakote) for impulsivity, gabapentin for anxiety, and hydroxyzine for sleep, which resulted in the resolution of his symptoms and development of reasonable insight and judgment. Approximately 6 months after discharge, the patient remained treatment compliant, as well as drug and symptom free. Conclusions: This case report illustrates an important example of substance-induced psychosis that resolved with antipsychotic treatment in a 42-year-old white man with no past psychiatric history likely attributable to the use of DMT. Given the increasing use of this substance, the emergency department, primary care, and inpatient services are likely to see a significant increase in similar cases. C1 [Paterson, Neil E.; Darby, W. Connor] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Psychiat Residency Training Program, Los Angeles, CA USA. [Sandhu, Preetpal S.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Sandhu, PS (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Preetpal.Sandhu@va.gov NR 17 TC 0 Z9 0 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-5664 EI 1537-162X J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUL-AUG PY 2015 VL 38 IS 4 BP 141 EP 143 DI 10.1097/WNF.0000000000000078 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CP3JJ UT WOS:000359774900005 PM 26166234 ER PT J AU Arnason, JE Brown, JR AF Arnason, Jon E. Brown, Jennifer R. TI Obinutuzumab: its use in the management of chronic lymphocytic leukemia SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Article DE CD20; chronic lymphocytic leukemia; obinutuzumab; rituximab ID B-CELL MALIGNANCIES; PLUS CHLORAMBUCIL; RITUXIMAB; CYTOTOXICITY; OFATUMUMAB; GA101; FLUDARABINE; ANTIBODY; THERAPY; CHEMOIMMUNOTHERAPY AB Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia. Over the last 40 years, the evolution of chemotherapeutic options and the addition of the anti-CD20 antibody rituximab have improved response rates significantly. Obinutuzumab, a next generation CD20 antibody, continues that evolution. Areas covered: In this review, we discuss the pre-clinical and recent clinical experiences with obintuzumab and discuss its potential future role in the management of CLL as well as the interest in combining this next generation CD20 antibody with B-cell receptor pathway inhibitors. Obinutuzumab has a number of modifications that increase its efficacy relative to rituximab resulting in improved antibody-dependent cell-mediated cytotoxicity and direct cell death. These biological attributes have translated into improved clinical responses. The clinical superiority of obinutuzumab relative to rituximab is best demonstrated in the CLL11 trial. In this randomized Phase III trial, for patients requiring upfront CLL treatment, the combination of obinutuzumab and chlorambucil was found to result in improved response and progression-free survival relative to the combination of rituximab and chlorambucil. Expert opinion: Obinutuzumab has clear pre-clinical and clinical superiority to rituximab and will be a central agent in the evolving management of CLL. C1 [Arnason, Jon E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, CLL Ctr, Boston, MA 02115 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, CLL Ctr, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_Brown@dfci.harvard.edu NR 45 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD JUL PY 2015 VL 3 IS 7 BP 843 EP 853 DI 10.1517/21678707.2015.1045488 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP4MW UT WOS:000359857300009 ER PT J AU Menendez, ME Ring, D Heng, M AF Menendez, Mariano E. Ring, David Heng, Marilyn TI Proximal humerus fracture with injury to the axillary artery: A population-based study SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Proximal humerus fracture; Axillary artery injury; Vascular injury; Epidemiology; Prevalence; Outcomes ID UNITED-STATES; VASCULAR TRAUMA; OUTCOMES; NECK; EPIDEMIOLOGY; MANAGEMENT; THROMBOSIS; SAMPLE; CARE AB Background: The available evidence regarding axillary artery injury as a result of proximal humerus fracture consists of individual case reports or small series. This study used nationally representative data to determine the prevalence and predictors of axillary artery injury secondary to proximal humerus fracture, and to characterise its influence on inpatient mortality, length of stay, cost and discharge disposition. Methods: An estimated 388,676 inpatients with a proximal humerus fracture were identified in the Nationwide Inpatient Sample between 2002 and 2011, 331 with concomitant axillary artery injury (8.5 per 10,000). Multivariable regression modelling was used to identify independent predictors of axillary artery injury and to assess its relationship with inpatient outcomes. Results: Factors associated with axillary artery injury were male sex (odds ratio (OR): 1.6, 95% confidence interval (CI): 1.2-2.0), atherosclerosis (OR: 3.7, 95% CI: 2.5-5.4), open fracture (OR: 2.9, 95% CI: 1.9-4.5) and the presence of concomitant injuries, including brachial plexus injury (OR: 109, 95% CI: 79-151), shoulder dislocation (OR: 3.4, 95% CI: 2.0-5.8), scapula fracture (OR: 3.4, 95% CI: 2.1-5.4) and rib fracture (OR: 2.5, 95% CI: 1.6-4.0). Axillary artery injury was associated with increased length of stay, costs and mortality, but it did not affect discharge disposition. Conclusion: Our study provides important baseline information regarding the epidemiology of axillary artery injury secondary to proximal humerus fracture. Prompt identification of at-risk patients upon admission might lead to improved diagnosis and management of this vascular injury. Level of Evidence: Prognostic level II. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Menendez, Mariano E.; Ring, David; Heng, Marilyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 41 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 2015 VL 46 IS 7 BP 1367 EP 1371 DI 10.1016/j.injury.2015.04.026 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CP8EK UT WOS:000360124800031 PM 25986664 ER PT J AU Chaus, GW Heng, M Smith, RM AF Chaus, George W. Heng, Marilyn Smith, Raymond M. TI Occult internal iliac arterial injury identified during open reduction internal fixation of an acetabular fracture: A report of two cases SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Acetabular fracture; Vascular injury; Internal iliac artery ID PELVIC RING DISRUPTIONS; VASCULAR INJURY; COMPLICATIONS; THROMBOSIS; PATTERN; TRAUMA AB We present two cases of occult internal iliac arterial injury identified during operative reduction of a widely displaced posterior column posterior wall acetabular fracture. This complication was not recognised until reduction of the column fracture. There were no preoperative signs or symptoms indicative of a vascular injury. These cases emphasise the heightened awareness one must have when treating widely displaced posterior column fractures of the acetabulum, especially those fractures with extension into the greater sciatic notch, as previously formed clot can become dislodged and hemostasis lost. We also present management options when this complication occurs. We believe any surgeon treating acetabular fractures should be aware of this serious and potentially fatal complication. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Chaus, George W.; Heng, Marilyn; Smith, Raymond M.] Harvard Univ, Dept Orthopaed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chaus, GW (reprint author), Harvard Univ, Dept Orthopaed, Massachusetts Gen Hosp, Yawkey Ctr, Suite 3C, Boston, MA 02114 USA. EM George.Chaus@me.com NR 20 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 2015 VL 46 IS 7 BP 1417 EP 1422 DI 10.1016/j.injury.2015.04.030 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CP8EK UT WOS:000360124800042 PM 25986669 ER PT J AU Gunduz, A Morita, H Rossi, PJ Allen, WL Alterman, RL Bronte-Stewart, H Butson, CR Charles, D Deckers, S de Hemptinne, C DeLong, M Dougherty, D Ellrich, J Foote, KD Giordano, J Goodman, W Greenberg, BD Greene, D Gross, R Judy, JW Karst, E Kent, A Kopell, B Lang, A Lozano, A Lungu, C Lyon, KE Machado, A Martens, H McIntyre, C Min, HK Neimat, J Ostrem, J Pannu, S Ponce, F Pouratian, N Reymers, D Schrock, L Sheth, S Shih, L Stanslaski, S Steinke, GK Stypulkowski, P Troster, AI Verhagen, L Walker, H Okun, MS AF Gunduz, Aysegul Morita, Hokuto Rossi, P. Justin Allen, William L. Alterman, Ron L. Bronte-Stewart, Helen Butson, Christopher R. Charles, David Deckers, Sjaak de Hemptinne, Coralie DeLong, Mahlon Dougherty, Darin Ellrich, Jens Foote, Kelly D. Giordano, James Goodman, Wayne Greenberg, Benjamin D. Greene, David Gross, Robert Judy, Jack W. Karst, Edward Kent, Alexander Kopell, Brian Lang, Anthony Lozano, Andres Lungu, Codrin Lyon, Kelly E. Machado, Andre Martens, Hubert McIntyre, Cameron Min, Hoon-Ki Neimat, Joseph Ostrem, Jill Pannu, Sat Ponce, Francisco Pouratian, Nader Reymers, Donnie Schrock, Lauren Sheth, Sameer Shih, Ludy Stanslaski, Scott Steinke, G. Karl Stypulkowski, Paul Troester, Alexander I. Verhagen, Leo Walker, Harrison Okun, Michael S. TI Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Review DE deep brain stimulation; Movement disorders; Neuroethics; Electrophysiology; neurotechnology ID HIGH-FREQUENCY STIMULATION; HUMAN SUBTHALAMIC NUCLEUS; SHORT-LATENCY ACTIVATION; PRIMARY MOTOR CORTEX; PARKINSONS-DISEASE; NONMOTOR SYMPTOMS; GLOBUS-PALLIDUS; THALAMIC SEGMENTATION; CLINICAL ARTICLE; BOLD ACTIVATION AB The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies. C1 [Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin; Allen, William L.; Foote, Kelly D.; Judy, Jack W.; Okun, Michael S.] Univ Florida, Gainesville, FL USA. [Alterman, Ron L.; Shih, Ludy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bronte-Stewart, Helen] Stanford Univ, Stanford, CA 94305 USA. [Butson, Christopher R.; Schrock, Lauren] Univ Utah, Salt Lake City, UT USA. [Charles, David; Neimat, Joseph] Vanderbilt Univ, Nashville, TN 37235 USA. [Deckers, Sjaak; Ellrich, Jens; Martens, Hubert] Sapiens Steering Brain Stimulat, Eindhoven, Netherlands. [de Hemptinne, Coralie; Ostrem, Jill] Univ Calif San Francisco, San Francisco, CA 94143 USA. [DeLong, Mahlon; Gross, Robert] Emory Univ, Atlanta, GA 30322 USA. [Dougherty, Darin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giordano, James] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Goodman, Wayne; Kopell, Brian] Mt Sinai Hosp, New York, NY 10029 USA. [Greenberg, Benjamin D.] Brown Univ, Providence, RI 02912 USA. [Greene, David] Neuropace Univ, Mountain View, CA USA. [Karst, Edward] St Jude Med, Sylmar, CA USA. [Kent, Alexander] St Jude Med, Sunnyvale, CA USA. [Lang, Anthony; Lozano, Andres] Univ Toronto, Toronto, ON, Canada. [Lungu, Codrin] NIH, Bethesda, MD 20892 USA. [Lyon, Kelly E.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Machado, Andre] Cleveland Clin, Cleveland, OH 44106 USA. [McIntyre, Cameron] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Min, Hoon-Ki] Mayo Clin, Rochester, MN USA. [Pannu, Sat] Lawrence Livermore Natl Lab, Livermore, CA USA. [Ponce, Francisco; Troester, Alexander I.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Pouratian, Nader] Univ Calif Los Angeles, Los Angeles, CA USA. [Reymers, Donnie] Funct Neuromodulat Ltd, Toronto, ON, Canada. [Sheth, Sameer] Columbia Univ, New York, NY USA. [Stanslaski, Scott; Stypulkowski, Paul] Medtronic, Minneapolis, MN USA. [Steinke, G. Karl] Boston Sci Neuromodulat, Valencia, CA USA. [Verhagen, Leo] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Walker, Harrison] Univ Alabama Birmingham, Birmingham, AL USA. RP Okun, MS (reprint author), Univ Florida, Dept Neurol, Gainesville, FL 32611 USA. EM okun@neurology.ufl.edu RI Gunduz, Aysegul/Q-2336-2016; OI Okun, Michael/0000-0002-6247-9358 FU Medtronic, Inc.; Allergan; Ipsen; Merz; Medtronic; Alliance for Patient Access for education or consulting services; Cyberonics; Eli Lilly; Roche; St. Jude; Boston Scientific; Neuropace; Brain Canada; Canadian Institutes of Health Research; Edmond J Safra Philanthropic Foundation; Michael J. Fox Foundation; Ontario Brain Institute; National Parkinson Foundation; Parkinson Society Canada; Tourette Syndrome Association; W. Garfield Weston Foundation; MRI Interventions; St Jude Medical; Glaxo Smith Kone; NIH; NPF; Parkinson Alliance; Smallwood Foundation; Bachmann-Strauss Foundation; UP Foundation FX AG: Grant support from Medtronic, Inc.; HK: None; PJR: None; WLA: None; RLA: Consultant for Medtronic, Inc.; HB-S: None; CRB: Consultant for St Jude Medical, Boston Scientific; IP related to DBS; DC: Vanderbilt receives income from grants or contracts from Allergan, Ipsen, Merz and Medtronic for research led by DC; DC receives income from Allergan, Ipsen, Medtronic and, the Alliance for Patient Access for education or consulting services; SD: Employee and shareholder of Sapiens Steering Brain Stimulation GmbH (Medtronic Eindhoven Design Center); CDH: None; MDL: None; DD: Grant support from Medtronic, Cyberonics, Eli Lilly, Roche, Honoraria from Medtronic, Insys, Johnson & Johnson; JE: Chief Medical Officer at Sapiens Steering Brain Stimulation GmbH; KDF: Grant support from Medtronic, St. Jude, Boston Scientific, Neuropace; Consultant for Medtronic, Neuropace; JG: None; WG: None; BDG: None; DG: Employee of Neuropace; RG: None; JJ: None; EK. Employee of St. Jude Medical; AK: Employee of St. Jude Medical; BK. Consultant for Medtronic, St Jude Neuromodulation, MRI Interventions; ALang: Consultant for Abbvie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec, Boerhinger-Ingelheim, Ceregene, Lilly, Medtronic, Merck, Novartis, NeuroPhage Pharmaceuticals, Teva, UCB; Honoraria from Medtronic, Teva, UCB, AbbVie; Grant support from Brain Canada, Canadian Institutes of Health Research, Edmond J Safra Philanthropic Foundation, Michael J. Fox Foundation, the Ontario Brain Institute, National Parkinson Foundation, Parkinson Society Canada, Tourette Syndrome Association, W. Garfield Weston Foundation; Publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, Cambridge University Press; ALozano: Consultant for Medtronic, St Jude and Boston Scientific, Co-Founder of Functional Neuromodulation; CL: None; KL: Consultant for Medtronic, St. Jude Medical; AM: IP in Enspire, ATI, Cardionomics, Grant support from Medtronic, Inc., Consultant for Functional Neuromodulation, Spinal Modulation; HM: Employee and shareholder of Sapiens Steering Brain Stimulation GmbH (Medtronic Eindhoven Design Center); CM: IP in Boston Scientific Neuromodulation; Consultant for Boston Scientific Neuromodulation; Shareholder in Autonomic Technologies, Inc., Cardionomics, Inc., Neuros Medical, Inc., Surgical Information Sciences, Inc.; BM: None; HKM: None; JN: Grant support from Medtronic, Inc.; Consultant for Medtronic, Inc., Montens Inc.; JO: Grant support from Boston Scientific, MRI Interventions, St Jude Medical, Medtronic; SP: None; FP: Consultant for Medtronic, Inc; NP: None; DR: Employee of Neuromodulation, Inc; LSchrock: Site PI for the Boston Scientific INTREPID DBS trial; SSheth: None; LShih: None; SStanslanski: Employee of Medtronic, Inc.; GKS: Employee of Boston Scientific Neuromodulation; PS: Employee of Medtronic, Inc.; AT: Consultant for St Jude Medical, Boston Scientific, Theravance, Teva; Grant support from Glaxo Smith Kone, Speaker for Medtronic; Royalties from Oxford University Press; LV: None; HW: None; MSO: Consultant for National Parkinson Foundation; Grant support from NIH, NPF, Michael J. Fox Foundation, Parkinson Alliance, Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syndrome Association, UP Foundation. NR 79 TC 5 Z9 5 U1 2 U2 19 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0020-7454 EI 1563-5279 J9 INT J NEUROSCI JI Int. J. Neurosci. PD JUL PY 2015 VL 125 IS 7 BP 475 EP 485 DI 10.3109/00207454.2014.999268 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CP4WV UT WOS:000359884200001 PM 25526555 ER PT J AU Mughal, TI Barbui, T Abdel-Wahab, O Kralovics, R Jamieson, C Kvasnicka, HM Mullaly, A Rampal, R Mesa, R Kiladjian, JJ Deininger, M Prchal, J Hehlmann, R Saglio, G Van Etten, RA AF Mughal, Tariq I. Barbui, Tiziano Abdel-Wahab, Omar Kralovics, Robert Jamieson, Catriona Kvasnicka, Hans-Michael Mullaly, Ann Rampal, Raajit Mesa, Ruben Kiladjian, Jean-Jacques Deininger, Michael Prchal, Josef Hehlmann, Ruediger Saglio, Giuseppe Van Etten, Richard A. TI Novel insights into the biology and treatment of chronic myeloproliferative neoplasms SO LEUKEMIA & LYMPHOMA LA English DT Review DE Myeloid leukemias and dysplasias; molecular genetics; signaling therapies; prognostication; myeloproliferative disorders ID CHRONIC MYELOID-LEUKEMIA; WORLD-HEALTH-ORGANIZATION; DEEP MOLECULAR RESPONSE; JANUS KINASE 2; POLYCYTHEMIA-VERA; JAK2 INHIBITOR; ESSENTIAL THROMBOCYTHEMIA; AVAILABLE THERAPY; CONTROLLED-TRIAL; TYROSINE KINASE AB Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoiesis characterized by a high frequency of genetic alterations, and include chronic myeloid leukemia (CML) and the BCR-ABL1-negative MPNs. Herein we summarize recent advances and controversies in our understanding of the biology and therapy of these disorders, as discussed at the 8th post-American Society of Hematology CML-MPN workshop. The principal areas addressed include the breakthrough discovery of CALR mutations in patients with JAK2/MPL wild type MPN, candidate therapies based on novel genetic findings in leukemic transformation and new therapeutic targets in MPNs, and an appraisal of bone marrow histopathology in MPNs with a focus on the potential new clinical entity of "masked" polycythemia vera. An update on clinical trials of Janus kinase (JAK) inhibitors is presented as well as current understanding regarding the definitions and mechanisms of resistance to JAK inhibitors, and updated information on the safety and efficacy of discontinuation of tyrosine kinase inhibitors in patients with CML. C1 [Mughal, Tariq I.] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Barbui, Tiziano] Papa Giovani XXIII Hosp & Res Ctr, Bergamo, Italy. [Abdel-Wahab, Omar; Rampal, Raajit] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kralovics, Robert] CeMM Res Ctr Mol Med, Vienna, Austria. [Jamieson, Catriona] Univ San Diego, La Jolla, CA USA. [Kvasnicka, Hans-Michael] Goethe Univ Frankfurt, Senckenberg Inst Pathol, D-60054 Frankfurt, Germany. [Mullaly, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mesa, Ruben] Mayo Clin, Ctr Canc, Scottsdale, AZ USA. [Kiladjian, Jean-Jacques] Hop St Louis, Paris, France. [Deininger, Michael; Prchal, Josef] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Hehlmann, Ruediger] Heidelberg Univ, Mannheim, Germany. [Saglio, Giuseppe] Orbassano Univ Hosp, Turin, Italy. [Van Etten, Richard A.] Univ Calif Irvine, Irvine, CA USA. RP Mughal, TI (reprint author), Tufts Univ, Med Ctr, Div Hematol & Oncol, Boston, MA 02111 USA. EM tmughal911@hotmail.com RI Kvasnicka, Hans Michael/E-7993-2011; OI Kvasnicka, Hans Michael/0000-0002-3081-1395; Kralovics, Robert/0000-0002-6997-8539 FU NCI NIH HHS [P01 CA108671, R01 CA090576, R01 CA178397] NR 61 TC 3 Z9 3 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUL PY 2015 VL 56 IS 7 BP 1938 EP 1948 DI 10.3109/10428194.2014.974594 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CP4YO UT WOS:000359888700007 PM 25330439 ER PT J AU Petsalaki, E Helbig, AO Gopal, A Pasculescu, A Roth, FP Pawson, T AF Petsalaki, Evangelia Helbig, Andreas O. Gopal, Anjali Pasculescu, Adrian Roth, Frederick P. Pawson, Tony TI SELPHI: correlation-based identification of kinase-associated networks from global phospho-proteomics data sets SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PHOSPHORYLATION NETWORKS; SYSTEMATIC DISCOVERY; ACQUIRED-RESISTANCE; SIGNALING NETWORKS; PHOSPHOPROTEOMICS; SOFTWARE; RESOURCE; GENE; GEFITINIB; ERLOTINIB AB While phospho-proteomics studies have shed light on the dynamics of cellular signaling, they mainly describe global effects and rarely explore mechanistic details, such as kinase/substrate relationships. Tools and databases, such as NetworKIN and PhosphoSitePlus, provide valuable regulatory details on signaling networks but rely on prior knowledge. They therefore provide limited information on less studied kinases and fewer unexpected relationships given that better studied signaling events can mask condition-or cell-specific 'network wiring'. SELPHI is a web-based tool providing in-depth analysis of phospho-proteomics data that is intuitive and accessible to non-bioinformatics experts. It uses correlation analysis of phospho-sites to extract kinase/phosphatase and phospho-peptide associations, and highlights the potential flow of signaling in the system under study. We illustrate SELPHI via analysis of phospho-proteomics data acquired in the presence of erlotinib-a tyrosine kinase inhibitor (TKI)-in cancer cells expressing TKIresistant and -sensitive variants of the Epidermal Growth Factor Receptor. In this data set, SELPHI revealed information overlooked by the reporting study, including the known role of MET and EPHA2 kinases in conferring resistance to erlotinib in TKI sensitive strains. SELPHI can significantly enhance the analysis of phospho-proteomics data contributing to improved understanding of sample-specific signaling networks. SELPHI is freely available via http://llama.mshri.on.ca/SELPHI. C1 [Petsalaki, Evangelia; Helbig, Andreas O.; Gopal, Anjali; Pasculescu, Adrian; Roth, Frederick P.; Pawson, Tony] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X8, Canada. [Helbig, Andreas O.] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X5, Canada. [Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5G 1X8, Canada. [Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X8, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5G 1X8, Canada. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada. RP Roth, FP (reprint author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X8, Canada. EM petsalakis@lunenfeld.ca; fritz.roth@utoronto.ca RI Pawson, Tony/E-4578-2013; Roth, Frederick/H-6308-2011; OI Petsalaki, Evangelia/0000-0002-8294-2995; Roth, Frederick/0000-0002-6628-649X FU Ontario Research Fund Research Excellence [RE-05-029, GL2-01-025, ORF-RE-037]; Krembil Foundation; NIH/NHGRI [HG001715, HG004233]; Canada Excellence Research Chairs Program; Avon Foundation FX Ontario Research Fund Research Excellence [RE-05-029, GL2-01-025 to T.P. ORF-RE-037 to T.P. and F.P.R.]; Krembil Foundation; NIH/NHGRI [HG001715, HG004233]; Canada Excellence Research Chairs Program; Avon Foundation. Canadian Institutes of Health Research [MOP-6849 to T.P.]. Funding for open access charge: Canada Excellence Research Chairs Program. NR 41 TC 1 Z9 1 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2015 VL 43 IS W1 BP W276 EP W282 DI 10.1093/nar/gkv459 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP3IP UT WOS:000359772700043 PM 25948583 ER PT J AU Sadreyev, IR Ji, F Cohen, E Ruvkun, G Tabach, Y AF Sadreyev, Ilyas R. Ji, Fei Cohen, Emiliano Ruvkun, Gary Tabach, Yuval TI PhyloGene server for identification and visualization of co-evolving proteins using normalized phylogenetic profiles SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PREDICTION; CILIA AB Proteins that function in the same pathways, protein complexes or the same environmental conditions can show similar patterns of sequence conservation across phylogenetic clades. In species that no longer require a specific protein complex or pathway, these proteins, as a group, tend to be lost or diverge. Analysis of the similarity in patterns of sequence conservation across a large set of eukaryotes can predict functional associations between different proteins, identify new pathway members and reveal the function of previously uncharacterized proteins. We used normalized phylogenetic profiling to predict protein function and identify new pathway members and disease genes. The phylogenetic profiles of tens of thousands conserved proteins in the human, mouse, Caenorhabditis elegans and Drosophila genomes can be queried on our new web server, PhyloGene. PhyloGene provides intuitive and user-friendly platform to query the patterns of conservation across 86 animal, fungal, plant and protist genomes. A protein query can be submitted either by selecting the name from whole-genome protein sets of the intensively studied species or by entering a protein sequence. The graphic output shows the profile of sequence conservation for the query and the most similar phylogenetic profiles for the proteins in the genome of choice. The user can also download this output in numerical form. C1 [Sadreyev, Ilyas R.; Ji, Fei; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ji, Fei; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Cohen, Emiliano; Tabach, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Dev Biol & Canc Res, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel. RP Tabach, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Dev Biol & Canc Res, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel. EM yuvaltab@ekmd.huji.ac.il FU Hebrew University FX Hebrew University start-up funds. NR 13 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2015 VL 43 IS W1 BP W154 EP W159 DI 10.1093/nar/gkv452 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP3IP UT WOS:000359772700024 PM 25958392 ER PT J AU Qiu, ZF Mishra, A Li, M Farnsworth, SL Guerra, B Lanford, RE Hornsby, PJ AF Qiu, Zhifang Mishra, Anuja Li, Miao Farnsworth, Steven L. Guerra, Bernadette Lanford, Robert E. Hornsby, Peter J. TI Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide SO STEM CELL RESEARCH LA English DT Article ID BIOMEDICAL-RESEARCH; LINES; BIOLOGY AB The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. Published by Elsevier B.V. C1 [Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L.; Hornsby, Peter J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L.; Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst, Dept Physiol, San Antonio, TX 78229 USA. [Guerra, Bernadette; Lanford, Robert E.] Southwest Natl Primate Res Ctr, San Antonio, TX USA. [Guerra, Bernadette; Lanford, Robert E.] Texas Biomed Res Inst, San Antonio, TX USA. RP Hornsby, PJ (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. EM hornsby@uthscsa.edu FU VA grant [I01BX001454]; NIH [R21AG033286, R03AG045481]; Owens Medical Research Foundation; Ted Nash Long Life Foundation; China Scholarship Council FX This work was supported by VA grant I01BX001454, NIH grants R21AG033286 and R03AG045481, and by grants from the Owens Medical Research Foundation and the Ted Nash Long Life Foundation. Miao Li acknowledges the support of the China Scholarship Council. NR 20 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD JUL PY 2015 VL 15 IS 1 BP 141 EP 150 DI 10.1016/j.scr.2015.05.010 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP6JZ UT WOS:000359994400014 PM 26070112 ER PT J AU Yamaguchi, J Liss, AS Sontheimer, A Mino-Kenudson, M Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF Yamaguchi, Junpei Liss, Andrew S. Sontheimer, Alexandra Mino-Kenudson, Mari Fernandez-del Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. TI Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair SO STEM CELL RESEARCH LA English DT Article ID STEM-CELLS; GROWTH-FACTOR; INJURY; REGENERATION; GENE; IDENTIFICATION; LOCALIZATION; EXPRESSION; PITFALLS; HEDGEHOG AB Pancreatic duct glands (PDGs) have molecular features known to mark stem cell niches, but their function remains to be determined. To investigate the role of PDGs as a progenitor niche, PDGs were analyzed in both humans and mice. Cells were characterized by immunohistochemistry and microarray analysis. In vivo proliferative activity and migration of PDG cells were evaluated using a BrdU tag-and-chase strategy in a mouse model of pancreatitis. In vitro migration assays were used to determine the role of trefoil factor (TFF) -1 and 2 in cell migration. Proliferative activity in the pancreatic epithelium in response to inflammatory injury is identified principally within the PDG compartment. These proliferating cells then migrate out of the PDG compartment to populate the pancreatic duct. Most of the pancreatic epithelial migration occurs within 5 days and relies, in part, on TFF-1 and -2. After migration, PDG cells lose their PDG-specific markers and gain a more mature pancreatic ductal phenotype. Expression analysis of the PDG epithelium reveals enrichment of embryonic and stem cell pathways. These results suggest that PDGs are an epithelial progenitor compartment that gives rise to mature differentiated progeny that migrate to the pancreatic duct. Thus PDGs are a progenitor niche important for pancreatic epithelial regeneration. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Yamaguchi, Junpei; Liss, Andrew S.; Sontheimer, Alexandra; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Andrew L Warshaw Inst Pancreat Canc Res, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Andrew L Warshaw Inst Pancreat Canc Res, Boston, MA 02114 USA. [Thayer, Sarah P.] Univ Nebraska Med Ctr, Dept Surg, Div Surg Oncol, Omaha, NE 68198 USA. RP Thayer, SP (reprint author), Univ Nebraska Med Ctr, 986345 Nebraska Med Ctr, Omaha, NE 68198 USA. EM sarah.thayer@UNMC.edu RI YAMAGUCHI, Junpei/E-4440-2015 FU Andrew L. Warshaw, MD Institute for Pancreatic Cancer Research, Massachusetts General Hospital; [NIH-P01CA117969] FX This work was supported by the Andrew L. Warshaw, MD Institute for Pancreatic Cancer Research, Massachusetts General Hospital, and by NIH-P01CA117969 to SPT. We would like to Thank Dr. Timothy Wang, Dorothy L. and Daniel H. Silberberg Professor of Medicine and Chief, Division of Digestive and Liver Diseases, Columbia University, for kindly providing TKK2 knockout mice. NR 42 TC 6 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD JUL PY 2015 VL 15 IS 1 BP 190 EP 202 DI 10.1016/j.scr.2015.05.006 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP6JZ UT WOS:000359994400019 PM 26100232 ER PT J AU Knapp, H Chan, K AF Knapp, Herschel Chan, Kee TI HIV Rapid Testing in a VA Emergency Department Setting: Cost Analysis at 5 Years SO VALUE IN HEALTH LA English DT Article DE AIDS; cost analysis; emergency; HIV; screening ID OF-VETERANS-AFFAIRS; HEALTH-CARE-SYSTEM; UNITED-STATES; IMPLEMENTATION AB Objectives: To conduct a comprehensive cost-minimization analysis to comprehend the financial attributes of the first 5 years of an implementation wherein emergency department (ED) registered nurses administered HIV oral rapid tests to patients. Methods: A health science research implementation team coordinated with ED stakeholders and staff to provide training, implementation guidelines, and support to launch ED registered nurse administered HIV oral rapid testing. Deidentified quantitative data were gathered from the electronic medical records detailing quarterly HIV rapid test rates in the Ell setting spanning the first 5 years. Comprehensive cost analyses were conducted to evaluate the financial impact of this implementation. Results: At 5 years, a total of 2,620 tests were conducted with a quarterly mean of 131 +/- 81. Despite quarterly variability in testing rates, regression analysis revealed an average increase of 3.58 tests per quarter. Over the course of this implementation, Veterans Health Administration policy transitioned from written to verbal consent for HIV testing, serving to reduce the time and cost(s) associated with the testing process. Conclusions: Our data indicated salient health outcome benefits for patients with respect to the potential for earlier detection, and associated long-run cost savings. (C) 2015 Published by Elsevier inc. on behalf of international Society for Pharmacoeconomics and Outcomes Research (ISPOR). C1 [Knapp, Herschel] Vet Affairs VA Qual Enhancement Res Initiat HIV &, Los Angeles, CA USA. [Knapp, Herschel] Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Knapp, Herschel] Greater Los Angeles Hlth Serv Res & Dev HSR&D Ctr, Los Angeles, CA USA. [Knapp, Herschel] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chan, Kee] Univ Illinois, Sch Publ Hlth, Chicago, IL 60612 USA. [Chan, Kee] Edith Nourse Rogers Mem Vet Hosp Home, Bedford, MA 01730 USA. [Chan, Kee] CHOIR, Boston, MA 02118 USA. RP Knapp, H (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210,Room 210, Los Angeles, CA 90073 USA. EM Herschel.Knapp@va.gov NR 10 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD JUL PY 2015 VL 18 IS 5 BP 735 EP 737 DI 10.1016/j.jval.2015.02.019 PG 3 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CP7VR UT WOS:000360097700023 PM 26297102 ER PT J AU Bell, DL Leslie-Mazwi, TM Yoo, AJ Rabinov, JD Butler, WE Bell, JE Hirsch, JA AF Bell, D. L. Leslie-Mazwi, T. M. Yoo, A. J. Rabinov, J. D. Butler, W. E. Bell, J. E. Hirsch, J. A. TI Application of a Novel Brain Arteriovenous Malformation Endovascular Grading Scale for Transarterial Embolization SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MULTIMODALITY TREATMENT; ONYX EMBOLIZATION; RANDOMIZED-TRIAL; COMPLICATIONS; SYSTEM; MANAGEMENT; FISTULAS; AVMS AB BACKGROUND AND PURPOSE: The advent of modern neuroendovascular techniques has highlighted the need for a simple, effective, and reliable brain arteriovenous malformation endovascular grading scale. A novel scale of this type has recently been described. It incorporates the number of feeding arteries, eloquence, and the presence of an arteriovenous fistula component. Our aim is to assess the validity of this grading scale. MATERIALS AND METHODS: We retrospectively reviewed all suspected brain arteriovenous malformations at Massachusetts General Hospital from 2005 to 2013, identifying 126 patients who met the inclusion criteria. Spearman correlations between endovascular and Spetzler-Martin grading scales and long-term outcomes were performed. Median endovascular grades were compared between treatment modalities and endovascular outcomes. Binary regression analysis was performed with major endovascular complications as a dichotomized dependent variable. Intraclass correlation coefficients were calculated for interobserver reliability of the endovascular grading scale. RESULTS: A significant Spearman correlation between the endovascular grade and the Spetzler-Martin grade was demonstrated (rho = 0.5, P < .01). Differences in the median endovascular grades between the endovascular cure (median = 2) and endovascular complication groups (median = 4) (P < .05) and between the endovascular cure and successful multimodal treatment groups (median = 3) (P < .05) were demonstrated. The endovascular grade was the only independent predictor of complications (OR = 0.5, P < .01). The intraclass correlation coefficient of the endovascular grade was 0.71 (P < .01). CONCLUSIONS: Validation of a brain arteriovenous malformation endovascular grading scale demonstrated that endovascular grades of = age 65 who presented to Dana-Farber Cancer Institute between 2006 and 2011 and completed a baseline quality of life questionnaire. Questions corresponding to functional status and symptoms and extracted clinical-pathologic data from medical records. Kaplan-Meier and Cox proportional hazards models were used to estimate survival. Results: One hundred fourteen patients consented and were available for analysis. Median age was 73 years, and the majority of patients were White, were male, and had a Charlson comorbidity score of <2. Few patients (24%) had an IPSS score consistent with lower-risk disease and the majority received chemotherapy. In addition to IPSS score and history of prior chemotherapy or radiation, significant univariate predictors of survival included low serum albumin, Charlson score, performance status, ability to take a long walk, and interference of physical symptoms in family life. The multivariate model that best predicted mortality included low serum albumin (HR = 2.3; 95% CI: 1.06-5.14), therapy-related MDS (HR = 2.1; 95% CI: 1.16-4.24), IPSS score (HR = 1.7; 95% CI: 1.14-2.49), and ease taking a long walk (HR = 0.44; 95% CI: 0.23-0.90). Conclusions: In this study of older adults with MDS, we found that low serum albumin and physical function added important prognostic information to the IPSS score. Self-reported physical function was more predictive than physician-assigned performance status. Published by Elsevier Ltd. C1 [Fega, K. Rebecca] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Abel, Gregory A.; Motyckova, Gabriela; DeAngelo, Daniel J.; Steensma, David P.; Galinsky, Ilene; Wadleigh, Martha; Stone, Richard M.; Driver, Jane A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sherman, Alexander E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Driver, Jane A.] Boston VA Med Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Driver, Jane A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. RP Driver, JA (reprint author), Boston VA Med Ctr, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM jdriver@partners.org FU Dana Farber Cancer Institute; MSTAR Program (American Federation for Aging Research/NIH Grant) [1T35AG038027-02 9]; Veterans' Administration Career Development Award FX This research was funded by a grant from the Dana Farber Cancer Institute (JAD) and the MSTAR Program (American Federation for Aging Research/NIH Grant #1T35AG038027-02 9); KAS, AES). Dr. Driver gratefully acknowledges support from a Veterans' Administration Career Development Award). NR 40 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JUL PY 2015 VL 6 IS 4 BP 288 EP 298 DI 10.1016/j.jgo.2015.05.003 PG 11 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA CO9QW UT WOS:000359511600006 PM 26073533 ER PT J AU Naik, AD Uy, N Anaya, DA Moye, J AF Naik, Aanand D. Uy, Natalie Anaya, Daniel A. Moye, Jennifer TI The effects of age, education, and treatment on physical, sexual and body concern symptoms among multimorbid, colorectal cancer survivors SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Cancer survivors; Colorectal cancer; Multimorbidity; Quality of life; Symptoms ID QUALITY-OF-LIFE; PSYCHOLOGICAL DISTRESS; RECTAL-CANCER; COLON-CANCER; COMORBIDITY AB Objective: Less is known about longitudinal changes in quality of life between treatment completion and early survivorship among multimorbid cancer survivors. The current study describes longitudinal changes in quality of life among a multimorbid cohort of US Veterans diagnosed and treated for colorectal cancer. Materials and Methods: A sample of 68 multimorbid adults with colon and/or rectal cancer who received one or more treatment options (surgery, chemo or radiation therapy) was recruited. Participants were not excluded by cancer stage unless they reported being in hospice or similar status. Comprehensive assessments of quality of life and treatment side-effects were conducted 6, 12, and 18 months after diagnosis. Descriptive statistics characterized treatment side-effects and changes in quality-of-life domains longitudinally. Multivariate Analysis of Variance identified sociodemographic and clinical variables associated with quality of life changes. Results: Many physical symptoms improved from 6 to 18 months following diagnosis, while some remained stable. Sexual symptoms worsened, attributable to increasing rates of dysfunction in older patients. Low education attainment was predictive of worse physical symptoms (F = 5.59, p = .023) and associated with body concerns (F = 5.7; p = .005) over time. Advanced cancer stage (F = 4.94; p < .04) and receipt of chemotherapy (F = 4.21; p < .05) independently predicted body concerns in multivariate analyses. Conclusion: Endorsement of physical and sexual symptoms and body concerns occurs in different patterns over time among multimorbid colorectal cancer survivors. Low education attainment is consistently associated with physical symptoms and body concerns. Cancer stage and chemotherapy are predictive of body concerns, but not physical or sexual symptoms. Published by Elsevier Ltd. C1 [Naik, Aanand D.; Uy, Natalie; Anaya, Daniel A.] Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Michael E DeBakey VA Med Ctr MEDVAMC 152, Houston, TX 77030 USA. [Naik, Aanand D.; Uy, Natalie] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Anaya, Daniel A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Moye, Jennifer] VA Boston Healthcare Syst, Geriatr Mental Hlth, Brockton Div, Brockton, MA 02301 USA. [Moye, Jennifer] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Naik, AD (reprint author), Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Michael E DeBakey VA Med Ctr MEDVAMC 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.edu; Natalie.Uy@bcm.edu; Daniel.anaya@va.gov; Jennifer.Moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Department of Veterans Affairs Rehabilitation Research and Development Service [5I01RX000104] FX Funding for this project was provided by the Department of Veterans Affairs Rehabilitation Research and Development Service #5I01RX000104. This material is also the result of work supported with resources and the use of facilities at the Boston VA Medical Center and the Houston VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety (CIN13-413) at the Michael E. DeBakey VA Medical Center. We thank the members of the Veterans Cancer Rehabilitation Study (Vetcares) Research team for assistance in subject recruitment and data collection. We are indebted to the Veterans who have participated in our research studies and allow us to contribute to their health care. The funders played no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and/or in the decision to submit the paper for publication. NR 18 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JUL PY 2015 VL 6 IS 4 BP 299 EP 306 DI 10.1016/j.jgo.2015.04.001 PG 8 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA CO9QW UT WOS:000359511600007 PM 25920578 ER PT J AU Berman, NC Fang, A Hansen, N Wilhelm, S AF Berman, Noah Chase Fang, Angela Hansen, Natasha Wilhelm, Sabine TI Cognitive-based therapy for OCD: Role of behavior experiments and exposure processes SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Cognitive therapy; Behavioral experiment; Expectancy mismatch; OCD ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; PSYCHOMETRIC VALIDATION; INTRUSIONS INVENTORY; OVERVALUED IDEAS; QUESTIONNAIRE; RELIABILITY; ADOLESCENTS; PREVENTION; MECHANISMS AB The current manuscript describes the rationale and pragmatics for conducting exposures (termed "behavioral experiments") in Cognitive Therapy (CT) for OCD. Given that the cognitive model of OCD focuses upon the assumptions and belief systems (e.g., threat perception) that underlie the misinterpretation of unwanted intrusions, CT employs cognitive strategies, such as behavioral experiments, to modify maladaptive interpretations and produce symptom reduction. We outline how to prepare for behavioral experiments through psychoeducation and empirically supported assessment procedures. Next, we describe how to operationalize the behavioral experiment and propose patient and therapist-related behaviors that will facilitate (or interfere with) the experiment's success. Lastly, we discuss how to process the findings of the behavioral experiment by integrating other CT strategies, such as calculation of harm and the downward arrow, to consolidate learning and ultimately strengthen and generalize skills use. (C) 2015 Elsevier Inc. All rights reserved. C1 [Berman, Noah Chase; Fang, Angela; Hansen, Natasha; Wilhelm, Sabine] Massachusetts Gen Hosp, OCD & Related Disorders Program, Boston, MA 02114 USA. RP Berman, NC (reprint author), Massachusetts Gen Hosp, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM nberman@mgh.harvard.edu OI Fang, Angela/0000-0002-7666-9988 NR 39 TC 2 Z9 2 U1 5 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD JUL PY 2015 VL 6 BP 158 EP 166 DI 10.1016/j.jocrd.2015.01.001 PG 9 WC Psychiatry SC Psychiatry GA CP1CB UT WOS:000359612400021 ER PT J AU Grashow, R Sparrow, D Hu, H Weisskopf, MG AF Grashow, Rachel Sparrow, David Hu, Howard Weisskopf, Marc G. TI Cumulative lead exposure is associated with reduced olfactory recognition performance in elderly men: The Normative Aging Study SO NEUROTOXICOLOGY LA English DT Article DE Olfaction; Aging; Bone lead; HFE; ApoE; GSTP1 ID S-TRANSFERASE POLYMORPHISMS; PREDICTS COGNITIVE DECLINE; SMELL IDENTIFICATION TEST; DWELLING OLDER-ADULTS; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BONE LEAD; ODOR IDENTIFICATION; APOLIPOPROTEIN-E; INORGANIC LEAD AB Introduction: Olfactory dysfunction has been identified as an early warning sign for Alzheimer's disease, Parkinson's disease, dementia and more. A few occupational and environmental exposures have also been associated with reduced olfactory function, although the effects of long term environmental exposure to lead on olfactory dysfunction have not been explored. Here we performed olfactory recognition testing in elderly men in a community-dwelling cohort and examined the association with cumulative lead exposure, as assessed by lead in tibial and patellar bone. Methods: Olfactory recognition was measured in 165 men from the Normative Aging Study (NAS) who had previously taken part in bone lead measurements using K-X-ray fluorescence (KXRF). Olfactory recognition was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Associations between olfactory recognition, global cognition and cumulative lead exposure were estimated using linear regression, with additional adjustment for age, smoking, and functional polymorphism status for hemochromatosis (HFE), transferrin (TfC2), glutathione-s-transferase Pi1 (GSTP1) and apolipoprotein E (APOE) genotypes. Sensitivity analyses explored olfactory recognition in men with high global cognitive function as measured using the Mini-Mental Status Exam (MMSE). Results: The average age of the NAS participants at the time of olfactory recognition testing was 80.3 (standard deviation or SD = 5.7) years. Mean tibia lead was 16.3 (SD = 12.0) mu g/g bone, mean patella lead was 22.4 (SD = 14.4) mu g/g bone, and mean UPSIT score was 26.9 out of 40 (SD = 7.0). Consistent with previous findings, age at olfaction testing was negatively associated with UPSIT score. Tibia (but not patella) bone lead was negatively associated with olfaction recognition (per 15 mu g/g tibia lead: beta = -1.57; 95% CI: -2.93, -0.22; p = 0.02) in models adjusted for smoking and age. Additional adjustment for education did not significantly change results. Of all the genes explored, only the presence of one or more HFE variant alleles was significantly associated with olfaction recognition (HFE beta = 2.26; 95% CI: 0.09, 4.43; p = 0.04). In a model containing the HFE term and a lead term, the tibia lead parameter estimate dropped by 21% (per 15 mu g/g tibia lead: beta = -1.25; 95% CI: -2.64, 0.14; p = 0.08) while the HFE term dropped 15% (beta = 1.91; 95% CI: -0.28, 4.10; p = 0.09). None of the other gene terms were associated with olfactory recognition in this cohort, nor were any gene-lead interaction terms significant. Additional sensitivity analysis in men with MMSE scores of 25 or higher (n = 149) showed a similar but slightly attenuated association between lead and olfactory recognition (per 15 mu g/g tibia lead beta = -1.39; 95% CI: -3.00, 0.22; p = 0.09). Conclusion: Cumulative exposure to lead is associated with reduced olfactory recognition in a cohort of elderly men. The association was similar but not significant in men with better cognitive function as measured by the MMSE. Iron metabolism gene status may also affect olfactory function. (C) 2015 Elsevier Inc. All rights reserved. C1 [Grashow, Rachel; Weisskopf, Marc G.] Harvard Univ, Dept Environm Hlth, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Grashow, Rachel] Northeastern Univ, Dept Civil & Environm Engn, Boston, MA 02115 USA. [Sparrow, David] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. [Sparrow, David] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Sparrow, David] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Grashow, R (reprint author), Northeastern Univ, Dept Civil & Environm Engn, 360 Huntington Ave,Stearns 513, Boston, MA 02115 USA. EM r.grashow@neu.edu OI Hu, Howard/0000-0002-3676-2707 FU NIEHS [T32 ES007069, R01 ES005257, P01-ES000002]; VA Research Career Scientist award; Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs FX This study was supported by grants NIEHS T32 ES007069, R01 ES005257, P01-ES000002 and a VA Research Career Scientist award to David Sparrow. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. NR 79 TC 0 Z9 1 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUL PY 2015 VL 49 BP 158 EP 164 DI 10.1016/j.neuro.2015.06.006 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA CO5DQ UT WOS:000359180200019 PM 26121922 ER PT J AU Blaine, RE Fisher, JO Taveras, EM Geller, AC Rimm, EB Land, T Perkins, M Davison, KK AF Blaine, Rachel E. Fisher, Jennifer Orlet Taveras, Elsie M. Geller, Alan C. Rimm, Eric B. Land, Thomas Perkins, Meghan Davison, Kirsten K. TI Reasons Low-Income Parents Offer Snacks to Children: How Feeding Rationale Influences Snack Frequency and Adherence to Dietary Recommendations SO NUTRIENTS LA English DT Article DE snacks; parenting; childhood obesity prevention; child feeding ID DEMONSTRATION MA-CORD; CHILDHOOD OBESITY; YOUNG-CHILDREN; WEIGHT STATUS; FOOD-HABITS; PREVENTION; MASSACHUSETTS; OVERWEIGHT; ASSOCIATION; PERCEPTIONS AB Although American children snack more than ever before, the parental role in promoting snacking is not well understood. In 2012-2013 at baseline in an intervention study to prevent childhood obesity in low-income Massachusetts communities, n = 271 parents of children aged 2-12 years completed surveys regarding nutritive and non-nutritive reasons they offered children snacks, demographics, and dietary factors. An analysis of variance demonstrated that parents reported offering snacks (mean/week; standard deviation (SD)) for nutritive reasons like promoting growth (x = 2.5; SD 2.2) or satisfying hunger (x = 2.4; SD 2.1) almost twice as often as non-nutritive reasons like keeping a child quiet (x = 0.7; SD 1.5) or celebrating events/holidays (x = 0.8; SD 1.1). Parents reported giving young children (2-5 years) more snacks to reward behavior (1.9 vs. 1.1, p < 0.001), keep quiet (1.0 vs. 0.5, p < 0.001), and celebrate achievements (1.7 vs. 1.0, p < 0.001) than parents of older children (6-12 years). Multivariable logistic regression models were used to obtain adjusted odds ratios, which indicated reduced child adherence to dietary recommendations when parents offered snacks to reward behavior (Odds Ratio (OR) = 0.83; 95% Confidence Interval (CI) 0.70-0.99), celebrate events/holidays (OR = 0.72; 95% CI 0.52-0.99), or achievements (OR = 0.82; 95% CI 0.68-0.98). Parental intentions around child snacking are likely important targets for obesity prevention efforts. C1 [Blaine, Rachel E.] Calif State Univ Long Beach, Dept Family & Consumer Sci, Long Beach, CA 90840 USA. [Blaine, Rachel E.; Rimm, Eric B.; Davison, Kirsten K.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fisher, Jennifer Orlet] Temple Univ, Dept Publ Hlth, Ctr Obes Res & Educ, Coll Publ Hlth, Philadelphia, PA 19140 USA. [Taveras, Elsie M.; Perkins, Meghan] MassGen Hosp Children, Div Gen Acad Pediat, Dept Pediat, Boston, MA 02114 USA. [Geller, Alan C.] Harvard HT Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Land, Thomas] Massachusetts Dept Publ Hlth, Off Data Management & Outcomes Assessment, Boston, MA 02108 USA. RP Blaine, RE (reprint author), Calif State Univ Long Beach, Dept Family & Consumer Sci, 1250 Bellflower Blvd,FCS FA-15, Long Beach, CA 90840 USA. EM rachel.blaine@csulb.edu; jofisher@temple.edu; elsie.taveras@mgh.harvard.edu; ageller@hsph.harvard.edu; erimm@hsph.harvard.edu; thomas.land@state.ma.us; meperkins@mgh.harvard.edu; kdavison@hsph.harvard.edu FU Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion [U18DP003370]; National Institutes of Health (NIH) [T32 CA 0900] FX This study was supported by the Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion (Award #U18DP003370). Rachel E. Blaine, a doctoral graduate, was supported by a National Institutes of Health (NIH) Doctoral Training Grant in Cancer Epidemiology: T32 CA 0900 at the Harvard T.H. Chan School of Public Health. The work is solely the responsibility of the authors and does not represent official views of the CDC or the NIH. NR 42 TC 1 Z9 1 U1 2 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD JUL PY 2015 VL 7 IS 7 BP 5982 EP 5999 DI 10.3390/nu7075265 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CO7OQ UT WOS:000359349800056 PM 26197335 ER PT J AU Abu Sayeed, M Bufano, MK Xu, P Eckhoff, G Charles, RC Alam, MM Sultana, T Rashu, MR Berger, A Gonzalez-Escobedo, G Mandlik, A Bhuiyan, TR Leung, DT LaRocque, RC Harris, JB Calderwood, SB Qadri, F Vann, WF Kovac, P Ryan, ET AF Abu Sayeed, Md. Bufano, Meagan Kelly Xu, Peng Eckhoff, Grace Charles, Richelle C. Alam, Mohammad Murshid Sultana, Tania Rashu, Md. Rasheduzzaman Berger, Amanda Gonzalez-Escobedo, Geoffrey Mandlik, Anjali Bhuiyan, Taufiqur Rahman Leung, Daniel T. LaRocque, Regina C. Harris, Jason B. Calderwood, Stephen B. Qadri, Firdausi Vann, W. F. Kovac, Pavol Ryan, Edward T. TI A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NEONATAL FC-RECEPTOR; B-CELL RESPONSES; FREE MOUSE MODEL; VIBRIO-CHOLERAE; ORAL IMMUNIZATION; IMMUNE-RESPONSES; TRANSCUTANEOUS IMMUNIZATION; CHEMOENZYMATIC SYNTHESIS; HOUSEHOLD CONTACTS; CONTROLLED-TRIAL AB Background Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Methodology Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 mu g), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. Principle Findings Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 mu g). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. Conclusion We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. C1 [Abu Sayeed, Md.; Bufano, Meagan Kelly; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Abu Sayeed, Md.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Bhuiyan, Taufiqur Rahman; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka, Bangladesh. [Xu, Peng] Natl Inst Diabet Digest & Kidney Dis NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Eckhoff, Grace; Charles, Richelle C.; Kovac, Pavol; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA. [Leung, Daniel T.] Univ Utah, Sch Med, Div Infect Dis, Salt Lake City, UT USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Vann, W. F.] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Abu Sayeed, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@mgh.harvard.edu RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012 OI Kovac, Pavol/0000-0001-5044-3449; FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [UO1 AI106878, U01 AI058935, K08 AI089721]; Fogarty International Center [TW005572]; NIH; NIDDK FX This research was supported by core grants to the icddr,b and through programs funded by the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (UO1 AI106878 [ETR and FQ], U01 AI058935 [SBC, FQ and ETR], and K08 AI089721 [RCC]), the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [MAS, MMA, TS, MRR, TRB and FQ]), and the Intramural Research Program of the NIH and NIDDK (PX and PK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 0 Z9 0 U1 3 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUL PY 2015 VL 9 IS 7 AR e0003881 DI 10.1371/journal.pntd.0003881 PG 18 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CO3SM UT WOS:000359079700013 ER PT J AU Niell, BL Bennett, D Sharma, A Gazelle, GS AF Niell, Bethany L. Bennett, Debbie Sharma, Amita Gazelle, G. Scott TI Extramammary Findings on Breast MR Examinations: Frequency, Clinical Relevance, and Patient Outcomes SO RADIOLOGY LA English DT Article ID RESONANCE-IMAGING USE; RANDOMIZED CONTROLLED-TRIAL; ACR INCIDENTAL FINDINGS; HIGH FAMILIAL RISK; EXTRACARDIAC FINDINGS; CT COLONOGRAPHY; WHITE PAPER; CANCER; MAMMOGRAPHY; MANAGEMENT AB Purpose: To evaluate the frequency of extramammary findings on breast magnetic resonance (MR) images, recommendations for further imaging evaluation of each finding, and the subsequent effect on patient outcomes and health care expenditures. Materials and Methods: Institutional review board approval was acquired for this HIPAA-compliant study. Informed consent was waived. Review of the institutional database identified 2324 breast MR examinations performed in women from January 1, 2010, to December 31, 2010. Breast MR imaging reports were reviewed for extramammary findings. Extramammary findings were categorized by using the computed tomography (CT) colonography reporting and data system (C-RADS). The electronic medical record was reviewed for each patient with a C-RADS category E3 and E4 finding to assess clinical relevance and pathologic outcome. If an E3 or E4 finding was previously described and evaluated, the finding was downgraded and assigned a final C-RADS E2 category. The cost of additional imaging was estimated by using the Medicare physician fee schedule. Statistical significance was assessed by using chi(2) statistics. A P value less than.05 indicated statistical significance, and 95% exact confidence intervals (CIs) were constructed. Results: Extramammary findings were identified in 391 of 2324 breast MR examinations (16.8%), which included 105 patients (4.5%) with E3 or E4 findings. Of the 2324 patients, 86 patients (3.7% [95% CI: 3.0%, 4.5%]) were recommended to undergo further imaging. After undergoing evaluation for additional imaging, a clinically important finding was found in nine patients (0.4% [95% CI: 0.2%, 0.7%]). Most frequently, hepatic lesions were the indication for additional imaging. Abdominal MR examinations accounted for 55% of costs related to additional imaging. Averaged across the entire cohort, further imaging evaluation and follow-up of incidental findings contributed an additional $16 to each breast MR imaging performed. Conclusion: Additional imaging evaluation for E3 and E4 extramammary findings at breast MR imaging can identify clinically important disease without substantially increasing cost. (C) RSNA, 2015 C1 [Niell, Bethany L.; Bennett, Debbie; Gazelle, G. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Sharma, Amita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Niell, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Avon Comprehens Breast Evaluat Ctr, 55 Fruit St,Wang Bldg Suite 240, Boston, MA 02114 USA. EM bniell@partners.org FU GE Healthcare FX B.L.N. disclosed no relevant relationships. D.B. disclosed no relevant relationships. A.S. disclosed no relevant relationships. G.S.G. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author disclosed personal fees for consultancy from GE Healthcare. Other relationships: disclosed no relevant relationships. NR 26 TC 3 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2015 VL 276 IS 1 BP 56 EP 64 DI 10.1148/radiol.14141539 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP2LL UT WOS:000359708400006 PM 25584711 ER PT J AU Scott, JA Palmer, EL Connolly, LP AF Scott, James A. Palmer, Edwin L. Connolly, Leonard P. TI Reading the Writing in Radiology: 1923-2013 SO RADIOLOGY LA English DT Article AB The style and tone of the writing in Radiology has changed over the years since its first publication in 1923. Many of the tonal changes have occurred transiently and likely in relation to political and professional issues in play at a particular time. Others represent more consistent trends in the evolution of the professional writing style. In this report, we analyze the tone of the editorial content from 1923 to 2013 in a historical context as well as progressive changes in readability parameters involving both editorial and technical content. C1 [Scott, James A.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. EM scott@helix.mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2015 VL 276 IS 1 BP 250 EP 257 DI 10.1148/radiol.15141940 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP2LL UT WOS:000359708400028 PM 25734555 ER PT J AU Mitchell, JE Steffen, K Engel, S King, WC Chen, JY Winters, K Sogg, S Sondag, C Kalarchian, M Elder, K AF Mitchell, James E. Steffen, Kristine Engel, Scott King, Wendy C. Chen, Jia-Yuh Winters, Ken Sogg, Stephanie Sondag, Cindy Kalarchian, Melissa Elder, Katherine TI Addictive disorders after Roux-en-Y gastric bypass SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Addictive use disorders; Alcohol use disorders; Bariatric surgery ID SWEDISH OBESE SUBJECTS; BARIATRIC SURGERY; LONGITUDINAL ASSESSMENT; BEHAVIORAL ADDICTIONS; EXERCISE ADDICTION; MENTAL-DISORDERS; ALCOHOL; PREVALENCE; EPIDEMIOLOGY; DEPENDENCE AB Background: Recent literature suggests that some patients may develop addictive disorders after bariatric surgery, in particular after Roux-en-Y gastric bypass (RYGB). These may include traditional addictions and so called "behavioral addictions," although prevalence data on the latter have not been published. The objective of this study was to establish the prevalence of addictive behaviors in adults after RYGB. Methods: Participants from a large observational study of bariatric surgery who had undergone RYGB were recruited to complete additional measures. Of 241 consented participants, 201 provided data (i.e., Structured Clinical Interview for DSM-IV Axis I [SCID], additional Impulsive Control Disorder Modules, and various self-report measures, including the Alcohol Use Disorder Identification Test [AUDIT]) to assess status before surgery and in the first 3 postoperative years. Results: Based on the SCID, 16 (8.0%) developed alcohol use disorder [AUD] within 3 years post-RYGB, 7 (43.8%) of whom had no history of AUD. When both the SOD and AUDIT were used to identify AUD, the corresponding numbers/percentages were 32 (18.4%) and 13 (40.6%). Data on other behavioral addictive disorders indicated 19 (9.5%) had a postsurgery disorder, 6 (31.6%) of whom had no history. Conclusion: These data add to a growing literature suggesting there is a substantial risk for the development of AUD after bariatric surgery. Understanding the risk for nondrug-related addictive disorders requires more data from larger studies before clear conclusions can be drawn. (C) 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [Mitchell, James E.; Steffen, Kristine; Engel, Scott; Sondag, Cindy] NRI, Fargo, ND 58103 USA. [Mitchell, James E.; Steffen, Kristine; Engel, Scott; Sondag, Cindy] Univ N Dakota, Sch Med, Fargo, ND USA. [King, Wendy C.; Chen, Jia-Yuh] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Winters, Ken] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA USA. [Kalarchian, Melissa] Duquesne Univ, Pittsburgh, PA 15219 USA. [Elder, Katherine] Univ Pacific, Hillsboro, OR USA. RP Mitchell, JE (reprint author), NRI, 120 8th St South, Fargo, ND 58103 USA. EM jmitchell@nrifargo.com OI King, Wendy/0000-0002-0740-0029; Kalarchian, Melissa/0000-0003-2099-9299 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK066557, U01-DK66667, UL1-RR024996, U01-DK66568, M01 RR-00037, U01-DK66471, U01-DK66526, U01-DK66585, UL1-RR024153, U01-DK66555]; National Institute of Drug Abuse; National Institute for Alcoholism and Alcohol Abuse [U01-DK66471] FX LABS-2 was funded by a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants U01 DK066557 (data coordinating center); U01-DK66667 and UL1-RR024996 (Columbia-Presbyterian in collaboration with Cornell University Medical Center Clinical and Translational Research Center [CIRC]); U01-DK66568 and M01 RR-00037 (University of Washington in collaboration with Cornell University Medical Center CTRC); U01-DK66471 (Neuropsychiatric Research Institute); U01-DK66526 (East Carolina University); U01-DK66585 and UL1-RR024153 (University of Pittsburgh Medical Center in collaboration with Cornell University Medical Center CTRC); and U01-DK66555 (Oregon Health & Science University). This particular part of the LABS-2 study was also funded by a Supplement from the National Institute of Drug Abuse and the National Institute for Alcoholism and Alcohol Abuse to U01-DK66471 (Neuropsychiatric Research Institute). NR 38 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JUL-AUG PY 2015 VL 11 IS 4 BP 897 EP 905 DI 10.1016/j.soard.2014.10.026 PG 9 WC Surgery SC Surgery GA CO7HF UT WOS:000359329500032 PM 25862182 ER PT J AU Zeng, XQ Shi, HJ Wang, JP Cui, SZ Tang, HS Zhang, XL AF Zeng, Xiaoqi Shi, Huijuan Wang, Jiping Cui, Shuzhong Tang, Hongsheng Zhang, Xiangliang TI Long noncoding RNA aberrant expression profiles after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy of AGC ascertained by microarray analysis SO TUMOR BIOLOGY LA English DT Article DE Advanced gastric cancer (AGC); Cytoreductive surgery (CRS); Hyperthermic intraperitoneal chemotherapy (HIPEC); LncRNAs ID GASTRIC-CANCER; PERITONEAL CARCINOMATOSIS; CELL-PROLIFERATION; POOR-PROGNOSIS; C-MYC; PROMOTES; TRANSCRIPTION; HOTAIR; METASTASIS; INVASION AB Long noncoding RNAs (lncRNAs) have been shown to be involved in the development and progression of advanced gastric cancer (AGC). However, the roles of lncRNAs in advanced gastric cancer during the process of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are not well understood. A high-throughput microarray analysis was performed to compare the expression profiles of lncRNAs and messenger RNAs (mRNAs) in AGC serum samples during the process of CRS+HIPEC. Several potentially AGC-associated lncRNAs were verified by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis. Using abundant and varied probes, we were able to assess 33,045 lncRNAs and 30,215 mRNAs in our microarray. We found that 566 lncRNAs were differentially expressed (2-fold change) in AGC serum samples, indicating the significantly up-or down-regulated lncRNAs play important roles in AGC during the process of CRS+HIPEC. Quantitative PCR results further verified that eight lncRNAs were aberrantly expressed in AGC serum samples after CRS+HIEC compared with matched serum sample before CRS+HIPEC. Among them, BC031243 and RP11-356I2.2 were the most aberrantly expressed lncRNAs, as estimated by quantitative PCR in six pairs of AGC serum samples. Our study demonstrated the expression patterns of lncRNAs in AGC serums before and after CRS+HIPEC by microarray. These results revealed that lncRNAs were differentially expressed during the process of CRS+HIPEC, suggesting that they might play key roles in tumor development. C1 [Zeng, Xiaoqi; Cui, Shuzhong; Tang, Hongsheng; Zhang, Xiangliang] Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg, Sect 2, Guangzhou 510095, Guangdong, Peoples R China. [Shi, Huijuan] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Jiping] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wang, Jiping] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Jiping] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Wang, Jiping] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhang, XL (reprint author), Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg, Sect 2, 78 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China. EM zhxl7229@163.com FU Guangdong Province Natural Science Fund [S2013010016662]; health bureau of Guangdong province [A2014224, B2014196]; Science and Technology Planning Project of Guangdong Province [2013B021800284]; National Natural Science Foundation of China [81201932, 81372493] FX This work was supported by Guangdong Province Natural Science Fund (No. S2013010016662), the health bureau of Guangdong province (Nos. A2014224 and B2014196), Science and Technology Planning Project of Guangdong Province (No. 2013B021800284), and the National Natural Science Foundation of China (Nos. 81201932 and 81372493). NR 30 TC 3 Z9 3 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1010-4283 EI 1423-0380 J9 TUMOR BIOL JI Tumor Biol. PD JUL PY 2015 VL 36 IS 7 BP 5021 EP 5029 DI 10.1007/s13277-015-3153-4 PG 9 WC Oncology SC Oncology GA CP0MI UT WOS:000359569000020 PM 25652469 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI 50TH ANNIVERSARY LANDMARK COMMENTARY ON GRILLO HC. TRACHEAL TUMORS: SURGICAL MANAGEMENT. ANN THORAC SURG 1978;26:112-25 SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Thorac Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@mgh.harvard.edu NR 1 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 JUL PY 2015 VL 100 IS 1 BP 6 EP 7 DI 10.1016/j.athoracsur.2015.05.049 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CN9UZ UT WOS:000358796800012 PM 26140755 ER PT J AU Garcia, JM Chen, JA Guillory, B Donehower, LA Smith, RG Lamb, DJ AF Garcia, Jose M. Chen, Ji-an Guillory, Bobby Donehower, Lawrence A. Smith, Roy G. Lamb, Dolores J. TI Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE GHSR; growth hormone secretagogue; infertility; testis ID HORMONE SECRETAGOGUE RECEPTOR; GERM-CELL CANCER; RAT TESTIS; C57/BL/6J MICE; MESSENGER-RNA; MOUSE TESTIS; FOOD-INTAKE; CHEMOTHERAPY; EXPRESSION; APOPTOSIS AB Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms. C1 [Garcia, Jose M.; Chen, Ji-an; Guillory, Bobby] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, CTRID, Div Endocrinol Diabet & Metab,Dept Med,MCL, Houston, TX 77030 USA. [Chen, Ji-an] Third Mil Med Univ, Coll Prevent Med, Dept Hlth Educ, Chongqing, Peoples R China. [Garcia, Jose M.; Lamb, Dolores J.] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA. [Garcia, Jose M.; Smith, Roy G.; Lamb, Dolores J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Garcia, Jose M.; Guillory, Bobby; Smith, Roy G.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Donehower, Lawrence A.; Lamb, Dolores J.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Smith, Roy G.] Scripps Res Inst Florida, Dept Metab & Aging, Jupiter, FL USA. [Lamb, Dolores J.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Michael E DeBakey VA Med Ctr, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd,Bldg 109,Rm 210, Houston, TX 77030 USA. EM Jgarcia1@bcm.edu FU NICHD [U54-HD28934] FX We thank the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core (supported by NICHD U54-HD28934) and Baylor DERC (P30 DK079638) for their help. NR 61 TC 5 Z9 5 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD JUL 1 PY 2015 VL 93 IS 1 AR 24 DI 10.1095/biolreprod.115.129759 PG 8 WC Reproductive Biology SC Reproductive Biology GA CO8SP UT WOS:000359441800018 PM 26019260 ER PT J AU Piotrowska, Z Niederst, MJ Karlovich, CA Wakelee, HA Neal, JW Mino-Kenudson, M Fulton, L Hata, AN Lockerman, EL Kalsy, A Digumarthy, S Muzikansky, A Raponi, M Garcia, AR Mulvey, HE Parks, MK DiCecca, RH Dias-Santagata, D Iafrate, AJ Shaw, AT Allen, AR Engelman, JA Sequist, LV AF Piotrowska, Zofia Niederst, Matthew J. Karlovich, Chris A. Wakelee, Heather A. Neal, Joel W. Mino-Kenudson, Mari Fulton, Linnea Hata, Aaron N. Lockerman, Elizabeth L. Kalsy, Anuj Digumarthy, Subba Muzikansky, Alona Raponi, Mitch Garcia, Angel R. Mulvey, Hillary E. Parks, Melissa K. DiCecca, Richard H. Dias-Santagata, Dora Iafrate, A. John Shaw, Alice T. Allen, Andrew R. Engelman, Jeffrey A. Sequist, Lecia V. TI Heterogeneity Underlies the Emergence of EGFR(T790) Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor SO CANCER DISCOVERY LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; INTRATUMOR HETEROGENEITY; DRUG-COMBINATIONS; MET AMPLIFICATION; MUTATIONS; GEFITINIB; TUMORS; ADENOCARCINOMAS AB Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type rociletinib-resistant biopsies. Two T790-wild-type cancers underwent small cell lung cancer transformation; three T790M-positive cancers acquired EGFR amplification. We documented T790-wild-type and T790M-positive clones coexisting within a single pre-rociletinib biopsy. The pretreatment fraction of T790M-positive cells affected response to rociletinib. Longitudinal circulating tumor DNA (ctDNA) analysis revealed an increase in plasma EGFR-activating mutation, and T790M heralded rociletinib resistance in some patients, whereas in others the activating mutation increased but T790M remained suppressed. Together, these findings demonstrate the role of tumor heterogeneity when therapies targeting a singular resistance mechanism are used. To further improve outcomes, combination regimens that also target T790-wild-type clones are required. SIGNIFICANCE: This report documents that half of T790M-positive EGFR-mutant lung cancers treated with rociletinib are T790-wild-type upon progression, suggesting that T790-wild-type clones can emerge as the dominant source of resistance. We show that tumor heterogeneity has important clinical implications and that plasma ctDNA analyses can sometimes predict emerging resistance mechanisms. (C) 2015 AACR. C1 [Piotrowska, Zofia; Niederst, Matthew J.; Mino-Kenudson, Mari; Fulton, Linnea; Hata, Aaron N.; Lockerman, Elizabeth L.; Kalsy, Anuj; Digumarthy, Subba; Muzikansky, Alona; Garcia, Angel R.; Mulvey, Hillary E.; Parks, Melissa K.; DiCecca, Richard H.; Dias-Santagata, Dora; Iafrate, A. John; Shaw, Alice T.; Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karlovich, Chris A.; Raponi, Mitch; Allen, Andrew R.] Clovis Oncol, San Francisco, CA USA. [Wakelee, Heather A.; Neal, Joel W.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Piotrowska, Zofia; Niederst, Matthew J.; Mino-Kenudson, Mari; Hata, Aaron N.; Digumarthy, Subba; Muzikansky, Alona; Dias-Santagata, Dora; Iafrate, A. John; Engelman, Jeffrey A.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Dept Med, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM lvsequist@partners.org FU NIH [R01CA137008]; Department of Defense; LunGevity; Uniting Against Lung Cancer; Lung Cancer Research Foundation; Targeting a Cure for Lung Cancer; Be a Piece of the Solution; Clovis Oncology FX This study was funded by support from NIH R01CA137008 (to J.A. Engelman), the Department of Defense (to L.V. Sequist and J.A. Engelman), LunGevity (to L.V. Sequist, J.A. Engelman, and J.W. Neal), Uniting Against Lung Cancer (to Z. Piotrowska and M.J. Niederst), the Lung Cancer Research Foundation (to M.J. Niederst), Targeting a Cure for Lung Cancer, and Be a Piece of the Solution. Plasma analyses were funded by Clovis Oncology. NR 28 TC 80 Z9 81 U1 5 U2 20 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 JUL PY 2015 VL 5 IS 7 BP 713 EP 722 DI 10.1158/2159-8290.CD-15-0399 PG 10 WC Oncology SC Oncology GA CO7CY UT WOS:000359316800021 PM 25934077 ER PT J AU Paiva, C Godbersen, JC Berger, A Brown, JR Danilov, AV AF Paiva, C. Godbersen, J. C. Berger, A. Brown, J. R. Danilov, A. V. TI Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents SO CELL DEATH & DISEASE LA English DT Article ID NEDD8-ACTIVATING ENZYME-INHIBITOR; PHASE-II TRIAL; S-PHASE; UBIQUITIN LIGASES; CANCER-CELLS; CLL CELLS; MLN4924; BENDAMUSTINE; APOPTOSIS; PROLIFERATION AB Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-kappa B (NF-kappa B) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-kappa B pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-kappa B inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents. C1 [Paiva, C.; Danilov, A. V.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Godbersen, J. C.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Berger, A.] Takeda Pharmaceut Co Ltd, Millennium Pharmaceut Inc, Cambridge, MA USA. [Brown, J. R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. RP Danilov, AV (reprint author), Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM danilov@ohsu.edu FU Lymphoma Research Foundation; Leukemia Lymphoma Society; American Cancer Society FX We thank Drs. Eric Lightcap, Christopher Danes and Alan Eastman for their very helpful review of this manuscript. This work was supported by the Lymphoma Research Foundation Clinical Investigator Career Development Award to AVD. JRB is supported by the Leukemia Lymphoma Society and the American Cancer Society and is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 45 TC 3 Z9 3 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JUL PY 2015 VL 6 AR e1807 DI 10.1038/cddis.2015.161 PG 12 WC Cell Biology SC Cell Biology GA CN9SH UT WOS:000358788800007 PM 26158513 ER PT J AU Moy, ML Collins, RJ Martinez, CH Kadri, R Roman, P Holleman, RG Kim, HM Nguyen, HQ Cohen, MD Goodrich, DE Giardino, ND Richardson, CR AF Moy, Marilyn L. Collins, Riley J. Martinez, Carlos H. Kadri, Reema Roman, Pia Holleman, Robert G. Kim, Hyungjin Myra Nguyen, Huong Q. Cohen, Miriam D. Goodrich, David E. Giardino, Nicholas D. Richardson, Caroline R. TI An Internet-Mediated Pedometer-Based Program Improves Health-Related Quality-of-Life Domains and Daily Step Counts in COPD A Randomized Controlled Trial SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC LUNG-DISEASE; PHYSICAL-ACTIVITY; WALKING PROGRAM; ONLINE COMMUNITY; US COHORT; REHABILITATION; MAINTENANCE; TIOTROPIUM; MORTALITY AB BACKGROUND: Low levels of physical activity (PA) are associated with poor outcomes in people with COPD. Interventions to increase PA could improve outcomes. METHODS: We tested the efficacy of a novel Internet-mediated, pedometer-based exercise intervention. Veterans with COPD (N = 239) were randomized in a 2:1 ratio to the (1) intervention group (Omron HJ-720 ITC pedometer and Internet-mediated program) or (2) wait-list control group (pedometer). The primary outcome was health-related quality of life (HRQL), assessed by the St. George's Respiratory Questionnaire (SGRQ), at 4 months. We examined the SGRQ total score (SGRQ-TS) and three domain scores: Symptoms, Activities, and Impact. The secondary outcome was daily step counts. Linear regression models assessed the effect of intervention on outcomes. RESULTS: Participants had a mean age of 67 +/- 9 years, and 94% were men. There was no significant between-group difference in mean 4-month SGRQ-TS (2.3 units, P = .14). Nevertheless, a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS, the minimum clinically important difference (53% vs 39%, respectively, P = .05). For domain scores, the intervention group had a lower (reflecting better HRQL) mean than the control group by 4.6 units for Symptoms (P = .046) and by 3.3 units for Impact (P = .049). There was no significant difference in Activities score between the two groups. Compared with the control subjects, intervention participants walked 779 more steps per day at 4 months (P - .005). CONCLUSIONS: An Internet-mediated, pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD. C1 [Moy, Marilyn L.] VA Boston Healthcare Syst, Dept Vet Affairs, Rehabil Res & Dev Serv, Boston, MA USA. [Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Moy, Marilyn L.] Harvard Univ, Sch Med, Boston, MA USA. [Collins, Riley J.] Univ Michigan, Sch Med, Ann Arbor, MI 48104 USA. [Martinez, Carlos H.] Univ Michigan Hlth Syst, Pulm & Crit Care Div, Ann Arbor, MI USA. [Kadri, Reema; Roman, Pia; Holleman, Robert G.; Kim, Hyungjin Myra; Goodrich, David E.; Richardson, Caroline R.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Hlth Serv Res & Dev Ctr Innovat, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48104 USA. [Nguyen, Huong Q.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Cohen, Miriam D.] VA New York Harbor, Brooklyn, NY USA. [Giardino, Nicholas D.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48104 USA. [Richardson, Caroline R.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48104 USA. RP Richardson, CR (reprint author), Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA. EM caroli@umich.edu OI Collins, Rachel/0000-0002-1559-8135; Goodrich, David/0000-0003-3232-2189 FU Department of Veterans Affairs, Health Services Research and Development Service [IIR 09-366]; Department of Veterans Affairs, Rehabilitation Research and Development Service [F6847W]; National Institutes of Health Heart, Lung, and Blood Institute [T32 HL007749-20] FX This study was funded by the Department of Veterans Affairs, Health Services Research and Development Service [Grant IIR 09-366 to Dr Richardson]; the Department of Veterans Affairs, Rehabilitation Research and Development Service [Career Development Award F6847W to Dr Moy]; and the National Institutes of Health Heart, Lung, and Blood Institute [Grant T32 HL007749-20 to Dr Martinez]. NR 50 TC 8 Z9 8 U1 3 U2 15 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2015 VL 148 IS 1 BP 128 EP 137 DI 10.1378/chest.14-1466 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO2QZ UT WOS:000359003000034 PM 25811395 ER PT J AU Vargas, M Pelosi, P Kacmarek, RM Servillo, G AF Vargas, Maria Pelosi, Paolo Kacmarek, Robert M. Servillo, Giuseppe TI Assessment of Ventilation During the Performance of Elective Endoscopic-Guided Percutaneous Tracheostomy What's New 10 Years Later? Response SO CHEST LA English DT Letter ID LUMEN ENDOTRACHEAL-TUBE C1 [Vargas, Maria; Servillo, Giuseppe] Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, I-80100 Naples, Italy. [Pelosi, Paolo] Univ Genoa, AOU IRCCS San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Servillo, G (reprint author), Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, Via Pansini 16,Via Pansini, I-80100 Naples, Italy. EM servillo@unina.it RI Vargas, Maria/H-6876-2014; Servillo, Giuseppe/M-9132-2016 OI Vargas, Maria/0000-0001-7652-970X; Servillo, Giuseppe/0000-0002-4618-3434 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2015 VL 148 IS 1 BP E27 EP E28 DI 10.1378/chest.15-0511 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO2QZ UT WOS:000359003000008 PM 26149560 ER PT J AU Mody, L Meddings, J Edson, BS McNamara, SE Trautner, BW Stone, ND Krein, SL Saint, S AF Mody, Lona Meddings, Jennifer Edson, Barbara S. McNamara, Sara E. Trautner, Barbara W. Stone, Nimalie D. Krein, Sarah L. Saint, Sanjay TI Enhancing Resident Safety by Preventing Healthcare-Associated Infection: A National Initiative to Reduce Catheter-Associated Urinary Tract Infections in Nursing Homes SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE nursing homes; post-acute care facilities; patient safety; CAUTIs ID LONG-TERM-CARE; QUALITY IMPROVEMENT; FACILITIES; MORTALITY; IMPLEMENTATION; COLONIZATION; SURVEILLANCE; DEFINITIONS; GUIDELINE; CRITERIA AB Preventing healthcare-associated infection (HAI) is a key contributor to enhancing resident safety in nursing homes. In 2013, the U.S. Department of Health and Human Services approved a plan to enhance resident safety by reducing HAIs in nursing homes, with particular emphasis on reducing indwelling catheter use and catheter-associated urinary tract infection (CAUTI). Lessons learned from a recent multimodal Targeted Infection Prevention program in a group of nursing homes as well as a national initiative to prevent CAUTI in over 950 acute care hospitals called "On the CUSP: STOP CAUTI" will now be implemented in nearly 500 nursing homes in all 50 states through a project funded by the Agency for Healthcare Research and Quality (AHRQ). This "AHRQ Safety Program in Long-Term Care: HAIs/CAUTI" will emphasize professional development in catheter utilization, catheter care and maintenance, and antimicrobial stewardship as well as promoting patient safety culture, team building, and leadership engagement. We anticipate that an approach integrating technical and socio-adaptive principles will serve as a model for future initiatives to reduce other infections, multidrug resistant organisms, and noninfectious adverse events among nursing home residents. C1 [Mody, Lona] Univ Michigan, Sch Med, Geriatr Res Educ & Clin Ctr, Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. [Mody, Lona; McNamara, Sara E.] Univ Michigan, Sch Med, Div Geriatr & Palliat Care Med, Ann Arbor, MI 48109 USA. [Meddings, Jennifer; Krein, Sarah L.; Saint, Sanjay] Univ Michigan, Sch Med, Div Gen Med, Ann Arbor, MI 48109 USA. [Meddings, Jennifer] Univ Michigan, Sch Med, Department Internal Med, Div Gen Pediat, Ann Arbor, MI 48109 USA. [Meddings, Jennifer] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Div Gen Pediat, Ann Arbor, MI 48109 USA. [Edson, Barbara S.] Hlth Res & Educ Trust, Chicago, IL USA. [Edson, Barbara S.] Baylor Coll Med, Ctr Innovat Qual Effectiveness & Safety IQuESt, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Trautner, Barbara W.] Baylor Coll Med, Dept Med, Sect Infect Dis, Houston, TX USA. [Edson, Barbara S.] Baylor Coll Med, Dept Surg, Houston, TX USA. [Stone, Nimalie D.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [Krein, Sarah L.; Saint, Sanjay] Ctr Clin Management Res, Ann Arbor, MI USA. [Saint, Sanjay] Vet Affairs Ann Arbor Healthcare Syst, Med Serv, Ann Arbor, MI USA. RP Mody, L (reprint author), Univ Michigan, Sch Med, Div Geriatr & Palliat Care Med, 300 N Ingalls Rd,Rm 905, Ann Arbor, MI 48109 USA. EM lonamody@umich.edu FU Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services [HHSA 2902010000251]; National Institutes of Health (NIH) [R01 AG032298, R01 AG41780, R18 HS019979, NIH DK092293]; University of Michigan Claude D. Pepper Older Americans Independence Center (NIA) [P30 AG024824]; AHRQ [1K08-HS019767-01]; National Institutes of Health Clinical Loan Repayment Program; Department of Veterans Affairs [VA] [RRP 12-433]; Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, Texas [CIN13-413] FX This work was supported by a contract from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, Contract Number: HHSA 2902010000251. Other Funding/Support provided by the National Institutes of Health (NIH) (R01 AG032298, R01 AG41780, R18 HS019979 to L. M.; NIH DK092293 to B. W. T.); the University of Michigan Claude D. Pepper Older Americans Independence Center (NIA P30 AG024824 to L. M.); AHRQ (1K08-HS019767-01to J. M.); National Institutes of Health Clinical Loan Repayment Program (2009-2015 to J. M.); Department of Veterans Affairs [VA RRP 12-433 to B. W. T.]; Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, Texas [CIN13-413 to B. W. T.]. NR 51 TC 9 Z9 9 U1 1 U2 14 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 JUL 1 PY 2015 VL 61 IS 1 BP 86 EP 94 DI 10.1093/cid/civ236 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CO7EX UT WOS:000359323500015 PM 25814630 ER PT J AU La Madrid, AM Hashizume, R Kieran, MW AF Morales La Madrid, Andres Hashizume, Rintaro Kieran, Mark W. TI Future clinical trials in DIPG: bringing epigenetics to the clinic SO FRONTIERS IN ONCOLOGY LA English DT Review DE DIPG; epigenetics; clinical trials; children ID INTRINSIC PONTINE GLIOMA; ACTIVATING ACVR1 MUTATIONS; CANCER; THERAPY; INHIBITION; SUBGROUPS AB In spite of major recent advances in diffuse intrinsic pontine glioma (DIPG) molecular characterization, this body of knowledge has not yet translated into better treatments. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents have failed to improve the dismal outcome when compared to palliative radiation alone. The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis; ideally, in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety. These pre-treatment tumor samples, and others coming from tissue obtained post-mortem, have yielded new insights into DIPG molecular pathogenesis. We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high-grade glioma, other non-pontine pediatric high-grade gliomas, and even between pontine gliomas. The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation, maintenance, and progression. Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG. To date, clinical trials of newly diagnosed or progressive DIPG with epigenetic (histone) modifiers have been unsuccessful. Whether this failure represents limited activity of the agents used, their CNS penetration, redundant pathways within the tumor, or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth, suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways and the drugs designed to target them. In this review, we will discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment strategies directed against the unique abnormalities present in this disease. C1 [Morales La Madrid, Andres] Hosp St Joan de Deu, Dept Pediat Hematol & Oncol, Pediat Neurooncol, Barcelona, Spain. [Hashizume, Rintaro] Northwestern Univ, Dept Neurol Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Hashizume, Rintaro] Northwestern Univ, Dept Biochem & Mol Genet, Feinberg Sch Med, Chicago, IL 60611 USA. [Kieran, Mark W.] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Pediat Neurooncol, Boston, MA USA. RP La Madrid, AM (reprint author), St Joan de Deu Childrens Hosp, Dept Pediat Hematol & Oncol, Neurooncol Unit, Passeig St Joan de Deu 2, Barcelona 08950, Spain. EM amorales@hsjdbcn.org; mark_kieran@dfci.harvard.edu NR 30 TC 0 Z9 0 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD JUL 1 PY 2015 VL 5 AR 148 DI 10.3389/fonc.2015.00148 PG 5 WC Oncology SC Oncology GA CO4RQ UT WOS:000359148700001 ER PT J AU Mutumba, M Musiime, V Tsai, AC Byaruhanga, J Kiweewa, F Bauermeister, JA Snow, RC AF Mutumba, Massy Musiime, Victor Tsai, Alexander C. Byaruhanga, Judith Kiweewa, Francis Bauermeister, Jose A. Snow, Rachel C. TI Disclosure of HIV Status to Perinatally Infected Adolescents in Urban Uganda: A Qualitative Study on Timing, Process, and Outcomes SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE adolescents; Africa; children; HIV care; infectious diseases; pediatrics ID HEALTH-CARE; CHILDREN; ZIMBABWE AB Disclosure of HIV status to children and adolescents living with HIV remains a challenge in pediatric HIV care. Many of the current disclosure guidelines from national and international bodies recommend that perinatally infected children be informed of their HIV status prior to adolescence, but rates of disclosure in both high- and low-income countries remains low. The applicability of the recommendations to low-income countries remains largely unknown, as few studies have explored the disclosure process in these settings. Our purpose was to explore disclosure experiences of HIV-infected adolescents in Uganda. Disclosure was a largely one-time event conducted by health care providers. The average age at disclosure was 13 years. Disclosure elicited a diverse array of positive and negative reactions, including suicidal ideation; reactions were closely associated with participant age, gender, knowledge about HIV, and health status at time of disclosure. Interventions to promote locally effective, process-oriented approaches to early disclosure are needed. Copyright (C) 2015 Association of Nurses in AIDS Care C1 [Mutumba, Massy] Univ Michigan, Sch Publ Hlth, Ctr Sexual & Hlth Dispar, Ann Arbor, MI 48109 USA. [Musiime, Victor] Makerere Univ, Coll Hlth Sci, Dept Pediat, Kampala, Uganda. [Musiime, Victor] Joint Clin Res Ctr, Kampala, Uganda. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Byaruhanga, Judith] Joint Clin Res Ctr, Kampala, Uganda. [Kiweewa, Francis] Makerere Univ, Walter Reed Project, Res & Sci Affairs, Kampala, Uganda. [Bauermeister, Jose A.; Snow, Rachel C.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. RP Mutumba, M (reprint author), Univ Michigan, Sch Publ Hlth, Ctr Sexual & Hlth Dispar, Ann Arbor, MI 48109 USA. OI Mutumba, Massy/0000-0002-0636-891X; Tsai, Alexander/0000-0001-6397-7917; Bauermeister, Jose/0000-0002-9276-2306 FU University of Michigan FX This study was facilitated through grants from various institutions at the University of Michigan. We are especially grateful for the management and staff at the Joint Clinical Research Center, Kampala, especially the Pediatric Clinic for their willingness to share their time and insights. Special thanks also to all the respondents who so willingly labored through the interviews and focus group discussions to share their unique insights. NR 33 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 1055-3290 EI 1552-6917 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD JUL-AUG PY 2015 VL 26 IS 4 BP 472 EP 484 DI 10.1016/j.jana.2015.02.001 PG 13 WC Nursing SC Nursing GA CO2QI UT WOS:000359001300018 PM 26066697 ER PT J AU Gant-Clark, V Skipper, J McCrackin, M Gaillard, S Coxe, DN AF Gant-Clark, Vanessa Skipper, Janice McCrackin, Monica Gaillard, Stacy Coxe, D. Nicole TI Veterans and HIV Screening Rates: Why Veterans Are Not Getting Tested, a Veterans Affairs Nursing Academic Partnership (VANAP) Study SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE barriers to HIV screening; HIV testing; veterans; Veterans Affairs Nursing Academic Partnership C1 [Gant-Clark, Vanessa; Skipper, Janice; Gaillard, Stacy] Ralph H Johnson VA Med Ctr VAMC, Clin Fac, VANAP, Charleston, SC 29401 USA. [McCrackin, Monica; Coxe, D. Nicole] Ralph H Johnson VAMC, Charleston, SC USA. RP Gant-Clark, V (reprint author), Ralph H Johnson VA Med Ctr VAMC, Clin Fac, VANAP, Charleston, SC 29401 USA. FU Center for Community Health Partnerships for the Community Engaged Scholars Program (MUSC) FX This study was an initiative of the Veterans Affairs Nursing Academic Partnership (VANAP) Clinical Nursing Faculty, and their academic partners, the Medical University of South Carolina's College of Nursing (MUSC CON) in cooperation with the VA Office of Academic Affiliations. It was funded by a collaborative grant from the Center for Community Health Partnerships for the Community Engaged Scholars Program (MUSC, 2012). Charlene Pope, PhD, MPH, RN, Associate Nurse Executive for Research at the Ralph H. Johnson VA Medical Center (VAMC), was instrumental in the grant writing and mentoring through the institutional review board process. During the implementation of the method, MUSC CON Community Health Students were involved for three different semesters. They were instrumental in conducting focus groups, marketing, recruiting, and data collection. Low Country AIDS Services provided initial data regarding the state of South Carolina's HIV infection test results, broken down by counties. Ms. Lynn Nes, PhD, RN, provided assistance with the NVivo program. Dr. Jan York, PhD, RN, brought expertise in the writing for journal specificity. Preston Church, MD, Chief of Infectious Diseases at Ralph H. Johnson VAMC, was supportive in assisting veterans with access to care. Stephen Lesieur, MSN, RN, and Erica Grate-Simmons, MSN, RN, were contributing VANAP Faculty. Finally, we wish to thank our veterans for their continued service to our country and their enthusiasm in helping conduct this research study. NR 10 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 EI 1552-6917 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD JUL-AUG PY 2015 VL 26 IS 4 BP 485 EP 491 DI 10.1016/j.jana.2015.03.002 PG 7 WC Nursing SC Nursing GA CO2QI UT WOS:000359001300019 PM 26066698 ER PT J AU Llico, AF Zanartu, M Gonzalez, AJ Wodicka, GR Mehta, DD Van Stan, JH Hillman, RE AF Llico, Andres F. Zanartu, Matias Gonzalez, Agustin J. Wodicka, George R. Mehta, Daryush D. Van Stan, Jarrad H. Hillman, Robert E. TI Real-time estimation of aerodynamic features for ambulatory voice biofeedback SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VOCAL HYPERFUNCTION AB The development of ambulatory voice monitoring devices has the potential to improve the diagnosis and treatment of voice disorders. In this proof-of-concept study, real-time biofeedback is incorporated into a smartphone-based platform that records and processes neck surface acceleration. The focus is on utilizing aerodynamic measures of vocal function as a basis for biofeedback. This is done using regressed Z-scores to compare recorded values to normative estimates based on sound pressure level and fundamental frequency. Initial results from the analysis of different voice qualities suggest that accelerometer-based estimates of aerodynamic parameters can be used for real-time ambulatory biofeedback. (C) 2015 Acoustical Society of America C1 [Llico, Andres F.; Zanartu, Matias; Gonzalez, Agustin J.] Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile. [Wodicka, George R.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Mehta, Daryush D.; Van Stan, Jarrad H.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Wodicka, George R.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. [Mehta, Daryush D.; Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mehta, Daryush D.; Van Stan, Jarrad H.; Hillman, Robert E.] MGH Inst Hlth Profess, Boston, MA 02114 USA. RP Zanartu, M (reprint author), Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile. EM andres.llico@usm.cl; matias.zanartu@usm.cl; agustin.gonzalez@usm.cl; wodicka@purdue.edu; mehta.daryush@mgh.harvard.edu; jvanstan@mghihp.edu; hillman.robert@mgh.harvard.edu RI Zanartu, Matias/I-3133-2012; researchers, ac3e/N-2008-2016 OI Zanartu, Matias/0000-0001-5581-4392; FU NIH-NIDCD [R33 DC011588, F31 DC014412]; MIT MISTI [MIT-Chile 2745333]; Voice Health Institute; CONICYT [FONDECYT 11110147, Basal FB0008] FX This work was supported by NIH-NIDCD Grants Nos. R33 DC011588 and F31 DC014412, CONICYT grants FONDECYT 11110147 and Basal FB0008, MIT MISTI Grant No. MIT-Chile 2745333, and a grant from the Voice Health Institute. A.F.L. acknowledges support provided by CONICYT and UTFSM. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 10 TC 2 Z9 2 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2015 VL 138 IS 1 BP EL14 EP EL19 DI 10.1121/1.4922364 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA CO1QB UT WOS:000358929000003 PM 26233054 ER PT J AU Tse, JR Zhang, ZY Long, JL AF Tse, Justin R. Zhang, Zhaoyan Long, Jennifer L. TI Effects of vocal fold epithelium removal on vibration in an excised human larynx model SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID PHONATION THRESHOLD PRESSURE AB This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure. (C) 2015 Acoustical Society of America C1 [Tse, Justin R.; Zhang, Zhaoyan; Long, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Long, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90074 USA. RP Long, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, CHS Room 62-132,650 Charles Young Dr, Los Angeles, CA 90095 USA. EM jrtse@mednet.ucla.edu; zyzhang@ucla.edu; jlong@mednet.ucla.edu RI Zhang, Zhaoyan/E-5215-2013; OI Zhang, Zhaoyan/0000-0002-2379-6086; Long, Jennifer/0000-0002-4185-2328 FU National Institute on Deafness and Other Communication Disorders at the National Institutes of Health [R01DC011299]; Department of Veteran's Affairs Career Development Award [IK2BX001944]; AOmegaA Carolyn L. Kuckien Student Research Fellowship FX This study was supported by Research Grant No. R01DC011299 from the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health (Z.Z.); Research Grant No. IK2BX001944 from the Department of Veteran's Affairs Career Development Award (J.L.L.); and the A Omega A Carolyn L. Kuckien Student Research Fellowship (J.R.T.). We would like to thank Dr. Yue Xuan for technical support. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2015 VL 138 IS 1 BP EL60 EP EL64 DI 10.1121/1.4922765 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA CO1QB UT WOS:000358929000011 PM 26233062 ER PT J AU Caceres, CF O'Reilly, KR Mayer, KH Baggaley, R AF Caceres, Carlos F. O'Reilly, Kevin R. Mayer, Kenneth H. Baggaley, Rachel TI PrEP implementation: moving from trials to policy and practice SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Editorial Material DE HIV; PrEP; key populations; scale-up; implementation science AB Introduction: It is increasingly clear that the HIV response will not be sustainable if the number of infections is not significantly reduced. Discussion: For two decades, research has been ongoing to identify new behavioural and biomedical strategies to prevent HIV infection. In the past few years, the efficacy of several new strategies has been demonstrated, including oral pre-exposure prophylaxis (PrEP; i.e. daily use of tenofovir/emtricitabine). Because several social, political and logistic barriers remain, however, optimal PrEP implementation will require a better dissemination of new evidence in a number of areas and additional implementation research from various disciplinary perspectives (i.e. social science, policy and ethics; health systems; and economics, including cost-effectiveness studies). Discussion of new evidence on those topics, as well as case studies of potential PrEP implementation in diverse environments, can improve the understanding of the role that PrEP may play in addressing the global HIV/AIDS epidemic. In light of these needs, the Network for Multidisciplinary Studies in ARV-based HIV Prevention (NEMUS) and the World Health Organization (WHO) were honoured to co-organize a special issue of JIAS aimed at contributing to a scholarly discussion of current conditions surrounding PrEP implementation, potential impact and efficiency, social science concerns and the study of PrEP implementation in specific country cases. The papers included in this monograph identify and cover many of the main aspects of the complex yet promising discussions around PrEP implementation today. Conclusions: This is a collection of timely contributions from global leaders in HIV research and policy that addresses geographic diversity, uses a trans-disciplinary approach and covers a variety of the complex issues raised by PrEP. As this publication will become accessible to all, we hope that it will remain a valuable resource for policy makers, programme managers, researchers and activists around the world at a moment of a paradigm shift of the global response to HIV. C1 [Caceres, Carlos F.] Cayetano Heredia Univ, Ctr Interdisciplinary Studies Sexual AIDS & Soc, Lima 18, Peru. [O'Reilly, Kevin R.; Baggaley, Rachel] WHO, HIV Programme, CH-1211 Geneva, Switzerland. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr Boston, Fenway Hlth, Boston, MA USA. RP Caceres, CF (reprint author), Cayetano Heredia Univ, Ctr Interdisciplinary Studies Sexual AIDS & Soc, Av Armendariz 445, Lima 18, Peru. EM Carlos.caceres@upch.pe OI Caceres, Carlos/0000-0002-8101-0790 FU NIAID NIH HHS [R01 AI099727]; NIMH NIH HHS [R21 MH102135]; World Health Organization [001] NR 10 TC 9 Z9 9 U1 2 U2 7 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PD JUL PY 2015 VL 18 SU 3 BP 1 EP 4 AR 20222 DI 10.7448/IAS.18.4.20222 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN8FQ UT WOS:000358675400001 PM 26198349 ER PT J AU Ajibola, G Shapiro, R Zash, R Holmes, L Batlang, O Ramogothobeng, K Chilisa, F Bennett, K Makhema, J Lockman, S Powis, K AF Ajibola, Gbolahan Shapiro, Roger Zash, Rebecca Holmes, Lewis Batlang, Oganne Ramogothobeng, Kerapetse Chilisa, Florence Bennett, Kara Makhema, Joseph Lockman, Shahin Powis, Kathleen TI Importance of programmatic longitudinal surveillance for identification of congenital anomalies among infants exposed to HIV-1 and antiretrovirals: findings from the Mpepu Study, Botswana SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Meeting Abstract C1 [Ajibola, Gbolahan; Zash, Rebecca; Batlang, Oganne; Ramogothobeng, Kerapetse; Chilisa, Florence; Makhema, Joseph; Lockman, Shahin; Powis, Kathleen] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Shapiro, Roger; Lockman, Shahin; Powis, Kathleen] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Shapiro, Roger; Zash, Rebecca] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Holmes, Lewis] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Bennett, Kara] Bennett Stat Consulting, Ballston Lake, NY USA. [Lockman, Shahin] Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PD JUL PY 2015 VL 18 SU 4 MA MOPDB0104 DI 10.7448/IAS.18.5.20428 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN8FS UT WOS:000358675700146 ER PT J AU Karn, J Das, B Dobrowolski, C Scully, E Deeks, S Gandhi, M Johnston, R AF Karn, Jonathan Das, Biswajit Dobrowolski, Curtis Scully, Eileen Deeks, Steven Gandhi, Monica Johnston, Rowena TI Oestrogen blocks HIV re-emergence from latency and points to gender-specific differences in HIV reservoirs SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Meeting Abstract C1 [Karn, Jonathan; Das, Biswajit; Dobrowolski, Curtis] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Scully, Eileen] Brigham & Womens, Boston, MA USA. [Scully, Eileen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deeks, Steven; Gandhi, Monica] UCSF Sch Med, San Francisco, CA USA. [Johnston, Rowena] Fdn AIDS Res, AmfAR, New York, NY USA. EM jonathan.karn@case.edu NR 0 TC 0 Z9 0 U1 1 U2 4 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PD JUL PY 2015 VL 18 SU 4 MA TUAA0205LB DI 10.7448/IAS.18.5.20543 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN8FS UT WOS:000358675700056 ER PT J AU Lin, AP Abbas, S Kim, SW Ortega, M Bouamar, H Escobedo, Y Varadarajan, P Qin, YJ Sudderth, J Schulz, E Deutsch, A Mohan, S Ulz, P Neumeister, P Rakheja, D Gao, XL Hinck, A Weintraub, ST DeBerardinis, RJ Sill, H Dahia, PLM Aguiar, RCT AF Lin, An-Ping Abbas, Saman Kim, Sang-Woo Ortega, Manoela Bouamar, Hakim Escobedo, Yissela Varadarajan, Prakash Qin, Yuejuan Sudderth, Jessica Schulz, Eduard Deutsch, Alexander Mohan, Sumitra Ulz, Peter Neumeister, Peter Rakheja, Dinesh Gao, Xiaoli Hinck, Andrew Weintraub, Susan T. DeBerardinis, Ralph J. Sill, Heinz Dahia, Patricia L. M. Aguiar, Ricardo C. T. TI D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2 SO NATURE COMMUNICATIONS LA English DT Article ID B-CELL LYMPHOMA; D-2-HYDROXYGLUTARIC ACIDURIA; L-2-HYDROXYGLUTARATE DEHYDROGENASE; GENETIC-HETEROGENEITY; TUMOR-CELLS; MUTATIONS; CANCER; 2-HYDROXYGLUTARATE; ONCOMETABOLITE; PATHWAY AB Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (alpha-KG). In cancer, mutant IDH1/2 reduces alpha-KG to D2-hydroxyglutarate (D2-HG) disrupting alpha-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into alpha-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates alpha-KG levels, influencing histone and DNA methylation, and HIF1 alpha hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate alpha-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and alpha-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases. C1 [Lin, An-Ping; Abbas, Saman; Kim, Sang-Woo; Ortega, Manoela; Bouamar, Hakim; Escobedo, Yissela; Varadarajan, Prakash; Qin, Yuejuan; Dahia, Patricia L. M.; Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, San Antonio, TX 78229 USA. [Sudderth, Jessica; Rakheja, Dinesh; DeBerardinis, Ralph J.] Univ Texas Southwestern, Dept Pediat, Childrens Med Ctr, Res Inst, Dallas, TX 75390 USA. [Schulz, Eduard; Deutsch, Alexander; Neumeister, Peter; Sill, Heinz] Med Univ Graz, Div Hematol, A-8036 Graz, Austria. [Mohan, Sumitra; Ulz, Peter] Med Univ Graz, Inst Human Genet, A-8036 Graz, Austria. [Rakheja, Dinesh] Univ Texas SW Med Ctr Dallas, Dept Pathol & Pediat, Dallas, TX 75390 USA. [Gao, Xiaoli; Hinck, Andrew; Weintraub, Susan T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Dahia, Patricia L. M.; Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Dahia, Patricia L. M.; Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] South Texas Vet Hlth Care Syst, Audie Murphy VA Hosp, San Antonio, TX 78229 USA. RP Aguiar, RCT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, San Antonio, TX 78229 USA. EM aguiarr@uthscsa.edu OI Sill, Heinz/0000-0003-0993-4371; Ulz, Peter/0000-0001-5941-1160 FU NIH [R01-CA138747]; CPRIT [RP140452]; Voelcker Fund; Leukamiehilfe Steiermark; Cancer Center support grant [P30 CA054174]; UTHSCSA; National Institutes of Health [1S10RR031586-01] FX We thank Marsha Kinney and the Pathology Core Laboratory at the University of Texas HSC San Antonio for procurement of the primary DLBCL samples; C. Beham-Schmid for providing bone marrow specimens; K. Lind and S. Hofer for VNTR analyses. This work was supported by an NIH grant R01-CA138747 (to R.C.T.A.), a CPRIT award RP140452 (to R.C.T.A.), Young Investigator Awards from the Voelcker Fund (to P.L.M.D. and R.C.T.A.), Leukamiehilfe Steiermark (to H.S.), and a Cancer Center support grant P30 CA054174. Mass spectrometry analyses were conducted in the metabolomics component of the UTHSCSA Mass Spectrometry Laboratory, supported by UTHSCSA and by an award from the National Institutes of Health, 1S10RR031586-01 (S.T.W.). NR 45 TC 6 Z9 6 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2015 VL 6 AR 7768 DI 10.1038/ncomms8768 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO0RK UT WOS:000358859700005 PM 26178471 ER PT J AU Reddy, VB Sun, SH Azimi, E Elmariah, SB Dong, XZ Lerner, EA AF Reddy, Vemuri B. Sun, Shuohao Azimi, Ehsan Elmariah, Sarina B. Dong, Xinzhong Lerner, Ethan A. TI Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs SO NATURE COMMUNICATIONS LA English DT Article ID MOLECULAR-CLONING; ATOPIC-DERMATITIS; PAIN; MECHANISM; GPCRS; HYPERALGESIA; PSORIASIS; PRURITUS; PEPTIDE; NEURONS AB Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs) mediate histamine-independent itch. We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-dependent scratching in mice. In contrast to its activation of conventional protease-activated receptors, cathepsin S-mediated activation of MrgprC11 did not involve the generation of a tethered ligand. We demonstrate further that different cysteine proteases selectively activate specific mouse and human Mrgpr family members. This expansion of our understanding by which proteases interact with G-protein-coupled receptors (GPCRs) redefines the concept of what constitutes a protease-activated receptor. The findings also implicate proteases as ligands to members of this orphan receptor family while providing new insights into how cysteine proteases contribute to itch. C1 [Reddy, Vemuri B.; Azimi, Ehsan; Elmariah, Sarina B.; Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA 02129 USA. [Sun, Shuohao; Dong, Xinzhong] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA 02129 USA. EM elerner@mgh.harvard.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Neurological Disease and Stroke of the National Institutes of Health [R01AR05744, R21AR067399, R01NS054791]; LEO Pharma; Dermatology Foundation; Women's Dermatologic Society; National Eczema Association FX Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Neurological Disease and Stroke of the National Institutes of Health under Award Numbers R01AR05744 and R21AR067399 to E.A.L. and R01NS054791 to X.D. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. X.D. is an Early Career Scientist of the Howard Hughes Medical Institute. Support was also provided by a grant from LEO Pharma to E.A.L. S.B.E. is the recipient of a Career Development Award from the Dermatology Foundation and received support from the Women's Dermatologic Society. E.A. is the recipient of a grant from the National Eczema Association. NR 37 TC 9 Z9 9 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2015 VL 6 AR 7864 DI 10.1038/ncomms8864 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO0SD UT WOS:000358861700004 PM 26216096 ER PT J AU Rehani, MM AF Rehani, M. M. TI LOOKING INTO FUTURE: CHALLENGES IN RADIATION PROTECTION IN MEDICINE SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID COMPUTED-TOMOGRAPHY; CANCER-RISK; CT SCANS; EXPOSURE; TRACKING; CHILDHOOD AB Radiation protection in medicine is becoming more and more important with increasing wider use of X-rays, documentation of effects besides the potential for long-term carcinogenic effects. With computed tomography (CT) likely to become sub-mSv in coming years, positron emission tomography (PET), single photon emission computed tomography (SPECT) and some of the nuclear medical examination will become focus of attraction as high-dose examinations, even though they are less-frequent ones. Clarity will be needed on radiation effects at levels of radiation doses encountered in a couple of CT scans and if effects are really cumulative. There is challenge to develop radiation metrics that can be used as easily as units of temperature and length and avoidance of multiple meaning of a single dose metric. Other challenges include development of biological indicators of radiation dose, transition from dose to a representative phantom to dose to individual patient, system for tracking of radiation exposure history of patient, avoidance of radiation-induced skin injury in patients and radiation cataract in staff, cutting down inappropriate referrals for radiological examinations, confidence building in patient and patient safety in radiotherapy. C1 [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 19 TC 2 Z9 2 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 3 EP 6 DI 10.1093/rpd/ncv071 PG 4 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 CN5DF UT WOS:000358449300002 PM 25848110 ER PT J AU Rehani, MM AF Rehani, M. M. TI RADIATION EFFECTS AND RISKS: OVERVIEW AND A NEW RISK PERCEPTION INDEX SO RADIATION PROTECTION DOSIMETRY LA English DT Article AB Uncertainty provides opportunities for differences in perception, and radiation risks at low level of exposures involved in few computed tomography scans fall in this category. While there is good agreement among national and international organisations on risk probability of cancer, risk perception has barely been dealt with by these organisations. Risk perception is commonly defined as the subjective judgment that people make about the characteristics and severity of a risk. Severity and latency are important factors in perception. There is a need to connect all these. Leaving risk perception purely as a subjective judgement provides opportunities for people to amplifying risk. The author postulates a risk perception index as severity divided by latency that becomes determining factor for risk perception. It is hoped that this index will bring rationality in risk perception. C1 [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 6 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 7 EP 9 DI 10.1093/rpd/ncv117 PG 3 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 CN5DF UT WOS:000358449300003 PM 25836696 ER PT J AU Rehani, MM Holmberg, O AF Rehani, M. M. Holmberg, O. TI IAEA EXPERIENCE IN COMMUNICATING RADIATION RISKS THROUGH THE RPOP WEBSITE SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID PROTECTION AB The authors report here their successful experience of communicating information to health professionals, patients and the public on benefits and risks of ionising radiation in medical applications. The approaches used have been based on giving importance to clinical benefits against risks, as well as safety in use against risk of use. Communicating brief messages against catchy questions with positive and pragmatic approach resulted in making website on radiation protection of patients (RPOP) as the top website of the world in this area. Credibility of information has been maintained. The results show immense outreach in 213 countries/territories. C1 [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA USA. [Rehani, M. M.] Exint Atom Energy Agcy, Vienna, Austria. [Holmberg, O.] IAEA, A-1400 Vienna, Austria. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 22 EP 24 DI 10.1093/rpd/ncv042 PG 3 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 CN5DF UT WOS:000358449300007 PM 25813478 ER PT J AU Rehani, MM AF Rehani, M. M. TI TRACKING OF EXAMINATION AND DOSE: OVERVIEW SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID PATIENT EXPOSURE TRACKING; RADIATION-EXPOSURE; SMART CARD AB This paper reviews the developments in tracking of patient exposures and dose after the earlier paper published in the same journal in 2011. A global survey in which 76 countries responded indicated strong interest in programme and another survey among referring physicians showed vast majority (71.7 %) of physicians expressing that awareness of previous history of CT scans would always or mostly lead them to a better decision on referring patients for CT scans. A sizable number of countries have system of assigning permanent ID to individuals and nearly half of them use this ID in medical records. This can easily permit tracking of exposures. Templates for tracking at different levels of health care have been provided, and experience from a country where tracking is routinely practised has been published. C1 [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA USA. [Rehani, M. M.] Exint Atom Energy Agcy, Vienna, Austria. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 10 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 50 EP 52 DI 10.1093/rpd/ncv026 PG 3 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 CN5DF UT WOS:000358449300014 PM 25790824 ER PT J AU Rehani, MM AF Rehani, Madan M. TI DOSE SURVEYS AND DRLS: CRITICAL LOOK AND WAY FORWARD SO RADIATION PROTECTION DOSIMETRY LA English DT Article AB The main purpose of dose surveys has been to detect and bring down wide variation in radiation doses for any particular radiological examination and to avoid doses that are on higher side. Diagnostic reference levels (DRLs) have been used for over two decades as an aid in this objective. With very limited success that has been achieved through DRL, the author has recently described a new term 'acceptable quality dose' (AQD) that is aimed at optimisation within the DRL, is facility initiated and takes into account all three important parameters-image quality, dose and patient's body build. It is hoped that AQD will be found easy to establish, will be a useful tool to achieve optimisation in the facilities and will serve as the standard dose. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Rehani, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM madan.rehani@gmail.com NR 15 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 67 EP 69 DI 10.1093/rpd/ncv063 PG 3 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 CN5DF UT WOS:000358449300018 PM 25809110 ER PT J AU Vassileva, J Rehani, M Kostova-Lefterova, D Al-Naemi, HM Al Suwaidi, JS Arandjic, D Bashier, EHO Renha, SK El-Nachef, L Aguilar, JG Gershan, V Gershkevitsh, E Gruppetta, E Hustuc, A Jauhari, A Kharita, MH Khelassi-Toutaoui, N Khosravi, HR Khoury, H Kralik, I Mahere, S Mazuoliene, J Mora, P Muhogora, W Muthuvelu, P Nikodemova, D Novak, L Pallewatte, A Pekarovic, D Shaaban, M Shelly, E Stepanyan, K Thelsy, N Visrutaratna, P Zaman, A AF Vassileva, J. Rehani, M. Kostova-Lefterova, D. Al-Naemi, H. M. Al Suwaidi, J. S. Arandjic, D. Bashier, E. H. O. Kodlulovich Renha, S. El-Nachef, L. Aguilar, J. G. Gershan, V. Gershkevitsh, E. Gruppetta, E. Hustuc, A. Jauhari, A. Kharita, Mohammad Hassan Khelassi-Toutaoui, N. Khosravi, H. R. Khoury, H. Kralik, I. Mahere, S. Mazuoliene, J. Mora, P. Muhogora, W. Muthuvelu, P. Nikodemova, D. Novak, L. Pallewatte, A. Pekarovic, D. Shaaban, M. Shelly, E. Stepanyan, K. Thelsy, N. Visrutaratna, P. Zaman, A. TI A STUDY TO ESTABLISH INTERNATIONAL DIAGNOSTIC REFERENCE LEVELS FOR PAEDIATRIC COMPUTED TOMOGRAPHY SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID RADIATION-EXPOSURE; LATIN-AMERICA; 40 COUNTRIES; CT EXPOSURE; IAEA SURVEY; RISK; CHILDREN; CANCER; EUROPE; ASIA AB The article reports from the largest international dose survey in paediatric computed tomography (CT) in 32 countries and proposes international diagnostic reference levels (DRLs) in terms of computed tomography dose index (CTDIvol) and dose length product (DLP). It also assesses whether mean or median values of individual facilities should be used. A total of 6115 individual patient data were recorded among four age groups: <1 y, >1-5 y, >5-10 y and >10-15 y. CTDIw, CTDIvol and DLP from the CT console were recorded in dedicated forms together with patient data and technical parameters. Statistical analysis was performed, and international DRLs were established at rounded 75th percentile values of distribution of median values from all CT facilities. The study presents evidence in favour of using median rather than mean of patient dose indices as the representative of typical local dose in a facility, and for establishing DRLs as third quartile of median values. International DRLs were established for paediatric CT examinations for routine head, chest and abdomen in the four age groups. DRLs for CTDIvol are similar to the reference values from other published reports, with some differences for chest and abdomen CT. Higher variations were observed between DLP values, based on a survey of whole multi-phase exams. It may be noted that other studies in literature were based on single phase only. DRLs reported in this article can be used in countries without sufficient medical physics support to identify non-optimised practice. Recommendations to improve the accuracy and importance of future surveys are provided. C1 [Vassileva, J.] IAEA, A-1400 Vienna, Austria. [Rehani, M.] Harvard Univ, Sch Med, Boston, MA USA. [Rehani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kostova-Lefterova, D.] Natl Ctr Radiobiol & Radiat Protect, Sofia, Bulgaria. [Al-Naemi, H. M.] Hamad Med Corp, Doha, Qatar. [Al Suwaidi, J. S.] Dubai Hlth Author, Med Educ Dept, Dubai, U Arab Emirates. [Arandjic, D.] Vinca Inst Nucl Sci, Radiat Protect Dept, Belgrade, Serbia. [Bashier, E. H. O.] Sudan Atom Energy Commiss, Khartoum, Sudan. [Kodlulovich Renha, S.] Natl Nucl Energy Commiss, Rio De Janeiro, Brazil. [El-Nachef, L.] Lebanese Atom Eneregy Commiss, Beirut, Lebanon. [Aguilar, J. G.] Natl Inst Nucl Res, La Marquesa, Ocoyoacac, Mexico. [Gershan, V.] Ss Cyril & Methodius Univ, Inst Phys, Skopje, Macedonia. [Gershkevitsh, E.] North Estonia Med Ctr, Tallinn, Estonia. [Gruppetta, E.] Mater Dei Hosp, Msida, Malta. [Hustuc, A.] Natl Ctr Publ Hlth, Kishinev, Moldova. [Jauhari, A.] Pusat Kajian Radiog Dan Imajing, Depok, Indonesia. [Kharita, Mohammad Hassan] Atom Energy Commiss Syria, Damascus, Syria. [Khelassi-Toutaoui, N.] Ctr Rech Nucl Alger, Dept Phys Med, Algiers, Algeria. [Khosravi, H. R.] Iranian Nucl Regulatory Author, Natl Radiat Protect Dept, Tehran, Iran. [Khoury, H.] Univ Fed Pernambuco, Recife, PE, Brazil. [Kralik, I.] State Off Radiol & Nucl Safety, Zagreb, Croatia. [Mahere, S.] Children Clin Univ Hosp, Riga, Latvia. [Mazuoliene, J.] Hosp Lithuanian Univ Hlth Sci Kauno Klin, Kaunas, Lithuania. [Mora, P.] Univ Costa Rica, Ctr Invest Ciencias Atom Nucl & Mol, San Jose, Costa Rica. [Muhogora, W.] Tanzania Atom Energy Commiss, Arusha, Tanzania. [Muthuvelu, P.] Minist Hlth Malaysia, Putrajaya Wilayah Persek, Malaysia. [Nikodemova, D.] Slovak Med Univ, Bratislava, Slovakia. [Novak, L.] Natl Radiat Protect Inst, Prague, Czech Republic. [Pallewatte, A.] Natl Hosp Sri Lanka, Dept Radiol, Colombo, Sri Lanka. [Pekarovic, D.] Univ Med Ctr, Clin Radiol Inst, Ljubljana, Slovenia. [Shaaban, M.] Al Sabah Hosp, Kuwait, Kuwait. [Shelly, E.] Minist Hlth, Med Technol & Infrastruct Adm, Jerusalem, Israel. [Stepanyan, K.] Res Ctr Radiat Med & Burns, Yerevan, Armenia. [Thelsy, N.] Minist Hlth, Yangon, Myanmar. [Visrutaratna, P.] Chiang Mai Univ, Fac Med, Dept Radiol, Chiang Mai 50000, Thailand. [Zaman, A.] PAEC, Inst Nucl Med & Oncol, Lahore, Pakistan. RP Vassileva, J (reprint author), IAEA, A-1400 Vienna, Austria. EM j.vassileva@iaea.org NR 31 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 70 EP 80 DI 10.1093/rpd/ncv116 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 CN5DF UT WOS:000358449300019 PM 25836685 ER PT J AU Vassileva, J Rehani, M AF Vassileva, J. Rehani, M. TI PATIENT GROUPING FOR DOSE SURVEYS AND ESTABLISHMENT OF DIAGNOSTIC REFERENCE LEVELS IN PAEDIATRIC COMPUTED TOMOGRAPHY SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID LATIN-AMERICA; 40 COUNTRIES; CT EXPOSURE; IAEA SURVEY; EUROPE; ASIA AB There has been confusion in literature on whether paediatric patients should be grouped according to age, weight or other parameters when dealing with dose surveys. The present work aims to suggest a pragmatic approach to achieve reasonable accuracy for performing patient dose surveys in countries with limited resources. The analysis is based on a subset of data collected within the IAEA survey of paediatric computed tomography (CT) doses, involving 82 CT facilities from 32 countries in Asia, Europe, Africa and Latin America. Data for 6115 patients were collected, in 34.5 % of which data for weight were available. The present study suggests that using four age groups, <1, >1-5, >5-10 and >10-15 y, is realistic and pragmatic for dose surveys in less resourced countries and for the establishment of DRLs. To ensure relevant accuracy of results, data for >30 patients in a particular age group should be collected if patient weight is not known. If a smaller sample is used, patient weight should be recorded and the median weight in the sample should be within 5-10 % from the median weight of the sample for which the DRLs were established. Comparison of results from different surveys should always be performed with caution, taking into consideration the way of grouping of paediatric patients. Dose results can be corrected for differences in patient weight/age group. C1 [Vassileva, J.] IAEA, A-1400 Vienna, Austria. [Rehani, M.] Harvard Univ, Sch Med, Boston, MA USA. [Rehani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vassileva, J (reprint author), IAEA, A-1400 Vienna, Austria. EM j.vassileva@iaea.org NR 28 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 81 EP 85 DI 10.1093/rpd/ncv113 PG 5 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 CN5DF UT WOS:000358449300020 PM 25836695 ER PT J AU Rehani, MM AF Rehani, M. M. TI EYE DOSE ASSESSMENT AND MANAGEMENT: OVERVIEW SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID INTERVENTIONAL RADIOLOGY; LENS DOSIMETRY; NUCLEAR-MEDICINE; RADIATION; POSITIONS; HOSPITALS; CATARACT; WORKERS AB Some publications have shown that Hp((0.07)) or even Hp((10)) can be used as good operational quantities for X-rays in view of difficulties with Hp(3). With increasing awareness, there is tendency to use whatever dosimeter is available with correction factor to estimate eye lens dose. The best position for an eye lens dosimeter has been reported to be at the side of the head nearest to the radiation source, close to the eye. Recent studies have reported eye doses with cone beam CT (CBCT) both for patients and staff, and there are many papers reporting eye lens doses to staff in nuclear medicine. To minimise the dose to eyes, the user can take advantage of a feature of CBCT of projections acquired over an angular span of 1808 plus cone angle of the X-ray tube and with tube under scan arcs. C1 [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 20 TC 1 Z9 1 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUL PY 2015 VL 165 IS 1-4 BP 276 EP 278 DI 10.1093/rpd/ncv048 PG 3 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 CN5DF UT WOS:000358449300062 PM 25813481 ER PT J AU Wong, JC Li, WJ Gao, X AF Wong, Janice C. Li, Weijuan Gao, Xiang TI Restless Legs Syndrome as a Prognostic Tool for Cardiovascular Disease SO SLEEP LA English DT Editorial Material ID CLINICAL CHARACTERISTICS; WOMEN; HYPERTENSION; ASSOCIATION; POPULATION; OBESITY; RISK C1 [Wong, Janice C.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wong, Janice C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wong, Janice C.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Weijuan] Penn State Univ, Albert Einstein Coll Med, Dept Med, University Pk, PA 16802 USA. [Gao, Xiang] Penn State Univ, Dept Nutr Hlth, University Pk, PA 16802 USA. RP Gao, X (reprint author), Penn State Univ, Dept Nutr Sci, 109 Chandlee Lab, University Pk, PA 16802 USA. EM xxg14@psu.edu NR 14 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JUL 1 PY 2015 VL 38 IS 7 BP 995 EP 996 AR PII sp-00285-15 DI 10.5665/sleep.4790 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO0JO UT WOS:000358837000001 PM 26085294 ER PT J AU Pace-Schott, EF AF Pace-Schott, Edward F. TI Analog Flashbacks SO SLEEP LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA FILM PARADIGM; EMOTIONAL MEMORY; REM-SLEEP; CONDITIONED FEAR; PTSD SYMPTOMS; EXTINCTION; CONSOLIDATION; PROPRANOLOL; RECONSOLIDATION C1 [Pace-Schott, Edward F.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Pace-Schott, Edward F.] Massachusetts Gen Hosp, Charlestown, MA USA. RP Pace-Schott, EF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat, East 149 13th St,Room 2624, Charlestown, MA 02129 USA. EM epace-schott@mgh.harvard.edu NR 48 TC 1 Z9 1 U1 1 U2 7 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JUL 1 PY 2015 VL 38 IS 7 BP 997 EP 999 AR PII sp-00284-15 DI 10.5665/sleep.4792 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO0JO UT WOS:000358837000002 PM 26085293 ER PT J AU Mehta, SJ Polsky, D Zhu, JS Lewis, JD Kolstad, JT Loewenstein, G Volpp, KG AF Mehta, Shivan J. Polsky, Daniel Zhu, Jingsan Lewis, James D. Kolstad, Jonathan T. Loewenstein, George Volpp, Kevin G. TI ACA-Mandated Elimination of Cost Sharing for Preventive Screening Has Had Limited Early Impact SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID DIRECTED HEALTH PLANS; MYOCARDIAL-INFARCTION; MEDICATION ADHERENCE; COLONOSCOPY; COPAYMENTS; INSURANCE; SERVICES; CARE AB Objectives: The Affordable Care Act eliminated patient cost sharing for evidence-based preventive care, yet the impact of this policy on colonoscopy and mammography rates is unclear. We examined the elimination of cost sharing among small business beneficiaries of Humana, a large national insurer. Study Design: This was a retrospective interrupted time series analysis of whether the change in cost-sharing policy was associated with a change in screening utilization, using grandfathered plans as a comparison group. Methods: We compared beneficiaries in small business non-grandfathered plans that were required to eliminate cost sharing (intervention) with those in grandfathered plans that did not have to change cost sharing (control). There were 63,246 men and women aged 50 to 64 years eligible for colorectal cancer screening, and 30,802 women aged 50 to 64 years eligible for breast cancer screening. The primary outcome variables were rates of colonoscopy and mammography per person-month, with secondary analysis of colonoscopy rates coded as preventive only. Results: There was no significant change in the level or slope of colonoscopy and mammography utilization for intervention plans relative to the control plans. There was also no significant relevant change among those colonoscopies coded as preventive. Conclusions: The results suggest that the implementation of the policy is not having its intended effects, as cost sharing rates for colonoscopy and mammography did not change substantially, and utilization of colonoscopy and mammography changed little, following this new policy approach. C1 [Mehta, Shivan J.; Polsky, Daniel; Lewis, James D.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Lewis, James D.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lewis, James D.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mehta, Shivan J.; Polsky, Daniel; Zhu, Jingsan; Lewis, James D.; Kolstad, Jonathan T.; Loewenstein, George; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Mehta, Shivan J.; Volpp, Kevin G.] Penn Med Ctr Hlth Care Innovat, Philadelphia, PA USA. [Kolstad, Jonathan T.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Mehta, SJ (reprint author), Univ Penn, Perelman Sch Med, 1318 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shivan.mehta@uphs.upenn.edu FU Humana, National Institutes of Health [K24 DK078228, T32 DK007740] FX Humana, National Institutes of Health (K24 DK078228, T32 DK007740). NR 24 TC 3 Z9 3 U1 0 U2 6 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2015 VL 21 IS 7 BP 511 EP U59 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN8CC UT WOS:000358664000007 PM 26247741 ER PT J AU Hershenberg, R Paulson, D Gros, DF Acierno, R AF Hershenberg, Rachel Paulson, Daniel Gros, Daniel F. Acierno, Ron TI Does Amount and Type of Activity Matter in Behavioral Activation? A Preliminary Investigation of the Relationship between Pleasant, Functional, and Social Activities and Outcome SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY LA English DT Article DE Behavioral activation; positive events; functional events; social events; depression; bereavement ID BECK DEPRESSION INVENTORY; COMPLICATED GRIEF; POSTPARTUM DEPRESSION; THERAPEUTIC EXPOSURE; COGNITIVE THERAPY; DAILY EVENTS; BEREAVEMENT; DISORDER; ADULTS; METAANALYSIS AB Background: Accumulating evidence supports behavioral activation (BA) as an effective stand-alone treatment for improving depression and related conditions, though little is known about the factors that influence positive outcomes. Such research is ripe for future dissemination and implementation efforts, particularly among vulnerable older adult populations in need of such efficacious and transportable treatments. Aims: Given the central but largely unexamined role that increasing activities plays in BA, we investigated the association between participation in weekly activities and treatment outcome. Method: As a preliminary study of this research question, we report on a sample of 20 older adults with symptoms of depression and complicated bereavement who completed 5 weeks of BA, pre-and posttreatment measures, and weekly planners of BA activities. All activities were coded as either functional or pleasurable (by participants) and if they were social in nature (by trained coders). Results: Overall, BA was associated with reductions in symptomatology. However, participants' total number of reported activities, and their relative proportion of functional, pleasurable, and social activities, did not significantly relate to their improvement in symptoms. Conclusion: One interpretation of the findings suggests that countering avoidance more generally, potentially independent of the specific type or total amount of activation activities, may be associated with amelioration of symptomatology. C1 [Hershenberg, Rachel] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Philadelphia, PA 19104 USA. [Paulson, Daniel] Univ Cent Florida, Orlando, FL 32816 USA. [Gros, Daniel F.; Acierno, Ron] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Gros, Daniel F.; Acierno, Ron] Med Univ S Carolina, Charleston, SC USA. RP Hershenberg, R (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM rhersh@mail.med.upenn.edu FU National Institute of Aging [R21-AG023495-01A2]; VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA FX This work was partially supported by a grant from the National Institute of Aging (R21-AG023495-01A2). This paper was prepared with the support of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. The views expressed in the article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There were no conflicts of interest related to this project or its authors. We would like to thank Carl Lejuez and Julia Rossi for their feedback during the preparation of this manuscript. NR 45 TC 2 Z9 2 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1352-4658 EI 1469-1833 J9 BEHAV COGN PSYCHOTH JI Behav. Cognit. Psychther. PD JUL PY 2015 VL 43 IS 4 BP 396 EP 411 DI 10.1017/S1352465813001185 PG 16 WC Psychology, Clinical SC Psychology GA CN8VM UT WOS:000358723500002 PM 24621452 ER PT J AU Glavey, SV Huynh, D Reagan, MR Manier, S Moschetta, M Kawano, Y Roccaro, AM Ghobrial, IM Joshi, L O'Dwyer, ME AF Glavey, Siobhan V. Huynh, Daisy Reagan, Michaela R. Manier, Salomon Moschetta, Michele Kawano, Yawara Roccaro, Aldo M. Ghobrial, Irene M. Joshi, Lokesh O'Dwyer, Michael E. TI The cancer glycome: Carbohydrates as mediators of metastasis SO BLOOD REVIEWS LA English DT Review DE Post-translational modification; Glycans; Glycosylation; Glycome; Cancer; Trafficking; Metastasis ID SIALYL-TN ANTIGENS; N-ACETYLGLUCOSAMINYLTRANSFERASE-V; BETA-1-6 BRANCHED OLIGOSACCHARIDES; SELECTIN LIGAND EXPRESSION; MULTIPLE-MYELOMA CELLS; HUMAN BREAST-CARCINOMA; TUMOR PROGRESSION; GENE-EXPRESSION; ADHESION MOLECULES; PANCREATIC-CANCER AB Glycosylation is a frequent post-translational modification which results in the addition of carbohydrate determinants, "glycans", to cell surface proteins and lipids. These glycan structures form the "glycome" and play an integral role in cell-cell and cell-matrix interactions through modulation of adhesion and cell trafficking. Glycosylation is increasingly recognized as a modulator of the malignant phenotype of cancer cells, where the interaction between cells and the tumor micro-environment is altered to facilitate processes such as drug resistance and metastasis. Changes in glycosylation of cell surface adhesion molecules such as selectin ligands, integrins and mucins have been implicated in the pathogenesis of several solid and hematological malignancies, often with prognostic implications. In this review we focus on the functional significance of alterations in cancer cell glycosylation, in terms of cell adhesion, trafficking and the metastatic cascade and provide insights into the prognostic and therapeutic implications of recent findings in this fast-evolving niche. (c) 2015 Elsevier Ltd. All rights reserved. C1 [Glavey, Siobhan V.; Huynh, Daisy; Reagan, Michaela R.; Manier, Salomon; Moschetta, Michele; Kawano, Yawara; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Glavey, Siobhan V.; Joshi, Lokesh; O'Dwyer, Michael E.] Natl Univ Ireland Univ Coll Galway, Glycosci Res Grp, Galway, Ireland. [O'Dwyer, Michael E.] Natl Univ Ireland Univ Coll Galway, Dept Hematol, Galway, Ireland. [O'Dwyer, Michael E.] Galway Univ Hosp, Galway, Ireland. RP O'Dwyer, ME (reprint author), Natl Univ Ireland Univ Coll Galway, Dept Hematol, Galway, Ireland. EM siobhan_glavey@dfci.harvard.edu; Daisy_Huynh@DFCI.HARVARD.EDU; MichaelaR_Reagan@DFCI.HARVARD.EDU; Salomon_Manier@DFCI.HARVARD.EDU; MICHELE_MOSCHETTA@DFCI.HARVARD.EDU; Yawara_Kawano@DFCI.HARVARD.EDU; Aldo_Roccaro@dfci.harvard.edu; irene_ghobrial@dfci.harvard.edu; lokesh.joshi@nuigalway.ie; michael.odwyer@nuigalway.ie RI Reagan, Michaela/E-3549-2017; OI Roccaro, Aldo/0000-0002-1872-5128; o'dwyer, michael/0000-0002-6173-7140; Reagan, Michaela/0000-0003-2884-6481 FU Science Foundation Ireland [08/SRC/B1393, 07/SK/B1250]; EU [260600]; Health Research Board [CSA/2012/10] FX LJ acknowledges the Science Foundation Ireland [Alimentary Glycoscience Research Cluster, grant number 08/SRC/B1393 and Stokes Professor for Glycosciences, grant number 07/SK/B1250] and EU-FP7 GlycoHIT (grant number 260600) for their support. MO'D acknowledges the support of the Health Research Board, grant number CSA/2012/10. NR 158 TC 18 Z9 19 U1 6 U2 54 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X EI 1532-1681 J9 BLOOD REV JI Blood Rev. PD JUL PY 2015 VL 29 IS 4 BP 269 EP 279 DI 10.1016/j.blre.2015.01.003 PG 11 WC Hematology SC Hematology GA CN5IB UT WOS:000358461900007 PM 25636501 ER PT J AU Braga-Neto, P Pedroso, JL Barsottini, OGP Schmahmann, JD AF Braga-Neto, Pedro Pedroso, Jose Luiz Barsottini, Orlando G. P. Schmahmann, Jeremy D. TI Cognition in SCA21 reflects developmental and adult onset cerebellar cognitive affective syndrome SO BRAIN LA English DT Letter ID MACHADO-JOSEPH-DISEASE; SPINOCEREBELLAR ATAXIA TYPE-3; DYSFUNCTION; NONMOTOR; FEATURES; DEFICITS C1 [Braga-Neto, Pedro] Univ Estadual Ceara, Ctr Hlth Sci, BR-60714903 Fortaleza, Ceara, Brazil. [Braga-Neto, Pedro; Pedroso, Jose Luiz; Barsottini, Orlando G. P.] Univ Fed Sao Paulo, Dept Neurol, Ataxia Unit, Sao Paulo, Brazil. [Schmahmann, Jeremy D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Lab Neuroanat & Cerebellar Neurobiol, Ataxia Unit,Cognit Behav Neurol Unit,Dept Neurol, Boston, MA 02114 USA. RP Braga-Neto, P (reprint author), Univ Estadual Ceara, Ctr Hlth Sci, Ave Dr Silas Munguba,1700,Campus Itaperi, BR-60714903 Fortaleza, Ceara, Brazil. EM pbraganeto@gmail.com RI Braga-Neto, Pedro/C-5951-2013; Barsottini, O/E-9117-2010; Pedroso, Jose/F-1757-2013 OI Braga-Neto, Pedro/0000-0001-9186-9243; FU NIMH NIH HHS [R01MH67980] NR 25 TC 1 Z9 1 U1 1 U2 6 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 JUL 1 PY 2015 VL 138 AR e364 DI 10.1093/brain/awu382 PN 7 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN6HY UT WOS:000358536600005 PM 25576310 ER PT J AU Vidaurre, OG Haines, JD Sand, IK Adula, KP Huynh, JL McGraw, CA Zhang, F Varghese, M Sotirchos, E Bhargava, P Venkata, V Bandaru, R Pasinetti, G Zhang, WJ Inglese, M Calabresi, PA Wu, G Miller, AE Haughey, NJ Lublin, FD Casaccia, P AF Vidaurre, Oscar G. Haines, Jeffery D. Sand, Ilana Katz Adula, Kadidia P. Huynh, Jimmy L. McGraw, Corey A. Zhang, Fan Varghese, Merina Sotirchos, Elias Bhargava, Pavan Venkata, Veera Bandaru, Ratnam Pasinetti, Giulio Zhang, Weijia Inglese, Matilde Calabresi, Peter A. Wu, Gang Miller, Aaron E. Haughey, Norman J. Lublin, Fred D. Casaccia, Patrizia TI Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics (vol 137, pg 2271, 2014) SO BRAIN LA English DT Correction C1 [Pasinetti, Giulio] James J Peters Vet Affairs Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUL 1 PY 2015 VL 138 AR e367 DI 10.1093/brain/awv090 PN 7 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN6HY UT WOS:000358536600008 ER PT J AU Reed, GW Guo, JP Cannon, CP Kumar, A Aranki, S Shekar, P Agnihotri, A Maree, AO McLean, DS Rosenfield, K AF Reed, Grant W. Guo, Jianping Cannon, Christopher P. Kumar, Amit Aranki, Sary Shekar, Prem Agnihotri, Arvind Maree, Andrew O. McLean, Dalton S. Rosenfield, Kenneth TI Platelet Function Testing and Prediction of Bleeding in Patients Exposed to Clopidogrel Undergoing Coronary Artery Surgery Reply SO CLINICAL CARDIOLOGY LA English DT Letter ID RISK C1 [Reed, Grant W.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Reed, Grant W.; Guo, Jianping] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. [Kumar, Amit] Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA USA. [Aranki, Sary; Shekar, Prem] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Agnihotri, Arvind] St Elizabeths Med Ctr, Dept Surg, Brighton, MA USA. [Maree, Andrew O.] St James Hosp, Div Cardiol, Dublin 8, Ireland. [McLean, Dalton S.] Le Bauer Cardiol, Greensboro, NC USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Reed, GW (reprint author), Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2015 VL 38 IS 7 BP 444 EP U63 DI 10.1002/clc.22413 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN7IH UT WOS:000358607300008 PM 26216006 ER PT J AU Weiner, RB Baggish, AL AF Weiner, Rory B. Baggish, Aaron L. TI Cardiovascular Adaptation and Remodeling to Rigorous Athletic Training SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Cardiac remodeling; Exercise; Sports; Endurance ID LEFT-VENTRICULAR HYPERTROPHY; PHYSIOLOGICAL CARDIAC-HYPERTROPHY; PROFESSIONAL SOCCER PLAYERS; AORTIC ROOT SIZE; CLINICAL-SIGNIFICANCE; ETHNIC-DIFFERENCES; DIASTOLIC FUNCTION; REFERENCE VALUES; WALL THICKNESS; RIGHT ATRIAL AB Exercise-induced cardiac remodeling is a complex process by which the cardinal hemodynamic stresses of pressure and volume lead to a host of structural or functional adaptations. In aggregate, the constellation of changes that accompany this process serve to facilitate athletic performance by minimizing the cardiac work inherent in athletic activity. Although several key determinants of athletic cardiac adaptation have been described, observed variability across athlete cohorts remains an incompletely understood area. Ongoing and future work are required to further understand this process and ultimately to determine where the boundary lies between adaptive physiology and maladaptive disease. C1 [Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 78 TC 3 Z9 3 U1 2 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 EI 1556-228X J9 CLIN SPORT MED JI Clin. Sports Med. PD JUL PY 2015 VL 34 IS 3 BP 405 EP + DI 10.1016/j.csm.2015.03.007 PG 16 WC Sport Sciences SC Sport Sciences GA CN5FO UT WOS:000358455400005 PM 26100418 ER PT J AU Jelly, CA Alston, TA AF Jelly, Christina A. Alston, Theodore A. TI The Heart of Diabetes SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE beta-adrenoceptor; Ahlquist (Raymond P. Ahlquist); leptin; metreleptin; obesity ID OBESITY PARADOX; PLASMA LEPTIN; SEPSIS; STIMULATION C1 [Jelly, Christina A.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02138 USA. RP Jelly, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02138 USA. NR 15 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2015 VL 43 IS 7 BP 1552 EP 1554 DI 10.1097/CCM.0000000000001048 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA CN2XK UT WOS:000358285900035 PM 26079241 ER PT J AU Peyrot, M Egede, LE Funnel, MM Hsu, WC Ruggiero, L Siminerio, LM Stuckey, HL AF Peyrot, Mark Egede, Leonard E. Funnel, Martha M. Hsu, William C. Ruggiero, Laurie Siminerio, Linda M. Stuckey, Heather L. TI Ethnic differences in family member diabetes involvement and psychological outcomes: results from the second Diabetes Attitudes, Wishes and Needs (DAWN2) study in the USA SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE DAWN2; Ethnic disparities; Psychological outcomes; Quality of life; Well-being ID QUALITY-OF-LIFE; DISEASE MANAGEMENT; EUROPEAN-AMERICAN; AFRICAN-AMERICAN; LATINO PATIENTS; CARE; PEOPLE AB Objective: To assess differences among USA ethnic groups in psychological status of adult family members (FMs) and their involvement with the diabetes of another adult. Research methods: Data are from the FM survey of the USA DAWN2 study, including 105 White non-Hispanics, 47 African Americans, 46 Hispanic Americans and 40 Chinese Americans. All FMs lived with and cared for an adult with diabetes. Analysis of covariance controlled for respondent and patient characteristics to assess ethnic group differences (P< 0.05). Multiple regression analyses identified significant (P<0.05) independent correlates of psychological outcomes. Main outcome measures: FM psychological outcomes measured include well-being, quality of life (QoL), impact of diabetes on life domains, diabetes distress, and burden. Clinical trial registration: NCT01507116. Results: White non-Hispanics reported less diabetes burden and distress, more negative life impact, and lower wellbeing than FMs from ethnic minority groups. African Americans reported the highest well-being and lowest negative life impact, Chinese Americans reported the most diabetes burden, Hispanic Americans reported the highest distress. There were no ethnic group differences in QoL. Ethnic minority FMs reported having more involvement with diabetes, greater support success, and more access to a diabetes support network than White non-Hispanics. Higher FM diabetes involvement was associated with negative psychological outcomes, while diabetes education, support success and diabetes support network size were associated with better psychological outcomes. Potential limitations are the sample sizes and representativeness. Conclusions: Minority ethnic FMs experienced both advantages and disadvantages in psychological outcomes relative to each other and to White non-Hispanics. Ethnic minority FMs had more involvement in diabetes care, support success and support from others, with the first associated with worse and the latter two with better psychological outcomes. Additional studies are needed with larger samples and broader representation of ethnic groups to better understand these associations and identify areas for intervention. C1 [Peyrot, Mark] Loyola Univ Maryland, Baltimore, MD 21210 USA. [Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Funnel, Martha M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Ruggiero, Laurie] Univ Illinois, Sch Publ Hlth, Inst Hlth Res & Policy, Chicago, IL USA. [Siminerio, Linda M.] Univ Pittsburgh, Inst Diabet, Pittsburgh, PA USA. [Stuckey, Heather L.] Penn State Univ, Coll Med, Hershey, PA USA. RP Peyrot, M (reprint author), Loyola Univ Maryland, 4501 N Charles St, Baltimore, MD 21210 USA. EM mark.peyrot@gmail.com FU Novo Nordisk A/S, Bagsvaerd, Denmark FX This study was funded by Novo Nordisk A/S, Bagsvaerd, Denmark. NR 30 TC 2 Z9 2 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUL PY 2015 VL 31 IS 7 BP 1297 EP 1307 DI 10.1185/03007995.2015.1043251 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CN4HW UT WOS:000358392200006 PM 25907127 ER PT J AU Pilotte, AP AF Pilotte, Amy Potter TI Current management of patients with gastrointestinal stromal tumor receiving the multitargeted tyrosine kinase inhibitor sunitinib SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Review DE GIST; Sarcoma; Side-effect management; Sunitinib; Tyrosine kinase inhibitors ID RENAL-CELL CARCINOMA; FOOT SKIN REACTION; TARGETED THERAPIES; TREATMENT PATTERNS; IMATINIB MESYLATE; ADJUVANT IMATINIB; RANDOMIZED-TRIAL; SAFETY; HYPERTENSION; EFFICACY AB Background: Gastrointestinal stromal tumor (GIST), a form of soft tissue sarcoma, is often detected incidentally or at an advanced stage. The tyrosine kinase inhibitor sunitinib malate (Sutent*) is established as second-line treatment for the management of GIST after disease progression on, or intolerance to, first-line imatinib treatment. Several published reviews give guidance on management of side effects in patients with advanced renal cell carcinoma treated with sunitinib, but fewer publications cover side-effect management in patients with GIST. Scope: Using published articles and abstracts, prescribing information, and personal experience in managing patients with GIST at a specialized center of excellence for cancer care, I review side-effect management recommendations for patients with GIST treated with sunitinib and provide an overview of GIST. Findings: Sunitinib has a well described side-effect profile: most side effects occurring in patients with GIST can be easily managed by standard medical intervention and/or dose modification. Conclusion: Care of patients with GIST can be enhanced through communication, support, knowledge, and education, with the goal of providing effective therapy and optimal symptom control. C1 [Pilotte, Amy Potter] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Pilotte, Amy Potter] Rhode Isl Hosp, Ctr Comprehens Canc, Providence, RI USA. RP Pilotte, AP (reprint author), Rhode Isl Hosp, Comprehens Canc Ctr East Greenwich, 1454 South Cty Trail, East Greenwich, RI 02818 USA. EM amyspotter@gmail.com FU Pfizer FX Editorial assistance for this study was funded by Pfizer. The manuscript was written, the content was controlled, and the decision to submit the paper for publication was made solely by the author, who received no financial support or other compensation related to the development of this paper. Pfizer Inc., the manufacturer of sunitinib and the sponsor of many of the studies described in this manuscript, reviewed the paper for scientific accuracy. NR 72 TC 0 Z9 0 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUL PY 2015 VL 31 IS 7 BP 1363 EP 1376 DI 10.1185/03007995.2015.1045470 PG 14 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CN4HW UT WOS:000358392200012 PM 25912466 ER PT J AU Mahoney, DF LaRose, S Mahoney, EL AF Mahoney, Diane F. LaRose, Sharon Mahoney, Edward L. TI Family caregivers' perspectives on dementia-related dressing difficulties at home: The preservation of self model SO DEMENTIA-INTERNATIONAL JOURNAL OF SOCIAL RESEARCH AND PRACTICE LA English DT Article DE activities of daily living; Alzheimer's disease; family caregiving; medical textiles; major neurocognitive disorder ID ALZHEIMERS-DISEASE; ISSUES; CARE AB Alzheimer's caregiving literature acknowledges dressing as a major daily stressor but research on this topic is negligible. A qualitative grounded theory approach was used to explore Alzheimer's family caregivers' perspectives about issues that arise when their family members lose the ability to dress independently. Three focus groups and seven individual interviews were conducted and audio recorded with 25 information rich caregivers. Constant comparative analyses and coding of the transcripts identified six major themes leading to a Preservation of Self Model: Care Recipient to Care Giver' that portrays the caregiving trajectory. Initially, caregivers tried to protect the self dignity of the family member by maintaining usual routines and absorbing blame for difficulties. Dressing battles' occurred and caregivers learned management through trial and error. Crossing adult-child-gender role boundaries escalated discomfort. When facing unrelenting demands, concern shifted to preservation of the caregivers' health and self. Results suggest that caregivers would benefit from more pro-active dressing counseling to shorten the trial and error periods, dressing aids more relevant to dementia and more knowledgeable helpers. The preservation model can facilitate understanding of the caregiving trajectory and guide intervention support. C1 [Mahoney, Diane F.] MGH Inst Hlth Profess, Gerontechnol Res & Dev, Boston, MA 02129 USA. [LaRose, Sharon; Mahoney, Edward L.] MGH Inst Hlth Profess, Boston, MA 02129 USA. [LaRose, Sharon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahoney, Edward L.] EDDEE Consulting, Charlestown, MA USA. RP Mahoney, DF (reprint author), MGH Inst Hlth Profess, Sch Nursing, 36 1st Ave, Boston, MA 02129 USA. EM dmahoney@mghihp.edu OI Mahoney, Diane/0000-0002-6415-475X FU Alzheimer's Association of the United States of America, ETAC grant [11-200316] FX This work was supported by Alzheimer's Association of the United States of America, 2011 ETAC grant 11-200316. NR 36 TC 1 Z9 1 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1471-3012 EI 1741-2684 J9 DEMENTIA-LONDON JI Dement.-Int. J. soc. Res. Pract. PD JUL PY 2015 VL 14 IS 4 BP 494 EP 512 DI 10.1177/1471301213501821 PG 19 WC Gerontology SC Geriatrics & Gerontology GA CN6LM UT WOS:000358546300008 PM 24339112 ER PT J AU Gradus, JL Farkas, DK Svensson, E Ehrenstein, V Lash, TL Milstein, A Adler, N Sorensen, HT AF Gradus, Jaimie L. Farkas, Dora Koermendine Svensson, Elisabeth Ehrenstein, Vera Lash, Timothy L. Milstein, Arnold Adler, Nancy Sorensen, Henrik Toft TI Posttraumatic stress disorder and cancer risk: a nationwide cohort study SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Stress disorders; Posttraumatic; Neoplasms; Cohort studies ID BREAST-CANCER; PSYCHOSOCIAL FACTORS; REGISTER; MORTALITY; DENMARK; BURDEN; SYSTEM AB The association between stress and cancer incidence has been studied for more than seven decades. Despite plausible biological mechanisms and evidence from laboratory studies, findings from clinical research are conflicting. The objective of this study was to examine the association between PTSD and various cancer outcomes. This nation-wide cohort study included all Danish-born residents of Denmark from 1995 to 2011. The exposure was PTSD diagnoses (n = 4131). The main outcomes were cancer diagnoses including: (1) all malignant neoplasms; (2) hematologic malignancies; (3) immune-related cancers; (4) smoking- and alcohol-related cancers; (5) cancers at all other sites. Standardized incidence ratios (SIR) were calculated. Null associations were found between PTSD and nearly all cancer diagnoses examined, both overall [SIR for all cancers = 1.0, 95 % confidence interval (CI) = 0.88, 1.2] and in analyses stratified by gender, age, substance abuse history and time since PTSD diagnosis. This study is the most comprehensive examination to date of PTSD as a predictor of many cancer types. Our data show no evidence of an association between PTSD and cancer in this nationwide cohort. C1 [Gradus, Jaimie L.] 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. [Gradus, Jaimie L.; Farkas, Dora Koermendine; Svensson, Elisabeth; Ehrenstein, Vera; Lash, Timothy L.; Sorensen, Henrik Toft] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Lash, Timothy L.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Milstein, Arnold] Stanford Univ, Clin Excellence Res Ctr, Stanford, CA 94305 USA. [Adler, Nancy] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S 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 (1R21MH094551-01A1). NR 25 TC 0 Z9 0 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD JUL PY 2015 VL 30 IS 7 BP 563 EP 568 DI 10.1007/s10654-015-0032-7 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CN7XU UT WOS:000358649900005 PM 25957083 ER PT J AU Baggish, AL AF Baggish, Aaron L. TI Athletic Left Atrial Dilation Size Matters? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE athlete; echocardiography; left atrium ID HEART; FIBRILLATION C1 Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 13 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUL PY 2015 VL 8 IS 7 BP 763 EP 765 DI 10.1016/j.jcmg.2014.12.031 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CN4JK UT WOS:000358396200002 PM 26183550 ER PT J AU Lee, JM Buist, DSM Houssami, N Dowling, EC Halpern, EF Gazelle, GS Lehman, CD Henderson, LM Hubbard, RA AF Lee, Janie M. Buist, Diana S. M. Houssami, Nehmat Dowling, Emily C. Halpern, Elkan F. Gazelle, G. Scott Lehman, Constance D. Henderson, Louise M. Hubbard, Rebecca A. TI Five-Year Risk for Interval-Invasive Second Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PERSONAL HISTORY; MAMMOGRAPHIC SURVEILLANCE; LOCOREGIONAL RECURRENCES; RANDOMIZED-TRIALS; TUMOR RECURRENCE; LASAGNA PLOTS; SCREENING MRI; FOLLOW-UP; WOMEN; THERAPY AB Background: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. Methods: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. Results: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. Conclusions: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. C1 [Lee, Janie M.; Lehman, Constance D.] Univ Washington, Dept Radiol, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Lee, Janie M.; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Janie M.; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Buist, Diana S. M.; Hubbard, Rebecca A.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Houssami, Nehmat] Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Screening & Test Evaluat Program, Sydney, NSW 2006, Australia. [Henderson, Louise M.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. RP Lee, JM (reprint author), Seattle Canc Care Alliance, 825 Eastlake Ave East,G2-600, Seattle, WA 98109 USA. EM jmlee58@uw.edu FU National Cancer Institute [P01CA154292]; Breast Cancer Surveillance Consortium [HHSN261201100031C]; National Institutes of Health [K07CA128816]; National Breast Cancer Foundation (NBCF Australia) FX This work was supported by a National Cancer Institute-funded Program Project grant (P01CA154292) and the Breast Cancer Surveillance Consortium (HHSN261201100031C). Additional support was provided by National Institutes of Health grant K07CA128816 (to JML) and the National Breast Cancer Foundation (NBCF Australia to NH). NR 52 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUL PY 2015 VL 107 IS 7 AR djv109 DI 10.1093/jnci/djv109 PG 9 WC Oncology SC Oncology GA CN9QC UT WOS:000358782900012 ER PT J AU Lin, CC Gray, PJ Jemal, A Efstathiou, JA AF Lin, Chun Chieh Gray, Phillip J. Jemal, Ahmedin Efstathiou, Jason A. TI Androgen Deprivation With or Without Radiation Therapy for Clinically Node-Positive Prostate Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADICAL PROSTATECTOMY; DATA-BASE; FOLLOW-UP; RADIOTHERAPY; TRIAL; SUPPRESSION; GUIDELINES; REGISTRIES; DIAGNOSIS; QUALITY AB Background: Clinically lymph node-positive (cN+) prostate cancer (PCa) is an often-fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+ PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. Methods: Patients with cN+ PCa and without distant metastases diagnosed between 2004 and 2011 were included. Five-year overall survival for patients diagnosed between 2004 and 2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics, and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. Results: Of 3540 total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT. Compared with ADT alone, patients treated with ADT+RT were younger and more likely to have private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values. After PS matching, 318 patients remained in each group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk of five-year all-cause mortality (HR = 0.50, 95% CI = 0.37 to 0.67, two-sided P < .001; crude OS rate: 71.5% vs 53.2%). Conclusions: Using a large national database, we have identified a statistically significant survival benefit for patients with cN+ PCa treated with ADT+RT. These data, if appropriately validated by randomized trials, suggest that a substantial proportion of such patients at high risk for prostate cancer death may be undertreated, warranting a reevaluation of current practice guidelines. C1 [Lin, Chun Chieh; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Intramural Res, Atlanta, GA 30329 USA. [Gray, Phillip J.; Efstathiou, Jason A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org FU American Cancer Society Intramural Research Department; Prostate Cancer Foundation Young Investigator Award FX This work was supported by the American Cancer Society Intramural Research Department and a Prostate Cancer Foundation Young Investigator Award (JAE). NR 31 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUL PY 2015 VL 107 IS 7 AR djv119 DI 10.1093/jnci/djv119 PG 10 WC Oncology SC Oncology GA CN9QC UT WOS:000358782900013 ER PT J AU Iscla, I Wray, R Blount, P Larkins-Ford, J Conery, AL Ausubel, FM Ramu, S Kavanagh, A Huang, JX Blaskovich, MA Cooper, MA Obregon-Henao, A Orme, I Tjandra, ES Stroeher, UH Brown, MH Macardle, C van Holst, N Tong, CL Slattery, AD Gibson, CT Raston, CL Boulos, RA AF Iscla, Irene Wray, Robin Blount, Paul Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. Ramu, Soumya Kavanagh, Angela Huang, Johnny X. Blaskovich, Mark A. Cooper, Matthew A. Obregon-Henao, Andres Orme, Ian Tjandra, Edwin S. Stroeher, Uwe H. Brown, Melissa H. Macardle, Cindy van Holst, Nick Tong, Chee Ling Slattery, Ashley D. Gibson, Christopher T. Raston, Colin L. Boulos, Ramiz A. TI A new antibiotic with potent activity targets MscL SO JOURNAL OF ANTIBIOTICS LA English DT Article ID MECHANOSENSITIVE CHANNEL; ESCHERICHIA-COLI; PARABENS; RESIDUE; PROTEIN; DYES AB The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections. C1 [Iscla, Irene; Wray, Robin; Blount, Paul] UT Southwestern Med Ctr, Dept Physiol, Dallas, TX USA. [Larkins-Ford, Jonah; Conery, Annie L.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ramu, Soumya; Kavanagh, Angela; Huang, Johnny X.; Blaskovich, Mark A.; Cooper, Matthew A.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. [Obregon-Henao, Andres; Orme, Ian] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Tjandra, Edwin S.] Univ Western Australia, Sch Anim Biol, Crawley, WA, Australia. [Stroeher, Uwe H.; Brown, Melissa H.] Flinders Univ S Australia, Sch Biol Sci, Bedford Pk, SA 5042, Australia. [Macardle, Cindy; van Holst, Nick] Flinders Univ S Australia, Flinders Med Sci & Technol Immunol Allergy & Arth, Bedford Pk, SA 5042, Australia. [Blount, Paul; Tong, Chee Ling; Slattery, Ashley D.; Gibson, Christopher T.; Raston, Colin L.; Boulos, Ramiz A.] Flinders Univ S Australia, Ctr NanoScale Sci & Technol, Sch Chem & Phys Sci, Bedford Pk, SA 5042, Australia. RP Blount, P (reprint author), Flinders Univ S Australia, Ctr NanoScale Sci & Technol, Sch Chem & Phys Sci, Bedford Pk, SA 5042, Australia. EM Paul.blount@UTSouthwestern.edu; ramiz.boulos@flinders.edu.au RI Gibson, Christopher/G-3626-2010; Cooper, Matthew/C-7988-2009; Huang, Johnny/A-4041-2012; OI Gibson, Christopher/0000-0003-3334-5059; Iscla, Irene/0000-0001-8936-430X; Macardle, Cindy/0000-0001-9880-4258; Cooper, Matthew/0000-0003-3147-3460; Blaskovich, Mark/0000-0001-9447-2292; Raston, Colin/0000-0003-4753-0079 FU Welch Foundation [I-1420]; Cancer Prevention & Research Institute of Texas [RP100146]; National Institutes of Health [AI08080701, GM061028, P01 AI083214]; National American Heart Association [12SDG8740012]; Wellcome Trust Seeding Drug Discovery Award [094977/Z/10/Z]; NHMRC Principal Research Fellowship [APP1059354]; NHMRC Project Grant [535053]; Australian Research Council; Government of South Australia; Australian Microscopy and Microanalysis Research Facility (AMMRF) FX The in vivo growth inhibition experiments and the electrophysiology experiments were supported by Grant I-1420 of the Welch Foundation, Grant RP100146 from the Cancer Prevention & Research Institute of Texas, and Grants AI08080701 and GM061028 from the National Institutes of Health. The C. elegans experiments were supported by grant P01 AI083214 from the National Institutes of Health. II is supported by Grant 12SDG8740012 from the National American Heart Association. The funding bodies had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. MAB, JXH, SR and AK were supported by a Wellcome Trust Seeding Drug Discovery Award (094977/Z/10/Z), and MAC by an NHMRC Principal Research Fellowship (APP1059354). UHS is supported by NHMRC Project Grant 535053. We gratefully acknowledge support of this work by the Australian Research Council and the Government of South Australia. RAB gratefully acknowledges supervision from Allan J McKinley during his Honors year when the modeling work was undertaken. SEM analysis was carried out at Adelaide Microscopy and AFM studies were carried out using facilities in the School of Chemical and Physical Sciences, Flinders University. Both of these microscopy facilities are supported by the Australian Microscopy and Microanalysis Research Facility (AMMRF). Flow Cytometry experiments were carried out at Flow Cytometry Immunology facility at Flinders Medical Centre. Ramizol is a Trademark fully registered in Australia. NR 35 TC 5 Z9 6 U1 1 U2 12 PU JAPAN ANTIBIOTICS RESEARCH ASSOC PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD JUL PY 2015 VL 68 IS 7 BP 453 EP 462 DI 10.1038/ja.2015.4 PG 10 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA CN7HR UT WOS:000358605700005 PM 25649856 ER PT J AU Padole, A Singh, S Lira, D Blake, MA Pourjabbar, S Khawaja, RDA Choy, G Saini, S Do, S Kalra, MK AF Padole, Atul Singh, Sarabjeet Lira, Diego Blake, Michael A. Pourjabbar, Sarvenaz Khawaja, Ranish Deedar Ali Choy, Garry Saini, Sanjay Do, Synho Kalra, Mannudeep K. TI Assessment of Filtered Back Projection, Adaptive Statistical, and Model-Based Iterative Reconstruction for Reduced Dose Abdominal Computed Tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article ID CHEST CT; OPTIMIZATION; PROTECTION AB Purpose To compare standard of care and reduced dose (RD) abdominal computed tomography (CT) images reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), model-based iterative reconstruction (MBIR) techniques. Materials and Methods In an Institutional Review Board-approved, prospective clinical study, 28 patients (mean age 59 +/- 13 years ), undergoing clinically indicated routine abdominal CT on a 64-channel multi-detector CT scanner, gave written informed consent for acquisition of an additional RD (<1 milli-Sievert) abdomen CT series. Sinogram data of RD series were reconstructed with FBP, ASIR, and MBIR and compared with FBP images of standard dose abdomen CT. Two radiologists performed randomized, independent, and blinded comparison for lesion detection, lesion margin, visibility of normal structures, and diagnostic confidence. Results Mean CT dose index volume was 10 +/- 3.4 mGy and 1.3 +/- 0.3 mGy for standard and RD CT, respectively. There were 73 "true positive" lesions detected on standard of care CT. Nine lesions (<8 mm in size) were missed on RD abdominal CT images which included liver lesions, liver cysts, kidney cysts, and paracolonic abscess. These lesions were missed regardless of patient size and types of iterative reconstruction techniques used for reconstruction of RD data sets. The visibility of lesion margin was suboptimal in (23/28) patients with RD FBP, (15/28) patients with RD ASIR, and (14/28) patients with RD MBIR compared to standard of care FBP images (P < 0.001). Diagnostic confidence for the assessment of lesions on RD images was suboptimal in most patients regardless of iterative reconstruction techniques. Conclusions Clinically significant lesions (< 8 mm) can be missed on abdominal CT examinations acquired at a CT dose index volume of 1.3 mGy regardless of patients' size and reconstruction techniques (FBP, ASIR, and MBIR). C1 [Padole, Atul; Singh, Sarabjeet; Lira, Diego; Blake, Michael A.; Pourjabbar, Sarvenaz; Khawaja, Ranish Deedar Ali; Choy, Garry; Saini, Sanjay; Do, Synho; Kalra, Mannudeep K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Padole, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM apadole@partners.org FU Radiological Society of North America (RSNA) Research and Education Foundation's Educational Scholar grant; GE Healthcare; Siemens Healthcare; Philips Healthcare; Society of Thoracic Radiology FX M.K.K. and S.S. have received Radiological Society of North America (RSNA) Research and Education Foundation's Educational Scholar grant. S.S. has received research grant from GE Healthcare, Siemens Healthcare, Philips Healthcare, and Society of Thoracic Radiology. None of the other coauthors have any pertinent financial disclosures and had complete unrestricted access to the data at all times. NR 19 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2015 VL 39 IS 4 BP 462 EP 467 DI 10.1097/RCT.0000000000000231 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN7CJ UT WOS:000358591000002 PM 25734468 ER PT J AU Khawaja, RDA Singh, S Blake, M Harisinghani, M Choy, G Karosmanoglu, A Padole, A Pourjabbar, S Do, S Kalra, MK AF Khawaja, Ranish Deedar Ali Singh, Sarabjeet Blake, Michael Harisinghani, Mukesh Choy, Gary Karosmanoglu, Ali Padole, Atul Pourjabbar, Saravenaz Do, Synho Kalra, Mannudeep K. TI Ultralow-Dose Abdominal Computed Tomography: Comparison of 2 Iterative Reconstruction Techniques in a Prospective Clinical Study SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article ID FILTERED BACK-PROJECTION; IMAGE-QUALITY; RADIATION-EXPOSURE; CT ANGIOGRAPHY; LIVER PHANTOM; ALGORITHM; MDCT; FEASIBILITY; REDUCTION; SUMMIT AB Purpose To assess lesion detection and image quality of ultralow-dose (ULD) abdominal computed tomography (CT) reconstructed with filtered back projection (FBP) and 2 iterative reconstruction techniques: hybrid-based iDose, and image-based SafeCT. Materials and Methods In this institutional review board-approved ongoing prospective clinical study, 41 adult patients provided written informed consent for an additional ULD abdominal CT examination immediately after standard dose (SD) CT exam on a 256-slice multidetector computed tomography (iCT, Philips-Healthcare). The SD examination (size-specific dose estimate, 10 +/- 3 mGy) was performed at 120 kV with automatic exposure control, and reconstructed with FBP. The ULD examination (1.5 +/- 0.4 mGy) was performed at 120 kV and fixed tube current of 17 to 20 mAs/slice to achieve ULD radiation dose, with the rest of the scan parameters same as SD examination. The ULD data were reconstructed with (a) FBP, (b) iDose, and (c) SafeCT. Lesions were detected on ULD FBP series and compared to SD FBP "reference-standard" series. True lesions, pseudolesions, and missed lesions were recorded. Four abdominal radiologists independently blindly performed subjective image quality. Objective image quality included image noise calculation and noise spectral density plots. Results All true lesions (n, 52: liver metastases, renal cysts, diverticulosis) in SD FBP images were detected in ULD images. Although there were no missed or pseudolesions on ULD iDose and ULD SafeCT images, appearance of small low-contrast hepatic lesions was suboptimal. The ULD FBP images were unacceptable across all patients for both lesion detection and image quality. In patients with a body mass index (BMI) of 25 kg/m(2) or less, ULD iDose and ULD SafeCT images were acceptable for image quality that was close to SD FBP for both normal and abnormal abdominal and pelvic structures. With increasing BMI, the image quality of ULD images was deemed unacceptable due to photo starvation. Evaluation of kidney stones with ULD iDose/SafeCT images was found acceptable regardless of patient size. Image noise levels were significantly lower in ULD iDose and ULD SafeCT images compared to ULD FBP (P < 0.01). Conclusions Preliminary results show that ULD abdominal CT reconstructed with iterative reconstruction techniques is achievable in smaller patients (BMI <= 25 kg/m(2)) but remains a challenge for overweight to obese patients. Lesion detection is similar in full-dose SD FBP and ULD iDose/SafeCT images, with suboptimal visibility of low-contrast lesions in ULD images. C1 [Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Padole, Atul; Pourjabbar, Saravenaz; Do, Synho; Kalra, Mannudeep K.] Massachusetts Gen Hosp, MGH Imaging, Boston, MA 02114 USA. [Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmanoglu, Ali] Massachusetts Gen Hosp, Div Abdominal Imaging, Boston, MA 02114 USA. [Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmanoglu, Ali] Harvard Univ, Sch Med, Boston, MA USA. RP Khawaja, RDA (reprint author), 25 New Chardon St,4th Floor, Boston, MA 02114 USA. EM ranish.khawaja@gmail.com FU GE Healthcare; Philips Healthcare; Radiological Society of North America (RSNA) FX S.S. received research grant from GE Healthcare, Philips Healthcare and the Radiological Society of North America (RSNA). S.D. received research grant from Philips Healthcare. The other authors declare no conflict of interest. NR 41 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2015 VL 39 IS 4 BP 489 EP 498 DI 10.1097/RCT.0000000000000248 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN7CJ UT WOS:000358591000007 PM 26182223 ER PT J AU Hayano, K Tian, F Kambadakone, AR Yoon, SS Duda, DG Ganeshan, B Sahani, DV AF Hayano, Koichi Tian, Fang Kambadakone, Avinash R. Yoon, Sam S. Duda, Dan G. Ganeshan, Balaji Sahani, Dushyant V. TI Texture Analysis of Non-Contrast-Enhanced Computed Tomography for Assessing Angiogenesis and Survival of Soft Tissue Sarcoma SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article ID PROGNOSTIC-FACTORS; LOCAL RECURRENCE; CT TEXTURE; TUMOR HETEROGENEITY; FRENCH-FEDERATION; POTENTIAL MARKER; CANCER; EXTREMITY; THERAPY; GRADE AB Objective To evaluate the role of computed tomographic (CT) texture analysis in assessing tumor angiogenesis and survival of soft tissue sarcoma (STS). Methods In 20 patients with STSs, tumor texture parameters, which were measured on pretherapeutic CT using CT texture analysis software with the spatial scale filter extracting fine to coarse texture, were compared with microvessel density, plasma vascular endothelial growth factor (VEGF), soluble VEGF receptor-1, and overall survival (OS). Results Mean of positive pixels (MPP) showed a positive correlation with microvessel density (P = 0.02). Entropy at medium texture scales (spatial scale filter = 3, 4, 5) showed positive correlations with VEGF (P = 0.03, P = 0.009, and P = 0.02, respectively), and entropy without filtration showed a positive correlation with soluble VEGF receptor-1 (P = 0.02). In the univariate analysis, kurtosis at a medium texture scale and MPP showed significant correlations with OS (P = 0.04 and P = 0.007), and multivariate analysis demonstrated that MPP was an independent prognostic factor (P = 0.01). Conclusion Texture parameters are associated with tumor angiogenesis and OS in STS. C1 [Hayano, Koichi; Tian, Fang; Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Tian, Fang] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Dept Radiol, Shanghai, Peoples R China. [Yoon, Sam S.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Duda, Dan G.] Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. [Ganeshan, Balaji] UCL, Inst Nucl Med, London WC1E 6BT, England. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org FU National Institutes of Health [1 R21 CA117128, 1R01 CA158301] FX Supported by National Institutes of Health Grants 1 R21 CA117128 and 1R01 CA158301 (S.S.Y.). One of the authors (B.G.) is the scientific director of TexRAD and provided technical advices for the software used for this analysis. All other authors have no conflicts of interest. NR 35 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2015 VL 39 IS 4 BP 607 EP 612 DI 10.1097/RCT.0000000000000239 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN7CJ UT WOS:000358591000025 PM 25793653 ER PT J AU Yonker, LM Cigana, C Hurley, BP Bragonzi, A AF Yonker, Lael M. Cigana, Cristina Hurley, Bryan P. Bragonzi, Alessandra TI Host-pathogen interplay in the respiratory environment of cystic fibrosis SO JOURNAL OF CYSTIC FIBROSIS LA English DT Review DE Cystic fibrosis; Host-pathogen interaction; Microbiota; Innate and adaptive immunity; Lung disease ID PSEUDOMONAS-AERUGINOSA BIOFILMS; NEUTROPHIL TRANSEPITHELIAL MIGRATION; TRANSMEMBRANE CONDUCTANCE REGULATOR; BRONCHIAL EPITHELIAL-CELLS; FACTOR-KAPPA-B; STAPHYLOCOCCUS-AUREUS; AIRWAY INFLAMMATION; DOUBLE-BLIND; POLYMORPHONUCLEAR LEUKOCYTES; EXTRACELLULAR TRAPS AB Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Yonker, Lael M.; Hurley, Bryan P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Mucosal Immunol & Biol Res Ctr,Pediat, Charlestown, MA USA. [Cigana, Cristina; Bragonzi, Alessandra] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, Infect & Cyst Fibrosis Unit, Milan, Italy. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, CNY 114 114-3503, Charlestown, MA 02129 USA. EM bphurley@partners.org; bragonzi.alessandra@hsr.it RI Cigana, Cristina/D-2883-2016; OI Cigana, Cristina/0000-0003-0436-9721; Bragonzi, Alessandra/0000-0002-5808-7669 FU Ministero della Salute [GR/2009/1579812]; Italian Cystic Fibrosis Research Foundation; NIH/NIAID [R01 AI095338]; Delegazione FFC di Milano [FFC#9/2014, FFC#14/2013]; Department of Pediatrics at MGHfC FX Supported by the Ministero della Salute (project. GR/2009/1579812) to AB, and Italian Cystic Fibrosis Research Foundation with the contribution of the Delegazione FFC di Milano (FFC#9/2014) to AB and (FFC#14/2013) to CC. Support for BPH and LMY include NIH/NIAID R01 AI095338 and the Department of Pediatrics at MGHfC respectively. NR 103 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JUL PY 2015 VL 14 IS 4 BP 431 EP 439 DI 10.1016/j.jcf.2015.02.008 PG 9 WC Respiratory System SC Respiratory System GA CO0CX UT WOS:000358818800003 PM 25800687 ER PT J AU Putman, MS Baker, JF Uluer, A Herlyn, K Lapey, A Sicilian, L Tillotson, AP Gordon, CM Merkel, PA Finkelstein, JS AF Putman, Melissa S. Baker, Joshua F. Uluer, Ahmet Herlyn, Karen Lapey, Allen Sicilian, Leonard Tillotson, Angela Pizzo Gordon, Catherine M. Merkel, Peter A. Finkelstein, Joel S. TI Trends in bone mineral density in young adults with cystic fibrosis over a 15 year period SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Cystic fibrosis; Osteoporosis; Dual energy X-ray absorptiometry; Bone turnover markers; Vitamin D ID VERTEBRAL FRACTURES; BODY-COMPOSITION; PREVALENCE; CHILDREN; OSTEOPOROSIS; ADOLESCENTS; OSTEOPENIA; KYPHOSIS; CFTR AB Background: Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear. Methods: This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines. Results: The cohorts were similar in terms of age, BM, pancreatic insufficiency, presence of F508del mutation, and reproductive history. In the most recent cohort, pulmonary function was superior; and fewer patients had vitamin D deficiency or secondary hyperparathyroidism. Areal BMD measures of the PA spine, lateral spine, and distal radius were similarly low in the two cohorts. Conclusions: Although pulmonary function and vitamin D status were better in patients in the present-day cohort, areal BMD of the spine was reduced in a significant number of patients and was no different in patients with CF today than in the late 1990s. Further attention to optimizing bone health may be necessary to prevent CF-related bone disease. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Putman, Melissa S.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Putman, Melissa S.; Gordon, Catherine M.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Baker, Joshua F.; Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Uluer, Ahmet] Boston Childrens Hosp, Div Resp Dis, Boston, MA USA. [Herlyn, Karen] Univ Hosp Schleswig Holstein, Poliklin Rheumatol, Campus Luebeck, Germany. [Lapey, Allen] Massachusetts Gen Hosp, Dept Pediat, Div Pulm, Boston, MA 02114 USA. [Sicilian, Leonard] Massachusetts Gen Hosp, Dept Med, Div Pulm, Boston, MA 02114 USA. [Tillotson, Angela Pizzo] Mercy Hosp, Mattina R Proctor Diabet Ctr, Portland, ME USA. [Gordon, Catherine M.] Hasbro Childrens Hosp, Div Adolescent Med & Endocrinol, Providence, RI USA. RP Putman, MS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,THR-1051, Boston, MA 02114 USA. EM msputman@partners.org FU Cystic Fibrosis Foundation; Boomer Esaison Heroes Foundation; Mallinckrodt General Clinical Research Center Massachusetts General Hospital; NIH [M01 RR 01066]; Harvard Clinical and Translational Science Center [8 UL1 TR000170-05, 1 UL1TR001102-01, 1 UL1RR025758-04]; Vertex Pharmaceuticals; Endocrine Society Amgen Fellowship; VA Clinical Science Research and Development; NIH including a Clinical Associate Physician Award from the National Center for Research Resources (NCRR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [K24-AR-02224] FX This work was supported in part by a research grant from The Cystic Fibrosis Foundation, The Boomer Esaison Heroes Foundation, and the Mallinckrodt General Clinical Research Center Massachusetts General Hospital, NIH Grant M01 RR 01066. This project was also supported by the Harvard Clinical and Translational Science Center (Grant numbers 8 UL1 TR000170-05, 1 UL1TR001102-01, and 1 UL1RR025758-04). A Vertex Pharmaceuticals Investigator Initiated Studies Grant provided partial support for procedures in this study. Dr. Putman was supported by an NIH T32 award and the Endocrine Society Amgen Fellowship Award. Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award. Dr. Merkel was supported by grants from the NIH including a Clinical Associate Physician Award from the National Center for Research Resources (NCRR) and a Mid-Career Development Award in Clinical Investigation (K24-AR-02224) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). NR 30 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JUL PY 2015 VL 14 IS 4 BP 526 EP 532 DI 10.1016/j.jcf.2015.01.011 PG 7 WC Respiratory System SC Respiratory System GA CO0CX UT WOS:000358818800016 PM 25698451 ER PT J AU Abbott, J Elborn, JS Georgiopoulos, AM Goldbeck, L Marshall, BC Sabadosa, KA Smith, BA Quittner, AL AF Abbott, J. Elborn, J. S. Georgiopoulos, A. M. Goldbeck, L. Marshall, B. C. Sabadosa, K. A. Smith, B. A. Quittner, A. L. TI Cystic Fibrosis Foundation and European Cystic Fibrosis Society, Survey of cystic fibrosis mental health care delivery SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Depression; Anxiety; Screening ID QUALITY-OF-LIFE; COMPARING RESPONSE RATES; CHRONIC DISEASES; LUNG-FUNCTION; DEPRESSION; ANXIETY; METAANALYSIS; ASSOCIATION; CAREGIVERS; ADHERENCE AB Background: Psychological morbidity in individuals with cystic fibrosis (CF) and their caregivers is common. The Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) Guidelines Committee on Mental Health sought the views of CF health care professionals concerning mental health care delivery. Methods: An online survey which focused on the current provision and barriers to mental health care was distributed to CF health care professionals. Results: Of the 1454 respondents, many did not have a colleague trained in mental health issues and 20% had no one on their team whose primary role was focused on assessing or treating these issues. Insufficient resources and a lack of competency were reported in relation to mental health referrals. Seventy-three percent of respondents had no experience with mental health screening. Of those who did, they utilized 48 different, validated scales. Conclusions: These data have informed the decision-making, dissemination and implementation strategies of the Mental Health Guidelines Committee sponsored by the CFF and ECFS. (C) 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Abbott, J.] Univ Cent Lancashire, Sch Psychol, Preston PR1 2HE, Lancs, England. [Elborn, J. S.] Queens Univ, Sch Med, Belfast BT7 1NN, Antrim, North Ireland. [Georgiopoulos, A. M.] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Goldbeck, L.] Univ Ulm, Med Ctr, Child & Adolescent Psychiat, D-89075 Ulm, Germany. [Marshall, B. C.] Cyst Fibrosis Fdn, Dept Med, Maryland, MD 20814 USA. [Sabadosa, K. A.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03766 USA. [Smith, B. A.] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14202 USA. [Quittner, A. L.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. RP Abbott, J (reprint author), Univ Cent Lancashire, Sch Psychol, Preston PR1 2HE, Lancs, England. EM jabbott@uclan.ac.uk OI elborn, joseph/0000-0002-2323-442X FU Cystic Fibrosis Foundation; European Cystic Fibrosis Society FX We are grateful to Christine Dubois for her time and expertise in mailing out the survey and to the Cystic Fibrosis Foundation and the European Cystic Fibrosis Society for their sponsorship. NR 30 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JUL PY 2015 VL 14 IS 4 BP 533 EP 539 DI 10.1016/j.jcf.2014.12.015 PG 7 WC Respiratory System SC Respiratory System GA CO0CX UT WOS:000358818800017 PM 25592657 ER PT J AU Jacques, SL Walsh, JT AF Jacques, Steven L. Walsh, Joseph T. TI Entropy and enthalpy for triggering cutaneous erythema SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES LA English DT Article DE Skin; erythema; thermal; entropy; enthalpy AB The molar entropy (Delta S) and molar enthalpy (Delta H) for the denaturation event that triggers cutaneous erythema was determined to be Delta S = 190 J/(mole K) and Delta H = 146.9 x 10(3) J/mole. The experiment involved placing heated water against the skin of the forearm, for a range of temperatures and exposure times. Exposing the skin to 45 degrees C for 22 s was at the threshold for producing erythema, which was similar to the threshold for a slight degree of pain. C1 [Jacques, Steven L.; Walsh, Joseph T.] Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. [Walsh, Joseph T.] Harvard Univ, Sch Med, MIT, Cambridge, MA 02138 USA. RP Jacques, SL (reprint author), Oregon Hlth & Sci Univ, 3303 SW Bond Ave, Portland, OR 97239 USA. EM jacquess@ohsu.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 1793-5458 EI 1793-7205 J9 J INNOV OPT HEAL SCI JI J. Innov. Opt. Health Sci. PD JUL PY 2015 VL 8 IS 4 SI SI AR 1550026 DI 10.1142/S1793545815500261 PG 4 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA CN4VB UT WOS:000358427300008 ER PT J AU Lagerqvist, EL Finnin, BA Elliott, DA Anderson, DJ Wu, SM Pouton, CW Haynes, JM AF Lagerqvist, E. L. Finnin, B. A. Elliott, D. A. Anderson, D. J. Wu, S. M. Pouton, C. W. Haynes, J. M. TI Comparing mouse and human pluripotent stem cell derived cardiac cells: Both systems have advantages for pharmacological and toxicological screening SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE Calcium imaging; Oscillation frequency; Stem cell-derived cardiomyocytes; Ischemia; Toxicity ID RABBIT SINOATRIAL NODE; CONDUCTION SYSTEM; ATRIOVENTRICULAR NODE; PACEMAKER FUNCTION; PRECURSOR CELLS; PURKINJE-CELLS; BREAST-CANCER; HEART; CARDIOMYOCYTES; CA2+ AB Pluripotent stem cells offer an unparalleled opportunity to investigate cardiac physiology, pharmacology, toxicology and pathophysiology. In this paper we describe the use of both mouse (Nkx2-5(eGFP/w)) and human (NKX2-5(eGFP/w)) pluripotent stem cell reporter lines, differentiated toward cardiac lineage, for live single cell high acquisition rate calcium imaging. We also assess the potential of NKX2-5(eGFP/w) cardiac lineage cells for use toxicological screening as well as establish their sensitivity to a shift between low and high oxygen environments. Differentiated mouse Nkx2-5(eGFP/w) cells demonstrated a wide range of spontaneous oscillation rates that could be reduced by ryanodine (10 mu M), thapsigargin (1 mu M) and ZD7288 (10 mu M). In contrast human NKX2-5(eGFP/w) cell activity was only reduced by thapsigargin (1 mu M). Human cell survival was sensitive to the addition of trastuzumab and doxorubicin, while the switch from a low to a high oxygen environment affected oscillation frequency. We suggest that the human NKX2-5(eGFP/w) cells are less suitable for studies of compounds affecting cardiac pacemaker activity than mouse Nkx2-5(eGFP/w) cells, but are very suitable for cardiac toxicity studies. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lagerqvist, E. L.; Finnin, B. A.; Pouton, C. W.; Haynes, J. M.] Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Melbourne, Vic 3004, Australia. [Elliott, D. A.; Anderson, D. J.] Monash Univ, Murdoch Childrens Res Inst, Clayton, Vic, Australia. [Wu, S. M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Haynes, JM (reprint author), 381 Royal Parade, Parkville, Vic 3052, Australia. EM john.haynes@monash.edu OI , john/0000-0003-3075-1553; Pouton, Colin/0000-0003-0224-3308 FU Australian Stem Cell Centre FX This work was supported by the Australian Stem Cell Centre. We thank the Monash University Core Flow Cytometry Facility Flowcore for their FACS work. NR 63 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 1056-8719 EI 1873-488X J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD JUL-AUG PY 2015 VL 74 BP 17 EP 25 DI 10.1016/j.vascn.2015.04.009 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CN6MM UT WOS:000358548900003 PM 25957031 ER PT J AU Lorenz, TK Harte, CB Meston, CM AF Lorenz, Tierney K. Harte, Christopher B. Meston, Cindy M. TI Changes in Autonomic Nervous System Activity are Associated with Changes in Sexual Function in Women with a History of Childhood Sexual Abuse SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Childhood Sexual Abuse; Heart Rate Variability; Sexual Function; Autonomic Nervous System; Expressive Writing ID HEART-RATE-VARIABILITY; FUNCTION INDEX FSFI; DEPRESSION; AROUSAL; SATISFACTION; DYSFUNCTION; VALIDATION; FAILURE; INDIVIDUALS; EXPERIENCES AB Introduction. Women with histories of childhood sexual abuse (CSA) have higher rates of sexual difficulties, as well as high sympathetic nervous system response to sexual stimuli. Aim. The study aims to examine whether treatment-related changes in autonomic balance, as indexed by heart rate variability (HRV), were associated with changes in sexual arousal and orgasm function. Methods. In study 1, we measured HRV while writing a sexual essay in 42 healthy, sexually functional women without any history of sexual trauma. These data, along with demographics, were used to develop HRV norms equations. In study 2, 136 women with a history of CSA were randomized to one of three active expressive writing treatments that focused on their trauma, sexuality, or daily life (control condition). We recorded HRV while writing a sexual essay at pretreatment, posttreatment, and 2-week, and 1- and 6-month follow-ups; we also calculated the expected HRV for each participant based on the norms equations from study 1. Main Outcome Measures. The main outcome measures used were HRV, Female Sexual Function Index, Sexual Satisfaction ScaleWomen. Results. The difference between expected and observed HRV decreased over time, indicating that, posttreatment, CSA survivors displayed HRV closer to the expected HRV of a demographics-matched woman with no history of sexual trauma. Also, over time, participants whose HRV became less dysregulated showed the biggest gains in sexual arousal and orgasm function. These effects were consistent across condition. Conclusions. Treatments that reduce autonomic imbalance may improve sexual well-being among CSA populations. Lorenz TK, Harte CB, and Meston CM. Changes in autonomic nervous system activity are associated with changes in sexual function in women with a history of childhood sexual abuse. C1 [Lorenz, Tierney K.] Indiana Univ, Kinsey Inst Res Sex Gender & Reprod, Bloomington, IN USA. [Harte, Christopher B.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Harte, Christopher B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Meston, Cindy M.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. RP Meston, CM (reprint author), Univ Texas Austin, Dept Psychol, 1 Univ Stn A8000, Austin, TX 78712 USA. EM meston@psy.utexas.edu FU National Institute of Child Health and Human Development (NICHD) [RO1 HD051676, T32HD049336] FX This research was supported by a grant from the National Institute of Child Health and Human Development (NICHD, RO1 HD051676) to Cindy M. Meston. Tierney Lorenz was supported by a grant from the NICHD (T32HD049336). The views presented here are solely those of the authors and do necessarily not represent the official views of the National Institutes of Health or the Department of Veterans Affairs. NR 46 TC 0 Z9 0 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2015 VL 12 IS 7 BP 1545 EP 1554 DI 10.1111/jsm.12908 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CN5QM UT WOS:000358484300004 PM 25963394 ER PT J AU Ellingsen, DM AF Ellingsen, Dan-Mikael TI How Do C-Tactile Skin Afferents Contribute to Erotic Affect? SO JOURNAL OF SEXUAL MEDICINE LA English DT Letter ID TOUCH C1 [Ellingsen, Dan-Mikael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02114 USA. [Ellingsen, Dan-Mikael] Univ Oslo, Dept Psychol, Oslo, Norway. RP Ellingsen, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02114 USA. NR 4 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2015 VL 12 IS 7 BP 1656 EP 1656 DI 10.1111/jsm.12929 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CN5QM UT WOS:000358484300022 PM 26061119 ER PT J AU Folmer, RL Theodoroff, S AF Folmer, Robert L. Theodoroff, Sarah TI Response to: "All treatments in tinnitus are Experimental, Controversial and Futuristic" by De Ridder et al (2015) SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Letter ID TRANSCRANIAL MAGNETIC STIMULATION; EFFICACY C1 [Folmer, Robert L.; Theodoroff, Sarah] Oregon Hlth & Sci Univ, NCRAR, Portland VA Med Ctr, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Oregon Hlth & Sci Univ, NCRAR, Portland VA Med Ctr, Dept Otolaryngol, Portland, OR 97201 USA. NR 10 TC 0 Z9 0 U1 0 U2 3 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUL-AUG PY 2015 VL 26 IS 7 BP 678 EP 679 DI 10.3766/jaaa.14049 PG 2 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA CN5JL UT WOS:000358465500009 PM 26218056 ER PT J AU Huh, J Kim, KW Park, SJ Kim, HJ Lee, JS Ha, HK Tirumani, H Ramaiya, NH AF Huh, Jimi Kim, Kyung Won Park, Seong Joon Kim, Hyoung Jung Lee, Jong Seok Ha, Hyun Kwon Tirumani, Harsha Ramaiya, Nikhil H. TI Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE Ewing sarcoma family of tumors; Extraskeletal Ewing sarcoma; Computed tomography; Imaging ID TISSUE AB Objective: To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods: We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results: Among the 70 patients (mean age, 35.8 +/- 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9 %). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), Lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion: Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. C1 [Huh, Jimi; Kim, Kyung Won; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Park, Seong Joon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul 138736, South Korea. [Tirumani, Harsha; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Med Sch, Boston, MA 02115 USA. RP Kim, KW (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. EM medimash@gmail.com FU Ministry of Health & Welfare, Republic of Korea [HI14C1090]; National Research Foundation of Korea (NRF) - Ministry of Science, ICT, & Future Planning [2014R1A1A1006823] FX This study was supported by a grant from the Ministry of Health & Welfare, Republic of Korea (Grant No. HI14C1090) and a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, & Future Planning (No. 2014R1A1A1006823). NR 15 TC 2 Z9 2 U1 1 U2 4 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 JUL-AUG PY 2015 VL 16 IS 4 BP 783 EP 790 DI 10.3348/kjr.2015.16.4.783 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN5GZ UT WOS:000358459100010 PM 26175577 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 Malignant Solid Neoplasms of the Kidney: Cross-Sectional Imaging Findings SO KOREAN JOURNAL OF RADIOLOGY LA English DT Editorial Material DE Kidney; Malignant tumors; Computed tomography; Magnetic resonance imaging ID RADIOLOGIC-PATHOLOGICAL CORRELATION; FIBROUS HISTIOCYTOMA; SYNOVIAL SARCOMA; CARCINOID-TUMORS; CT; OSTEOSARCOMA; EXPERIENCE; DIAGNOSIS; FEATURES; RARE AB Malignant kidney neoplasms are the most frequently encountered solid kidney masses. Although renal cell carcinoma is the major renal malignancy, other solid malignant renal masses should be considered in the differential diagnosis of solid renal masses that do not contain a macroscopic fatty component. In this pictorial essay, we present the imaging findings of a primitive neuroectodermal tumor, primary liposarcoma of the kidney, primary neuroendocrine tumor, Leiomyosarcoma, synovial sarcoma, malignant fibrous histiocytoma, sclerosing fibrosarcoma and renal metastasis of osteosarcoma. C1 [Karaosmanoglu, Ali Devrim; Hahn, Peter F.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Onur, Mehmet Ruhi] Hacettepe Univ, Sch Med, Dept Radiol, TR-06100 Ankara, Turkey. [Shirkhoda, Ali] Univ Calif Irvine, Sch Med, Dept Radiol, Irvine, CA 92697 USA. [Ozmen, Mustafa] Hacettepe Univ, Fac Med, Dept Radiol, TR-06100 Ankara, Turkey. RP Onur, MR (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, TR-06100 Ankara, Turkey. EM ruhionur@yahoo.com NR 35 TC 1 Z9 2 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 JUL-AUG PY 2015 VL 16 IS 4 BP 853 EP 859 DI 10.3348/kjr.2015.16.4.853 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN5GZ UT WOS:000358459100018 PM 26175585 ER PT J AU Bar-Nur, O Verheul, C Sommer, AG Brumbaugh, J Schwarz, BA Lipchina, I Huebner, AJ Mostoslavsky, G Hochedlinger, K AF Bar-Nur, Ori Verheul, Cassandra Sommer, Andreia G. Brumbaugh, Justin Schwarz, Benjamin A. Lipchina, Inna Huebner, Aaron J. Mostoslavsky, Gustavo Hochedlinger, Konrad TI Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage SO NATURE BIOTECHNOLOGY LA English DT Article ID SMALL MOLECULES FACILITATE; NEURAL STEM-CELLS; MOUSE FIBROBLASTS; DEFINED FACTORS; GENERATION; NANOG AB Brief expression of pluripotency-associated factors such as Oct4, Klf4, Sox2 and c-Myc (OKSM), in combination with differentiation-inducing signals, has been reported to trigger transdifferentiation of fibroblasts into other cell types. Here we show that OKSM expression in mouse fibroblasts gives rise to both induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) under conditions previously shown to induce only iNSCs. Fibroblast-derived iNSC colonies silenced retroviral transgenes and reactivated silenced X chromosomes, both hallmarks of pluripotent stem cells. Moreover, lineage tracing with an Oct4-CreER labeling system demonstrated that virtually all iNSC colonies originated from cells transiently expressing Oct4, whereas ablation of Oct4(+) cells prevented iNSC formation. Lastly, an alternative transdifferentiation cocktail that lacks Oct4 and was reportedly unable to support induced pluripotency yielded iPSCs and iNSCs carrying the Oct4-CreER-derived lineage label. Together, these data suggest that iNSC generation from fibroblasts using OKSM and other pluripotency-related reprogramming factors requires passage through a transient iPSC state. C1 [Bar-Nur, Ori; Verheul, Cassandra; Brumbaugh, Justin; Schwarz, Benjamin A.; Lipchina, Inna; Huebner, Aaron J.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Bar-Nur, Ori; Verheul, Cassandra; Brumbaugh, Justin; Schwarz, Benjamin A.; Lipchina, Inna; Huebner, Aaron J.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Bar-Nur, Ori; Verheul, Cassandra; Brumbaugh, Justin; Schwarz, Benjamin A.; Lipchina, Inna; Huebner, Aaron J.; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Bar-Nur, Ori; Verheul, Cassandra; Brumbaugh, Justin; Schwarz, Benjamin A.; Lipchina, Inna; Huebner, Aaron J.; Hochedlinger, Konrad] Howard Hughes Med Inst, Chevy Chase, MD USA. [Bar-Nur, Ori; Verheul, Cassandra; Brumbaugh, Justin; Schwarz, Benjamin A.; Lipchina, Inna; Huebner, Aaron J.; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA USA. [Sommer, Andreia G.; Mostoslavsky, Gustavo] Boston Univ, Sch Med, Ctr Regenerat Med CReM, Boston, MA 02118 USA. [Sommer, Andreia G.; Mostoslavsky, Gustavo] Boston Med Ctr, Boston, MA USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM khochedlinger@mgh.harvard.edu FU EGL foundation; Postdoctoral Fellowship Award by MGH Executive Committee on Research Fund; US National Institutes of Health (NIH) [1F32HD078029-01A1, 1F32HD079225-01A1]; NIH [R01HD058013]; Howard Hughes Medical Institute; [T32 (5-T32-CA-9216-33)] FX We thank members of the Hochedlinger laboratory for critical evaluation and discussion of this manuscript. We thank E. Apostolou and S. Cheloufi for helpful comments and N. Maherali for suggesting the idea of X chromosome reactivation. We are also grateful to B. Payer and J. Lee for providing tail-tip fibroblasts carrying an X-linked GFP reporter and to A. Brack for sharing Rosa26-lsl-DTA mice. We are grateful to L. Prickett, M. Weglarz and K. Folz-Donahue at the MGH/HSCI flow cytometry core for their constant assistance and support. O.B.-N, is supported by a Gruss-Lipper postdoctoral fellowship from the EGL foundation. B.A.S. has been supported by a T32 (5-T32-CA-9216-33) grant and through a Postdoctoral Fellowship Award by the MGH Executive Committee on Research Fund for Medical Discovery. J.B. and I.L. are supported by Ruth L. Kirschstein F32 Post-doctoral Fellowships from the US National Institutes of Health (NIH) (1F32HD078029-01A1 to J.B. and 1F32HD079225-01A1 to I.L.). Support to K.H. is from the NIH (R01HD058013) and Howard Hughes Medical Institute. NR 27 TC 30 Z9 30 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2015 VL 33 IS 7 BP 761 EP 768 DI 10.1038/nbt.3247 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CN4JJ UT WOS:000358396100033 PM 26098450 ER PT J AU Graham, DB Becker, CE Doan, A Goel, G Villablanca, EJ Knights, D Mok, A Ng, ACY Doench, JG Root, DE Clish, CB Xavier, RJ AF Graham, Daniel B. Becker, Christine E. Doan, Aivi Goel, Gautam Villablanca, Eduardo J. Knights, Dan Mok, Amanda Ng, Aylwin C. Y. Doench, John G. Root, David E. Clish, Clary B. Xavier, Ramnik J. TI Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst SO NATURE COMMUNICATIONS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC GRANULOMATOUS-DISEASE; NADPH OXIDASE; RHEUMATOID-ARTHRITIS; SIGNALING PATHWAYS; INTERFERON-GAMMA; DENDRITIC CELLS; VAV PROTEINS; HOST-DEFENSE; COMPLEX AB The phagocyte oxidative burst, mediated by Nox2 NADPH oxidase-derived reactive oxygen species, confers host defense against a broad spectrum of bacterial and fungal pathogens. Loss-of-function mutations that impair function of the Nox2 complex result in a life-threatening immunodeficiency, and genetic variants of Nox2 subunits have been implicated in pathogenesis of inflammatory bowel disease (IBD). Thus, alterations in the oxidative burst can profoundly impact host defense, yet little is known about regulatory mechanisms that fine-tune this response. Here we report the discovery of regulatory nodes controlling oxidative burst by functional screening of genes within loci linked to human inflammatory disease. Implementing a multi-omics approach, we define transcriptional, metabolic and ubiquitin-cycling nodes controlled by Rbpj, Pfkl and Rnf145, respectively. Furthermore, we implicate Rnf145 in proteostasis of the Nox2 complex by endoplasmic reticulum-associated degradation. Consequently, ablation of Rnf145 in murine macrophages enhances bacterial clearance, and rescues the oxidative burst defects associated with Ncf4 haploinsufficiency. C1 [Graham, Daniel B.; Doan, Aivi; Villablanca, Eduardo J.; Mok, Amanda; Ng, Aylwin C. Y.; Doench, John G.; Root, David E.; Clish, Clary B.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Graham, Daniel B.; Villablanca, Eduardo J.; Xavier, Ramnik J.] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Becker, Christine E.; Goel, Gautam; Villablanca, Eduardo J.; Xavier, Ramnik J.] Harvard Univ, Ctr Computat & Integrat Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Knights, Dan] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA. [Ng, Aylwin C. Y.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aylwin C. Y.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA. RP Graham, DB (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM dgraham@broadinstitute.org; xavier@molbio.mgh.harvard.edu OI Villablanca, Eduardo/0000-0001-9522-9729; Mok, Amanda/0000-0001-6981-1547 FU Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis Foundation of America Genetics Initiative; National Institutes of Health [DK043351] FX We are grateful to Dr Agnes Gardet for her help in designing, optimizing and completing the screen, and Bihua Li for technical assistance. We thank Drs Jeffrey Silva and Matthew Stokes at Cell Signaling Technology for expert assistance with proteomics. In addition, we thank Drs Moran Yassour, Isabel Latorre and Natalia Nedelsky for critical comments and advice. R.J.X. was supported by funding from The Leona M. and Harry B. Helmsley Charitable Trust, the Crohn's and Colitis Foundation of America Genetics Initiative and the National Institutes of Health grant DK043351. NR 50 TC 4 Z9 4 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2015 VL 6 AR 7838 DI 10.1038/ncomms8838 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO0RZ UT WOS:000358861300002 PM 26194095 ER PT J AU Schumacher, FR Schmit, SL Jiao, S Edlund, CK Wang, HS Zhang, B Hsu, L Huang, SC Fischer, CP Harju, JF Idos, GE Lejbkowicz, F Manion, FJ McDonnell, K McNeil, CE Melas, M Rennert, HS Shi, W Thomas, DC Van Den Berg, DJ Hutter, CM Aragaki, AK Butterbach, K Caan, BJ Carlson, CS Chanock, SJ Curtis, KR Fuchs, CS Gala, M Giocannucci, EL Gogarten, SM Hayes, RB Henderson, B Hunter, DJ Jackson, RD Kolonel, LN Kooperberg, C Kury, S LaCroix, A Laurie, CC Laurie, CA Lemire, M Levine, D Ma, J Makar, KW Qu, CH Taverna, D Ulrich, CM Wu, KN Kono, S West, DW Berndt, SI Bezieau, S Brenner, H Campbell, PT Chan, AT Chang-Claude, J Coetzee, GA Conti, DV Duggan, D Figueiredo, JC Fortini, BK Gallinger, SJ Gauderman, WJ Giles, G Green, R Haile, R Harrison, TA Hoffmeister, M Hopper, JL Hudson, TJ Jacobs, E Iwasaki, M Jee, SH Jenkins, M Jia, WH Joshi, A Li, L Lindor, NM Matsuo, K Moreno, V Mukherjee, B Newcomb, PA Potter, JD Raskin, L Rennert, G Rosse, S Severi, G Schoen, RE Seminara, D Shu, XO Slattery, ML Tsugane, S White, E Xiang, YB Zanke, BW Zheng, W Le Marchand, L Casey, G Gruber, SB Peters, U AF Schumacher, Fredrick R. Schmit, Stephanie L. Jiao, Shuo Edlund, Christopher K. Wang, Hansong Zhang, Ben Hsu, Li Huang, Shu-Chen Fischer, Christopher P. Harju, John F. Idos, Gregory E. Lejbkowicz, Flavio Manion, Frank J. McDonnell, Kevin McNeil, Caroline E. Melas, Marilena Rennert, Hedy S. Shi, Wei Thomas, Duncan C. Van Den Berg, David J. Hutter, Carolyn M. Aragaki, Aaron K. Butterbach, Katja Caan, Bette J. Carlson, Christopher S. Chanock, Stephen J. Curtis, Keith R. Fuchs, Charles S. Gala, Manish Giocannucci, Edward L. Gogarten, Stephanie M. Hayes, Richard B. Henderson, Brian Hunter, David J. Jackson, Rebecca D. Kolonel, Laurence N. Kooperberg, Charles Kury, Sebastian LaCroix, Andrea Laurie, Cathy C. Laurie, Cecelia A. Lemire, Mathiew Levine, David Ma, Jing Makar, Karen W. Qu, Conghui Taverna, Darin Ulrich, Cornelia M. Wu, Kana Kono, Suminori West, Dee W. Berndt, Sonja I. Bezieau, Stephane Brenner, Hermann Campbell, Peter T. Chan, Andrew T. Chang-Claude, Jenny Coetzee, Gerhard A. Conti, David V. Duggan, David Figueiredo, Jane C. Fortini, Barbara K. Gallinger, Steven J. Gauderman, W. James Giles, Graham Green, Roger Haile, Robert Harrison, Tabitha A. Hoffmeister, Michael Hopper, John L. Hudson, Thomas J. Jacobs, Eric Iwasaki, Motoki Jee, Sun Ha Jenkins, Mark Jia, Wei-Hua Joshi, Amit Li, Li Lindor, Noralene M. Matsuo, Keitaro Moreno, Victor Mukherjee, Bhramar Newcomb, Polly A. Potter, John D. Raskin, Leon Rennert, Gad Rosse, Stephanie Severi, Gianluca Schoen, Robert E. Seminara, Daniela Shu, Xiao-Ou Slattery, Martha L. Tsugane, Shoichiro White, Emily Xiang, Yong-Bing Zanke, Brent W. Zheng, Wei Le Marchand, Loic Casey, Graham Gruber, Stephen B. Peters, Ulrike TI Genome-wide association study of colorectal cancer identifies six new susceptibility loci SO NATURE COMMUNICATIONS LA English DT Article ID NEGATIVE REGULATOR LRIG1; GENOTYPE IMPUTATION; PANCREATIC-CANCER; RISK LOCUS; METAANALYSIS; SCAN; 8Q24; CARCINOMA; VARIANTS; RECEPTOR AB Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E - 08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies. C1 [Schumacher, Fredrick R.; Schmit, Stephanie L.; Edlund, Christopher K.; Huang, Shu-Chen; Idos, Gregory E.; McDonnell, Kevin; McNeil, Caroline E.; Melas, Marilena; Thomas, Duncan C.; Van Den Berg, David J.; Henderson, Brian; Coetzee, Gerhard A.; Conti, David V.; Figueiredo, Jane C.; Fortini, Barbara K.; Gauderman, W. James; Raskin, Leon; Rennert, Gad; Casey, Graham; Gruber, Stephen B.] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. [Schmit, Stephanie L.; Gruber, Stephen B.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. [Jiao, Shuo; Hsu, Li; Aragaki, Aaron K.; Carlson, Christopher S.; Curtis, Keith R.; Kooperberg, Charles; LaCroix, Andrea; Makar, Karen W.; Qu, Conghui; Ulrich, Cornelia M.; Harrison, Tabitha A.; Rosse, Stephanie; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98124 USA. [Wang, Hansong; Le Marchand, Loic] Univ Hawaii Canc Ctr, Program Epidemiol, Honolulu, HI 96822 USA. [Zhang, Ben] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing 400038, Peoples R China. [Fischer, Christopher P.; Harju, John F.; Manion, Frank J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48105 USA. [Lejbkowicz, Flavio; Rennert, Hedy S.; Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, IL-34361 Haifa, Israel. [Lejbkowicz, Flavio; Rennert, Hedy S.; Rennert, Gad] Clalit Hlth Serv Natl Canc Control Ctr, IL-34361 Haifa, Israel. [Shi, Wei] Childrens Hosp, Dept Surg, Los Angeles, CA 90027 USA. [Hutter, Carolyn M.] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20892 USA. [Butterbach, Katja; Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69121 Heidelberg, Germany. [Caan, Bette J.] Kaiser Permanente Med Care Program Northern Calif, Div Res, Oakland, CA 94612 USA. [Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Brookline, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Brookline, MA 02115 USA. [Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Giocannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Giocannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Gogarten, Stephanie M.; Laurie, Cathy C.; Laurie, Cecelia A.; Levine, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY 10016 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Jackson, Rebecca D.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Kolonel, Laurence N.] Univ Hawaii Manoa, Off Publ Hlth Studies, Honolulu, HI 96822 USA. [Kury, Sebastian] CHU Nantes, Serv Genet Med, F-44093 Nantes, France. [Lemire, Mathiew] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Ma, Jing] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. [Taverna, Darin] Phoenix Coll, Phoenix, AZ 85013 USA. [Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany. [Ulrich, Cornelia M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kono, Suminori; Matsuo, Keitaro] Kyushu Univ, Dept Prevent Med, Fukuoka 8128582, Japan. [West, Dee W.] Inst Publ Hlth, Canc Registry Greater Calif, Sacramento, CA 95825 USA. [Bezieau, Stephane] Ctr Hosp Univ Hotel Dieu, F-44093 Nantes, France. [Campbell, Peter T.; Jacobs, Eric] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, D-69121 Heidelberg, Germany. [Conti, David V.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. [Duggan, David] Translat Genom Res Inst, Genet Basis Human Dis Div, Phoenix, AZ 85004 USA. [Gallinger, Steven J.] Mt Sinai Hosp, Zane Cohen Ctr Digest Dis, Toronto, ON M5T 3L9, Canada. [Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Green, Roger] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada. [Haile, Robert] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Hopper, John L.] Univ Melbourne, Ctr MEGA Epidemiol, Carlton, Vic 3010, Australia. [Hudson, Thomas J.] Ontario Inst Canc Res, Dept Genom, Toronto, ON M5G 0A3, Canada. [Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Tokyo 1040045, Japan. [Jee, Sun Ha] Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. [Jenkins, Mark] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Parkville, Vic 3010, Australia. [Jia, Wei-Hua] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China. [Joshi, Amit] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Li, Li] Case Western Reserve Univ, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA. [Lindor, Noralene M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. [Moreno, Victor] IDIBELL, Catalan Inst Oncol, Canc Epidemiol Serv, Barcelona 08908, Spain. [Mukherjee, Bhramar] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Newcomb, Polly A.; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA. [Raskin, Leon; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Nashville, TN 37203 USA. [Raskin, Leon; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Rennert, Gad] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-3200003 Haifa, Israel. [Severi, Gianluca] HuGeF, I-10126 Turin, Italy. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. [Seminara, Daniela] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37203 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT 84132 USA. [Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai 220025, Peoples R China. [Zanke, Brent W.] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Zanke, Brent W.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON K1Y 4E9, Canada. RP Gruber, SB (reprint author), Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. EM sgruber@usc.edu RI Hoffmeister, Michael/B-5745-2012; Bezieau, stephane/G-5621-2015; Raskin, Leon/P-5765-2015; Jenkins, Mark/P-7803-2015; U-ID, Kyushu/C-5291-2016; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; Potter, John/0000-0001-5439-1500; Bezieau, stephane/0000-0003-0095-1319; Raskin, Leon/0000-0003-1195-7214; Jenkins, Mark/0000-0002-8964-6160; Gogarten, Stephanie/0000-0002-7231-9745; Hayes, Richard/0000-0002-0918-661X; Moreno, Victor/0000-0002-2818-5487; Brenner, Hermann/0000-0002-6129-1572; Giles, Graham/0000-0003-4946-9099 FU National Cancer Institute, National Institutes of Health under RFA [CA-09-002, NIH/NCI U19 CA148107] FX CORECT: this work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-09-002, NIH/NCI U19 CA148107. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CORECT consortium, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CORECT Consortium. ASTERISK: we are very grateful to Dr Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students. DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik and Ursula Eilber for excellent technical assistance. GECCO: we thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. HPFS, NHS and PHS: we acknowledge Patrice Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS and PHS under the supervision of Dr Immaculata Devivo and Dr David Hunter, Qin (Carolyn) Guo and Lixue Zhu who assisted in programming for NHS and HPFS and Haiyan Zhang who assisted in programming for the PHS. We thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. We assume full responsibility for analyses and interpretation of these data. PLCO: we thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services Inc., Ms Barbara O'Brien and staff, Westat Inc. and Drs Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions for making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. PMH: we thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20 Investigator%20Short%20List.pdf. ACC: we thank all study participants and research staff of all studies for their contributions and commitment to this project, Regina Courtney for DNA preparation and Jing He for data processing. NR 54 TC 14 Z9 14 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2015 VL 6 AR 7138 DI 10.1038/ncomms8138 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO0NZ UT WOS:000358850000001 PM 26151821 ER PT J AU Henly, SJ McCarthy, DO Wyman, JF Heitkemper, MM Redeker, NS Titler, MG McCarthy, AM Stone, PW Moore, SM Alt-White, AC Conley, YP Dunbar-Jacob, J AF Henly, Susan J. McCarthy, Donna O. Wyman, Jean F. Heitkemper, Margaret M. Redeker, Nancy S. Titler, Marita G. McCarthy, Ann Marie Stone, Patricia W. Moore, Shirley M. Alt-White, Anna C. Conley, Yvette P. Dunbar-Jacob, Jacqueline TI Emerging areas of science: Recommendations for Nursing Science Education from the Council for the Advancement of Nursing Science Idea Festival SO NURSING OUTLOOK LA English DT Article DE Nursing research; Nursing science ID TEAM SCIENCE; HEALTH; COLLABORATION; SCIENTISTS AB The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee (IFAC) to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2005 National Research Council report Advancing The Nation's Health Needs and the 2010 American Association of Colleges of Nursing Position Statement on the Research-Focused Doctorate Pathways to Excellence, the IFAC specifically addressed the capacity of PhD programs to prepare nursing scientists to conduct cutting-edge research in the following key emerging and priority areas of health sciences research: omics and the microbiome; health behavior, behavior change, and biobehavioral science; patient-reported outcomes; big data, e-science, and informatics; quantitative sciences; translation science; and health economics. The purpose of this article is to (a) describe IFAC activities, (b) summarize 2014 discussions hosted as part of the Idea Festival, and (c) present IFAC recommendations for incorporating these emerging areas of science and technology into research-focused doctoral programs committed to preparing graduates for lifelong, competitive careers in nursing science. The recommendations address clearer articulation of program focus areas; inclusion of foundational knowledge in emerging areas of science in core courses on nursing science and research methods; faculty composition; prerequisite student knowledge and skills; and in-depth, interdisciplinary training in supporting area of science content and methods. C1 [Henly, Susan J.; Wyman, Jean F.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [McCarthy, Donna O.] Marquette Univ, Coll Nursing, Milwaukee, WI 53233 USA. [Heitkemper, Margaret M.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Redeker, Nancy S.] Yale Univ, Sch Nursing, West Haven, CT USA. [Titler, Marita G.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [McCarthy, Ann Marie] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Stone, Patricia W.] Columbia Univ, Sch Nursing, New York, NY USA. [Moore, Shirley M.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Alt-White, Anna C.] US Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. [Conley, Yvette P.; Dunbar-Jacob, Jacqueline] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Henly, SJ (reprint author), Univ Minnesota, Sch Nursing, 5-140 WDH,308 Harvard St SE, Minneapolis, MN 55455 USA. EM henly003@umn.edu RI Redeker, Nancy/Q-8252-2016; OI Redeker, Nancy/0000-0001-7817-2708; Moore, Shirley M./0000-0003-2712-6896; Henly, Susan/0000-0002-2995-4161 NR 28 TC 14 Z9 14 U1 3 U2 24 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 JUL-AUG PY 2015 VL 63 IS 4 BP 398 EP 407 DI 10.1016/j.outlook.2015.04.007 PG 10 WC Nursing SC Nursing GA CN6NT UT WOS:000358552200006 PM 26187079 ER PT J AU Henly, SJ McCarthy, DO Wyman, JF Stone, PW Redeker, NS McCarthy, AM Alt-White, AC Dunbar-Jacob, J Titler, MG Moore, SM Heitkemper, MM Conley, YP AF Henly, Susan J. McCarthy, Donna O. Wyman, Jean F. Stone, Patricia W. Redeker, Nancy S. McCarthy, Ann Marie Alt-White, Anna C. Dunbar-Jacob, Jacqueline Titler, Marita G. Moore, Shirley M. Heitkemper, Margaret M. Conley, Yvette P. TI Integrating emerging areas of nursing science into PhD programs SO NURSING OUTLOOK LA English DT Article DE Nursing research; Nursing science; Nursing scientist education; Research-focused doctorate ID TRANSLATIONAL RESEARCH; DOCTORAL EDUCATION; HUMAN GENOME; HEALTH; PATIENT; INFORMATION; MODEL; COMMUNICATION; ADVANCEMENT; MICROBIOME AB The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2010 American Association of Colleges of Nursing Position Statement "The Research-Focused Doctoral Program in Nursing: Pathways to Excellence," Idea Festival Advisory Committee members focused on emerging areas of science and technology that impact the ability of research-focused doctoral programs to prepare graduates for competitive and sustained programs of nursing research using scientific advances in emerging areas of science and technology. The purpose of this article is to describe the educational and scientific contexts for the Idea Festival, which will serve as the foundation for recommendations for incorporating emerging areas of science and technology into research-focused doctoral programs in nursing. C1 [Henly, Susan J.; Wyman, Jean F.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [McCarthy, Donna O.] Marquette Univ, Milwaukee, WI 53233 USA. [Stone, Patricia W.] Columbia Univ, Sch Nursing, New York, NY USA. [Redeker, Nancy S.] Yale Univ, Sch Nursing, West Haven, CT USA. [McCarthy, Ann Marie] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Alt-White, Anna C.] US Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. [Dunbar-Jacob, Jacqueline; Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Titler, Marita G.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Moore, Shirley M.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Heitkemper, Margaret M.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Henly, SJ (reprint author), Univ Minnesota, Sch Nursing, 5-140 WDH,308 Harvard St SE, Minneapolis, MN 55455 USA. EM henly003@umn.edu RI Redeker, Nancy/Q-8252-2016; OI Redeker, Nancy/0000-0001-7817-2708; Henly, Susan/0000-0002-2995-4161 NR 89 TC 14 Z9 14 U1 5 U2 12 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 JUL-AUG PY 2015 VL 63 IS 4 BP 408 EP 416 DI 10.1016/j.outlook.2015.04.010 PG 9 WC Nursing SC Nursing GA CN6NT UT WOS:000358552200007 PM 26187080 ER PT J AU Henly, SJ McCarthy, DO Wyman, JF Alt-White, AC Stone, PW McCarthy, AM Redeker, NS Dunbar-Jacob, J Titler, MG Conley, YP Heitkemper, MM Moore, SM AF Henly, Susan J. McCarthy, Donna O. Wyman, Jean F. Alt-White, Anna C. Stone, Patricia W. McCarthy, Ann Marie Redeker, Nancy S. Dunbar-Jacob, Jacqueline Titler, Marita G. Conley, Yvette P. Heitkemper, Margaret M. Moore, Shirley M. TI Emerging areas of nursing science and PhD education for the 21st century: Response to commentaries SO NURSING OUTLOOK LA English DT Article DE Doctoral education; Health; Nursing science; Nursing research; Research-focused doctorate ID BIOBEHAVIORAL RESEARCH; IDEA FESTIVAL; HEALTH; PROGRAMS; RECOMMENDATIONS; SCIENTISTS; BIOLOGY; FUTURE; HOLISM AB We respond to commentaries from the American Academy of Nursing, the American Association of Colleges of Nursing, and the National Institute of Nursing Research on our thoughts about integrating emerging areas of science into nursing PhD programs. We identify areas of agreement and focus our response on cross-cutting issues arising from cautions about the unique focus of nursing science and how best to proceed with incorporation of emerging areas of science into nursing PhD programs. C1 [Henly, Susan J.; Wyman, Jean F.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [McCarthy, Donna O.] Marquette Univ, Milwaukee, WI 53233 USA. [Alt-White, Anna C.] US Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. [Stone, Patricia W.] Columbia Univ, Sch Nursing, New York, NY USA. [McCarthy, Ann Marie] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Redeker, Nancy S.] Yale Univ, Sch Nursing, West Haven, CT USA. [Dunbar-Jacob, Jacqueline; Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Titler, Marita G.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Heitkemper, Margaret M.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Moore, Shirley M.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. RP Henly, SJ (reprint author), Univ Minnesota, Sch Nursing, 5-140 WDH,308 Harvard St SE, Minneapolis, MN 55455 USA. EM henly003@umn.edu RI Redeker, Nancy/Q-8252-2016; OI Redeker, Nancy/0000-0001-7817-2708; Henly, Susan/0000-0002-2995-4161 NR 42 TC 2 Z9 2 U1 1 U2 5 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 JUL-AUG PY 2015 VL 63 IS 4 BP 439 EP 445 DI 10.1016/j.outlook.2015.05.003 PG 7 WC Nursing SC Nursing GA CN6NT UT WOS:000358552200012 PM 26187083 ER PT J AU LeBaron, VT Iribarren, SJ Perri, S Beck, SL AF LeBaron, Virginia T. Iribarren, Sarah J. Perri, Seneca Beck, Susan L. TI A practical field guide to conducting nursing research in low- and middle-income countries SO NURSING OUTLOOK LA English DT Article DE Global health; International research; Developing countries; Low- and middle-income countries; Research methods; Nursing ID CANCER PAIN MANAGEMENT; CROSS-CULTURAL RESEARCH; ETHICAL CONSIDERATIONS; SOUTH-AFRICA; COLLABORATION; CHALLENGES; INDIA AB Objectives: The purpose of this report is to offer practical guidance to nurse investigators interested in international research in low- and middle-income countries (LMICs). Lessons learned and strategies for planning and implementing an international research project are addressed. Methods: Four nurse researchers who conducted studies in diverse international settings (Argentina, India, South Africa, and Tanzania) describe their collective experiences regarding study planning and implementation; data collection using a variety of methods; and cultural, contextual and ethical considerations. Results: Nurses who undertake international health research projects, particularly in LMICs, can face unique challenges and opportunities. Recommendations for success include advance planning, remaining flexible, having a backup plan, cultivating an attitude of curiosity and cultural humility, establishing collaborative and respectful partnerships, and budgeting adequate time. Conclusions: Nurse scientists often receive little training and support to conduct international research. Guidance to undertake research projects in LMICs can build capacity for nurses to make significant contributions to global health. C1 [LeBaron, Virginia T.] Dana Farber Canc Inst, Boston, MA 02215 USA. [LeBaron, Virginia T.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Iribarren, Sarah J.] Columbia Univ, Sch Nursing, New York, NY USA. [Perri, Seneca] Univ Utah, Biomed Informat, Salt Lake City, UT USA. [Beck, Susan L.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. RP LeBaron, VT (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 517, Boston, MA 02215 USA. EM virginia_lebaron@dfci.harvard.edu FU American Cancer Society [117214-DSCN-09-141-01-SCN, 121673-DSCNR-09-141-03-SCN]; University of Utah Graduate Program; Fulbright-Nehru Research Scholar Program; National Institute of Nursing Research NRSA [F31NR012614]; Sigma Theta Tau Gamma Rho Chapter; NIH/Fogarty International Clinical Research Scholar program; NIH Fogarty Center International Challenge Award [5RC1TW008567-02]; CIES/Fulbright Research Scholar Program Sub-Saharan Africa; NIH [1U54CA156734, 1T32NR014205-01] FX The original research projects referenced in this article were supported by American Cancer Society (grant no. 117214-DSCN-09-141-01-SCN and grant no. 121673-DSCNR-09-141-03-SCN), the University of Utah Graduate Program, and the Fulbright-Nehru Research Scholar Program (Virginia T. LeBaron); National Institute of Nursing Research NRSA (grant no. F31NR012614), Sigma Theta Tau Gamma Rho Chapter, research collaboration established through NIH/Fogarty International Clinical Research Scholar program (Sarah J. Iribarren); NIH Fogarty Center International Challenge Award (grant no. 5RC1TW008567-02) (Seneca Perri): and CIES/Fulbright Research Scholar Program Sub-Saharan Africa (Susan L. Beck). Drs. LeBaron and Iribarren are both currently funded by NIH grants (1U54CA156734; 1T32NR014205-01, respectively). NR 35 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 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD JUL-AUG PY 2015 VL 63 IS 4 BP 462 EP 473 DI 10.1016/j.outlook.2015.02.003 PG 12 WC Nursing SC Nursing GA CN6NT UT WOS:000358552200015 PM 26187086 ER PT J AU Amar, AF Tuccinardi, N Heislein, J Simpson, S AF Amar, Angela F. Tuccinardi, Nicole Heislein, Julie Simpson, Somatra TI Friends Helping Friends: A nonrandomized control trial of a peer-based response to dating violence SO NURSING OUTLOOK LA English DT Article DE Partner violence; Prevention; Sexual violence ID SEXUAL ASSAULT PREVENTION; BYSTANDER INTERVENTION; EDUCATION; BEHAVIOR; CONSEQUENCES; PROGRAM; IMPACT; MODEL; RAPE AB Dating violence is a significant problem for older adolescents with implications for the survivor's health. Survivors disclose the violence to friends who are often ill equipped to help them manage the consequences. The purpose of this pilot study was to evaluate the effectiveness and feasibility of Friends Helping Friends, a community-level education program to teach older adolescents to recognize and intervene in dating violence. A convenience sample of 101 students aged 18 to 22 years were nonrandomly allocated to a treatment or control group and completed pre- and post-test measures. Compared with the control group, treatment group participants reported increased perceived responsibility to help, skills to act as a bystander, and intention to help and decreased rape myth acceptance. Friends Helping Friends shows promise as an effective strategy for older adolescent females in the prevention and response to dating violence. C1 [Amar, Angela F.] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. [Tuccinardi, Nicole] Whidden Hosp, Everett, MA USA. [Heislein, Julie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simpson, Somatra] Community Counseling Bristol Cty, Bristol Cty, MA USA. RP Amar, AF (reprint author), Emory Univ, Nell Hodgson Woodruff Sch Nursing, 1520 Clifton Rd, Atlanta, GA 30322 USA. EM angela.amar@emory.edu FU Robert Wood Johnson Nurse Faculty Scholar grant [64204] FX Supported in part by a Robert Wood Johnson Nurse Faculty Scholar grant (grant no. 64204). NR 33 TC 0 Z9 0 U1 8 U2 12 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 JUL-AUG PY 2015 VL 63 IS 4 BP 496 EP 503 DI 10.1016/j.outlook.2015.01.004 PG 8 WC Nursing SC Nursing GA CN6NT UT WOS:000358552200019 PM 26187089 ER PT J AU Boswell, MV Manchikanti, L Kaye, AD Bakshi, S Gharibo, CG Gupta, S Jha, S Nampiaparampil, DE Simopoulos, TT Hirsch, JA AF Boswell, Mark V. Manchikanti, Laxmaiah Kaye, Alan D. Bakshi, Sanjay Gharibo, Christopher G. Gupta, Sanjeeva Jha, Sachin Sunny Nampiaparampil, Devi E. Simopoulos, Thomas T. Hirsch, Joshua A. TI A Best-Evidence Systematic Appraisal of the Diagnostic Accuracy and Utility of Facet (Zygapophysial) Joint Injections in Chronic Spinal Pain SO PAIN PHYSICIAN LA English DT Review DE Chronic spinal pain; lumbar facet or zygapophysial joint pain; cervical facet or zygapophysial joint pain; thoracic facet or zygapophysial joint pain; facet joint nerve blocks; medial branch blocks; controlled comparative local anesthetic blocks ID LOW-BACK-PAIN; MEDIAL BRANCH BLOCKS; LOCAL-ANESTHETIC BLOCKS; GENE-RELATED PEPTIDE; 2-YEAR FOLLOW-UP; CERVICAL DORSAL RAMI; FALSE-POSITIVE RATE; LONG-TERM RELIEF; NECK PAIN; NERVE BLOCKS AB Background: Spinal zygapophysial, or facet, joints are a source of axial spinal pain and referred pain in the extremities. Conventional clinical features and other noninvasive diagnostic modalities are unreliable in diagnosing zygapophysial joint pain. Study Design: A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. Objective: To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. Methods: A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. The level of evidence was classified as Level I to V based on the grading of evidence utilizing best evidence synthesis. Data sources included relevant literature identified through searches of PubMed and other electronic searches published from 1966 through March 2015, Cochrane reviews, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: Studies must have been performed utilizing controlled local anesthetic blocks. The criterion standard must have been at least 50% pain relief from baseline scores and the ability to perform previously painful movements. Results: The available evidence is Level I for lumbar facet joint nerve blocks with the inclusion of a total of 17 studies with dual diagnostic blocks, with at least 75% pain relief with an average prevalence of 16% to 41% and false-positive rates of 25% to 44%. The evidence for diagnosis of cervical facet joint pain with cervical facet joint nerve blocks is Level II based on a total of 11 controlled diagnostic accuracy studies, with significant variability among the prevalence in a heterogenous population with internal inconsistency. The prevalence rates ranged from 36% to 67% with at least 80% pain relief as the criterion standard and a false-positive rate of 27% to 63%. The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II with 80% or higher pain relief as the criterion standard with a prevalence ranging from 34% to 48% and false-positive rates ranging from 42% to 48%. Limitations: The shortcomings of this systematic review include a paucity of literature related to the thoracic spine, continued debate on an appropriate gold standard, appropriateness of diagnostic blocks, and utility. Conclusion: The evidence is Level I for the diagnostic accuracy of lumbar facet joint nerve blocks, Level II for cervical facet joint nerve blocks, and Level II for thoracic facet joint nerve blocks in assessment of chronic spinal pain. C1 [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40202 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40202 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA USA. [Bakshi, Sanjay] Manhattan Spine & Pain Med, New York, NY USA. [Gharibo, Christopher G.] NYU, Sch Med, Dept Anesthesiol, NYU Langone Hosp Joint Dis,Pain Med, New York, NY 10016 USA. [Gharibo, Christopher G.] NYU, Sch Med, Dept Anesthesiol, NYU Langone Hosp Joint Dis,Anesthesiol & Orthoped, New York, NY 10016 USA. [Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford Royal Infirm, Pain Med & Anaesthesia, Bradford, W Yorkshire, England. [Jha, Sachin Sunny] RUMC, Chicago, IL USA. [Nampiaparampil, Devi E.] NYU, Sch Med, Rehabil Med, New York, NY USA. [Simopoulos, Thomas T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Serv & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Boswell, MV (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, 530 S Jackson St,Room C2A01, Louisville, KY 40202 USA. EM boswellmv@earthlink.net NR 212 TC 7 Z9 8 U1 0 U2 2 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JUL-AUG PY 2015 VL 18 IS 4 BP E497 EP E533 PG 37 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CO1FS UT WOS:000358900300003 PM 26218947 ER PT J AU Manchikanti, L Benyamin, R Helm, S Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin Helm, Standiford, II Hirsch, Joshua A. TI Epidural Ahesiolysis Provides Misinformation SO PAIN PHYSICIAN LA English DT Letter ID CENTRAL SPINAL STENOSIS; LOW-BACK-PAIN; EQUIVALENCE CONTROLLED-TRIAL; LUMBAR SURGERY SYNDROME; ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; DOUBLE-BLIND; PERCUTANEOUS ADHESIOLYSIS; INJECTIONS; MANAGEMENT C1 [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Benyamin, Ramsin] Millennium Pain Ctr, Bloomington, IL 61701 USA. [Helm, Standiford, II] Helm Ctr Pain Management Ctr, Laguna Hills, CA 92637 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NeuroIntervent Spine Serv, Boston, MA USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Intervent Care, Boston, MA USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Radiol, Boston, MA USA. RP Manchikanti, L (reprint author), Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. EM drlm@thepainmd.com; ramsinbenyamin@yahoo.com; drhelm@thehelmcenter.com; HIrsch@snisonline.org NR 16 TC 0 Z9 1 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JUL-AUG PY 2015 VL 18 IS 4 BP E670 EP E671 PG 2 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CO1FS UT WOS:000358900300020 PM 26218964 ER PT J AU Manchikanti, L Kaye, AD Boswell, MV Bakshi, S Gharibo, CG Grami, V Grider, JS Gupta, S Jha, S Mann, DP Nampiaparampil, DE Sharma, ML Shroyer, LN Singh, V Soin, A Vallejo, R Wargo, BW Hirsch, JA AF Manchikanti, Laxmaiah Kaye, Alan D. Boswell, Mark V. Bakshi, Sanjay Gharibo, Christopher G. Grami, Vahid Grider, Jay S. Gupta, Sanjeeva Jha, Sachin Sunny Mann, Dharam P. Nampiaparampil, Devi E. Sharma, Manohar Lal Shroyer, Lindsay N. Singh, Vijay Soin, Amol Vallejo, Ricardo Wargo, Bradley W. Hirsch, Joshua A. TI A Systematic Review and Best Evidence Synthesis of Effectiveness of Therapeutic Facet Joint Interventions in Managing Chronic Spinal Pain SO PAIN PHYSICIAN LA English DT Review DE Spinal pain; chronic low back pain; chronic neck pain; chronic thoracic pain; intraarticular facet joint blocks; facet joint nerve blocks; conventional radiofrequency neurotomy; pulsed radiofrequency neurolysis ID LOW-BACK-PAIN; MEDIAL BRANCH BLOCKS; INTERLAMINAR EPIDURAL INJECTIONS; ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; CLINICALLY IMPORTANT DIFFERENCE; CERVICAL ZYGAPOPHYSEAL JOINTS; LUMBAR DISC HERNIATION; BLIND CONTROLLED-TRIAL; CHRONIC NECK PAIN AB Background: The therapeutic spinal facet joint interventions generally used for the treatment of axial spinal pain of facet joint origin are intraarticular facet joint injections, facet joint nerve blocks, and radiofrequency neurotomy. Despite interventional procedures being common as treatment strategies for facet joint pathology, there is a paucity of literature investigating these therapeutic approaches. Systematic reviews assessing the effectiveness of various therapeutic facet joint interventions have shown there to be variable evidence based on the region and the modality of treatment utilized. Overall, the evidence ranges from limited to moderate. Objective: To evaluate and update the clinical utility of therapeutic lumbar, cervical, and thoracic facet joint interventions in managing chronic spinal pain. Study Design: A systematic review of therapeutic lumbar, cervical, and thoracic facet joint interventions for the treatment of chronic spinal pain. Methods: The available literature on lumbar, cervical, and thoracic facet joint interventions in managing chronic spinal pain was reviewed. The quality assessment criteria utilized were the Cochrane Musculoskeletal Review Group criteria and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM - QRB) for randomized trials and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM - QRBNR) for observational studies. The level of evidence was classified at 5 levels from Level I to Level V. Data sources included relevant literature identified through searches on PubMed and EMBASE from 1966 through March 2015, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake consumption. Results: A total of 21 randomized controlled trials meeting appropriate inclusion criteria were assessed in this evaluation. A total of 5 observational studies were assessed. In the lumbar spine, for long-term effectiveness, there is Level II evidence for radiofrequency neurotomy and lumbar facet joint nerve blocks, whereas the evidence is Level III for lumbosacral intraarticular injections. In the cervical spine, for long-term improvement, there is Level II evidence for cervical radiofrequency neurotomy and cervical facet joint nerve blocks, and Level IV evidence for cervical intraarticular injections. In the thoracic spine there is Level II evidence for thoracic facet joint nerve blocks and Level IV evidence for radiofrequency neurotomy for long-term improvement. Limitations: The limitations of this systematic review include an overall paucity of high quality studies and more specifically the lack of investigations related to thoracic facet joint injections. Conclusion: Based on the present assessment for the management of spinal facet joint pain, the evidence for long-term improvement is Level II for lumbar and cervical radiofrequency neurotomy, and therapeutic facet joint nerve blocks in the cervical, thoracic, and lumbar spine; Level III for lumbar intraarticular injections; and Level IV for cervical intraarticular injections and thoracic radiofrequency neurotomy. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Bakshi, Sanjay] Manhattan Spine & Pain Med, New York, NY USA. [Gharibo, Christopher G.] NYU, Sch Med, NYU Langone Hosp Joint Dis, New York, NY USA. [Grami, Vahid] Geisinger Med Ctr, Intervent Pain Ctr Woodbine, Danville, PA 17822 USA. [Grider, Jay S.] Univ Kentucky, UK Healthcare Pain Serv, Lexington, KY USA. [Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England. [Jha, Sachin Sunny] RUMC, Chicago, IL USA. [Mann, Dharam P.] Garden State Pain Management, Whiting, NJ USA. [Nampiaparampil, Devi E.] NYU, Sch Med, New York, NY USA. [Sharma, Manohar Lal] Walton Ctr Neurol & Neurosurg NHS Fdn Trust, Liverpool, Merseyside, England. [Shroyer, Lindsay N.] Florida Pain Management Associates, Sebastian, FL USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Soin, Amol] Ohio Pain Clin, Centerville, OH USA. [Vallejo, Ricardo] Millennium Pain Ctr, Bloomington, IL USA. [Vallejo, Ricardo] Illinois State Univ, Normal, IL 61761 USA. [Wargo, Bradley W.] McFarland Clin, Mary Greeley Med Ctr, Dept Pain Med, Ames, IA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; BioDelivery Sciences International, Inc.; Mundipharma Research GmbH Co.; AstraZeneca; Purdue Pharma, LP; Theravance FX Dr. Vallejo receives research support from Cephalon/Teva, BioDelivery Sciences International, Inc., Mundipharma Research GmbH & Co., AstraZeneca, Purdue Pharma, LP, and Theravance, and is a consultant for Nevro and Kimberly-Clark. NR 219 TC 12 Z9 13 U1 0 U2 6 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JUL-AUG PY 2015 VL 18 IS 4 BP E535 EP E582 PG 48 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CO1FS UT WOS:000358900300004 PM 26218948 ER PT J AU Fisher, JG Sparks, EA Khan, FA Alexander, JL Asaro, LA Wypij, D Gaies, M Modi, BP Duggan, C Agus, MSD Yu, YM Jaksic, T AF Fisher, Jeremy G. Sparks, Eric A. Khan, Faraz A. Alexander, Jamin L. Asaro, Lisa A. Wypij, David Gaies, Michael Modi, Biren P. Duggan, Christopher Agus, Michael S. D. Yu, Yong-Ming Jaksic, Tom TI Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation During the Early Postoperative Period Following Pediatric Cardiac Surgery SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE catabolism; children; critical illness; insulin; proteolysis; tight glycemic control ID CRITICALLY-ILL PATIENTS; 3-METHYLHISTIDINE EXCRETION; PROTEIN-METABOLISM; RANDOMIZED-TRIAL; BURN INJURY; PROTEOLYTIC ACTIVITY; NUTRITIONAL SUPPORT; URINARY-EXCRETION; INTENSIVE-CARE; MAJOR SURGERY AB Objective: Critical illness is associated with significant catabolism, and persistent protein loss correlates with increased morbidity and mortality. Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal muscle protein breakdown in critically ill pediatric surgical patients. However, insulin's effect on protein catabolism when given at clinically utilized doses has not been studied. The objective was to evaluate the effect of postoperative tight glycemic control and clinically dosed insulin on skeletal muscle degradation in children after cardiac surgery with cardiopulmonary bypass. Design: Secondary analysis of a two-center, prospective randomized trial comparing tight glycemic control with standard care. Randomization was stratified by study center. Patients: Children 0-36 months who were admitted to the ICU after cardiac surgery requiring cardiopulmonary bypass. Interventions: In the tight glycemic control arm, insulin was titrated to maintain blood glucose between 80 and 110 mg/dL. Patients in the control arm received standard care. Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine to urinary creatinine. Measurements and Main Results: A total of 561 patients were included: 281 in the tight glycemic control arm and 280 receiving standard care. There was no difference in 3-methylhistidine to creatinine between groups (tight glycemic control, 249 127 vs standard care, 253 +/- 112, mean +/- sd in mol/g; p = 0.72). In analyses restricted to the patients in tight glycemic control arm, higher 3-methylhistidine to creatinine correlated with younger age, as well as lower weight, weight-for-age z score, length, and body surface area (p < 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p = 0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to creatinine. During urine collection, 245 patients (87%) received insulin. However, any insulin exposure did not impact 3-methylhistidine to creatinine (t test, p = 0.45), and there was no dose-dependent effect of insulin on 3-methylhistidine to creatinine (r = -0.03; p = 0.60). Conclusion: Although high-dose insulin has an anabolic effect in experimental conditions, at doses necessary to achieve normoglycemia, insulin appears to have no discernible impact on skeletal muscle degradation in critically ill pediatric cardiac surgical patients. C1 [Fisher, Jeremy G.; Sparks, Eric A.; Khan, Faraz A.; Modi, Biren P.; Jaksic, Tom] Boston Childrens Hosp, Ctr Adv Intestinal Rehabil, Boston, MA 02115 USA. [Fisher, Jeremy G.; Sparks, Eric A.; Khan, Faraz A.; Modi, Biren P.; Jaksic, Tom] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Fisher, Jeremy G.; Sparks, Eric A.; Khan, Faraz A.; Wypij, David; Modi, Biren P.; Duggan, Christopher; Agus, Michael S. D.; Yu, Yong-Ming; Jaksic, Tom] Harvard Univ, Sch Med, Boston, MA USA. [Alexander, Jamin L.; Agus, Michael S. D.] Boston Childrens Hosp, Div Med Crit, Boston, MA 02115 USA. [Asaro, Lisa A.; Wypij, David] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Wypij, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gaies, Michael] Univ Michigan, CS Mott Childrens Hosp, Div Pediat Cardiol, Ann Arbor, MI 48109 USA. [Gaies, Michael] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Duggan, Christopher] Boston Childrens Hosp, Ctr Adv Intestinal Rehabil, Boston, MA 02115 USA. [Duggan, Christopher] Boston Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Yu, Yong-Ming] Shriners Hosp Children, Boston, MA USA. [Yu, Yong-Ming] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jaksic, T (reprint author), Boston Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM tom.jaksic@childrens.harvard.edu FU National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Disease; Nutrition and Obesity Center at Harvard; National Institutes of Health [5P30DK040561-17]; Safe Pediatric Euglycemia after Cardiac Surgery ClinicalTrials. gov [NCT00443599]; National Institutes of Health FX Supported, in part, by the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Disease, and others; Safe Pediatric Euglycemia after Cardiac Surgery ClinicalTrials. gov number, NCT00443599; Nutrition and Obesity Center at Harvard; National Institutes of Health, 5P30DK040561-17.; The authors received support for article research from the National Institutes of Health. Their institutions received grant support from the National Heart, Lung, and Blood Institute. NR 44 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JUL PY 2015 VL 16 IS 6 BP 515 EP 521 DI 10.1097/PCC.0000000000000413 PG 7 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA CN2YQ UT WOS:000358289700003 PM 25850865 ER PT J AU Baek, JH Park, JI Ahn, J Roh, SW Heo, JY Fava, M Mischoulon, D Jeon, HJ AF Baek, Ji Hyun Park, Jong-Ik Ahn, Jeonghoon Roh, Sung-won Heo, Jung-Yoon Fava, Maurizio Mischoulon, David Jeon, Hong Jin TI Review of Suicide Prevention Programs: Massachusetts, United States, in Comparison with Seoul SO PSYCHIATRY INVESTIGATION LA English DT Review DE Suicide; Suicide prevention strategy ID NATIONWIDE AB Suicide is a tragedy that has massive impact on society In order to prevent suicide, active government intervention is necessary. The suicide rate in Seoul is rapidly increasing and is more than five times higher than that in the state of Massachusetts (MA) during the last decade, especially in the elderly. The suicide prevention program of MA is one of the most effective suicide prevention programs in the United States. The program views suicide as a preventable public health problem, and emphasizes treatment of depression and de-stigmatization of mental health illnesses to prevent suicide. Also, through active collaboration with mental health professionals, they try to identify at risk populations and help them to get medical interventions. The program also actively collaborates with the regional coalition program and the Samaritans in taking care of the elderly, and supports the elderly in feeling worthwhile after retirement by helping them to work for communities as volunteers. For its part, the Seoul suicide prevention program puts more emphasis on "life respect culture" and "emotional support to high risk individuals by regular visiting". The annual budget of the Seoul suicide prevention program is one-quarter and that for mental health is about one-twentieth that of MA. Considering the high suicide rate and lower mental health service usage in Seoul, it is crucial to raise awareness of depression and decrease the stigma on mental illnesses. Furthermore, educational efforts with long-term investment in research on suicide are necessary. C1 [Baek, Ji Hyun; Heo, Jung-Yoon; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul 135710, South Korea. [Baek, Ji Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. [Park, Jong-Ik] Kangwon Natl Univ, Coll Med, Dept Psychiat, Chunchon, South Korea. [Ahn, Jeonghoon] Natl Evidence Based Healthcare Collaborating Agcy, Seoul, South Korea. [Roh, Sung-won] Seoul Natl Hosp, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol, Dept Med Device Management & Res, Seoul, South Korea. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol, Dept Clin Res Design, Seoul, South Korea. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol, Dept Evaluat, Seoul, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, 81 Irwon Ro, Seoul 135710, South Korea. EM jeonhj@skku.edu OI Ahn, Jeonghoon/0000-0002-0177-0192 FU Small Research Society Fund from Policy Research Institute of the Korean NeuroPsychiatric Association; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461] FX This research was supported by the Small Research Society Fund from the Policy Research Institute of the Korean NeuroPsychiatric Association. It was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064) and the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461. We thank Mr. Alan Holmlund, Director, and Ms. Christine M. Farrell-O'Reilly, Deputy Director of Suicide Prevention Program, Massachusetts Department of Public Health for their great comments and review the manuscript. NR 21 TC 1 Z9 1 U1 2 U2 11 PU KOREAN NEUROPSYCHIATRIC ASSOC PI SEOUL PA RN 522, G-FIVE CENTRAL PLAZA 1685-8 SEOCHO 4-DONG, SEOCHO-GU, SEOUL, 137-882, SOUTH KOREA SN 1738-3684 EI 1976-3026 J9 PSYCHIAT INVEST JI Psychiatry Investig. PD JUL PY 2015 VL 12 IS 3 BP 281 EP 287 DI 10.4306/pi.2015.12.3.281 PG 7 WC Psychiatry SC Psychiatry GA CN5JN UT WOS:000358465700001 PM 26207119 ER PT J AU Maughan-Brown, B Godlonton, S Thornton, R Venkataramani, AS AF Maughan-Brown, Brendan Godlonton, Susan Thornton, Rebecca Venkataramani, Atheendar S. TI What Do People Actually Learn from Public Health Campaigns? Incorrect Inferences About Male Circumcision and Female HIV Infection Risk Among Men and Women in Malawi SO AIDS AND BEHAVIOR LA English DT Article DE Male circumcision; Female HIV risk; Risk beliefs; Information; HIV prevention; Southern Africa ID RANDOMIZED CONTROLLED-TRIAL; PREVENTION; TRANSMISSION; ATTITUDES; AFRICA; UGANDA; RAKAI AB Qualitative studies and polling data from sub-Saharan Africa indicate that many individuals may mistakenly believe that male circumcision directly protects women from contracting HIV. This study examines whether individuals who learn that male circumcision reduces female-to-male HIV transmission also erroneously infer a reduction in direct male-to-female transmission risk (i.e. from an HIV-positive man to an uninfected woman). We used data on Malawian men (n = 917) randomized to receive information about voluntary medical male circumcision (VMMC) and HIV risk in 2008 and a random sample of their wives (n = 418). We found that 72 % of men and 82 % of women who believed that male circumcision reduces HIV risk for men also believed that it reduces HIV risk for women. Regression analyses indicated that men randomly assigned to receive information about the protective benefits of circumcision were more likely to adopt the erroneous beliefs, and that the underlying mechanism was the formation of the belief that male circumcision reduces HIV risk for men. The results suggest the need for VMMC campaigns to make explicit that male circumcision does not directly protect women from HIV-infection. C1 [Maughan-Brown, Brendan] Univ Cape Town, Southern Africa Labour & Dev Res Unit, ZA-7701 Cape Town, South Africa. [Godlonton, Susan] Williams Coll, Dept Econ, Williamstown, MA 01267 USA. [Godlonton, Susan] Int Food Policy Res Inst, Markets Trade & Inst Div, Washington, DC 20006 USA. [Thornton, Rebecca] Univ Michigan, Dept Econ, Ann Arbor, MI 48109 USA. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, Boston, MA 02114 USA. RP Venkataramani, AS (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM avenkataramani@partners.org FU National Research Foundation (NRF); Massachusetts General Hospital Global Primary Care Program; Michigan Center for Demography of Aging (MiCDA); OVPR; Rackham at the University of Michigan; Institute for Research on Women and Gender; NICHD Center Grant [R24] FX We would like to thank Martin Abel, Nicola Branson, Arden Finn, David Maughan-Brown, Rebecca Maughan-Brown, Elizabeth Gummerson, Edward Okeke, and three anonymous referees for helpful comments and suggestions. Brendan Maughan-Brown is grateful for funding from the National Research Foundation (NRF) Research Chair in Poverty and Inequality Research for his Postdoctoral Research Fellowship. Atheendar S. Venkataramani is grateful to the Massachusetts General Hospital Global Primary Care Program for travel and research support. We acknowledge the extensive contributions of the field team including James Amani, Sheena Kayira, Collins Kwizombe, Denise Matthijsse, Ernest Mlenga, and Christopher Nyirenda. We also thank assistance from Kondwani Chidziwisano, Jessica Kraft, Erica Marks, Julie Moran, Jason Stanley, and Kondwani Tomoko. Funding for this study was provided by Michigan Center for Demography of Aging (MiCDA), OVPR and Rackham at the University of Michigan as well as the Institute for Research on Women and Gender. Godlonton and Thornton gratefully acknowledge use of the services and facilities of the Population Studies Center at the University of Michigan, funded by NICHD Center Grant R24. NR 24 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUL PY 2015 VL 19 IS 7 BP 1170 EP 1177 DI 10.1007/s10461-014-0882-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CN2KA UT WOS:000358248600005 PM 25155700 ER PT J AU Jack, CR Barnes, J Bernstein, MA Borowski, BJ Brewer, J Clegg, S Dale, AM Carmichael, O Ching, C DeCarli, C Desikan, RS Fennema-Notestine, C Fjell, AM Fletcher, E Fox, NC Gunter, J Gutman, BA Holland, D Hua, X Insel, P Kantarci, K Killiany, RJ Krueger, G Leung, KK Mackin, S Maillard, P Malone, IB Mattsson, N McEvoy, L Modat, M Mueller, S Nosheny, R Ourselin, S Schuff, N Senjem, ML Simonson, A Thompson, PM Rettmann, D Vemuri, P Walhovd, K Zhao, YS Zuk, S Weiner, M AF Jack, Clifford R., Jr. Barnes, Josephine Bernstein, Matt A. Borowski, Bret J. Brewer, James Clegg, Shona Dale, Anders M. Carmichael, Owen Ching, Christopher DeCarli, Charles Desikan, Rahul S. Fennema-Notestine, Christine Fjell, Anders M. Fletcher, Evan Fox, Nick C. Gunter, Jeff Gutman, Boris A. Holland, Dominic Hua, Xue Insel, Philip Kantarci, Kejal Killiany, Ron J. Krueger, Gunnar Leung, Kelvin K. Mackin, Scott Maillard, Pauline Malone, Ian B. Mattsson, Niklas McEvoy, Linda Modat, Marc Mueller, Susanne Nosheny, Rachel Ourselin, Sebastien Schuff, Norbert Senjem, Matthew L. Simonson, Alix Thompson, Paul M. Rettmann, Dan Vemuri, Prashanthi Walhovd, Kristine Zhao, Yansong Zuk, Samantha Weiner, Michael TI Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2 SO ALZHEIMERS & DEMENTIA LA English DT Review DE Alzheimer's disease; Alzheimer's Disease Neuroimaging Initiative; ADNI; Diffusion; MRI; Neuroimaging; Perfusion; Resting functional MRI ID MILD COGNITIVE IMPAIRMENT; TENSOR-BASED MORPHOMETRY; PREDICT BRAIN ATROPHY; CSF BIOMARKERS; AMYLOID-BETA; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; CLINICAL-TRIALS; NEURODEGENERATIVE DISEASE AB Introduction: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. Methods: We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Results: Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Discussion: Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. C1 [Jack, Clifford R., Jr.; Bernstein, Matt A.; Borowski, Bret J.; Gunter, Jeff; Kantarci, Kejal; Senjem, Matthew L.; Vemuri, Prashanthi; Zuk, Samantha] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Barnes, Josephine; Clegg, Shona; Fox, Nick C.; Malone, Ian B.; Modat, Marc; Ourselin, Sebastien] UCL, Dementia Res Ctr, Inst Neurol, Dept Neurodegenerat Dis, London, England. [Brewer, James; Dale, Anders M.; Gutman, Boris A.; Holland, Dominic; Hua, Xue] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Carmichael, Owen; DeCarli, Charles; Fletcher, Evan; Maillard, Pauline] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Ching, Christopher; Thompson, Paul M.] Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Dept Neurol, Marina Del Rey, CA USA. [DeCarli, Charles; Fletcher, Evan; Maillard, Pauline] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Desikan, Rahul S.; Fennema-Notestine, Christine; McEvoy, Linda] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Fjell, Anders M.; Walhovd, Kristine] Univ Oslo, Dept Psychol, Oslo, Norway. [Insel, Philip; Mackin, Scott; Mueller, Susanne; Nosheny, Rachel; Schuff, Norbert; Simonson, Alix; Weiner, Michael] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, Dept Radiol & Biomed Imaging, San Francisco, CA USA. [Killiany, Ron J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Krueger, Gunnar] Siemens Med Solut, Boston, MA USA. [Leung, Kelvin K.; Modat, Marc; Ourselin, Sebastien] UCL, Ctr Med Image Comp, Translat Imaging Grp, London, England. [Mackin, Scott; Weiner, Michael] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mattsson, Niklas] Univ Gothenburg, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Mueller, Susanne; Nosheny, Rachel; Schuff, Norbert; Weiner, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Rettmann, Dan] GE Healthcare, MR Applicat & Workflow, Rochester, MN USA. [Zhao, Yansong] Philips Healthcare, Cleveland, OH USA. [Weiner, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Ourselin, Sebastien/K-6960-2015; Barnes, Josesphine/P-5698-2014; Fox, Nick/B-1319-2009; Jack, Clifford/F-2508-2010; OI Ourselin, Sebastien/0000-0002-5694-5340; Fox, Nick/0000-0002-6660-657X; Jack, Clifford/0000-0001-7916-622X; Bernstein, Matt/0000-0003-3770-0441 FU NIA NIH HHS [R01 AG011378, R01 AG040060, R01 AG041851, U01 AG024904]; NIBIB NIH HHS [P41 EB015922]; NIMH NIH HHS [R01 MH098062] NR 177 TC 6 Z9 6 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2015 VL 11 IS 7 BP 740 EP 756 DI 10.1016/j.jalz.2015.05.002 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA CN1RS UT WOS:000358198400004 PM 26194310 ER PT J AU Saykin, AJ Shen, L Yao, X Kim, S Nho, K Risacher, SL Ramanan, VK Foroud, TM Faber, KM Sarwar, N Munsie, LM Hu, X Soares, HD Potkin, SG Thompson, PM Kauwe, JSK Kaddurah-Daouk, R Green, RC Toga, AW Weiner, MW AF Saykin, Andrew J. Shen, Li Yao, Xiaohui Kim, Sungeun Nho, Kwangsik Risacher, Shannon L. Ramanan, Vijay K. Foroud, Tatiana M. Faber, Kelley M. Sarwar, Nadeem Munsie, Leanne M. Hu, Xiaolan Soares, Holly D. Potkin, Steven G. Thompson, Paul M. Kauwe, John S. K. Kaddurah-Daouk, Rima Green, Robert C. Toga, Arthur W. Weiner, Michael W. CA Alzheimer's Dis Neuroimaging Init TI Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans SO ALZHEIMERS & DEMENTIA LA English DT Review DE Alzheimer's disease (AD); Mild cognitive impairment (MCI); Genome-wide association studies (GWAS); Next generation sequencing (NGS); Copy number variation (CNV); Biomarkers; Magnetic resonance imaging (MRI); Positron emission tomography (PET); Cerebrospinal fluid (CSF); DNA; RNA; Memory; Cognition; Bioethical issues; Precision medicine ID GENOME-WIDE ASSOCIATION; MILD COGNITIVE IMPAIRMENT; PLURIPOTENT STEM-CELLS; MANAGING INCIDENTAL FINDINGS; FAMILIAL ALZHEIMERS-DISEASE; ALLELE-SPECIFIC PCR; APOLIPOPROTEIN-E; HUMAN-MEMORY; HIPPOCAMPAL ATROPHY; CEREBROSPINAL-FLUID AB Introduction: Genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have been crucial in advancing the understanding of Alzheimer's disease (AD) pathophysiology. Here, we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans. Methods: Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome-wide association study (GWAS), and whole exome and whole genome sequencing data have been obtained and disseminated. Results: ADNI genetic data have been downloaded thousands of times, and >300 publications have resulted, including reports of large-scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies used ADNI data, including some of the earliest GWAS and pathway-based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first whole exome and whole genome sequencing data sets and reports in healthy controls, mild cognitive impairment, and AD. Discussion: Numerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multiomics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological processes. Fortunately, a broad swath of the scientific community has accepted this grand challenge. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. C1 [Saykin, Andrew J.; Shen, Li; Yao, Xiaohui; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Ramanan, Vijay K.] Indiana Univ, Ctr Neuroimaging, Dept Radiol & Imaging Sci, Sch Med, Indianapolis, IN 46204 USA. [Saykin, Andrew J.; Shen, Li; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Ramanan, Vijay K.; Foroud, Tatiana M.] Indiana Univ, Indiana Alzheimer Dis Ctr, Sch Med, Indianapolis, IN 46204 USA. [Saykin, Andrew J.; Ramanan, Vijay K.; Foroud, Tatiana M.; Faber, Kelley M.] Indiana Univ, Dept Med & Mol Genet, Sch Med, Indianapolis, IN 46204 USA. [Shen, Li] Indiana Univ, Ctr Computat Biol & Bioinformat, Sch Med, Indianapolis, IN 46204 USA. [Yao, Xiaohui] Indiana Univ, Sch Informat & Comp, Purdue Univ, Indianapolis, IN 46204 USA. [Sarwar, Nadeem] Eisai Ltd, Hatfield, Herts, England. [Munsie, Leanne M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Hu, Xiaolan; Soares, Holly D.] Bristol Myers Squibb, Wallingford, CT USA. [Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Thompson, Paul M.] Univ So Calif, Dept Neurol, Keck Sch Med, Marina Del Rey, CA USA. [Thompson, Paul M.] Univ So Calif, Imaging Genet Ctr, Keck Sch Med, Marina Del Rey, CA USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Neurosci, Provo, UT USA. [Kaddurah-Daouk, Rima] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Kaddurah-Daouk, Rima] Duke Univ, Duke Inst Brain Sci, Durham, NC USA. [Green, Robert C.] Partners Ctr Personalized Genet Med, Boston, MA USA. [Green, Robert C.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Green, Robert C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Toga, Arthur W.] Univ So Calif, Lab Neuroimaging, Inst Neuroimaging & Neuroinformat, Keck Sch Med, Los Angeles, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Saykin, AJ (reprint author), Indiana Univ, Ctr Neuroimaging, Dept Radiol & Imaging Sci, Sch Med, Indianapolis, IN 46204 USA. EM asaykin@iupui.edu OI Shen, Li/0000-0002-5443-0503 FU Alzheimer's Disease Neuroimaging Initiative (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; National Institute on Aging [U24AG021886]; NIH [U01 AG024904, R01 LM011360, RC2 AG036535, R01 AG19771, P30 AG10133, UL1 TR001108]; DOD [W81XWH-14-2-0151]; NCAA [14132004]; Alzheimer's Association; NSF [IIS-1117335] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (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; Biogen Idec.; 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; Merck & Co., Inc.; Meso Scale Diagnostics; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern 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. Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement (U24AG021886) awarded by the National Institute on Aging, were used in this study. Data analysis was supported in part by NIH R01 LM011360, U01 AG024904, RC2 AG036535, R01 AG19771, P30 AG10133, UL1 TR001108, DOD W81XWH-14-2-0151, NCAA 14132004, the Alzheimer's Association, and NSF IIS-1117335. NR 173 TC 18 Z9 18 U1 6 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2015 VL 11 IS 7 BP 792 EP 814 DI 10.1016/j.jalz.2015.05.009 PG 23 WC Clinical Neurology SC Neurosciences & Neurology GA CN1RS UT WOS:000358198400007 PM 26194313 ER PT J AU Hendrix, JA Finger, B Weiner, MW Frisoni, GB Iwatsubo, T Rowe, CC Kim, SY Guinjoan, SM Sevlever, G Carrillo, MC AF Hendrix, James A. Finger, Brad Weiner, Michael W. Frisoni, Giovanni B. Iwatsubo, Takeshi Rowe, Christopher C. Kim, Seong Yoon Guinjoan, Salvador M. Sevlever, Gustavo Carrillo, Maria C. TI The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update SO ALZHEIMERS & DEMENTIA LA English DT Review DE Alzheimer's disease; Neuroimaging; Biomarkers; Cerebrospinal fluid ID MILD COGNITIVE IMPAIRMENT; HIPPOCAMPAL VOLUME; AMYLOID-BETA; CEREBROSPINAL-FLUID; LIFE-STYLE; PATHOLOGICAL CASCADE; COMMON VARIANTS; ALPHA-SYNUCLEIN; A-BETA; BIOMARKERS AB The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Hendrix, James A.; Carrillo, Maria C.] Alzheimers Assoc, Med & Sci Relat, Chicago, IL 60631 USA. [Finger, Brad] Independent Sci Writer, Evanston, IL USA. [Weiner, Michael W.] San Francisco VA Med Ctr, CIND, Northern Calif Inst Res, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Frisoni, Giovanni B.] Univ Hosp, Lab Neuroimaging Aging, Geneva, Switzerland. [Frisoni, Giovanni B.] Univ Geneva, Geneva, Switzerland. [Iwatsubo, Takeshi] Univ Hosp, Grad Sch Med, Dept Neuropathol, Tokyo, Japan. [Rowe, Christopher C.] Austin Hlth, Dept Mol Imaging, Melbourne, Australia. [Kim, Seong Yoon] Asian Med Ctr, Dept Psychiat, Seoul, South Korea. [Guinjoan, Salvador M.; Sevlever, Gustavo] Inst Invest Neurol Raul Carrea FLENI, Aging & Memory Ctr, Buenos Aires, DF, Argentina. RP Hendrix, JA (reprint author), Alzheimers Assoc, Med & Sci Relat, Chicago, IL 60631 USA. EM jhendrix@alz.org RI Frisoni, Giovanni B/K-1360-2016 OI Frisoni, Giovanni B/0000-0002-6419-1753 FU National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; European Commission; EFPIA in the context of the IMI - Innovative Medicines Initiative funding scheme; Ministry of Health, Labor and Welfare; Ministry of Economy, Trade and Industry (through New Energy and Development Organization), Japan; Astellas; Bristol Myers-Squibb; Chugai; Daiichi-Sankyo; Dainippon-Sumitomo; Eisai; Eli-Lilly; MSD; Novartis; Pfizer; Shionogi; Takeda; Tanabe-Mitsubishi; Australian Government sources - CSIRO; Science Industry Endowment Fund; NHMRC; Dementia CRC; CRC for Mental Health; Commercial sources - Janssen; Avid Radiopharmaceuticals; Navidea Biopharmaceuticals; Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI12C0713]; FLENI foundation; Perez Companc Foundation; Pan American Energy FX NA-ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. Pharmacog/E-ADNI is funded by the European Commission and EFPIA in the context of the IMI - Innovative Medicines Initiative funding scheme.; J-ADNI-1 and J-ADNI-2 research projects are supported by public funding from the Ministry of Health, Labor and Welfare, and the Ministry of Economy, Trade and Industry (through New Energy and Development Organization), Japan. Industry Scientific Advisory Board of J-ADNI, comprised of 13 pharma companies (Astellas, Bristol Myers-Squibb, Chugai, Daiichi-Sankyo, Dainippon-Sumitomo, Eisai, Eli-Lilly, MSD, Novartis, Pfizer, Shionogi, Takeda, Tanabe-Mitsubishi), contributed funding for J-ADNI-1/2 as a public research.; Funding for AIBL has been provided by Australian Government sources - CSIRO, the Science Industry Endowment Fund, NHMRC, the Dementia CRC and the CRC for Mental Health; Commercial sources - Janssen, GE Healthcare, Avid Radiopharmaceuticals, Navidea Biopharmaceuticals; and Alzheimer's Association, The Alzheimer's Drug Discovery Foundation, and an anonymous foundation.; Funding for K-ADNI is provided by a grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI12C0713).; Funding for ARG-ADNI is provided by the FLENI foundation, the Perez Companc Foundation and Pan American Energy. NR 86 TC 5 Z9 5 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2015 VL 11 IS 7 BP 850 EP 859 DI 10.1016/j.jalz.2015.05.008 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CN1RS UT WOS:000358198400012 PM 26194318 ER PT J AU Minguez-Alarcon, L Afeiche, MC Chiu, YH Vanegas, JC Williams, PL Tanrikut, C Toth, TL Hauser, R Chavarro, JE AF Minguez-Alarcon, L. Afeiche, M. C. Chiu, Y. -H. Vanegas, J. C. Williams, P. L. Tanrikut, C. Toth, T. L. Hauser, R. Chavarro, J. E. TI Male soy food intake was not associated with invitro fertilization outcomes among couples attending a fertility center SO ANDROLOGY LA English DT Article DE epidemiology; ICSI; IVF; male reproductive health; soy intake ID ESTROGEN-RECEPTOR-ALPHA; FREQUENCY QUESTIONNAIRE; SEMEN QUALITY; US ADULTS; MEN; PHYTOESTROGEN; WOMEN; INFERTILITY; REPRODUCIBILITY; VALIDITY AB Male factor etiology may be a contributing factor in up to 60% of infertility cases. Dietary intake of phytoestrogens has been related to abnormal semen quality and hormone levels. However, its effect on couple fecundity is still unclear. Intake of soy products was assessed in 184 men from couples undergoing infertility treatment with invitro fertilization. Couples were recruited between February 2007 and May 2014 and prospectively followed to document treatment outcomes including fertilization, implantation, clinical pregnancy and live birth. Multivariate generalized linear mixed models with random intercepts, binomial distribution and logit link function were used to examine this relation while accounting for repeated treatment cycles and adjusting for potential confounders. Male partner's intake of soy foods and soy isoflavones was unrelated to fertilization rates, the proportions of poor quality embryos, accelerated or slow embryo cleavage rate, and implantation, clinical pregnancy and live birth. The adjusted live birth rates per initiated cycle (95% CI) for partners of men in increasing categories of soy food intake were 0.36 (0.28-0.45), 0.42 (0.29-0.56), 0.36 (0.24-0.51), and 0.37 (0.24-0.52), respectively. Soy food intake in men was not related to clinical outcomes among couples presenting at an infertility clinic. Data on the relation between phytoestrogens and male reproductive potential remain scarce and additional research is required to clarify its role in human reproduction. C1 [Minguez-Alarcon, L.; Afeiche, M. C.; Hauser, R.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chiu, Y. -H.; Chavarro, J. E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Vanegas, J. C.] Pontificia Univ Javeriana, Sch Med, Bogota, Colombia. [Williams, P. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Williams, P. L.; Hauser, R.; Chavarro, J. E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tanrikut, C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Tanrikut, C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Toth, T. L.; Hauser, R.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Toth, T. L.; Hauser, R.; Chavarro, J. E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chavarro, J. E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Minguez-Alarcon, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM lminguez@hsph.harvard.edu FU NIH from NIEHS [R01-ES009718]; NIH from NIDDK [P30 DK046200]; NIDDK [T32 DK 007703-16] FX We thank the study participants whose continued dedication and commitment make this work possible and the research nurses Jennifer B. Ford, B.S.N., R.N. and Myra G. Keller, R.N.C., B.S.N. and senior research assistant Ramace Dadd. This work was supported by NIH grants R01-ES009718 from NIEHS, P30 DK046200 from NIDDK. MA was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. NR 39 TC 4 Z9 4 U1 8 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JUL PY 2015 VL 3 IS 4 BP 702 EP 708 DI 10.1111/andr.12046 PG 7 WC Andrology SC Endocrinology & Metabolism GA CN3LZ UT WOS:000358329300010 PM 26097060 ER PT J AU McKinley, ET Watchmaker, JM Chakravarthy, AB Meyerhardt, JA Engelman, JA Walker, RC Washington, MK Coffey, RJ Manning, HC AF McKinley, Eliot T. Watchmaker, Jennifer M. Chakravarthy, A. Bapsi Meyerhardt, Jeffrey A. Engelman, Jeffrey A. Walker, Ronald C. Washington, M. Kay Coffey, Robert J. Manning, H. Charles TI [F-18]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study SO ANNALS OF NUCLEAR MEDICINE LA English DT Article DE F-18-FLT; Rectal cancer; Cetuximab; EGFR; Treatment response ID POSITRON-EMISSION-TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; PHASE-II TRIAL; COLORECTAL-CANCER; IMAGING PROLIFERATION; INFUSION REACTIONS; CETUXIMAB; MULTICENTER; IRINOTECAN AB This pilot study evaluated the utility of 3'-deoxy-3'[18F]-fluorothymidine ([F-18]-FLT) positron emission tomography (PET) to predict response to neoadjuvant therapy that included cetuximab in patients with wild-type KRAS rectal cancers. Baseline [F-18]-FLT PET was collected prior to treatment initiation. Follow-up [F-18]-FLT was collected after three weekly infusions of cetuximab, and following a combined regimen of cetuximab, 5-FU, and radiation. Imaging-matched biopsies were collected with each PET study. Diminished [F-18]-FLT PET was observed in 3/4 of patients following cetuximab treatment alone and in all patients following combination therapy. Reduced [F-18]-FLT PET following combination therapy predicted disease-free status at surgery. Overall, [F-18]-FLT PET agreed with Ki67 immunoreactivity from biopsy samples and surgically resected tissue, and was predictive of treatment-induced rise in p27 levels. These results suggest that [F-18]-FLT PET is a promising imaging biomarker to predict response to neoadjuvant therapy that included EGFR blockade with cetuximab in patients with rectal cancer. C1 [McKinley, Eliot T.; Watchmaker, Jennifer M.; Walker, Ronald C.; Manning, H. Charles] Vanderbilt Univ, Sch Med, VUIIS, Nashville, TN 37232 USA. [McKinley, Eliot T.; Coffey, Robert J.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Watchmaker, Jennifer M.; Manning, H. Charles] Vanderbilt Univ, Program Chem & Phys Biol, Nashville, TN 37232 USA. [Chakravarthy, A. Bapsi; Walker, Ronald C.; Washington, M. Kay; Coffey, Robert J.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37232 USA. [Chakravarthy, A. Bapsi] Vanderbilt Univ, Dept Radiat Oncol, Sch Med, Nashville, TN 37232 USA. [Meyerhardt, Jeffrey A.; Engelman, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Walker, Ronald C.; Manning, H. Charles] Vanderbilt Univ, Sch Med, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Walker, Ronald C.] Tennessee Valley VA Healthcare Syst, Serv Radiol, Nashville, TN USA. [Washington, M. Kay] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. [Manning, H. Charles] Vanderbilt Univ, Sch Med, Dept Neurosurg, Nashville, TN 37232 USA. [Manning, H. Charles] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA. RP Manning, HC (reprint author), Vanderbilt Univ, Sch Med, VUIIS, 1161 21st Ave S,AA1105 MCN, Nashville, TN 37232 USA. EM henry.c.manning@vanderbilt.edu FU National Institutes of Health [R25 CA136440, R25 CA092043, K25 CA127349, P50 CA128323, P50 CA095103, R01 CA140628, RC1 CA145138, P30 DK058404, P50 CA127003, UL1 TR000445]; Kleberg Foundation; Bristol Meyers Squib FX The authors acknowledge funding from the National Institutes of Health (R25 CA136440, R25 CA092043, K25 CA127349, P50 CA128323, P50 CA095103, R01 CA140628, RC1 CA145138, P30 DK058404, P50 CA127003, UL1 TR000445), the Kleberg Foundation, and Bristol Meyers Squib. The authors acknowledge Frank Revetta for assistance with immunohistochemistry. NR 32 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0914-7187 EI 1864-6433 J9 ANN NUCL MED JI Ann. Nucl. Med. PD JUL PY 2015 VL 29 IS 6 BP 535 EP 542 DI 10.1007/s12149-015-0974-6 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN1JJ UT WOS:000358175300009 PM 25899481 ER PT J AU Kasenda, B Ferreri, AJM Marturano, E Forst, D Bromberg, J Ghesquieres, H Ferlay, C Blay, JY Hoang-Xuan, K Pulczynski, EJ Fossa, A Okoshi, Y Chiba, S Fritsch, K Omuro, A O'Neill, BP Bairey, O Schandelmaier, S Gloy, V Bhatnagar, N Haug, S Rahner, S Batchelor, TT Illerhaus, G Briel, M AF Kasenda, B. Ferreri, A. J. M. Marturano, E. Forst, D. Bromberg, J. Ghesquieres, H. Ferlay, C. Blay, J. Y. Hoang-Xuan, K. Pulczynski, E. J. Fossa, A. Okoshi, Y. Chiba, S. Fritsch, K. Omuro, A. O'Neill, B. P. Bairey, O. Schandelmaier, S. Gloy, V. Bhatnagar, N. Haug, S. Rahner, S. Batchelor, T. T. Illerhaus, G. Briel, M. TI First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis SO ANNALS OF ONCOLOGY LA English DT Review DE primary central nervous system lymphoma; PCNSL; elderly patients; individual patient data meta-analysis; systematic review ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; WHOLE-BRAIN RADIOTHERAPY; KETTERING CANCER CENTER; NON-HODGKIN-LYMPHOMA; TERM-FOLLOW-UP; PHASE-II; INITIAL TREATMENT; CHEMOTHERAPY; TRIAL AB Background: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. Patients and methods: A systematic review of studies about first-line therapy in immunocompetent patients = 60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out. Results: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS = 70% was the strongest prognostic factor for mortality [ hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74). Conclusions: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted. C1 [Kasenda, B.] Univ Basel Hosp, Dept Oncol, CH-4031 Basel, Switzerland. [Kasenda, B.; Schandelmaier, S.; Gloy, V.; Briel, M.] Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, CH-4031 Basel, Switzerland. [Ferreri, A. J. M.; Marturano, E.] Ist Sci San Raffaele, Dept Oncohematol, Unit Lymphoid Malignancies, I-20132 Milan, Italy. [Forst, D.; Batchelor, T. T.] Harvard Univ, Sch Med, Partners Neurol Residency Program, Boston, MA USA. [Bromberg, J.] Erasmus MC Univ Med Ctr, Daniel del Hoed Canc Ctr, Dept Neurooncol, Rotterdam, Netherlands. [Ghesquieres, H.; Ferlay, C.; Blay, J. Y.] Univ Lyon, Ctr Leon Berard, Dept Hematol, Lyon, France. [Hoang-Xuan, K.; Omuro, A.] Univ Paris 06, Dept Neurol Mazarin, LOC Natl Expert Ctr, APHP,IHU,CRICM,GH Pitie Salpetriere, Paris, France. [Pulczynski, E. J.] Aarhus Univ Hosp, Nord Lymphoma Grp, Dept Haematol, DK-8000 Aarhus, Denmark. [Fossa, A.] Radium Hosp, Nord Lymphoma Grp, Norwegian Dept Oncol, Oslo, Norway. [Okoshi, Y.; Chiba, S.] Univ Tsukuba, Fac Med, Dept Hematol, Tsukuba, Ibaraki, Japan. [Fritsch, K.] Univ Hosp Freiburg, Dept Hematol Oncol, Freiburg, Germany. [O'Neill, B. P.] Mayo Clin & Mayo Grad Sch Med, Dept Neurol, Rochester, MN USA. [Bairey, O.] Beilinson Med Ctr, Rabin Med Ctr, Inst Hematol, Tel Aviv, Israel. [Bairey, O.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Bhatnagar, N.; Briel, M.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Haug, S.] Univ Hosp Freiburg, Psychiat & Psychotherapy, Freiburg, Germany. [Rahner, S.] Univ Freiburg, Fac Med, D-79106 Freiburg, Germany. [Batchelor, T. T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Illerhaus, G.] Eva Mayr Stihl Tumor Ctr, Stuttgart Canc Ctr, Stuttgart, Germany. RP Kasenda, B (reprint author), Univ Basel Hosp, Dept Oncol, CH-4031 Basel, Switzerland. EM benjamin.kasenda@gmail.com RI Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; Briel, Matthias/0000-0002-2070-5230 FU Freiwillige Akademische Gesellschaft Basel in Switzerland FX This study was supported by the Freiwillige Akademische Gesellschaft Basel in Switzerland (no grant number). NR 50 TC 9 Z9 9 U1 4 U2 9 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 JUL PY 2015 VL 26 IS 7 BP 1305 EP 1313 DI 10.1093/annonc/mdv076 PG 9 WC Oncology SC Oncology GA CN1HV UT WOS:000358170400007 PM 25701456 ER PT J AU Mahal, BA Chen, MH Bennett, CL Kattan, MW Sartor, O Stein, K D'Amico, AV Nguyen, PL AF Mahal, B. A. Chen, M. -H. Bennett, C. L. Kattan, M. W. Sartor, O. Stein, K. D'Amico, A. V. Nguyen, P. L. TI High PSA anxiety and low health literacy skills: drivers of early use of salvage ADT among men with biochemically recurrent prostate cancer after radiotherapy? SO ANNALS OF ONCOLOGY LA English DT Article DE prostatic neoplasm; recurrence; health policy; androgen deprivation therapy; salvage therapy ID ANDROGEN DEPRIVATION THERAPY; HIV MEDICATION ADHERENCE; RADICAL PROSTATECTOMY; TRIAL; CARE; SURVEILLANCE; SUPPRESSION; VALIDATION; RADIATION; KNOWLEDGE AB Background: Although commonly used, early initiation of salvage androgen deprivation therapy (ADT) has not been proven to enhance survival. We evaluated whether prostate- specific antigen (PSA) anxiety or health literacy are associated with use of early salvage ADT among men with recurrent prostate cancer after radiotherapy. Patients and Methods: The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry was used to study 375 men with biochemically recurrent prostate cancer after external beam radiation or brachytherapy. Multivariable logistic regression was used to determine whether PSA anxiety and health literacy are associated with salvage ADT as initial management after biochemical recurrence. Results: Sixty- eight men (18.1%) received salvage ADT as initial management for PSA recurrence. Men with high PSA anxiety were twice as likely to receive salvage ADT compared with men who did not have high PSA anxiety on both univariable [ 28.8% versus 13.1%; odds ratio (OR) 2.15; 95% confidence interval (CI) 1.16- 4.00; P = 0.015] and multivariable analysis [ adjusted OR (AOR) 2.36; 95% CI 1.21- 4.62; P = 0.012]. Furthermore, men who had higher levels of health literacy were nearly half as likely to undergo salvage ADT compared with men who had lower levels of health literacy on univariable analysis (15.2% versus 26.3%; OR 0.50; 95% CI 0.29- 0.88; P = 0.016), with a trend toward this association on multivariable analysis (AOR 0.58; 95% CI 0.32- 1.05; P = 0.07). Conclusions: Among men with PSA recurrence after radiotherapy, odds of use of salvage ADT were nearly twice as great among men with high PSA anxiety or low health literacy, suggesting that these men are receiving higher rates of unproven treatment. Given that early salvage ADT is costly, worsens quality of life, and has not been shown to improve survival, quality improvement strategies are needed for these individuals. C1 [Mahal, B. A.] Harvard Univ, Boston, MA 02115 USA. [Chen, M. -H.] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Bennett, C. L.] South Carolina Coll Pharm, Charleston, SC USA. [Bennett, C. L.] Hollings Canc Ctr, Charleston, SC USA. [Kattan, M. W.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Sartor, O.] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Sartor, O.] Tulane Univ, Dept Urol, New Orleans, LA 70118 USA. [Stein, K.] Novartis, E Hanover, NJ USA. [D'Amico, A. V.; Nguyen, P. L.] Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. [D'Amico, A. V.; Nguyen, P. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Prostate Cancer Foundation; Fitz's Cancer Warriors; anonymous family foundation; National Cancer Institute [1R01CA165609-01A1]; South Carolina SmartState Program; Doris Levkoff Meddin Medication Safety Center FX This work is supported by David and Cynthia Chapin, the Prostate Cancer Foundation, Fitz's Cancer Warriors, Hugh Simons in honor of Frank and Anne Simons, a grant from an anonymous family foundation. Additional funding for CLB is from the National Cancer Institute (1R01CA165609-01A1), the South Carolina SmartState Program, and the Doris Levkoff Meddin Medication Safety Center. NR 32 TC 2 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2015 VL 26 IS 7 BP 1390 EP 1395 DI 10.1093/annonc/mdv185 PG 6 WC Oncology SC Oncology GA CN1HV UT WOS:000358170400018 PM 25926039 ER PT J AU Lago-Hernandez, CA Feldman, H O'Donnell, E Mahal, BA Perez, V Howard, S Rosenthal, M Cheng, SC Nguyen, PL Beard, C D'Amico, AV Sweeney, CJ AF Lago-Hernandez, C. A. Feldman, H. O'Donnell, E. Mahal, B. A. Perez, V. Howard, S. Rosenthal, M. Cheng, S. C. Nguyen, P. L. Beard, C. D'Amico, A. V. Sweeney, C. J. TI A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion SO ANNALS OF ONCOLOGY LA English DT Article DE nonseminoma germ-cell tumor; clinical stage 1; relapse; embryonal predominance; lymphovascular invasion; active surveillance ID GERM-CELL TUMORS; RESEARCH-COUNCIL TRIAL; I TESTICULAR CANCER; ACTIVE SURVEILLANCE; PROGNOSTIC-FACTORS; TESTIS CANCER; SEMINOMA; RELAPSE; MANAGEMENT; CARCINOMA AB Background: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy. Patients and methods: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method. Results: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median timeto- relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/ 8.5 months, 41%/ 6.8 months and 78%/ 3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108). Conclusion: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT. C1 [Lago-Hernandez, C. A.; Mahal, B. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lago-Hernandez, C. A.; Feldman, H.; O'Donnell, E.; Sweeney, C. J.] Dana Farber Canc Inst, Dept Med Oncol, Genitourinary Div, Boston, MA 02115 USA. [Feldman, H.] Albert Einstein Coll Med, Bronx, NY USA. [Mahal, B. A.; Nguyen, P. L.; Beard, C.; D'Amico, A. V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Perez, V.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Howard, S.; Rosenthal, M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Cheng, S. C.] Dana Farber Canc Inst, Dept Biostat Computat Biol, Boston, MA 02115 USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave 1230, Boston, MA 02115 USA. EM christopher_sweeney@dfci.harvard.edu FU Shawmut Design and Construction's Pan Mass Cycling Team FX We want to give special thanks to Shawmut Design and Construction's Pan Mass Cycling Team for their financial support. NR 21 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2015 VL 26 IS 7 BP 1396 EP 1401 DI 10.1093/annonc/mdv180 PG 6 WC Oncology SC Oncology GA CN1HV UT WOS:000358170400019 PM 25888612 ER PT J AU Kris, MG Camidge, DR Giaccone, G Hida, T Li, BT O'Connell, J Taylor, I Zhang, H Arcila, ME Goldberg, Z Janne, PA AF Kris, M. G. Camidge, D. R. Giaccone, G. Hida, T. Li, B. T. O'Connell, J. Taylor, I. Zhang, H. Arcila, M. E. Goldberg, Z. Jaenne, P. A. TI Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2 - mutant or amplified tumors SO ANNALS OF ONCOLOGY LA English DT Article DE dacomitinib; HER2 mutations; HER2 amplification; lung cancers; tyrosine kinase inhibitors ID SOLID TUMORS; MUTATIONS; DOMAIN; ERBB2; ADENOCARCINOMAS; TRASTUZUMAB; COMBINATION; THERAPY; EGFR AB Background: HER2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of HER2, EGFR ( HER1), and HER4 tyrosine kinases, has demonstrated activity in cell- line models with HER2 exon 20 insertions or amplifications. Here, we studied dacomitinib in patients with HER2mutant or amplified lung cancers. Patients and methods: As a prespecified cohort of a phase II study, we included patients with stage IIIB/ IV lung cancers with HER2 mutations or amplification. We gave oral dacomitinib at 30- 45 mg daily in 28- day cycles. End points included partial response rate, overall survival, and toxicity. Results: We enrolled 30 patients with HER2- mutant ( n = 26, all in exon 20 including 25 insertions and 1 missense mutation) or HER2- amplified lung cancers ( n = 4). Three of 26 patients with tumors harboring HER2 exon 20 mutations [ 12%; 95% confidence interval ( CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with HER2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 7-21 months) for patients with HER2 mutations and ranged from 5 to 22 months with amplifications. Treatment-related toxicities included diarrhea (90%; grade 3/ 4: 20%/ 3%), dermatitis (73%; grade 3/ 4: 3%/ 0%), and fatigue (57%; grade 3/ 4: 3%/ 0%). One patient died on study likely due to an interaction of dacomitinib with mirtazapine. Conclusions: Dacomitinib produced objective responses in patients with lung cancers with specific HER2 exon 20 insertions. This observation validates HER2 exon 20 insertions as actionable targets and justifies further study of HER2targeted agents in specific HER2-driven lung cancers. C1 [Kris, M. G.; Li, B. T.] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, Dept Med, Thorac Oncol Serv,Div Solid Tumor Oncol, New York, NY 10021 USA. [Camidge, D. R.] Univ Colorado, Dept Med Oncol, Denver, CO 80202 USA. [Giaccone, G.] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Hida, T.] Aichi Canc Ctr, Dept Thorac Oncol, Chikusa Ku, Nagoya, Aichi 464, Japan. [O'Connell, J.] Pfizer Inc, Pfizer Oncol, New York, NY USA. [Taylor, I.] Pfizer Inc, Translat Oncol, Groton, CT USA. [Zhang, H.] Pfizer Inc, Pfizer China Res & Dev Co Ltd, Shanghai, Peoples R China. [Arcila, M. E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, New York, NY 10021 USA. [Goldberg, Z.] Pfizer Inc, Pfizer Oncol, San Diego, CA USA. [Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, P. A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP Kris, MG (reprint author), Mem Sloan Kettering Canc Ctr, 300 E 66th St, New York, NY 10065 USA. EM krism@mskcc.org RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Kris, Mark/0000-0002-7317-5341; Li, Bob/0000-0001-6661-8733 FU Pfizer, Inc. FX This work was supported by Pfizer, Inc. No grant applied. NR 30 TC 14 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2015 VL 26 IS 7 BP 1421 EP 1427 DI 10.1093/annonc/mdv186 PG 7 WC Oncology SC Oncology GA CN1HV UT WOS:000358170400023 PM 25899785 ER PT J AU Zhu, Y Romitti, PA Conway, KMC Shen, DH Sun, LX Browne, ML Botto, LD Lin, AE Druschel, CM AF Zhu, Yong Romitti, Paul A. Conway, Kristin M. Caspers Shen, Dereck H. Sun, Lixian Browne, Marilyn L. Botto, Lorenzo D. Lin, Angela E. Druschel, Charlotte M. CA Natl Birth Defects Prevention Stud TI Maternal periconceptional alcohol consumption and congenital heart defects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE congenital heart defects; alcohol; pregnancy; epidemiology; birth defects ID VENTRICULAR SEPTAL-DEFECT; RISK-FACTORS; BIRTH-DEFECTS; UNITED-STATES; CARDIOVASCULAR MALFORMATIONS; ETHANOL EXPOSURE; CARDIAC DEFECTS; EARLY-PREGNANCY; BINGE DRINKING; PREVALENCE AB BackgroundCongenital heart defects (CHDs) are the leading cause of infant death from birth defects. Animal studies suggest in utero alcohol exposure is a teratogen for cardiogenesis; however, results from epidemiologic studies are mixed. MethodsData from the National Birth Defects Prevention Study were used to estimate associations between CHDs and case (n=7076) and control (n=7972) mother reports of periconceptional (1 month before pregnancy through the first trimester) alcohol consumption with expected delivery dates during 1997 to 2007. CHDs were examined by category (conotruncal, septal, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction, heterotaxy with CHD) and subtype (e.g., tetralogy of Fallot [TOF]). Alcohol measures examined were any consumption, maximum average drinks per month, binge drinking, and alcohol type. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression analysis. ResultsIncreased risks, albeit marginally statistically significant, were observed for TOF and each maternal alcohol measure examined and for right ventricular outflow tract obstruction and heterotaxy with CHD and consumption of distilled spirits. Significantly reduced risks were observed for several CHD categories (septal defects, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction) and some corresponding subtypes with different alcohol measures. Significant risks were not observed for the other CHDs examined. ConclusionAnalysis of this large, well-defined study sample did not show statistically significant increased risks between measures of maternal alcohol consumption and most CHDs examined. These findings may reflect, in part, limitations with retrospective exposure assessment or unmeasured confounders. Additional studies with continued improvement in measurement of alcohol consumption are recommended. Birth Defects Research (Part A) 103:617-629, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Zhu, Yong; Romitti, Paul A.; Conway, Kristin M. Caspers; Shen, Dereck H.; Sun, Lixian] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Albany, NY USA. [Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. [Botto, Lorenzo D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Romitti, PA (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, S416 CPHB,145 N Riverside Dr, Iowa City, IA 52242 USA. EM paul-romitti@uiowa.edu FU NCBDD CDC HHS [U01DD001035, U01DD000492]; NIEHS NIH HHS [P30 ES005605]; PHS HHS [PA 96043, PA 02081] NR 53 TC 4 Z9 4 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2015 VL 103 IS 7 BP 617 EP 629 DI 10.1002/bdra.23352 PG 13 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CN3CY UT WOS:000358302700007 PM 26118863 ER PT J AU Purdon, PL Pavone, KJ Akeju, O Smith, AC Sampson, AL Lee, J Zhou, DW Solt, K Brown, EN AF Purdon, P. L. Pavone, K. J. Akeju, O. Smith, A. C. Sampson, A. L. Lee, J. Zhou, D. W. Solt, K. Brown, E. N. TI The Ageing Brain: Age-dependent changes in the electroencephalogram during propofol and sevoflurane general anaesthesia SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE ageing; brain monitoring; EEG; elderly; electroencephalography; propofol; sevoflurane ID INDUCED ALPHA-RHYTHM; INDUCED UNCONSCIOUSNESS; BURST SUPPRESSION; BEHAVIORAL-EXPERIMENTS; BISPECTRAL ANALYSIS; COHERENCE ANALYSIS; EEG; HEALTHY; STATE; CONSCIOUSNESS AB Background: Anaesthetic drugs act at sites within the brain that undergo profound changes during typical ageing. We postulated that anaesthesia-induced brain dynamics observed in the EEG change with age. Methods: We analysed the EEG in 155 patients aged 18-90 yr who received propofol (n=60) or sevoflurane (n=95) as the primary anaesthetic. The EEG spectrum and coherence were estimated throughout a 2 min period of stable anaesthetic maintenance. Age-related effects were characterized by analysing power and coherence as a function of age using linear regression and by comparing the power spectrum and coherence in young (18-to 38-yr-old) and elderly (70- to 90-yr-old) patients. Results: Power across all frequency bands decreased significantly with age for both propofol and sevoflurane; elderly patients showed EEG oscillations similar to 2- to 3-fold smaller in amplitude than younger adults. The qualitative form of the EEG appeared similar regardless of age, showing prominent alpha (8-12 Hz) and slow (0.1-1 Hz) oscillations. However, alpha band dynamics showed specific age-related changes. In elderly compared with young patients, alpha power decreased more than slow power, and alpha coherence and peak frequency were significantly lower. Older patients were more likely to experience burst suppression. Conclusions: These profound age-related changes in the EEG are consistent with known neurobiological and neuroanatomical changes that occur during typical ageing. Commercial EEG-based depth-of-anaesthesia indices do not account for age and are therefore likely to be inaccurate in elderly patients. In contrast, monitoring the unprocessed EEG and its spectrogram can account for age and individual patient characteristics. C1 [Purdon, P. L.; Pavone, K. J.; Akeju, O.; Sampson, A. L.; Zhou, D. W.; Solt, K.; Brown, E. N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Purdon, P. L.; Akeju, O.; Solt, K.; Brown, E. N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Purdon, P. L.; Smith, A. C.; Brown, E. N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Lee, J.; Brown, E. N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, E. N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu; enb@neurostat.mit.edu OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, MD, USA [DP2-OD006454, DP1-OD003646, TR01-GM104948]; Foundation of Anesthesia Education and Research, Rochester, MN, USA; Massachusetts General Hospital Faculty Development Award, Boston, MA, USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA FX National Institutes of Health, Bethesda, MD, USA [DP2-OD006454 (to P.L.P.); DP1-OD003646 and TR01-GM104948 (to E.N.B.)]; Foundation of Anesthesia Education and Research, Rochester, MN, USA (to O.A.); Massachusetts General Hospital Faculty Development Award, Boston, MA, USA (to O.A.); funds from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. NR 66 TC 8 Z9 8 U1 0 U2 6 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 JUL PY 2015 VL 115 SU 1 SI SI BP 46 EP 57 DI 10.1093/bja/aev213 PG 12 WC Anesthesiology SC Anesthesiology GA CN1JG UT WOS:000358175000010 ER PT J AU Chemali, JJ Kenny, JD Olutola, O Taylor, NE Kimchi, EY Purdon, PL Brown, EN Solt, K AF Chemali, J. J. Kenny, J. D. Olutola, O. Taylor, N. E. Kimchi, E. Y. Purdon, P. L. Brown, E. N. Solt, K. TI Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE ageing; delayed emergence from anaesthesia; electroencephalography ID POSTOPERATIVE COGNITIVE DYSFUNCTION; VOLATILE ANESTHETICS; AGE; PROPOFOL; DELIRIUM; ISOFLURANE; METHYLPHENIDATE; SOLUBILITY; DECREASES; POTENCY AB Background: Little is known about ageing-related changes in the brain that affect emergence from general anaesthesia. We used young adult and aged Fischer 344 rats to test the hypothesis that ageing delays emergence from general anaesthesia by increasing anaesthetic sensitivity in the brain. Methods: Time to emergence was determined for isoflurane (1.5 vol% for 45 min) and propofol (8 mg kg(-1) i.v.). The dose of isoflurane required to maintain loss of righting (LOR) was established in young adult and aged rats. The efficacy of methylphenidate to reverse LOR from general anaesthesia was tested. Separate young adult and aged rats with implanted electroencephalogram (EEG) electrodes were used to test whether ageing increases sensitivity to anaesthetic-induced burst suppression. Results: Mean time to emergence from isoflurane anaesthesia was 47 s [95% CI 33, 60; young adult) compared with 243 s (95% CI 185, 308; aged). For propofol, mean time to emergence was 13.1 min (95% CI 11.9, 14.0; young adult) compared with 23.1 min (95% CI 18.8, 27.9; aged). These differences were statistically significant. When methylphenidate was administered after propofol, the mean time to emergence decreased to 6.6 min (95% CI 5.9, 7.1; young adult) and 10.2 min (95% CI 7.9, 12.3; aged). These reductions were statistically significant. Methylphenidate restored righting in all rats during continuous isoflurane anaesthesia. Aged rats had lower EEG power and were more sensitive to anaesthetic-induced burst suppression. Conclusions: Ageing delays emergence from general anaesthesia. This is due, at least in part, to increased anaesthetic sensitivity in the brain. Further studies are warranted to establish the underlying causes. C1 [Chemali, J. J.; Kenny, J. D.; Olutola, O.; Taylor, N. E.; Purdon, P. L.; Brown, E. N.; Solt, K.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kimchi, E. Y.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Taylor, N. E.; Purdon, P. L.; Brown, E. N.; Solt, K.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Kimchi, E. Y.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Brown, E. N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, E. N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM ksolt@mgh.harvard.edu OI Kenny, Jonathan/0000-0003-3745-3217; Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health [TR01-GM104948, DP1-OD003646, K08-GM094394, T32-NS048005] FX This work was supported by National Institutes of Health grant numbers TR01-GM104948 (E.N.B., K.S.), DP1-OD003646 (E.N.B.), K08-GM094394 (K.S.), and T32-NS048005 (E.K.). NR 40 TC 4 Z9 4 U1 0 U2 5 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 JUL PY 2015 VL 115 SU 1 SI SI BP 58 EP 65 DI 10.1093/bja/aev112 PG 8 WC Anesthesiology SC Anesthesiology GA CN1JG UT WOS:000358175000011 ER PT J AU Akeju, O Pavone, KJ Thum, JA Firth, PG Westover, MB Puglia, M Shank, ES Brown, EN Purdon, PL AF Akeju, O. Pavone, K. J. Thum, J. A. Firth, P. G. Westover, M. B. Puglia, M. Shank, E. S. Brown, E. N. Purdon, P. L. TI Age-dependency of sevoflurane-induced electroencephalogram dynamics in children SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE electroencephalography; pediatric; sevoflurane ID HUMAN PREFRONTAL CORTEX; INDUCED ALPHA-RHYTHM; BISPECTRAL INDEX; GENERAL-ANESTHESIA; THALAMOCORTICAL CONNECTIVITY; INDUCED UNCONSCIOUSNESS; PEDIATRIC ANESTHESIA; NEUROMUSCULAR BLOCK; PROPOFOL ANESTHESIA; COHERENCE ANALYSIS AB Background: General anaesthesia induces highly structured oscillations in the electroencephalogram (EEG) in adults, but the anaesthesia-induced EEG in paediatric patients is less understood. Neural circuits undergo structural and functional transformations during development that might be reflected in anaesthesia-induced EEG oscillations. We therefore investigated age-related changes in the EEG during sevoflurane general anaesthesia in paediatric patients. Methods: We analysed the EEG recorded during routine care of patients between 0 and 28 yr of age (n=54), using power spectral and coherence methods. The power spectrum quantifies the energy in the EEG at each frequency, while the coherence measures the frequency-dependent correlation or synchronization between EEG signals at different scalp locations. We characterized the EEG as a function of age and within 5 age groups: <1 yr old(n=4), 1-6yrold(n=12), >6-14 yr old(n=14), >14-21 yr old(n=11), >21-28 yr old(n=13). Results: EEG power significantly increased from infancy through similar to 6 yr, subsequently declining to a plateau at approximately 21 yr. Alpha (8-13 Hz) coherence, a prominent EEG feature associated with sevoflurane-induced unconsciousness in adults, is absent in patients <1 yr. Conclusions: Sevoflurane-induced EEG dynamics in children vary significantly as a function of age. These age-related dynamics likely reflect ongoing development within brain circuits that are modulated by sevoflurane. These readily observed paediatric-specific EEG signatures could be used to improve brain state monitoring in children receiving general anaesthesia. C1 [Akeju, O.; Pavone, K. J.; Firth, P. G.; Puglia, M.; Shank, E. S.; Brown, E. N.; Purdon, P. L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Firth, P. G.; Westover, M. B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Akeju, O.; Thum, J. A.; Westover, M. B.; Puglia, M.; Shank, E. S.; Brown, E. N.; Purdon, P. L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brown, E. N.; Purdon, P. L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, E. N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, E. N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Akeju, O (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM oluwaseun.akeju@mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu FU National Institutes of Health, Bethesda, MD USA [DP2-OD006454, DP1-OD003646, TR01-GM104948]; Foundation of Anesthesia Education and Research, Rochester, MN USA; Massachusetts General Hospital Faculty Development Award, Boston, MA USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA USA; Partners Innovation Award, Partners Healthcare, Boston, MA USA FX DP2-OD006454 (to P.L.P.); DP1-OD003646 and TR01-GM104948 (to E.N.B.) from the National Institutes of Health, Bethesda, MD USA; Foundation of Anesthesia Education and Research, Rochester, MN USA (to O.A.); Massachusetts General Hospital Faculty Development Award, Boston, MA USA (to O.A.); Funds from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA USA; Partners Innovation Award, Partners Healthcare, Boston, MA USA (to P.L.P.). NR 61 TC 4 Z9 4 U1 1 U2 4 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 JUL PY 2015 VL 115 SU 1 SI SI BP 66 EP 76 DI 10.1093/bja/aev114 PG 11 WC Anesthesiology SC Anesthesiology GA CN1JG UT WOS:000358175000012 ER PT J AU Solt, K AF Solt, K. TI The role of dopamine in reanimation from general anaesthesia SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 9th International Symposium on Memory and Awareness in Anesthesia (MAA) CY JUL 20-23, 2014 CL Tokyo, JAPAN ID ISOFLURANE ANESTHESIA; EMERGENCE; AROUSAL; SLEEP; METHYLPHENIDATE; INVOLVEMENT; PATHWAYS; RATS C1 [Solt, K.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM ksolt@mgh.harvard.edu NR 19 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2015 VL 115 SU 1 SI SI BP 128 EP 128 PG 1 WC Anesthesiology SC Anesthesiology GA CN1JG UT WOS:000358175000030 ER PT J AU Solt, K Chemali, JJ Olutola, O Kenny, JD Brown, EN AF Solt, K. Chemali, J. J. Olutola, O. Kenny, J. D. Brown, E. N. TI Aging delays emergence from general anaesthesia in rats SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 9th International Symposium on Memory and Awareness in Anesthesia (MAA) CY JUL 20-23, 2014 CL Tokyo, JAPAN C1 [Solt, K.; Chemali, J. J.; Olutola, O.; Kenny, J. D.; Brown, E. N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM ksolt@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2015 VL 115 SU 1 SI SI BP 134 EP 135 PG 2 WC Anesthesiology SC Anesthesiology GA CN1JG UT WOS:000358175000041 ER PT J AU Grewal, SK Chren, MM Parvataneni, R Stuart, SE Galles, E Linos, E AF Grewal, S. K. Chren, M. M. Parvataneni, R. Stuart, S. E. Galles, E. Linos, E. TI 'What is it about your skin cancer that bothers you the most?': 700 patients respond SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID SQUAMOUS-CELL CARCINOMA C1 [Grewal, S. K.] Commonwealth Med Coll, Scranton, PA USA. [Chren, M. M.; Parvataneni, R.; Stuart, S. E.; Linos, E.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, M. M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Galles, E.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Linos, E (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St, San Francisco, CA 94143 USA. EM linose@derm.ucsf.edu OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU NCATS NIH HHS [KL2 TR000143]; NCRR NIH HHS [KL2RR024130]; NIAMS NIH HHS [K24 AR052667, R01 AR054983] NR 4 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2015 VL 173 IS 1 BP 296 EP 297 DI 10.1111/bjd.13618 PG 2 WC Dermatology SC Dermatology GA CN3IK UT WOS:000358318700060 PM 25523523 ER PT J AU Bednar, F Schofield, HK Collins, MA Yan, W Zhang, YQ Shyam, N Eberle, JA Almada, LL Olive, KP Bardeesy, N Fernandez-Zapico, ME Nakada, D Simeone, DM Morrison, SJ di Magliano, MP AF Bednar, Filip Schofield, Heather K. Collins, Meredith A. Yan, Wei Zhang, Yaqing Shyam, Nikhil Eberle, Jaime A. Almada, Luciana L. Olive, Kenneth P. Bardeesy, Nabeel Fernandez-Zapico, Martin E. Nakada, Daisuke Simeone, Diane M. Morrison, Sean J. di Magliano, Marina Pasca TI Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism SO CARCINOGENESIS LA English DT Article ID CELL SELF-RENEWAL; DUCTAL ADENOCARCINOMA; ONCOGENIC KRAS; MICE; PROLIFERATION; SENESCENCE; POLYCOMB; MOUSE; TUMORIGENESIS; REGENERATION AB Bmi1, a Polycomb repressive complex member, is required for the initiation of pancreatic cancer, independently of its known ability to repress the p16 and p19 tumor suppressor genes. Additionally, we show that Bmi1 regulates reactive oxygen species accumulation in pancreatic cancer cells.Epigenetic dysregulation is involved in the initiation and progression of many epithelial cancers. BMI1, a component of the polycomb protein family, plays a key role in these processes by controlling the histone ubiquitination and long-term repression of multiple genomic loci. BMI1 has previously been implicated in pancreatic homeostasis and the function of pancreatic cancer stem cells. However, no work has yet addressed its role in the early stages of pancreatic cancer development. Here, we show that BMI1 is required for the initiation of murine pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination with a Kras(G12D)-driven pancreatic cancer mouse model. We also demonstrate that the requirement for Bmi1 in pancreatic carcinogenesis is independent of the Ink4a/Arf locus and at least partially mediated by dysregulation of reactive oxygen species. Our data provide new evidence of the importance of this epigenetic regulator in the genesis of pancreatic cancer. C1 [Bednar, Filip; Zhang, Yaqing; Simeone, Diane M.; di Magliano, Marina Pasca] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Schofield, Heather K.; Collins, Meredith A.; di Magliano, Marina Pasca] Univ Michigan, Program Cell & Mol Biol, Ann Arbor, MI 48109 USA. [Schofield, Heather K.; Shyam, Nikhil] Univ Michigan, Med Scientist Training Program, Ann Arbor, MI 48109 USA. [Yan, Wei] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Yan, Wei] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Eberle, Jaime A.; Olive, Kenneth P.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Dept Med, New York, NY 10032 USA. [Eberle, Jaime A.; Olive, Kenneth P.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Dept Pathol, New York, NY 10032 USA. [Almada, Luciana L.; Fernandez-Zapico, Martin E.] Mayo Clin, Div Oncol Res, Schulze Ctr Novel Therapeut, Rochester, MN 55905 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakada, Daisuke] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Simeone, Diane M.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Simeone, Diane M.; di Magliano, Marina Pasca] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA. [Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [di Magliano, Marina Pasca] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. RP di Magliano, MP (reprint author), Univ Michigan, Dept Surg, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. EM marinapa@umich.edu FU American College of Surgeons Resident Research Scholarship; National Institutes of Health [NIH T32 HD007505]; University of Michigan Program in Cellular and Molecular Biology Training Grant [NIH T32 GM07315]; University of Michigan Center for Organogenesis Training Grant [5-T32-HD007515]; National Cancer Institute [1R01CA151588-01]; American Chemical Society [RSG-14-173-01-CSM]; Elsa Pardee Foundation; National Pancreas Foundation Pilot Grant; Mayo Clinic Center for Cell Signaling in Gastroenterology Grant [DK84567]; NIH [1R21CA188857] FX F.B. was supported by the American College of Surgeons Resident Research Scholarship and by National Institutes of Health (NIH T32 HD007505). H.K.S. is supported by a University of Michigan Program in Cellular and Molecular Biology Training Grant (NIH T32 GM07315). M.A.C. was supported by a University of Michigan Program in Cellular and Molecular Biology Training Grant (NIH T32 GM07315), a University of Michigan Center for Organogenesis Training Grant (5-T32-HD007515). Research in the Pasca di Magliano lab is supported by National Cancer Institute (1R01CA151588-01), by American Chemical Society (RSG-14-173-01-CSM) and by the Elsa Pardee Foundation. This project was supported by a National Pancreas Foundation Pilot Grant. L.L.A. and M.E.F-Z. are supported by Mayo Clinic Center for Cell Signaling in Gastroenterology Grant (DK84567). K.P.O. is supported by NIH 1R21CA188857. NR 38 TC 6 Z9 6 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 JUL PY 2015 VL 36 IS 7 BP 730 EP 738 DI 10.1093/carcin/bgv058 PG 9 WC Oncology SC Oncology GA CN1JN UT WOS:000358175700004 PM 25939753 ER PT J AU Patel, PA Zhao, X Fonarow, GC Lytle, BL Smith, EE Xian, Y Bhatt, DL Peterson, ED Schwamm, LH Hernandez, AF AF Patel, Priyesh A. Zhao, Xin Fonarow, Gregg C. Lytle, Barbara L. Smith, Eric E. Xian, Ying Bhatt, Deepak L. Peterson, Eric D. Schwamm, Lee H. Hernandez, Adrian F. TI Novel Oral Anticoagulant Use Among Patients With Atrial Fibrillation Hospitalized With Ischemic Stroke or Transient Ischemic Attack SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE anticoagulation; anticoagulants; atrial fibrillation; ischemic attack; transient; stroke ID CLINICAL CLASSIFICATION SCHEMES; RISK STRATIFICATION SCHEMES; AMERICAN-HEART-ASSOCIATION; COST-EFFECTIVENESS; NATIONWIDE COHORT; GUIDELINES-STROKE; PREDICTING STROKE; DABIGATRAN; WARFARIN; VALIDATION AB Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack in patients with atrial fibrillation, yet diffusion of these therapies and patterns of use among atrial fibrillation patients with ischemic stroke and transient ischemic attack have not been well characterized. Methods and Results Using data from Get With The Guidelines-Stroke, we identified a cohort of 61 655 atrial fibrillation patients with ischemic stroke or transient ischemic attack hospitalized between October 2010 and September 2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16% to 17% plateau during the study period, although anticoagulation rates among eligible patients did not change appreciably (93.7% versus 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA(2)DS(2)-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% versus 40.9% with CHA(2)DS(2)-VASc 5, P<0.001 for difference in CHA(2)DS(2)-VASc). Conclusions NOACs have had modest but growing uptake over time among atrial fibrillation patients hospitalized with stroke or transient ischemic attack and are prescribed to patients with lower stroke risk compared with warfarin. C1 [Patel, Priyesh A.; Zhao, Xin; Lytle, Barbara L.; Xian, Ying; Peterson, Eric D.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC 27705 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles Med Ctr, Ronald Reagan Univ Calif, Los Angeles, CA 90024 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Peterson, Eric D.; Hernandez, Adrian F.] Duke Univ, Med Ctr, Durham, NC USA. RP Patel, PA (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM priyesh.patel@dm.duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association Young Investigator Database Research Seed Grant; National Institutes of Health [T32-HL007101] FX This study was funded by an American Heart Association Young Investigator Database Research Seed Grant. P.A. Patel received additional support from National Institutes of Health grant T32-HL007101. NR 30 TC 7 Z9 7 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2015 VL 8 IS 4 BP 383 EP 392 DI 10.1161/CIRCOUTCOMES.114.000907 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN1XL UT WOS:000358214000010 PM 26058721 ER PT J AU Dudok, DV Nagdee, I Cheung, K Liu, H Vedovelli, L Ghinelli, E Kenyon, K Parapuram, S Hutnik, CM AF Dudok, David V. Nagdee, Imraan Cheung, Kevin Liu, Hong Vedovelli, Luca Ghinelli, Emiliano Kenyon, Kenneth Parapuram, Sunil Hutnik, Cindy M. TI Effects of amniotic membrane extract on primary human corneal epithelial and limbal cells SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE Cornea; Corneal wound healing; Amniotic membrane ID TGF-BETA; TRANSPLANTATION; SUPPRESSION; OPHTHALMOLOGY; FIBROBLASTS; APOPTOSIS; KERATITIS; PROTEIN; BURNS AB BackgroundTo assess the effects of amniotic membrane extract (AMX) on cellular activity of primary human corneal epithelial (HCE) cells under mechanical and oxidative stress, and on human limbal cells under oxidative stress. MethodsCorneal mechanical stress was simulated with a linear scratch in confluent HCE cell plates, then incubated with 0.1% AMX for 48 and 72h. Subjecting HCE cultures to 0.5mmol/L tertiary-butylhydroperoxide for 1h simulated an oxidative stress. 0.1% AMX-treated cultures were compared with controls at 24 and 48h using cellular viability assay, along with 12-h AMX pretreatment and human limbal cell comparisons. ResultsMechanical stress on HCE cultures revealed a statistically significant distance ratio at 48 and 72h in favour of 0.1% AMX-treated cultures (P=0.021 and 0.035, respectively). Oxidative stress did not reveal any significant difference in cellular viability of AMX-treated versus control cultures. Twelve hour AMX pre-treatment prior to oxidative stress revealed a significant difference after 24h from oxidative injury (73.3% AMXvs. 66.0% control, P=0.035), but not after 48h. Human limbal cells demonstrated significantly improved oxidative viability compared with HCE cells, with (91.0% vs. 82.0% control, P=0.017) and without 0.1% AMX pre-treatment (91.2% vs. 83.7% control, P=0.019). ConclusionsHCE cells treated with AMX healed faster after mechanical insult, suggesting a potential benefit in acute corneal injuries. Under oxidative stress, human limbal cells, a more proliferative cell type, showed superior viability compared with HCE cells. C1 [Dudok, David V.; Nagdee, Imraan; Cheung, Kevin; Liu, Hong; Parapuram, Sunil; Hutnik, Cindy M.] Univ Western Ontario, Ivey Eye Inst, London, ON N6A 4V2, Canada. [Vedovelli, Luca] Massachusetts Gen Hosp, Div Nephrol Cell Biol Human Biol & Physiol, Boston, MA 02114 USA. [Ghinelli, Emiliano; Kenyon, Kenneth] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Kenyon, Kenneth] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. RP Dudok, DV (reprint author), Univ Western Ontario, Ivey Eye Inst, 268 Grosvenor St, London, ON N6A 4V2, Canada. EM david.dudok@gmail.com OI Vedovelli, Luca/0000-0003-4847-2333 NR 23 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD JUL PY 2015 VL 43 IS 5 BP 443 EP 448 DI 10.1111/ceo.12480 PG 6 WC Ophthalmology SC Ophthalmology GA CN0PQ UT WOS:000358116200009 PM 25495256 ER PT J AU Phitayakorn, R Levine, W Petrusa, E Daily, B Eromo, E Gee, D Hemingway, M Minehart, R Pian-Smith, M Gordon, JA AF Phitayakorn, Roy Levine, Wilton Petrusa, Emil Daily, Bethany Eromo, Ersne Gee, Denise Hemingway, Maureen Minehart, Rebecca Pian-Smith, May Gordon, James A. TI Making It Real Development and integration of in situ simulation operating rooms into the real operating room environment SO IEEE PULSE LA English DT Article C1 [Phitayakorn, Roy] Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Perioperat & Patient Care Serv, Boston, MA 02114 USA. RP Phitayakorn, R (reprint author), Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. EM rphitayakorn@mgh.harvard.edu OI Phitayakorn, Roy/0000-0002-8327-1484 NR 3 TC 0 Z9 0 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD JUL-AUG PY 2015 VL 6 IS 4 BP 10 EP 13 DI 10.1109/MPUL.2015.2428298 PG 4 WC Engineering, Biomedical SC Engineering GA CN1ZJ UT WOS:000358219400003 PM 26186046 ER PT J AU Mukherjee, B Sivaprakasam, M AF Mukherjee, Biswarup Sivaprakasam, Mohanasankar TI An Eye Toward Improving A new training approach in ophthalmic anesthesia provides qualitative and quantitative feedback SO IEEE PULSE LA English DT Article C1 [Mukherjee, Biswarup] Harvard Univ, Sch Med, Simulat Grp, Cambridge, MA 02138 USA. [Mukherjee, Biswarup] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sivaprakasam, Mohanasankar] Indian Inst Technol, Dept Elect Engn, Madras 600036, Tamil Nadu, India. [Sivaprakasam, Mohanasankar] IIT Madras, Healthcare Technol Innovat Ctr, Madras, Tamil Nadu, India. RP Mukherjee, B (reprint author), Harvard Univ, Sch Med, Simulat Grp, Cambridge, MA 02138 USA. EM bmukherjee@mgh.harvard.edu; mohan@ee.iitm.ac.in NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD JUL-AUG PY 2015 VL 6 IS 4 BP 20 EP 25 DI 10.1109/MPUL.2015.2428297 PG 6 WC Engineering, Biomedical SC Engineering GA CN1ZJ UT WOS:000358219400005 PM 26186048 ER PT J AU Shuster, M Tse, JY Smith, GP AF Shuster, Marina Tse, Julie Y. Smith, Gideon P. TI Breast carcinoma arising in ectopic breast tissue presenting as an enlarging axillary nodule SO INDIAN JOURNAL OF DERMATOLOGY VENEREOLOGY & LEPROLOGY LA English DT Letter C1 [Tse, Julie Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02215 USA. [Smith, Gideon P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02215 USA. RP Shuster, M (reprint author), Harvard Univ, Sch Med, 89 Pk Dr,Apt 2, Boston, MA 02215 USA. EM marina_shuster@hms.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0378-6323 EI 0973-3922 J9 INDIAN J DERMATOL VE JI Indian J. Dermatol. Venereol. Leprol. PD JUL-AUG PY 2015 VL 81 IS 4 DI 10.4103/0378-6323.158655 PG 3 WC Dermatology SC Dermatology GA CM8HN UT WOS:000357940000027 ER PT J AU Gao, L Park, SJ Jang, Y Lee, S Kim, CJ Minami, Y Ong, D Soeda, T Vergallo, R Lee, H Yu, B Uemura, S Jang, IK AF Gao, Lei Park, Seung-Jung Jang, Yangsoo Lee, Stephen Kim, Chong-Jin Minami, Yoshiyasu Ong, Daniel Soeda, Tsunenari Vergallo, Rocco Lee, Hang Yu, Bo Uemura, Shiro Jang, Ik-Kyung TI Comparison of Neoatherosclerosis and Neovascularization Between Patients With and Without Diabetes An Optical Coherence Tomography Study SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atherosclerosis; diabetes mellitus; drug-eluting stent ID ELUTING STENT IMPLANTATION; ATHEROSCLEROTIC LESIONS; GLYCOSYLATED HEMOGLOBIN; CORONARY STENTS; PLAQUE; PREDICTORS; RESTENOSIS; INFLAMMATION; PROGRESSION; MELLITUS AB OBJECTIVES This study aimed to investigate the characteristics of neoatherosclerosis (NA) in patients with diabetes mellitus (DM) after drug-eluting stent (DES) implantation using optical coherence tomography. BACKGROUND NA is an important substrate for stent failure. In vivo NA characteristics in DM patients have not been investigated. METHODS A total of 397 patients with 452 DES who underwent follow-up optical coherence tomography examination after DES implantation were enrolled. Characteristics of NA were compared between DM and non-DM patients. Neovascularization was defined as signal-poor holes or tubular structures with a diameter of 50 to 300 mm. RESULTS A total of 123 DES with NA lesions in 115 patients were identified. The incidence of NA was similar between DM and non-DM patients (29.6% vs. 28.6%; p = 0.825). Compared with the non-DM group, neovascularization was more frequently observed in the DM group (55.1% vs. 32.4%; p = 0.012). The multivariate logistic model demonstrated that DM (odds ratio: 3.00; 95% confidence interval: 1.31 to 6.81; p = 0.009) and follow-up duration (odds ratio: 1.03; 95% confidence interval: 1.02 to 1.05; p < 0.001) were the independent predictors for neovascularization in NA lesions. DM patients with glycated hemoglobin >= 7.0% had a higher prevalence of thin-cap fibroatheroma compared with those with glycated hemoglobin <7.0% (40.0% vs. 8.3%; p = 0.01). CONCLUSIONS The incidence of NA was similar between patients with and without DM. Neovascularization in NA lesions was more frequent in those with DM. Poorly controlled DM patients had a higher incidence of thin-cap fibroatheroma, compared with those with well-controlled DM. (C) 2015 by the American College of Cardiology Foundation. C1 [Gao, Lei; Minami, Yoshiyasu; Ong, Daniel; Soeda, Tsunenari; Vergallo, Rocco; Jang, Ik-Kyung] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Park, Seung-Jung] Univ Ulsan, Coll Med, Asan Med Ctr, Div Cardiol, Seoul, South Korea. [Jang, Yangsoo] Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Kim, Chong-Jin; Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. [Soeda, Tsunenari; Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Lee, Hang] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM IJANG@mgh.harvard.edu FU St. Jude Medical; Boston Scientific; Medtronic; Italian Society of Cardiology Award for Research Abroad; National Natural Science Foundation of China [30871064] FX Dr. Jang has received a research grant and honorarium from St. Jude Medical; and has received research grants from Boston Scientific and Medtronic. Dr. Vergallo was funded in part by the 2013 Italian Society of Cardiology Award for Research Abroad. Dr. Yu has received a grant from the National Natural Science Foundation of China (30871064). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 30 TC 2 Z9 3 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JUL PY 2015 VL 8 IS 8 BP 1044 EP 1052 DI 10.1016/j.jcin.2015.02.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN2OK UT WOS:000358261300012 PM 26117465 ER PT J AU Jaff, MR AF Jaff, Michael R. TI What's a Doctor to Do? Balloon, Stents, Drugs, Drills, and Treadmills Are We Closer to the Optimal Algorithm? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE atherectomy; drug-coated balloon; peripheral artery disease; stent ID PERIPHERAL ARTERY-DISEASE; SUPERVISED EXERCISE; REVASCULARIZATION; CLAUDICATION; ANGIOPLASTY; OUTCOMES; CLEVER C1 Massachusetts Gen Hosp, Paul & Phyllis Fireman Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Paul & Phyllis Fireman Vasc Ctr, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org NR 7 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 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JUL PY 2015 VL 8 IS 8 BP 1113 EP 1114 DI 10.1016/j.jcin.2015.05.003 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN2OK UT WOS:000358261300020 PM 26205447 ER PT J AU Chambers, KJ Raol, N Song, PC Randolph, GW Hartnick, CJ AF Chambers, Kyle J. Raol, Nikhila Song, Phillip C. Randolph, Gregory W. Hartnick, Christopher J. TI Laryngeal Reinnervation Using a Split-Hypoglossal Nerve Graft in a Canine Model SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID VOCAL FOLD PARALYSIS; QUALITY-OF-LIFE; CORD PARALYSIS; THYROARYTENOID MUSCLES; THYROID-SURGERY; ELECTROMYOGRAPHY; IMPACT; VOICE; NEURORRHAPHY; EXPERIENCE AB IMPORTANCE Vocal fold immobility following injury to the recurrent laryngeal nerve (RLN) may lead to substantial morbidity. A reinnervation treatment strategy offers several theoretical benefits over static treatment options. This study evaluates the robustness of reinnervation of the larynx using a split-hypoglossal nerve graft in an animal model, with outcomes assessed by independent blinded review. OBJECTIVES To assess whether a full-hypoglossal nerve graft to the RLN after RLN section can provide return of dynamic vocal fold motion in a canine model, and to validate that a split-hypoglossal nerve graft to the RLN may also provide dynamic vocal fold motion to rehabilitate laryngeal function in a canine model. DESIGN, SETTING, AND SUBJECTS A pilot animal study to assess the feasibility and morbidity of laryngeal reinnervation following RLN injury with an end-to-end full-hypoglossal or split-hypoglossal nerve graft was performed at an animal care and research facility in 10 adult female dogs. The study dates were January to July 2013. INTERVENTIONS We performed full-hypoglossal (full XII group [n = 5]) and split-hypoglossal (split XII group [ n = 5]) nerve grafts to the RLN in a canine model following RLN section. MAIN OUTCOMES AND MEASURES Morbidity was evaluated through scored feeding observation. Laryngeal function was assessed by video laryngoscopy and evoked laryngeal electromyography was performed at baseline and 6 months after surgery. Video laryngoscopy was graded by independent reviewers blinded to study intervention. RESULTS No clinically significant morbidity was identified after surgery. On review of video laryngoscopy, all 5 animals in the full XII group and all 5 animals in the split XII group demonstrated vocal fold motion by at least 1 independent reviewer. All 3 reviewers agreed on motion in 1 of 5 animals in the full XII group and in 1 of 5 animals in the split XII group. Stimulation of the hypoglossal nerve demonstrated neural connection on evoked laryngeal electromyography in all animals at 6 months. CONCLUSIONS AND RELEVANCE This study confirms that a full-hypoglossal or split-hypoglossal nerve graft may restore vocal fold motion, without significant functional morbidity, following RLN section in a canine model. C1 [Chambers, Kyle J.; Randolph, Gregory W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Raol, Nikhila; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otolaryngol, Div Pediat Otolaryngol, Boston, MA 02114 USA. [Song, Phillip C.] Harvard Univ, Sch Med, Dept Otolaryngol, Div Laryngol, Boston, MA 02114 USA. [Song, Phillip C.] Harvard Univ, Sch Med, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Div Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 41 TC 1 Z9 1 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JUL PY 2015 VL 141 IS 7 BP 620 EP 627 DI 10.1001/jamaoto.2015.0929 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CN0DB UT WOS:000358081900006 PM 26042741 ER PT J AU Lee, J AF Lee, Jarone TI Trauma Patients Health Insurance Reform Is Only the Beginning SO JAMA SURGERY LA English DT Editorial Material C1 [Lee, Jarone] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lee, Jarone] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Lee, Jarone] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Lee, J (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM lee.jarone@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JUL PY 2015 VL 150 IS 7 BP 616 EP 616 DI 10.1001/jamasurg.2014.2470 PG 1 WC Surgery SC Surgery GA CM8ZU UT WOS:000357994900004 PM 25945655 ER PT J AU Bauman, WA Cirnigliaro, CM La Fountaine, MF Martinez, L Kirshblum, SC Spungen, AM AF Bauman, William A. Cirnigliaro, Christopher M. La Fountaine, Michael F. Martinez, LeighAnn Kirshblum, Steven C. Spungen, Ann M. TI Zoledronic acid administration failed to prevent bone loss at the knee in persons with acute spinal cord injury: an observational cohort study SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE Spinal cord injury; Zoledronate; Bisphosphonates; Osteoporosis; Knee ID X-RAY ABSORPTIOMETRY; DISUSE OSTEOPOROSIS; MINERAL DENSITY; PAMIDRONATE; TERM; IMMOBILIZATION; TURNOVER; FRACTURE; INDIVIDUALS; METABOLISM AB After acute spinal cord injury (SCI), rapid depletion of the sublesional skeleton occurs, particularly at the distal femur and proximal tibia. Subsequently, fragility fractures of the knee may occur. We determined the efficacy of zoledronic acid to prevent sublesional bone mineral density (BMD) loss at 6 and 12 months after acute SCI. Thirteen subjects with acute motor-complete SCI were prospectively studied: 6 patients received zoledronic acid (5 mg) and 7 subjects did not receive the drug (controls). Zoledronic acid was administered intravenously within 16 weeks of acute injury. Areal BMD was performed by dual energy X-ray absorptiometry at baseline, 6, and 12 months after administration of drug. The treatment group demonstrated sparing of BMD at the total hip at month 6 (p < 0.0006) and at month 12 (p < 0.01). In contrast to the findings at the hip, the treatment group had a greater loss of BMD compared to the control group at the distal femur and proximal tibia at month 6 (-7.9 % +/- 3.4 vs.-2.7 % +/- 5.0, respectively, p = 0.054; and -10.5 % +/- 6.4 vs. -4.8 % +/- 6.8, respectively, p = NS) and at month 12 (-18.5 % +/- 3.9 vs. -8.4 % +/- 7.2, respectively, p = 0.01; and -20.4 % +/- 8.8 vs.-7.9 % +/- 12.3, respectively, p = 0.06). A single dose of zoledronic acid administered soon after acute SCI reduced the %BMD loss at the hip, but appeared to have no effect to prevent %BMD loss at the knee, the site where fracture risk is greatest in persons with SCI. C1 [Bauman, William A.; Cirnigliaro, Christopher M.; La Fountaine, Michael F.; Spungen, Ann M.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.; La Fountaine, Michael F.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Med & Rehabil Med, New York, NY 10029 USA. [La Fountaine, Michael F.] Seton Hall Univ, Dept Phys Therapy, Sch Hlth & Med Sci, S Orange, NJ USA. [Martinez, LeighAnn; Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU James J. Peters Veterans Affairs Medical Center; Kessler Institute for Rehabilitation, West Orange, NJ; Rehabilitation Research & Development Center of Excellence [B9212-C, B4162-C]; Veteran Affairs Rehabilitation Research and Development Service [B9212-C, B4162-C] FX The authors would like to thank the James J. Peters Veterans Affairs Medical Center, Bronx, NY, Department of Veterans Affairs Rehabilitation Research & Development Service, and Kessler Institute for Rehabilitation, West Orange, NJ, for their support to perform this work. Novartis Pharmaceuticals Corporation provided drug gratis to perform this clinical trial. This work was funded by a Rehabilitation Research & Development Center of Excellence for the Medical Consequences of Spinal Cord Injury grant (#B9212-C, B4162-C). Veteran Affairs Rehabilitation Research and Development Service (#B9212-C, #B4162-C) and the James J. Peters Veterans Affairs Medical Center. Novartis Pharmaceuticals graciously provided zoledronic acid (Reclast 5 mg) for use in our clinical trial. NR 44 TC 7 Z9 7 U1 2 U2 3 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0914-8779 EI 1435-5604 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PD JUL PY 2015 VL 33 IS 4 BP 410 EP 421 DI 10.1007/s00774-014-0602-x PG 12 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CN1QT UT WOS:000358195600006 PM 25158630 ER PT J AU Li, JT Melton, AC Su, G Hamm, DE LaFemina, M Howard, J Fang, XH Bhat, S Huynh, KM O'Kane, CM Ingram, RJ Muir, RR McAuley, DF Matthay, MA Sheppard, D AF Li, John T. Melton, Andrew C. Su, George Hamm, David E. LaFemina, Michael Howard, James Fang, Xiaohui Bhat, Sudarshan Huynh, Kieu-My O'Kane, Cecilia M. Ingram, Rebecca J. Muir, Roshell R. McAuley, Daniel F. Matthay, Michael A. Sheppard, Dean TI Unexpected Role for Adaptive alpha beta Th17 Cells in Acute Respiratory Distress Syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE LUNG INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EVANS BLUE-DYE; T-CELLS; TH17 CELLS; ALBUMIN CLEARANCE; HOST-DEFENSE; IL-17; MICE; INTERLEUKIN-17 AB Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. In this study, we report that expansion of Ag-specific alpha beta Th17 cells contributes to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability. Mice with a highly restrictive defect in Ag-specific alpha beta Th17 cells were protected from experimental ARDS induced by a single dose of endotracheal LPS. Loss of IL-17 receptor C or Ab blockade of IL-17A was similarly protective, further suggesting that IL-17A released by these cells was responsible for this effect. LPS induced a rapid and specific clonal expansion of alpha beta Th17 cells in the lung, as determined by deep sequencing of the hypervariable CD3R beta VJ region of the TCR. Our findings could be relevant to ARDS in humans, because we found significant elevation of IL-17A in bronchoalveolar lavage fluid from patients with ARDS, and rIL-17A directly increased permeability across cultured human alveolar epithelial monolayers. These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that alpha beta Th17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease. C1 [Li, John T.; Melton, Andrew C.; Huynh, Kieu-My; Sheppard, Dean] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. [Li, John T.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94110 USA. [Su, George] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Hamm, David E.] Adapt Biotechnol, Seattle, WA 98102 USA. [LaFemina, Michael] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Howard, James] UCSF Benioff Childrens Hosp Oakland, Dept Pediat, Oakland, CA 94609 USA. [Matthay, Michael A.] Cardiovasc Res Inst, Dept Anesthesia, San Francisco, CA 94158 USA. [Fang, Xiaohui; Matthay, Michael A.] Cardiovasc Res Inst, Dept Med, San Francisco, CA 94158 USA. [Bhat, Sudarshan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [O'Kane, Cecilia M.; Ingram, Rebecca J.; Muir, Roshell R.; McAuley, Daniel F.] Queens Univ Belfast, Ctr Infect & Immun, Belfast BT7 1NN, Antrim, North Ireland. RP Sheppard, D (reprint author), Univ Calif San Francisco, Lung Biol Ctr, 1550 4th St,Mission Bay, San Francisco, CA 94143 USA. EM dean.sheppard@ucsf.edu RI Ingram, Rebecca/F-9711-2013 OI Ingram, Rebecca/0000-0003-1832-2457 FU National Institutes of Health [R37HL53949, K08HL111208, R37HL51856]; Health and Social Care Research and Development Division, Public Health Agency Northern Ireland FX This work was supported by National Institutes of Health Grants R37HL53949 (to D.S.), K08HL111208 (to J.T.L.), and R37HL51856 (to M.A.M.), as well as by a grant from the Health and Social Care Research and Development Division, Public Health Agency Northern Ireland (to C.M.O. and D.F.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders. NR 41 TC 9 Z9 9 U1 1 U2 5 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 JUL 1 PY 2015 VL 195 IS 1 BP 87 EP 95 DI 10.4049/jimmunol.1500054 PG 9 WC Immunology SC Immunology GA CM9XU UT WOS:000358064500015 PM 26002979 ER PT J AU Reardon, DA Okada, H AF Reardon, David A. Okada, Hideho TI Re-defining response and treatment effects for neuro-oncology immunotherapy clinical trials SO JOURNAL OF NEURO-ONCOLOGY LA English DT Editorial Material DE Immunotherapy; Glioblastoma; Vaccine; Immune checkpoint inhibitor; Pseudoprogression ID METASTATIC MELANOMA; T-CELLS; CANCER-IMMUNOTHERAPY; ASSESSMENT CRITERIA; PLUS IPILIMUMAB; FOLLOW-UP; PHASE-II; GLIOBLASTOMA; ANTIBODY; SAFETY AB In much of medical oncology, including neuro-oncology, there is great interest to evaluate the therapeutic potential of immune-based therapies including vaccines, adoptive T cell strategies and modulators of immune checkpoint regulators such as cytotoxic T lymphocyte antigen 4 and programmed death 1. Immune-based treatments exert an indirect anti-tumor effect by generating potent, tumor-targeting immune responses. Robust anti-tumor immune responses have been shown to achieve encouraging radiographic responses across the spectrum of applied immunotherapeutics which are felt to be indicative of a bona fide anti-tumor effect. Conversely, worsening of imaging findings, particularly early in the course of immunotherapy administration, can be challenging to interpret with growing evidence demonstrating that at least a subset of such patients ultimately will derive meaningful clinical benefit. The immune related response criteria were generated to provide guidance regarding the interpretation of such complex imaging findings, for general medical oncologists prescribing immunotherapeutics. An analogous effort that addresses challenges associated with imaging assessment and incorporates nuances associated with neuro-oncology patients is underway and is referred to as the immunotherapy response assessment in neuro-oncology criteria. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Okada, Hideho] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,Dana 2134, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu NR 50 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2015 VL 123 IS 3 SI SI BP 339 EP 346 DI 10.1007/s11060-015-1748-7 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CN1EM UT WOS:000358160000004 PM 25707876 ER PT J AU Moran, CJ Kaplan, JL Winter, HS Masiakos, PT AF Moran, Christopher J. Kaplan, Jess L. Winter, Harland S. Masiakos, Peter T. TI Occult Blood and Perianal Examination: Value Added in Pediatric Inflammatory Bowel Disease Screening SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE fecal occult blood testing; inflammatory bowel disease; pediatric; perianal examination; sensitivity and specificity ID DIGITAL RECTAL EXAMINATION; DIAGNOSTIC DELAY; CHILDREN AB Objectives:Pediatric inflammatory bowel disease (IBD) often presents insidiously and standard blood tests are normal in 20% of patients. We hypothesize that fecal occult blood testing (FOBT) and the perianal examination in addition to blood tests provide important information during the screening process for IBD. The aim of the present study was to measure the diagnostic value of adding FOBT and perianal examination to standard screening laboratories in evaluating children and adolescents for IBD.Methods:The medical records of consecutive patients undergoing ileocolonoscopy for IBD were reviewed. Laboratory test results, FOBT, and perianal examination before the decision to perform the ileocolonoscopy were recorded. Standard limits of laboratory tests were used. Multivariate logistic regression was performed on a discovery cohort and applied to an independent validation cohort.Results:The discovery cohort included 335 patients (85 IBD and 250 non-IBD). A total of 61.2% had FOBT and perianal examination performed before the decision to perform the ileocolonoscopy. A total of 119 patients had complete blood testing, FOBT, and perianal examination available for full analysis. The sensitivity of the laboratory testing was 80.5% for IBD, and the sensitivity of FOBT with perianal examination was 66.9%. The combined sensitivity of laboratory testing and FOBT with perianal examination was, however, 97.6%. The most predictive model included C-reactive protein, platelet counts, and FOBT with perianal examination and was superior to the laboratory value-only model (P<0.001) that was validated in a separate cohort.Conclusions:Perianal examination and FOBT improve sensitivity in screening children for IBD. C1 [Moran, Christopher J.; Kaplan, Jess L.; Winter, Harland S.] MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. [Masiakos, Peter T.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Moran, CJ (reprint author), MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, 175 Cambridge St,561, Boston, MA 02114 USA. EM jmoran@mgh.harvard.edu FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NCRR, NIH); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NCATS, NIH) [UL1 TR001102]; Harvard University FX The present work was supported in part by philanthropic donations from Martin Schlaff (H.S.W) and the B. Hasso Family Foundation (May Serrano, President) (H.S.W), conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NCRR and NCATS, NIH Award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic health care centers. NR 16 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 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 2015 VL 61 IS 1 BP 52 EP 55 DI 10.1097/MPG.0000000000000754 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA CN1HC UT WOS:000358168300008 PM 25651490 ER PT J AU Hull, MA Niemierko, A Haynes, AB Jacobson, A Chen, YL DeLaney, TF Mullen, JT AF Hull, Melissa A. Niemierko, Andrzej Haynes, Alex B. Jacobson, Alex Chen, Yen-Lin DeLaney, Thomas F. Mullen, John T. TI Post-operative renal function following nephrectomy as part of en bloc resection of retroperitoneal sarcoma (RPS) SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE retroperitoneal sarcoma; nephrectomy; renal function; chronic kidney disease ID GLOMERULAR-FILTRATION-RATE; SOFT-TISSUE SARCOMAS; EXTENDED SURGERY AB Background and ObjectivesAlthough resection of RPS with en bloc nephrectomy confers the potential benefit of improved locoregional tumor control, little has been published about the long-term post-operative renal function of these patients. MethodsRetrospective review of 54 patients undergoing nephrectomy for RPS was performed. Clinicopathologic and treatment characteristics, pre- and post-operative creatinine (Cr) values, and estimated glomerular filtration rates (eGFR) were recorded. The primary outcome measure was progression of chronic kidney disease (CKD) stage. ResultsMedian preoperative eGFR was 85ml/min. Post-nephrectomy, median nadir eGFR was 44ml/min, rebounding to 62ml/min at median follow-up of 50 months. Of 49 patients with preoperative eGFR 60ml/min (CKD stage 1,2), 51% preserved eGFR 60 postoperatively, whereas 49% progressed to CKD stage 3 (eGFR 30-59). Independent risk factors for progression of CKD stage were age and preoperative eGFR. Eleven patients died of recurrent disease, whereas no patient died of end stage renal disease (ESRD) or required dialysis. ConclusionsAlthough progression of CKD stage occurs in nearly one-half of patients followed for more than 4 years after nephrectomy for RPS, no patient progressed to ESRD or had a limitation in systemic therapy options, even with progression to CKD stage 3. J. Surg. Oncol. 2015 111:98-102. (c) 2015 Wiley Periodicals, Inc. C1 [Hull, Melissa A.; Haynes, Alex B.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Niemierko, Andrzej; Jacobson, Alex; Chen, Yen-Lin; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept & Radiat Oncol, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org NR 24 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUL 1 PY 2015 VL 112 IS 1 BP 98 EP 102 DI 10.1002/jso.23949 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA CN3AR UT WOS:000358296100018 PM 26179132 ER PT J AU Partridge, AH AF Partridge, Ann H. TI More Options for Premenopausal Women With Early-Stage Hormone-Sensitive Breast Cancer SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID OVARIAN SUPPRESSION; TAMOXIFEN THERAPY; ADJUVANT; NONADHERENCE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2015 VL 29 IS 7 BP 482 EP + PG 2 WC Oncology SC Oncology GA CN4KI UT WOS:000358398600002 PM 26178335 ER PT J AU Rai, R Jakobiec, FA Fay, A AF Rai, Ruju Jakobiec, Frederick A. Fay, Aaron TI Ocular Metastatic Renal Carcinoma Presenting With Proptosis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CELL-CARCINOMA; PROGNOSTIC-FACTORS; CANCER; ORBIT; EYE; SURVIVAL; NEOPLASMS; DIAGNOSIS; IMMUNOHISTOCHEMISTRY; NEPHRECTOMY AB Metastatic renal carcinoma is the third most common source of ocular and second most common source of orbital metastases. This is the first published case of von Hippel-Lindau (vHL) disease that developed renal cell carcinoma metastatic to an eye with a retinal hemangioblastoma. A 73-year-old woman had a history of vHL disease that included prior retinal hemangioblastomas, 2 cerebellar hemangioblastomas, and bilateral renal cell carcinomas with sacral metastasis. After presenting with progressive, painful proptosis secondary to a large mass observable by ocular CT, an enucleation-orbitotomy was performed, and the surgical specimen was sent for histopathological analysis. The ophthalmic renal metastatic tumor, like the primary tumor, was a clear cell variant that involved both the eyeball and orbit in continuity. The intraocular component was larger than the extraocular portion, which was interpreted as an outward extension of an initial retinal metastasis that probably first settled within a hemangioblastoma. Clusters of ectatic ghost vessels with thickened walls produced by periodic acid Schiff-positive, redundant basement membrane material were partially infiltrated by tumor cells at their periphery, thereby lending some support for this hypothesis. Immunohistochemical positivity for the biomarkers cytokeratin 18, vimentin, carbonic anhydrase IX, PAX2, and PAX 8 confirmed the diagnosis. The patient has refused further treatment. Her anophthalmic socket has comfortably retained a porous polyethylene implant without clinical evidence of local recurrence during 5 months of follow up. C1 [Rai, Ruju; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Rai, Ruju; Jakobiec, Frederick A.; Fay, Aaron] Harvard Univ, Sch Med, Boston, MA USA. [Fay, Aaron] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast Surg, Boston, MA 02114 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 42 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 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2015 VL 31 IS 4 BP E100 EP E108 DI 10.1097/IOP.0000000000000119 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CM9QE UT WOS:000358043000009 PM 24828963 ER PT J AU Lisi, AJ Breuer, P Gallagher, RM Rodriguez, E Rossi, MI Schmader, K Scholten, JD Weiner, DK AF Lisi, Anthony J. Breuer, Paula Gallagher, Rollin M. Rodriguez, Eric Rossi, Michelle I. Schmader, Kenneth Scholten, Joel D. Weiner, Debra K. TI Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part II: Myofascial Pain SO PAIN MEDICINE LA English DT Review DE Low Back Pain; Myofascial Pain; Chronic Pain; Degenerative Disc Disease; Elderly; Chronic Low Back Pain; Lumbar; Older Adults; Pain Disorder; Spinal Stenosis ID POSTTRAUMATIC-STRESS-DISORDER; MUSCULOSKELETAL PAIN; TRIGGER POINT; SKELETAL-MUSCLE; MANAGEMENT; CARE; PREVALENCE; PHYSICIANS; DIAGNOSIS; FRAMEWORK AB ObjectiveTo present an algorithm of sequential treatment options for managing myofascial pain (MP) in older adults, along with a representative clinical case. MethodsA modified Delphi process was used to synthesize evidence-based recommendations. A multidisciplinary expert panel developed the algorithm, which was subsequently refined through an iterative process of input from a primary care physician panel. ResultsWe present an algorithm and supportive materials to help guide the care of older adults with MP, an important contributor to chronic low back pain (CLBP). Addressing any perpetuating factors should be the first step of managing MP. Patients should be educated on self-care approaches, home exercise, and the use of safe analgesics when indicated. Trigger point deactivation can be accomplished by manual therapy, injection therapy, dry needling, and/or acupuncture. ConclusionsThe algorithm presented gives a structured approach to guide primary care providers in planning treatment for patients with MP as a contributor to CLBP. C1 [Lisi, Anthony J.] VA Connecticut Healthcare Syst, Newington, CT USA. [Lisi, Anthony J.] Univ Bridgeport, Coll Chiropract, Bridgeport, CT 06601 USA. [Breuer, Paula] Univ Pittsburgh, Med Ctr, Ctr Rehab Serv, Pittsburgh, PA 15260 USA. [Gallagher, Rollin M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Penn, Dept Anesthesiol, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Pain Serv, Philadelphia, PA USA. [Rodriguez, Eric; Rossi, Michelle I.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. [Rossi, Michelle I.; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15240 USA. [Schmader, Kenneth] Durham VA Med Ctr, GRECC, Durham, NC USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27706 USA. [Scholten, Joel D.] Washington DC VA Med Ctr, Washington, DC USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Bldg 30,00GR, Pittsburgh, PA 15240 USA. EM debra.weiner@va.gov FU Veterans Administration Rehabilitation Research & Development Service FX Veterans Administration Rehabilitation Research & Development Service. NR 43 TC 1 Z9 1 U1 10 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JUL PY 2015 VL 16 IS 7 BP 1282 EP 1289 DI 10.1111/pme.12821 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CM9GY UT WOS:000358017000011 PM 26087225 ER PT J AU Accordino, RE Lucarelli, J Yan, AC AF Accordino, Robert E. Lucarelli, Jennifer Yan, Albert C. TI Cutaneous Disease in Autism Spectrum Disorder: A Review SO PEDIATRIC DERMATOLOGY LA English DT Review ID TUBEROUS SCLEROSIS; CANDIDATE GENE; ASSOCIATION; CHILDREN; HYPOMELANOSIS; ITO; MANIFESTATIONS; EXPERIENCES; POPULATION; SYMPTOMS AB Dermatologic comorbid symptoms and conditions in persons with autism spectrum disorder (ASD) are compelling for several reasons, including problems with tactile sensory dysfunction in this population, a large number of syndromes with dermatologic findings and high rates of autism, nutritional and hormonal problems in ASD and their dermatologic manifestations, and the potential for overrepresentation of dermatologic symptoms that are neurobehavioral in nature. The current article reviews the available literature on the prevalence of comorbid dermatologic symptoms and conditions in children with ASD and identifies strategies for diagnosing and managing cutaneous disease in this population. C1 [Accordino, Robert E.] Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. [Lucarelli, Jennifer] Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. [Yan, Albert C.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Sect Pediat Dermatol, Philadelphia, PA 19104 USA. RP Lucarelli, J (reprint author), Boston Childrens Hosp, Div Dev Med, Fegan 10,300 Longwood Ave, Boston, MA 02115 USA. EM Jennifer.lucarelli@childrens.harvard.edu NR 44 TC 0 Z9 0 U1 1 U2 2 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 JUL-AUG PY 2015 VL 32 IS 4 BP 455 EP 460 DI 10.1111/pde.12582 PG 6 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA CN1FJ UT WOS:000358163100027 PM 25824343 ER PT J AU Boyers, LN Karimkhani, C Guild, SR Dellavalle, RP AF Boyers, Lindsay N. Karimkhani, Chante Guild, Samantha R. Dellavalle, Robert P. TI Lessons from a Legislative Struggle to Ban Indoor Tanning for Children Younger than 18 SO PEDIATRIC DERMATOLOGY LA English DT Editorial Material C1 [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Guild, Samantha R.] AIM Melanoma, Richmond, CA USA. [Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, Denver, CO USA. [Dellavalle, Robert P.] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado Anschutz Med Campus, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), Dept Veteran Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu NR 8 TC 0 Z9 0 U1 0 U2 6 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 JUL-AUG PY 2015 VL 32 IS 4 BP 553 EP 556 DI 10.1111/pde.12491 PG 4 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA CN1FJ UT WOS:000358163100047 PM 26184402 ER PT J AU Paul, S Cheng, CE Kroshinsky, D AF Paul, Suchismita Cheng, Carol E. Kroshinsky, Daniela TI Combination Systemic Fluorouracil and Radiation for the Treatment of Recalcitrant Condyloma with Associated Squamous Cell Carcinoma in an Immunocompromised 15-Year-Old Girl SO PEDIATRIC DERMATOLOGY LA English DT Article ID WARTS; ACUMINATUM AB Condylomata acuminata (CA), or anogenital warts, are typically benign lesions caused by human papillomavirus infection. Although they are rare, immunocompromised individuals are at a higher risk of CA undergoing transformation into invasive anal squamous cell carcinoma (SCC). These patients need aggressive evaluation and management. Treatment of CA is challenging, particularly for immunocompromised hosts, in whom warts are resistant to treatment and commonly recur. Currently, there is no gold standard treatment for CA, especially in children and immunodeficient individuals. We report the case of a 15-year-old immunocompromised girl with severe recalcitrant condyloma that resolved after a course of systemic 5-fluorouracil, mitomycin C, and radiation therapy for SCC. C1 [Paul, Suchismita; Kroshinsky, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheng, Carol E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Paul, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM suchismita_paul@hms.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 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 JUL-AUG PY 2015 VL 32 IS 4 BP E148 EP E150 DI 10.1111/pde.12617 PG 3 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA CN1FJ UT WOS:000358163100004 PM 25940810 ER PT J AU Schnall, S Haidt, J Clore, GL Jordan, AH AF Schnall, Simone Haidt, Jonathan Clore, Gerald L. Jordan, Alexander H. TI Landy and Goodwin (2015) Confirmed Most of Our Findings Then Drew the Wrong Conclusions SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE LA English DT Editorial Material ID MORAL JUDGMENTS; DISGUST; MOOD; ATTENTION; EMOTION C1 [Schnall, Simone] Univ Cambridge, Cambridge CB2 3EB, England. [Haidt, Jonathan] New York Univ Stern Sch Business, New York, NY USA. [Clore, Gerald L.] Univ Virginia, Charlottesville, VA 22903 USA. [Jordan, Alexander H.] VA Boston Healthcare Syst, Boston, MA USA. [Jordan, Alexander H.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Schnall, S (reprint author), Univ Cambridge, Dept Psychol, Downing St,Off 406, Cambridge CB2 3EB, England. EM ss877@cam.ac.uk FU National Science Foundation [BCS-1252079] FX Gerald L. Chore wishes to acknowledge funding support from National Science Foundation Grant BCS-1252079. NR 17 TC 5 Z9 5 U1 3 U2 14 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1745-6916 EI 1745-6924 J9 PERSPECT PSYCHOL SCI JI Perspect. Psychol. Sci. PD JUL PY 2015 VL 10 IS 4 BP 537 EP 538 DI 10.1177/1745691615589078 PG 2 WC Psychology, Multidisciplinary SC Psychology GA CN0CU UT WOS:000358081000008 PM 26177952 ER PT J AU Bachhuber, MA McGinty, EE Kennedy-Hendricks, A Niederdeppe, J Barry, CL AF Bachhuber, Marcus A. McGinty, Emma E. Kennedy-Hendricks, Alene Niederdeppe, Jeff Barry, Colleen L. TI Messaging to Increase Public Support for Naloxone Distribution Policies in the United States: Results from a Randomized Survey Experiment SO PLOS ONE LA English DT Article ID OPIATE SUBSTITUTION TREATMENT; EMERGENCY MEDICAL-SERVICES; TAKE-HOME NALOXONE; OPIOID OVERDOSE; HEROIN OVERDOSE; INTRANASAL NALOXONE; SAN-FRANCISCO; DRUG-USERS; PREVENTION; DEATHS AB Background Barriers to public support for naloxone distribution include lack of knowledge, concerns about potential unintended consequences, and lack of sympathy for people at risk of overdose. Methods A randomized survey experiment was conducted with a nationally-representative web-based survey research panel (GfK KnowledgePanel). Participants were randomly assigned to read different messages alone or in combination: 1) factual information about naloxone; 2) pre-emptive refutation of potential concerns about naloxone distribution; and 3) a sympathetic narrative about a mother whose daughter died of an opioid overdose. Participants were then asked if they support or oppose policies related to naloxone distribution. For each policy item, logistic regression models were used to test the effect of each message exposure compared with the no-exposure control group. Results The final sample consisted of 1,598 participants (completion rate: 72.6%). Factual information and the sympathetic narrative alone each led to higher support for training first responders to use naloxone, providing naloxone to friends and family members of people using opioids, and passing laws to protect people who administer naloxone. Participants receiving the combination of the sympathetic narrative and factual information, compared to factual information alone, were more likely to support all policies: providing naloxone to friends and family members (OR: 2.0 [95% CI: 1.4 to 2.9]), training first responders to use naloxone (OR: 2.0 [95% CI: 1.2 to 3.4]), passing laws to protect people if they administer naloxone (OR: 1.5 [95% CI: 1.04 to 2.2]), and passing laws to protect people if they call for medical help for an overdose (OR: 1.7 [95% CI: 1.2 to 2.5]). Conclusions All messages increased public support, but combining factual information and the sympathetic narrative was most effective. Public support for naloxone distribution can be improved through education and sympathetic portrayals of the population who stands to benefit from these policies. C1 [Bachhuber, Marcus A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.; Barry, Colleen L.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.] Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. [McGinty, Emma E.; Kennedy-Hendricks, Alene; Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [McGinty, Emma E.; Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Niederdeppe, Jeff] Cornell Univ, Dept Commun, Ithaca, NY USA. RP Bachhuber, MA (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. EM marcus.bachhuber@gmail.com OI Bachhuber, Marcus/0000-0002-5610-8382 FU American International Group, Inc.; National Institute on Drug Abuse [R01DA026414] FX This work was funded by an unrestricted research grant from American International Group, Inc., and by the National Institute on Drug Abuse (R01DA026414). The funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. NR 49 TC 4 Z9 4 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 1 PY 2015 VL 10 IS 7 AR e0130050 DI 10.1371/journal.pone.0130050 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CN1CG UT WOS:000358153000050 PM 26132859 ER PT J AU Lange, DC Glidden, D Secemsky, EA Ordovas, K Deeks, SG Martin, JN Bolger, AF Hsue, PY AF Lange, David C. Glidden, David Secemsky, Eric A. Ordovas, Karen Deeks, Steven G. Martin, Jeffrey N. Bolger, Ann F. Hsue, Priscilla Y. TI Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals SO PLOS ONE LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; ALL-CAUSE MORTALITY; COMBINATION ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; INTIMA-MEDIA THICKNESS; VALVE CALCIFICATION; PROGNOSTIC VALUE; PREDICTIVE-VALUE; CALCIUM SCORE AB Background HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals. Methods and Results We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age-and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all). Conclusion In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death. C1 [Lange, David C.] Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. [Glidden, David] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Secemsky, Eric A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Ordovas, Karen] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV, AIDS Posit Hlth Program, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bolger, Ann F.; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. EM phsue@medsfgh.ucsf.edu FU National Heart, Lung and Blood Institute [RO1 HL095130, RO1 HL091526] FX This work was supported by the National Heart, Lung and Blood Institute RO1 HL095130 (P.Y.H.) and the National Heart, Lung and Blood Institute RO1 HL091526 (P.Y.H.). NR 49 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 1 PY 2015 VL 10 IS 7 AR e0130592 DI 10.1371/journal.pone.0130592 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CN1CG UT WOS:000358153000075 PM 26132465 ER PT J AU Kue, RC Temin, ES Weiner, SG Gates, J Coleman, MH Fisher, J Dyer, S AF Kue, Ricky C. Temin, Elizabeth S. Weiner, Scott G. Gates, Jonathan Coleman, Melissa H. Fisher, Jonathan Dyer, Sophia TI TOURNIQUET USE IN A CIVILIAN EMERGENCY MEDICAL SERVICES SETTING: A DESCRIPTIVE ANALYSIS OF THE BOSTON EMS EXPERIENCE SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE tourniquet; emergency medical services; trauma; hemorrhage ID HEMORRHAGE CONTROL; BATTLEFIELD; SURVIVAL; EVENTS; TRAUMA AB Introduction. Despite the resurgence of early tourniquet use for control of exsanguinating limb hemorrhage in the military setting, its appropriate role in civilian emergency medical services (EMS) has been less clear. Objective. To describe the experience of prehospital tourniquet use in an urban, civilian EMS setting. Methods. A retrospective review of EMS prehospital care reports was performed from January 1, 2005 to December 1, 2012. Data, including the time duration of prehospital tourniquet placement, EMS scene time, mechanisms of injury, and patient demographics, underwent descriptive analysis. Outcomes data for participating receiving hospitals were also reviewed. Results. Ninety-eight cases of prehospital tourniquet use were identified. The most common causes of injury were penetrating gunshot or stabbing wounds (67.4%, 66/98); 7.1% (7/98) of cases were due to blunt trauma; 23.5% (23/98) of cases were from non-traumatic hemorrhage related to uncontrolled hemodialysis shunt or wound bleeding; 45.4% (44/97) of cases were placed on a lower extremity; 54.6% (53/97) were placed on an upper extremity Placement was successful in hemorrhage control in 91% (87/95, 95%CI: 85.9-97.3%) of cases. The average prehospital tourniquet placement time was 14.9 minutes. Half of all tourniquet placements were performed by basic life support providers. Hospital follow-up was available for 96.9% (95/98) of cases. Of these, the tourniquet was removed by EMS in 3.2% (3/95), the emergency department in 54.7% (52/95), or in the operating room (OR) in 31.6% (30/95) of the time; 46.7% (14/30) of these OR cases had a documented vascular injury needing repair. Ten deaths with hospital follow-up data were identified, none of which were due to tourniquet use. There was one case of forearm numbness potentially due to nerve injury and one case with potential vascular complication, representing an overall complication rate of 2.1% (2/95). Conclusion. The early use of tourniquets for extremity hemorrhage in an urban civilian EMS setting appears to be safe, with complications occurring infrequently. C1 [Kue, Ricky C.] City Boston Emergency Med Serv, Boston, MA USA. [Kue, Ricky C.] Boston Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA. [Temin, Elizabeth S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Weiner, Scott G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Gates, Jonathan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc & Endovascular Surg,Trauma Burns & Surg, Boston, MA 02115 USA. [Coleman, Melissa H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Trauma Burns & Surg Crit Care, Boston, MA 02115 USA. [Fisher, Jonathan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Emergency Med, Boston, MA 02215 USA. RP Kue, RC (reprint author), Boston Emergency Med Serv, Res Training & Qual Improvement Div, 785 Albany St, Boston, MA 02118 USA. EM KUE@bostonems.org NR 23 TC 17 Z9 17 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1090-3127 EI 1545-0066 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PD JUL-SEP PY 2015 VL 19 IS 3 BP 399 EP 404 DI 10.3109/10903127.2014.995842 PG 6 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA CN1OL UT WOS:000358189200007 PM 25665102 ER PT J AU Traeger, L AF Traeger, Lara TI Developing a quantitative analytic plan that corresponds to study aims and design SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Traeger, Lara] 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA S5-1 BP 9 EP 10 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000018 ER PT J AU Greer, J AF Greer, Joseph TI Applications of behavioral theory and conceptual models in supportive oncology research SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Greer, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA S5-3 BP 10 EP 10 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000020 ER PT J AU Temel, J AF Temel, Jennifer TI Performing a successful supportive care clinical trial SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Temel, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA S5-2 BP 10 EP 10 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000019 ER PT J AU Patenaude, AF AF Patenaude, Andrea Farkas TI Prophylactic mastectomy decision-making: what help do women need? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Patenaude, Andrea Farkas] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA S8-4 BP 17 EP 17 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000032 ER PT J AU Recklitis, C AF Recklitis, Christopher TI Surviving cancer but succumbing to suicide: what explains the risk in long-term survivors? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Recklitis, Christopher] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 JUL PY 2015 VL 24 SU 2 SI SI MA S11-1 BP 18 EP 19 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000036 ER PT J AU Park, E Perez, G Hyland, K Ostroff, J AF Park, Elyse Perez, Giselle Hyland, Kelly Ostroff, Jamie TI Integrating tobacco treatment into Cancer Care: details of implementation SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Park, Elyse] Mass Gen Hosp, Boston, MA USA. [Perez, Giselle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hyland, Kelly] MGH, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA S19-3 BP 33 EP 34 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000063 ER PT J AU Semmel, E Salley, C Hewitt, L Gerhardt, CA Patenaude, AF Vannatta, KA AF Semmel, Eric Salley, Christina Hewitt, Larissa Gerhardt, Cynthia A. Patenaude, Andrea Farkas Vannatta, Kathryn A. TI Deficits in executive functioning and effortful control: explaining emotional adjustment in pediatric brain tumor survivors (PBTS) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Semmel, Eric; Gerhardt, Cynthia A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. [Salley, Christina] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Hewitt, Larissa; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA USA. Res Inst Nationwide Childrens, Columbus, OH USA. 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA D-4 BP 49 EP 50 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000092 ER PT J AU Meyer, F Farrell, E Yuppa, D AF Meyer, Fremonta Farrell, Elizabeth Yuppa, David TI When ethical dilemmas split teams: case studies of fertility preservation in the context of metastatic cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Meyer, Fremonta; Farrell, Elizabeth; Yuppa, David] Dana Farber Canc Inst, Boston, MA USA. 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA K-1 BP 64 EP 65 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000117 ER PT J AU Souza, P Fasciano, K Camuso, K AF Souza, Phoebe Fasciano, Karen Camuso, Kristen TI Improving the quality of psychosocial care for young adults in medical oncology SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Souza, Phoebe; Fasciano, Karen; Camuso, Kristen] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA Q-2 BP 77 EP 78 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000140 ER PT J AU Stagl, J Lechner, S Carver, C Bouchard, L Gudenkauf, L Jutagir, D Diaz, A Yu, QL Blomberg, B Ironson, G Gluck, S Antoni, M AF Stagl, Jamie Lechner, Suzanne Carver, Charles Bouchard, Laura Gudenkauf, Lisa Jutagir, Devika Diaz, Alain Yu, Qilu Blomberg, Bonnie Ironson, Gail Glueck, Stefan Antoni, Michael TI A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Stagl, Jamie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Lechner, Suzanne] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Carver, Charles; Bouchard, Laura; Gudenkauf, Lisa; Jutagir, Devika; Diaz, Alain; Blomberg, Bonnie; Ironson, Gail; Antoni, Michael] Univ Miami, Coral Gables, FL 33124 USA. [Yu, Qilu] Westat Corp, Rockville, MD USA. [Glueck, Stefan] Celgene Corp, Summit, NJ 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA U-1 BP 86 EP 87 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000154 ER PT J AU Park, E Perez, G Goldman, R Foxtree-McGrath, C Yang, MS Suarez, J Mutchler, J AF Park, Elyse Perez, Giselle Goldman, Roberta Foxtree-McGrath, Cheyenne Yang, Mai See Suarez, July Mutchler, Jan TI Development of a resiliency program for interpreters in cancer care SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Park, Elyse] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Perez, Giselle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yang, Mai See; Suarez, July; Mutchler, Jan] Univ Massachusetts Boston, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA X-2 BP 94 EP 94 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000167 ER PT J AU Fujisawa, D Temel, J Traeger, L Greer, J Lennes, I Mimura, M Pirl, W AF Fujisawa, Daisuke Temel, Jennifer Traeger, Lara Greer, Joseph Lennes, Inga Mimura, Masaru Pirl, William TI Psychological Factors at Early Stage of Treatment as Predictors of Receiving Chemotherapy at End of Life SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Fujisawa, Daisuke; Mimura, Masaru] Keio Univ, Sch Med, Tokyo 108, Japan. [Temel, Jennifer; Traeger, Lara; Greer, Joseph; Lennes, Inga; Pirl, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-11 BP 109 EP 109 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000192 ER PT J AU Landa-Ramirez, E Greer, J Riveros-Rosas, A Cardenas-Lopez, G Vite-Sierra, A Sanchez-Roman, S Salado-Avila, MM Templos-Esteban, LA AF Landa-Ramirez, Edgar Greer, Joseph Riveros-Rosas, Angelica Cardenas-Lopez, Georgina Vite-Sierra, Ariel Sanchez-Roman, Sofia Salado-Avila, Ma. Magdalena Templos-Esteban, Luz Adriana TI Brief Home-based Cognitive Behavioral Therapy on Depression and Anxiety in Mexicans Patients with Terminal Cancer: A Single-case Research SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Landa-Ramirez, Edgar] Univ Nacl Autonoma Mexico, Behav Med Program, Fac Psychol, Mexico City, DF, Mexico. [Greer, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Riveros-Rosas, Angelica; Cardenas-Lopez, Georgina; Vite-Sierra, Ariel] Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico. [Sanchez-Roman, Sofia] Inst Nacl Ciencias Med & Nutr INCMNSZ, Mexico City, DF, Mexico. [Salado-Avila, Ma. Magdalena; Templos-Esteban, Luz Adriana] Hosp Gen Dr Manuel Gea Gonzalez, Ciudad De Mexico, DF, Mexico. NR 0 TC 0 Z9 0 U1 4 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 JUL PY 2015 VL 24 SU 2 SI SI MA P1-71 BP 142 EP 142 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000252 ER PT J AU Irwin, K Park, E Henderson, D Pirl, W AF Irwin, Kelly Park, Elyse Henderson, David Pirl, William TI Schizophrenia and Lung Cancer Disparities: Eligibility for Screening and Access to Smoking Cessation SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Irwin, Kelly; Henderson, David; Pirl, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Park, Elyse] Mass Gen Hosp, Boston, MA 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-119 BP 167 EP 167 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000297 ER PT J AU Stagl, J Fujisawa, D Greer, J Traeger, L El-Jawahri, A Temel, J Pirl, W AF Stagl, Jamie Fujisawa, Daisuke Greer, Joseph Traeger, Lara El-Jawahri, Areej Temel, Jennifer Pirl, William TI Daytime Physical Activity and Emotional Distress in Advanced NSCLC Patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Stagl, Jamie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Fujisawa, Daisuke] Keio Univ, Sch Med, Tokyo 108, Japan. [Greer, Joseph; Traeger, Lara; El-Jawahri, Areej; Temel, Jennifer; Pirl, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-131 BP 173 EP 174 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000309 ER PT J AU Samsel, C Loucas, C Muriel, A AF Samsel, Chase Loucas, Caitlyn Muriel, Anna TI Treatment of Steroid-induced Mood Disorder in Co-morbid Developmentally Delayed Youth with Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Samsel, Chase] Dana Farber & Boston Childrens Hosp, Canc & Blood Disorders Ctr, Boston, MA USA. [Loucas, Caitlyn; Muriel, Anna] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-134 BP 175 EP 176 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000312 ER PT J AU de Arruda-Colli, MNF Zadeh, S Muriel, A Pellentier, W Wiener, L AF de Arruda-Colli, Marina Noronha Ferraz Zadeh, Sima Muriel, Anna Pellentier, Wendy Wiener, Lori TI In Good Times and in Bad: What Strengthens a Parental Relationship during a Child's Cancer Trajectory? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [de Arruda-Colli, Marina Noronha Ferraz; Zadeh, Sima; Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA. [Muriel, Anna] Dana Farber Canc Inst, Boston, MA USA. [Pellentier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-155 BP 185 EP 185 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000331 ER PT J AU Zhou, E Partridge, A Blackmon, J Morgan, E Recklitis, C AF Zhou, Eric Partridge, Ann Blackmon, Jaime Morgan, Evan Recklitis, Christopher TI Feasibility of an iPad-administered Group-based Stress Management Intervention SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zhou, Eric; Partridge, Ann; Blackmon, Jaime; Morgan, Evan; Recklitis, Christopher] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-179 BP 197 EP 198 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000355 ER PT J AU Zhou, E Partridge, A Recklitis, C AF Zhou, Eric Partridge, Ann Recklitis, Christopher TI Delivering an Adapted Group Cognitive Behavioral Treatment for Insomnia in a Cancer Survivorship Program SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zhou, Eric; Partridge, Ann; Recklitis, Christopher] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-180 BP 198 EP 198 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000356 ER PT J AU Tucker-Seeley, R Miller, M Gagne, J AF Tucker-Seeley, Reginald Miller, Melecia Gagne, Joshua TI Household Financial Well-being and Navigating Cancer Care: A Qualitative Study of Conceptualizing Financial Well-being among Social Workers and Resource Specialists SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Tucker-Seeley, Reginald] Harvard Univ, Chan Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Miller, Melecia; Gagne, Joshua] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P1-217 BP 218 EP 218 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000392 ER PT J AU Carr, A Traeger, L Cashavelly, B Pirl, W AF Carr, Alaina Traeger, Lara Cashavelly, Barbara Pirl, William TI Inpatient Acute Medical Oncology Registered Nurses: Challenges and Sources of Support SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Carr, Alaina; Traeger, Lara; Cashavelly, Barbara; Pirl, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-42 BP 251 EP 252 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000454 ER PT J AU Braun, I AF Braun, Ilana TI Systematic Review of Marijuana's Medicinal Aspects SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Braun, Ilana] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 JUL PY 2015 VL 24 SU 2 SI SI MA P2-46 BP 253 EP 254 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000458 ER PT J AU Loucas, C Brand, S Wiener, L Zadeh, S AF Loucas, Caitlyn Brand, Sarah Wiener, Lori Zadeh, Sima TI Preparing Youth with Cancer for Amputation: A Systematic Review SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Loucas, Caitlyn; Brand, Sarah] Dana Farber Canc Inst, Boston, MA USA. [Wiener, Lori; Zadeh, Sima] NCI, NIH, Bethesda, MD 20892 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-60 BP 261 EP 261 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000472 ER PT J AU Muriel, A Loucas, C White, M AF Muriel, Anna Loucas, Caitlyn White, Matthew TI Psychosocial Screening and Predictors of Mood Disturbance in Parents of children with Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Muriel, Anna; Loucas, Caitlyn] Dana Farber Canc Inst, Boston, MA USA. [White, Matthew] Boston Childrens Hosp, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-98 BP 279 EP 280 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000509 ER PT J AU Meyer, F Braun, I AF Meyer, Fremonta Braun, Ilana TI Impact of Fertility Preservation on Psychological Outcomes in Cancer Patients and Survivors: A Systematic Review SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Meyer, Fremonta; Braun, Ilana] Dana Farber Canc Inst, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-151 BP 308 EP 309 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000562 ER PT J AU Perez, G Kirchhoff, A Krull, K Leisenring, W Recklitis, C Armstrong, G Nathan, P Robison, L Kuhlthau, K Park, E AF Perez, Giselle Kirchhoff, Anne Krull, Kevin Leisenring, Wendy Recklitis, Christopher Armstrong, Gregory Nathan, Paul Robison, Leslie Kuhlthau, Karen Park, Elyse TI Mental Health Care Insurance Coverage, Utilization, and Perceived Value among Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study (CCSS) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Perez, Giselle; Kuhlthau, Karen; Park, Elyse] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirchhoff, Anne] Huntsman Canc Inst, Salt Lake City, UT USA. [Krull, Kevin; Armstrong, Gregory; Robison, Leslie] St Jude Childrens Res Hosp, Memphis, TN USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Memphis, TN USA. [Recklitis, Christopher] Dana Farber Canc Inst, Boston, MA USA. [Nathan, Paul] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-154 BP 310 EP 310 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000565 ER PT J AU Hyland, K Stagl, J Lennes, I Pirl, W Perez, G Park, E AF Hyland, Kelly Stagl, Jamie Lennes, Inga Pirl, William Perez, Giselle Park, Elyse TI What Cancer Survivors Want in Survivorship Care: A Qualitative Exploration of Preferences for Information and Resources SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Hyland, Kelly; Lennes, Inga; Pirl, William; Perez, Giselle; Park, Elyse] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stagl, Jamie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2015 VL 24 SU 2 SI SI MA P2-163 BP 315 EP 315 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000574 ER PT J AU Nisotel, L Fishbein, J MacDonald, J Amoyal, N Greer, J AF Nisotel, Lauren Fishbein, Joel MacDonald, James Amoyal, Nicole Greer, Joseph TI A Systematic Review of Interventions for Adherence to Oral Chemotherapy in Patients with Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Nisotel, Lauren; Fishbein, Joel; MacDonald, James; Amoyal, Nicole] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Greer, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 JUL PY 2015 VL 24 SU 2 SI SI MA P2-180 BP 325 EP 325 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN2MG UT WOS:000358255000591 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Untitled SO SPINE LA English DT Letter C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Dept Anesthesiol & Perioperat Med, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Dept Anesthesiol & Perioperat Med, Paducah, KY 42003 USA. NR 3 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 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUL 1 PY 2015 VL 40 IS 13 BP 1054 EP 1054 DI 10.1097/BRS.0000000000000950 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CM8JJ UT WOS:000357946000014 PM 25909349 ER PT J AU Katon, JG Washington, DL Cordasco, KM Reiber, GE Yano, EM Zephyrin, LC AF Katon, Jodie G. Washington, Donna L. Cordasco, Kristina M. Reiber, Gayle E. Yano, Elizabeth M. Zephyrin, Laurie C. TI Prenatal Care for Women Veterans Who Use Department of Veterans Affairs Health Care SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PRETERM BIRTH; MEDICAL-CENTER; MENTAL-HEALTH; VA; PREGNANCY; RISK; AVAILABILITY; AFGHANISTAN; DEPRESSION AB Objective: The number of women Veterans of childbearing age enrolling in Department of Veterans Affairs (VA) health care is increasing. Our objective was to describe characteristics of women veterans and resumption of VA care after delivery by use of VA prenatal benefits. Study design: We used data from the National Survey of Women Veterans, a population-based survey. VA-eligible women veterans with at least one live birth who had ever used VA and were younger than 45 years when VA pre-natal benefits became available were categorized based on self-reported receipt of VA prenatal benefits. Characteristics of by use of VA prenatal benefits were compared using chi(2) tests with Rao-Scott adjustment. All analyses used sampling weights. Results: In our analytic sample, of those who potentially had the opportunity to use VA prenatal benefits, 25% used these benefits and 75% did not. Compared with women veterans not using VA prenatal benefits, those who did were more likely to be 18 to 24 years old (39.9% vs. 3.7%; p = .03), and more likely to have self-reported diagnosed depression (62.5% vs. 24.5%; p = .02) and current depression or posttraumatic stress disorder (PTSD) symptoms (depression, 46.1% vs. 8% [ p - .02]; PTSD, 52.5% vs. 14.8% [ p - .02]). Compared with women veterans not using VA prenatal benefits, those who did were more likely to resume VA use after delivery (p < .001). Conclusion: Pregnant women veterans who use VA prenatal benefits are a high-risk group. Among those who opt not to use these benefits, pregnancy is an important point of attrition from VA health care, raising concerns regarding retention of women veterans within VA and continuity of care. Published by Elsevier Inc. C1 [Katon, Jodie G.; Reiber, Gayle E.] VA Med Ctr, HSR&D, Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Katon, Jodie G.; Zephyrin, Laurie C.] VA Cent Off, Womens Vet Hlth Serv, Off Patient Serv, Washington, DC USA. [Katon, Jodie G.; Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Washington, Donna L.; Cordasco, Kristina M.; Yano, Elizabeth M.] VA Greater Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implement &, North Hills, CA USA. [Washington, Donna L.; Cordasco, Kristina M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Zephyrin, Laurie C.] NYU, Dept Obstet & Gynecol, Langone Sch Med, New York, NY 10016 USA. RP Katon, JG (reprint author), VA Med Ctr, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM jkaton@u.washington.edu FU Department of Veterans Affairs (VA), Women's Health Services in the Office of Patient Care Services; Health Services Research and Development (HSRD) Service [SDR-08-270]; Office of Academic Affiliations' Associated Health Postdoctoral Fellowship [TTP 61-026]; VA HSR&D Senior Research Career Scientist awards [RCS-98-353, RCS-05-195] FX This study used data from the National Survey of Women Veterans, which was funded by the Department of Veterans Affairs (VA), Women's Health Services in the Office of Patient Care Services and the Health Services Research and Development (HSR&D) Service (#SDR-08-270). Dr. Katon was supported by an Office of Academic Affiliations' Associated Health Postdoctoral Fellowship (#TTP 61-026). Drs. Reiber (#RCS-98-353) and Yano (#RCS-05-195) are supported by VA HSR&D Senior Research Career Scientist awards. The authors gratefully acknowledge Su Sun Mor for data analysis support and Mark Canning for project management. NR 24 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2015 VL 25 IS 4 BP 377 EP 381 DI 10.1016/j.whi.2015.03.004 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7HK UT WOS:000358604800010 PM 25935821 ER PT J AU Slane, JD Levine, MD AF Slane, Jennifer D. Levine, Michele D. TI Association of Restraint and Disinhibition to Gestational Weight Gain among Pregnant Former Smokers SO WOMENS HEALTH ISSUES LA English DT Article ID POSTPARTUM SMOKING RELAPSE; BODY-MASS INDEX; DIETARY RESTRAINT; EATING BEHAVIORS; WOMEN; CESSATION; BIRTH; INTERVENTIONS; MANAGEMENT; BRAZIL AB Introduction: Gaining excessive weight during pregnancy is associated with immediate maternal and fetal complications as well as longer term obesity. Prepregnancy body mass index, age, and smoking cessation have been related to gestational weight gain (GWG); however, less is known about how eating behaviors, that may be amenable to modification and have been related to weight gain outside of pregnancy, affect GWG. Methods: The present study evaluated the relationship of dietary restraint and disinhibition to GWG in a sample of women (n = 248) who quit smoking before or early in pregnancy. Women self-reported height and prepregnancy weight during their third trimester. GWG was calculated by subtracting prepregnancy weight from third trimester weight. The Three-Factor Eating Questionnaire assessed restraint and disinhibition. Results: Average GWG was 14.60 (+/- 7.64) kg and 47% of women had a GWG greater than the Institute of Medicine recommendations. Linear regression models were used to examine restraint and disinhibition as correlates of GWG, and multinomial logistic regressions were utilized to determine whether eating behaviors were associated with inadequate or excessive GWG. Restraint was associated positively with total GWG, but disinhibition was not associated with GWG. Thus, conscious attempts to restrict intake were associated with GWG beyond the influence of covariates. Conclusion: These findings highlight the potential influence of modifiable eating behaviors on GWG and demonstrate the need for additional research to determine how these behaviors relate to GWG over the course of pregnancy. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Slane, Jennifer D.] VA Pittsburgh Healthcare Syst, VISN 4 Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Slane, Jennifer D.; Levine, Michele D.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Levine, MD (reprint author), Univ Pittsburgh, Med Ctr, 3811 OHara St, Pittsburgh, PA 15213 USA. EM levinem@upmc.edu FU NIH [K01 DA15396, R01 DA021608] FX NIH grants: K01 DA15396 and R01 DA021608; PI: Michele Levine, PhD. The authors do not have any financial conflicts of interest to disclose. This material is the result of work supported, in part, with resources and the use of facilities at the VISN 4 Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 33 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 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2015 VL 25 IS 4 BP 390 EP 395 DI 10.1016/j.whi.2015.03.005 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7HK UT WOS:000358604800012 PM 26048757 ER PT J AU Drapkin, ML Eddie, D Buffington, AJ McCrady, BS AF Drapkin, Michelle L. Eddie, David Buffington, Angela J. McCrady, Barbara S. TI Alcohol-Specific Coping Styles of Adult Children of Individuals with Alcohol Use Disorders and Associations with Psychosocial Functioning SO ALCOHOL AND ALCOHOLISM LA English DT Article ID PARENTAL ALCOHOL; COMMUNITY SAMPLE; FAMILY-HISTORY; YOUNG-ADULTS; PERSONALITY; DRUG; LIFE; DRINKING; EVENTS; SYMPTOMATOLOGY AB Parental alcohol use disorders (AUDs) have been conceptualized as a chronic stressor that can lead to deleterious long-term outcomes in children of individuals with AUDs. Yet, while many individuals are detrimentally affected by their parents' problematic alcohol use, and go on to manifest psychological problems, others do not. How individuals cope with the stress of having a parent with an AUD is believed to be an important moderator of this differential outcome. This study assessed whether individuals' alcohol-specific coping styles predicted alcohol use, positive or negative life events, and depression, using a sample of 465 college students, of whom 20% were adult children of individuals with alcohol use disorders, colloquially known as adult children of alcoholics (ACOAs), and a battery of well-validated, self-report measures. Participant ACOAs reported less 'engaged' and 'total' alcohol-specific coping strategies and more 'withdrawal' alcohol-specific coping strategies than their non adult children of alcoholics (NACOAs) counterparts. Across participants, women reported more 'engaged', 'tolerant/inactive', and 'total' coping than men. Although ACOAs reported significantly more negative life events, which predicted more passive coping styles, they did not differ significantly from NACOAs on measures of problematic alcohol use or depression, supporting theories of resilience in ACOAs regardless of their alcohol-specific coping styles. For NACOAs, 'tolerant' coping predicted greater depression and alcohol-related problems; 'engaged' coping predicted fewer alcohol problems. Results suggest that ACOAs cope differently with problematic alcohol use among relatives and friends compared with NACOAs and are more likely to experience negative life events. Additionally, alcohol-related coping strategies have more predictive utility in NACOAs than ACOAs. C1 [Drapkin, Michelle L.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Drapkin, Michelle L.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Eddie, David] Rutgers State Univ, Ctr Alcohol Studies, New Brunswick, NJ USA. [Buffington, Angela J.] Fielding Grad Univ, Sch Psychol, Santa Barbara, CA USA. [McCrady, Barbara S.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. RP Drapkin, ML (reprint author), Univ Penn, Dept Psychiat, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. EM michelledrapkin@gmail.com NR 39 TC 0 Z9 0 U1 4 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL-AUG PY 2015 VL 50 IS 4 BP 463 EP 469 DI 10.1093/alcalc/agv023 PG 7 WC Substance Abuse SC Substance Abuse GA CM7JF UT WOS:000357867100014 PM 25802055 ER PT J AU Spracklen, CN Saftlas, AF Triche, EW Bjonnes, A Keating, B Saxena, R Breheny, PJ Dewan, AT Robinson, JG Hoh, J Ryckman, KK AF Spracklen, Cassandra N. Saftlas, Audrey F. Triche, Elizabeth W. Bjonnes, Andrew Keating, Brendan Saxena, Richa Breheny, Patrick J. Dewan, Andrew T. Robinson, Jennifer G. Hoh, Josephine Ryckman, Kelli K. TI Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; dyslipidemia; genetic epidemiology; genetic risk score; hypertension; preeclampsia ID GENOME-WIDE ASSOCIATION; METAANALYSIS; HYPERTENSION; ECLAMPSIA; PREGNANCY; COMMON; WOMEN; PATHOGENESIS; POPULATION; VARIANTS AB BACKGROUND Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. METHODS Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. RESULTS The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). CONCLUSIONS Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. C1 [Spracklen, Cassandra N.; Saftlas, Audrey F.; Robinson, Jennifer G.; Ryckman, Kelli K.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. [Triche, Elizabeth W.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Bjonnes, Andrew; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bjonnes, Andrew; Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bjonnes, Andrew; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Keating, Brendan] Univ Penn, Perelman Sch Med, Penn Transplant Inst, Dept Surg, Philadelphia, PA 19104 USA. [Keating, Brendan] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Breheny, Patrick J.] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Dewan, Andrew T.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Hoh, Josephine] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA. RP Ryckman, KK (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. EM kelli-ryckman@uiowa.edu FU National Institute of Child Health and Human Development, National Institutes of Health [R01 HD32579]; Verto Institute; Gertie Marx Grant from the Society for Obstetric Anesthesia and Perinatology FX The SOPHIA study was supported by the National Institute of Child Health and Human Development, National Institutes of Health (R01 HD32579), and the Verto Institute. The replication study was funded in part by a Gertie Marx Grant from the Society for Obstetric Anesthesia and Perinatology. NR 37 TC 4 Z9 4 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUL PY 2015 VL 28 IS 7 BP 915 EP 923 DI 10.1093/ajh/hpu242 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CM7JC UT WOS:000357866800011 PM 25523295 ER PT J AU Orlov, S Cherney, DZI Pop-Busui, R Lovblom, LE Ficociello, LH Smiles, AM Warram, JH Krolewski, AS Perkins, BA AF Orlov, Steven Cherney, David Z. I. Pop-Busui, Rodica Lovblom, Leif E. Ficociello, Linda H. Smiles, Adam M. Warram, James H. Krolewski, Andrzej S. Perkins, Bruce A. TI Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; HEART-RATE-VARIABILITY; BLOOD-PRESSURE; UNITED-STATES; MICROALBUMINURIA; DYSFUNCTION; RISK; KIDNEY; COMPLICATIONS; ALBUMINURIA AB Background and objectives Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship withearly progressive renal decline in type 1 diabetes. Design, setting, participants, & measurements A subset of participants with normoalbuminutia (n=204) or microalbumimuia (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) <20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C <-3.3%/year) and incident advanced CKD (stage >= 3 defined by eGFR [calculated by Modification of Diet in Renal Disease method] <60 ml/min per 1.73 m(2)). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards. Results Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68(18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P<0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P<0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002). Conclusions Cardiac autonomic neuropathy was a strong independent predictor of the long-term risk of early progressive renal decline in type 1 diabetes. Future research should explore the mechanisms by which autonomic neuropathy may be associated with renal function loss. C1 [Orlov, Steven; Lovblom, Leif E.; Perkins, Bruce A.] Univ Toronto, Dept Med, Mt Sinai Hosp, Div Endocrinol & Metab, Toronto, ON M5T 3L9, Canada. [Cherney, David Z. I.] Univ Toronto, Toronto Gen Hosp, Div Nephrol, Toronto, ON M5T 3L9, Canada. [Pop-Busui, Rodica] Univ Michigan, Univ Michigan Hlth Syst, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Ficociello, Linda H.; Smiles, Adam M.; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Res Div,Dept Med, Boston, MA 02115 USA. RP Perkins, BA (reprint author), Univ Toronto, Leadership Sinai Ctr Diabet, Mt Sinai Hosp, Div Endocrinol & Metab, L5-210,60 Murray St,Mail Box 16, Toronto, ON M5T 3L9, Canada. EM bperkins@mtsinai.on.ca FU National Institutes of Health [R01-DK41526]; University of Toronto Internal Medicine Program FX This research was supported by the National Institutes of Health grant (R01-DK41526) to A.S.K. S.O. was supported by a Residency Research Elective from the University of Toronto Internal Medicine Program. NR 49 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2015 VL 10 IS 7 BP 1136 EP 1144 DI 10.2215/CJN.11441114 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CM5UJ UT WOS:000357754200007 PM 26092828 ER PT J AU Lakkis, FG Palevsky, PM AF Lakkis, Fadi G. Palevsky, Paul M. TI A New CJASN Series: Renal Immunology for the Clinician SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Lakkis, Fadi G.] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Lakkis, Fadi G.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Lakkis, Fadi G.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Lakkis, Fadi G.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Palevsky, PM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Mail Stop 111 F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM ppalevsky@cjasn.org OI Palevsky, Paul/0000-0002-7334-5400 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2015 VL 10 IS 7 BP 1273 EP 1273 DI 10.2215/CJN.03870415 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CM5UJ UT WOS:000357754200020 PM 26153102 ER PT J AU Haggerty, G Siefert, CJ Sinclair, SJ Zodan, J Babalola, R Blais, MA AF Haggerty, Greg Siefert, Caleb J. Sinclair, Samuel J. Zodan, Jennifer Babalola, Ronke Blais, Mark A. TI Validation of a Measure of Alliance for an Adolescent Inpatient Setting SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Adolescents; Alliance; Inpatient; I-TAS; SOS-10 ID THERAPEUTIC ALLIANCE; MENTAL-HEALTH; PSYCHOTHERAPY AB The link between alliance and treatment outcome is robust. Nevertheless, few, if any, self-report measures exist to assess the alliance between hospitalized adolescents and their treatment team as a whole. The present study looks to extend the use of a brief self-report measure of inpatient treatment alliance designed for adult inpatients to be used with adolescents. The scale is designed incorporating items that tap the three factors of alliance (bond, goals and collaboration) to assess the alliance that the patient has with his or her treatment team. Our results show that the Inpatient-Treatment Alliance Scale is unifactoral, shows good psychometrics and is linked in theoretically meaningful ways to global clinician ratings of engagement in individual psychotherapy. Copyright (c) 2014 John Wiley & Sons, Ltd. Key Practitioner Message Inpatient treatment of adolescents requires the assessment of alliance to be between the patient and his or her treatment team rather than an individual clinician. Assessment of the alliance can benefit clinicians treating hospitalized adolescents especially because these patients are difficult to engage with in treatment. This study shows that the Inpatient-Treatment Alliance Scale is a promising measure for assessing treatment alliance on an adolescent inpatient setting. C1 [Haggerty, Greg; Zodan, Jennifer; Babalola, Ronke] Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, Massapequa Pk, NY 11762 USA. [Siefert, Caleb J.] Univ Michigan, Dearborn, MI 48128 USA. [Sinclair, Samuel J.; Blais, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Haggerty, G (reprint author), Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, 320 1st Ave, Massapequa Pk, NY 11762 USA. EM Ghag541@aol.com FU American Psychoanalytic Association; National Institute of Mental Health Grant [1R21MH097781-01A1] FX This study was funded in part by a grant awarded to the first author from the American Psychoanalytic Association and by the National Institute of Mental Health Grant No. 1R21MH097781-01A1 received by the first author. NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1063-3995 EI 1099-0879 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD JUL-AUG PY 2015 VL 22 IS 4 BP 357 EP 363 DI 10.1002/cpp.1901 PG 7 WC Psychology, Clinical SC Psychology GA CM8OQ UT WOS:000357961900006 PM 24771710 ER PT J AU Nguyen, T Alsarraj, A El-Serag, HB AF Nguyen, T. Alsarraj, A. El-Serag, H. B. TI Brief report: the length of newly diagnosed Barrett's esophagus may be decreasing SO DISEASES OF THE ESOPHAGUS LA English DT Article DE Barrett's esophagus; epidemiological study; esophageal adenocarcinoma; length; risk factor; Veterans Affair ID HIGH-GRADE DYSPLASIA; RISK-FACTORS; PRAGUE C; ADENOCARCINOMA; THERAPY; TRENDS; METAANALYSIS; VALIDATION; CRITERIA; CANCER AB Few studies have examined the temporal trends of length in newly diagnosed Barrett's esophagus (BE) and arrived at conflicting results. The aim of this study was to identify whether there has been a change over time in the length of BE at the time of diagnosis. This is a retrospective, single-center, observational study from Houston, Texas on newly diagnosed BE between 2008 and 2013. All cases were defined by the presence of endoscopically visible BE and histologic confirmation of intestinalized columnar epithelium with goblet cells. The length of BE was measured using the Prague classification. We examined temporal changes in 1-year intervals in the length of BE at the time of diagnosis. Both the frequency and mean length of BE at diagnosis seemed to decrease over time from February 2008 to July 2013. The proportion of patients diagnosed with BE 3cm per year declined during the study period, while the proportion of patients with BE 1 and <3cm increased, and those with <1cm remained stable. The mean age and the gender of patients diagnosed with BE 3cm did not differ significantly by BE length or year of diagnosis. The mean length of newly diagnosed BE may be decreasing as a result of a decline in BE 3cm. These observations cannot be explained by changes in age and gender. C1 [Nguyen, T.; El-Serag, H. B.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [El-Serag, H. B.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [El-Serag, H. B.] Baylor Coll Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Nguyen, T.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.edu FU VA HSR&D Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, TX, USA [CIN 13-413] FX This research reported here was supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX, USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 EI 1442-2050 J9 DIS ESOPHAGUS JI Dis. Esophagus PD JUL PY 2015 VL 28 IS 5 BP 418 EP 421 DI 10.1111/dote.12216 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CM8LY UT WOS:000357954000003 PM 24708395 ER PT J AU Taudorff, EH Lerche, CM Vissing, AC Philipsen, PA Hannibal, J D'Alvise, J Hansen, SH Janfelt, C Paasch, U Anderson, RR Haedersdal, M AF Taudorff, Elisabeth Hjardem Lerche, Catharina Margrethe Vissing, Anne-Cathrine Philipsen, Peter Alshede Hannibal, Jens D'Alvise, Janina Hansen, Steen Honore Janfelt, Christian Paasch, Uwe Anderson, Richard Rox Haedersdal, Merete TI Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation SO EXPERT OPINION ON DRUG DELIVERY LA English DT Article DE desorption electro-spray ionization mass spectrometry imaging; fluorescence microscopy; fractional erbium laser; franz skin permeability cells; high performance liquid chromatography; laser-assisted drug delivery ID IONIZATION MASS-SPECTROMETRY; ASSISTED DRUG-DELIVERY; HISTOLOGICAL-EVALUATION; PSORIASIS-VULGARIS; IN-VIVO; GEL; METABOLITES; TISSUE AB Objectives: Methotrexate (MTX) is a chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects. This study investigated kinetics and biodistribution of MTX delivered topically by ablative fractional laser (AFXL). Methods: In vitro passive diffusion of 10 mg/ml MTX (1 w/v%) was measured from 0.25 to 24 h through AFXL-processed and intact porcine skin in Franz Cells (n = 46). A 2,940 nm fractional Erbium Yttrium Aluminium Garnet laser generated mid-dermal microchannels at 2.4% density, and 256 mJ/microchannel. HPLC quantified MTX-concentrations in extracts from mid-dermal skin sections, donor and receiver compartments. Fluorescence microscopy of UVC-activated MTX-fluorescence and desorption electro-spray ionization mass spectrometry imaging (DM-MSI) evaluated MTX biodistribution. Results: AFXL-processed skin facilitated rapid MTX delivery through cone-shaped nnicrochannels of 690 pm ablation depth, lined by the 47 mu m thermal coagulation zone (CZ). Quantitatively, MIX was detectable by HPLC in mid-dermis after 15 min, significantly exceeded deposition in intact skin after 1.5 h, and saturated skin after 7 h at a 10-fold increased MTX-deposition versus intact skin (3.08 vs 0.30 mg/cm(3), p = 0.002). Transdermal permeation was < 1.5% of applied MTX before skin saturation, and increased up to 8.0% after 24 h. Qualitatively, MTX distributed into CZ within 15 min (p = 0.015) and further into surrounding dermal tissue after 1.5 h (p = 0.004). After skin saturation at 7 h, MTX fluorescence intensities in CZ and tissue were similar and DESI-MSI confirmed MIX biodistribution throughout the mid-dermal skin section. Conclusions: MIX absorbs rapidly into mid-dermis of AFXL-processed skin with minimal transdermal permeation until skin saturation, suggesting a possible alternative to systemic MIX for some skin disorders. C1 [Taudorff, Elisabeth Hjardem; Lerche, Catharina Margrethe; Vissing, Anne-Cathrine; Philipsen, Peter Alshede; Haedersdal, Merete] Univ Copenhagen, Bispebjerg Univ Hosp, Dept Dermatol, DK-2400 Copenhagen, Denmark. [Hannibal, Jens] Univ Copenhagen, Bispebjerg Univ Hosp, Dept Clin Biochem, DK-2400 Copenhagen, Denmark. [D'Alvise, Janina; Hansen, Steen Honore; Janfelt, Christian] Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2400 Copenhagen, Denmark. [Paasch, Uwe] Univ Leipzig, Aesthet & Laserdermatol, Dept Dermatol, Div Dermatopathol, Copenhagen, NV, Germany. [Anderson, Richard Rox; Haedersdal, Merete] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Taudorff, EH (reprint author), Univ Copenhagen, Bispebjerg Univ Hosp, Dept Dermatol D 92, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. EM ehtaudorf@dadlnet.dk FU Pantec Biosolutions AG, Ruggell, Liechtenstein; Bispebjerg University Hospital FX M Haedersdal received a research grant from Pantec Biosolutions AG, Ruggell, Liechtenstein. The company had no influence on collection, interpretation or presentation of data. Bispebjerg University Hospital is acknowledged for financial support. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. NR 37 TC 5 Z9 5 U1 2 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5247 EI 1744-7593 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD JUL PY 2015 VL 12 IS 7 BP 1059 EP 1069 DI 10.1517/17425247.2015.1031216 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CM5XK UT WOS:000357762100003 PM 25893560 ER PT J AU Karimi, M Solati, N Amiri, M Mirshekari, H Mohamed, E Taheri, M Hashemkhani, M Saeidi, A Estiar, MA Kiani, P Ghasemi, A Basri, SMM Aref, AR Hamblint, MR AF Karimi, Mandi Solati, Navid Amiri, Mohammad Mirshekari, Hamed Mohamed, Elmira Taheri, Mandiar Hashemkhani, Mahshid Saeidi, Ahad Estiar, Mehrdad Asghari Kiani, Parnian Ghasemi, Amir Basri, Seyed Masoud Moosavi Aref, Amir R. Hamblint, Michael R. TI Carbon nanotubes part I: preparation of a novel and versatile drug-delivery vehicle SO EXPERT OPINION ON DRUG DELIVERY LA English DT Review DE addition reaction; carbon nanotubes; functional group; functionalization; purification; synthesis ID CHEMICAL-VAPOR-DEPOSITION; SOLID-PHASE EXTRACTION; HYDROGEN-ARC-DISCHARGE; LOW-TEMPERATURE GROWTH; LARGE-SCALE SYNTHESIS; LOW-COST SYNTHESIS; LOW-PRESSURE AIR; PROTEIN IMMOBILIZATION; FIELD-EMISSION; CANCER-CELLS AB Introduction: It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by lijima, who described them as "rolled graphite sheets inserted into each other". Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered: This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion: In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts. C1 [Karimi, Mandi] Iran Univ Med Sci, Dept Nanotechnol, Sch Adv Technol Med, Tehran, Iran. [Solati, Navid; Mohamed, Elmira; Taheri, Mandiar; Hashemkhani, Mahshid; Saeidi, Ahad; Kiani, Parnian] Iran Univ Med Sci, Sch Met & Mat Engn, Tehran, Iran. [Amiri, Mohammad; Ghasemi, Amir] Sharif Univ Technol, Dept Mat Sci & Engn, Polymer Mat Res Grp, Tehran 113659466, Iran. [Mirshekari, Hamed] Univ Kerala, Dept Biotechnol, Trivandrum 695001, Kerala, India. [Estiar, Mehrdad Asghari; Aref, Amir R.] Univ Tehran Med Sci, Sch Med, Dept Med Genet, Tehran, Iran. [Basri, Seyed Masoud Moosavi] Sharif Univ Technol, Biotechnol Res Ctr, Tehran 113658639, Iran. [Hamblint, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed,Sch Med, Boston, MA 02114 USA. [Hamblint, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblint, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU NIH [R01A1050875] FX This work was supported by NIH grant R01A1050875. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 154 TC 10 Z9 10 U1 11 U2 52 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1742-5247 EI 1744-7593 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD JUL PY 2015 VL 12 IS 7 BP 1071 EP 1087 DI 10.1517/17425247.2015.1003806 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CM5XK UT WOS:000357762100004 PM 25601356 ER PT J AU Karimi, M Solati, N Ghasemi, A Estiar, MA Hashemkhani, M Kiani, P Mohamed, E Saeidi, A Taheri, M Avci, P Aref, AR Amiri, M Baniasadi, F Hamblint, MR AF Karimi, Mandi Solati, Navid Ghasemi, Amir Estiar, Mehrdad Asghari Hashemkhani, Mahshid Kiani, Parnian Mohamed, Elmira Saeidi, Ahad Taheri, Mandiar Avci, Pinar Aref, Amir R. Amiri, Mohammad Baniasadi, Fazel Hamblint, Michael R. TI Carbon nanotubes part II: a remarkable carrier for drug and gene delivery SO EXPERT OPINION ON DRUG DELIVERY LA English DT Review DE biomolecule delivery; carbon nanotubes; drug delivery systems; gene delivery; toxicology ID ASSISTED MICROPARTICLE DELIVERY; HUMAN EPIDERMAL-KERATINOCYTES; CANCER-CELLS; IN-VIVO; MAMMALIAN-CELLS; RNA INTERFERENCE; TARGETED DELIVERY; AMPHOTERICIN-B; P53 GENE; DOXORUBICIN AB Introduction: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. Areas covered: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as nnethotrexate, taxol and gemcitabine. The delivery of the antifungal compound annphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. Expert opinion: CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects. C1 [Karimi, Mandi] Iran Univ Med Sci, Sch Adv Technol Med, Dept Nanotechnol, Tehran, Iran. [Solati, Navid; Hashemkhani, Mahshid; Kiani, Parnian; Mohamed, Elmira; Saeidi, Ahad; Taheri, Mandiar] Iran Univ Med Sci, Sch Met & Mat Engn, Tehran, Iran. [Ghasemi, Amir; Amiri, Mohammad; Baniasadi, Fazel] Sharif Univ Technol, Dept Mat Sci & Engn, Polymer Mat Res Grp, Tehran 113659466, Iran. [Estiar, Mehrdad Asghari] Univ Tehran Med Sci, Sch Med, Dept Med Genet, Tehran, Iran. [Avci, Pinar; Hamblint, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avci, Pinar; Hamblint, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Aref, Amir R.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Dept Canc Biol, Boston, MA 02215 USA. [Aref, Amir R.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02215 USA. [Hamblint, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblint, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu FU NIH [R01A1050875] FX This work was supported by NIH grant R01A1050875. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 112 TC 15 Z9 15 U1 11 U2 53 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1742-5247 EI 1744-7593 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD JUL PY 2015 VL 12 IS 7 BP 1089 EP 1105 DI 10.1517/17425247.2015.1004309 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CM5XK UT WOS:000357762100005 PM 25613837 ER PT J AU Kuehlewein, L Sadda, SR Sarraf, D AF Kuehlewein, L. Sadda, S. R. Sarraf, D. TI OCT angiography and sequential quantitative analysis of type 2 neovascularization after ranibizumab therapy SO EYE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MOTION CORRECTION AB Purpose To study the precise structural aspects of a type 2 neovascular membrane in a patient with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography and perform sequential quantitative analysis of the membrane after ranibizumab therapy. Patients and methods Split-spectrum amplitude-decorrelation (SSADA) OCT angiography macular cubes (3x3 mm) were acquired with a light source centered at 840 nm, a bandwidth of 45 nm, and an A-scan-rate of 70 000 scans per second. Visible pathologic vessels were outlined manually on average intensity projection en face images, and the area of the lesion and the vessel density were measured at baseline and follow-up. Results At baseline, the neovascular lesion measured 4.12 mm(2) and the vessel density was 19.83 mm(-1). Four weeks after the first, and 2 and 4 weeks after the second ranibizumab injection, OCT angiography revealed a progressively smaller vascular lesion (2.32, 1.77 and 1.64 mm(2)), and vessel density (10.24, 8.52 and 7.57 mm(-1)), although the large central trunks of the lesion were unchanged. Conclusions In this study, an obvious reduction in size and vessel density of the neovascular lesion was noted after treatment with ranibizumab using SSADA OCT angiography technology. Microvascular components can be delineated with precision, suggesting that this technique may be useful for the management of patients with neovascular AMD in a clinical setting as well as for future clinical trials. C1 [Kuehlewein, L.; Sadda, S. R.] Doheny Eye Inst, Los Angeles, CA 90033 USA. [Kuehlewein, L.; Sadda, S. R.; Sarraf, D.] Stein Eye Inst, Los Angeles, CA USA. [Sarraf, D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Sarraf, D.] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Carl Zeiss Meditec; Optos; Allergan FX Dr Sadda is a co-inventor of Doheny intellectual property related to optical coherence tomography that has been licensed by Topcon Medical Systems and is a member of the scientific advisory board for Heidelberg Engineering. Dr Sadda receives research support from and serves as a consultant for Carl Zeiss Meditec, Optos, and Allergan. He also serves as a consultant for Alcon, Novartis, and Iconic. NR 10 TC 33 Z9 35 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD JUL PY 2015 VL 29 IS 7 BP 932 EP 935 DI 10.1038/eye.2015.80 PG 4 WC Ophthalmology SC Ophthalmology GA CM5LC UT WOS:000357728300014 PM 25976641 ER PT J AU Abramovitch, A Dar, R Mittelman, A Wilhelm, S AF Abramovitch, Amitai Dar, Reuven Mittelman, Andrew Wilhelm, Sabine TI Comorbidity Between Attention Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder Across the Lifespan: A Systematic and Critical Review SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; FUNCTIONAL MAGNETIC-RESONANCE; COGNITIVE-BEHAVIORAL THERAPY; FAMILIAL RISK ANALYSIS; CLINICAL-FEATURES; NEUROPSYCHOLOGICAL PERFORMANCE; SYMPTOM DIMENSIONS; CHILDHOOD-ONSET; DISRUPTIVE BEHAVIOR; RESPONSE-INHIBITION AB The concept of comorbidity between attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) has been discussed for two decades. No review, however, has examined this question in light of the stark contrast in disorder-specific phenomenology and neurobiology. We review reported prevalence rates and the methodological, phenomenological, and theoretical issues concerning concomitant ADHD-OCD. Reported co-occurrence rates are highly inconsistent in the literature. Studies aimed at examining the potential for comorbidity have suffered from various methodological problems, including the existence of very few community samples, highly variable exclusionary criteria, and possible clinical misinterpretation of symptoms. Despite numerous studies suggesting an ADHD-OCD comorbidity, thus far etiological (i.e., genetic) backing has been provided only for a pediatric comorbidity. Additionally, inflated rates of ADHD-OCD co-occurrence may be mediated by the presence of tic disorders, and evidence of impaired neuronal maturational processes in pediatric OCD may lead to possibly transient phenotypical expressions that resemble ADHD symptomatology. Thus, clinicians are encouraged to consider the possibility that ADHD-like symptoms resulting from OCD-specific symptomatology may be misdiagnosed as ADHD. This suggestion may account for the lower co-occurrence rates reported in adolescents and adults and for the lack of a theoretical account for comorbidity in these age groups. Existing literature is summarized and critically reviewed, and recommendations are made for future research. C1 [Abramovitch, Amitai; Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Abramovitch, Amitai; Mittelman, Andrew; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dar, Reuven] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. RP Abramovitch, A (reprint author), SW Texas State Univ, Dept Psychol, San Marcos, TX 78666 USA. EM abramovitch@txstate.edu NR 157 TC 5 Z9 5 U1 8 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2015 VL 23 IS 4 BP 245 EP 262 DI 10.1097/HRP.0000000000000050 PG 18 WC Psychiatry SC Psychiatry GA CM8IA UT WOS:000357941700002 PM 26052877 ER PT J AU Rose, AB Liebson, ES Goldblatt, MJ Baldessarini, RJ AF Rose, A. Blythe Liebson, Elizabeth S. Goldblatt, Mark J. Baldessarini, Ross J. TI Intensely Suicidal Behavior with a First Manic Episode SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BIPOLAR-I DISORDER; RANDOMIZED CONTROLLED-TRIAL; MIXED STATES; INTERNATIONAL SOCIETY; DEPRESSIVE DISORDER; TASK-FORCE; ILLNESS; ANTIDEPRESSANTS; LITHIUM; RISK C1 [Rose, A. Blythe] Harvard Univ, Med Sch, Cambridge, MA 02138 USA. [Rose, A. Blythe] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rose, A. Blythe; Liebson, Elizabeth S.; Goldblatt, Mark J.; Baldessarini, Ross J.] McLean Hosp, Belmont, MA USA. [Goldblatt, Mark J.] Boston Psychoanalyt Soc & Inst, Boston, MA USA. RP Rose, AB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM arose2@partners.org FU Bruce J. Anderson Foundation; McLean Private Donors Research Fund FX Supported, in part, by the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund (Dr. Baldessarini). NR 46 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2015 VL 23 IS 4 BP 288 EP 295 DI 10.1097/HRP.0000000000000096 PG 8 WC Psychiatry SC Psychiatry GA CM8IA UT WOS:000357941700004 ER PT J AU Yamin, M Holbrook, EH Gray, ST Busaba, NY Lovett, B Hamilos, DL AF Yamin, Moshe Holbrook, Eric H. Gray, Stacey T. Busaba, Nicolas Y. Lovett, Brooke Hamilos, Daniel L. TI Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE nasal polyposis; chronic rhinosinusitis; epithelium; inflammation; profibrotic; transforming growth factor beta 1; TGF-beta 1; Activin A; cigarette smoke; Toll-like receptor 3; TLR 3; airway remodeling ID MESENCHYMAL TRANSITION; CHRONIC RHINOSINUSITIS; FLUTICASONE PROPIONATE; MESSENGER-RNA; EXPRESSION; CELLS; ASTHMA; TRANSFORMING-GROWTH-FACTOR-BETA-1; INFLAMMATION; EOSINOPHILS AB BackgroundThe mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF-1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli. MethodsFrozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF-1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double-stranded RNA (dsRNA) (a ligand for Toll-like receptor-3) and examined for inflammatory and profibrotic genes using real-time polymerase chain reaction (PCR). ResultsCRSwNP patients showed increased TGF-1 and activin A in the stroma, increased TGF-1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3-dependent Snail1 in the stroma. Immunostaining for TGF-1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF-1 and activin A and more strongly induced by dsRNA in terms of chemokines. ConclusionIncreased TGF-1 and activin A and increased downstream TGF-1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF-1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling. (C) 2015 ARS-AAOA, LLC. C1 [Yamin, Moshe; Lovett, Brooke; Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Holbrook, Eric H.; Gray, Stacey T.; Busaba, Nicolas Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org FU Flight Attendants Medical Research Institute (FAMRI); Merck FX Flight Attendants Medical Research Institute (FAMRI); Merck. NR 43 TC 1 Z9 1 U1 3 U2 3 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 JUL PY 2015 VL 5 IS 7 BP 573 EP 582 DI 10.1002/alr.21516 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA CM7PT UT WOS:000357888100003 PM 25914020 ER PT J AU Yao, WC Bleier, BS AF Yao, William C. Bleier, Benjamin S. TI A simple, single stage technique to harvest optimal ethmoid bone grafts for caudal septal deflections SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article ID BATTEN GRAFT; ENDOSCOPIC SEPTOPLASTY; DEVIATION; CORRECT AB BackgroundCurvature of the caudal septum is a challenging area to surgically address because it is a tip supporting structure. Several methods to straighten the caudal septal deviation have been described to date. One commonly described technique is the placement of a bony septal batten graft. However, the harvest and subsequent ex vivo shaping of the bone graft can be difficult and lead to fracture of the graft superstructure. Here we discuss a novel single stage endoscopic approach to harvest a preformed batten graft and apply it to correct a caudal septal curvature deformity. MethodsDescription of a novel endoscopic technique for the single stage harvest of a bone graft for the correction of a caudal septal deflection utilizing an open Jansen-Middleton septum forceps. ResultsWe have successfully utilized this technique in 10 patients with a caudal septal curvature deformity with no complications. All patients had symptomatic improvement of nasal obstruction symptoms. ConclusionThe open Jansen-Middleton septum forceps allow for a reproducible, single stage, harvest of a bone graft from the perpendicular plate or vomer when addressing a caudal septal deformity using an endoscopic septoplasty approach. (C) 2015 ARS-AAOA, LLC. C1 [Yao, William C.; Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Yao, WC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM will.yao@gmail.com NR 14 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2015 VL 5 IS 7 BP 622 EP 625 DI 10.1002/alr.21520 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CM7PT UT WOS:000357888100011 PM 25885185 ER PT J AU Zhang, Z Adappa, ND Chiu, AG Doghramji, LJ Cohen, NA Palmer, JN AF Zhang, Zi Adappa, Nithin D. Chiu, Alexander G. Doghramji, Laurel J. Cohen, Noam A. Palmer, James N. TI Biofilm-forming bacteria and quality of life improvement after sinus surgery SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; quality of life; biofilm; bacteria; functional endoscopic sinus surgery ID CHRONIC RHINOSINUSITIS; ANTIMICROBIAL RESISTANCE; BACTERIOLOGICAL FINDINGS; MAXILLARY SINUSITIS; SUSCEPTIBILITY; INFECTIONS; MICROSCOPY; OUTCOMES; TRENDS AB BackgroundIt remains unclear how much chronic rhinosinusitis (CRS) patients with bacterial biofilms can benefit from functional endoscopic sinus surgery (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with quality of life (QOL) improvement after FESS. MethodsThis retrospective cohort study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus samples were taken to evaluate for biofilm-formation in vitro using a modified Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3-month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Patients' characteristics and medications were collected. Clinical significant QOL change was defined as a difference of at least 0.5 standard deviation (SD) of baseline SNOT-22 score in the reference group. ResultsA total of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24). Patients with biofilm-forming bacteria had significantly worse preoperative SNOT-22 scores compared to patients without biofilm-forming bacteria (48 20 vs 38 +/- 23, p = 0.048). Both groups had clinically significant QOL improvement after FESS, and the differences in their 1-month (23 +/- 19 vs 17 +/- 20) and 3-month (27 +/- 18 vs 18 +/- 19) post-FESS SNOT-22 scores were not significant. However, patients with biofilm-forming bacteria demonstrated significantly less QOL improvement than patients without biofilm-forming bacteria from pre-FESS to 6-month post-FESS visits after adjusting for clinical factors (35 +/- 25 vs 14 +/- 15; -coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p = 0.016). ConclusionCRS patients with biofilm-forming bacteria demonstrated clinically significant QOL improvement following FESS, but the degree of improvement was decreased overtime and became significantly worse than patients without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was independent of other risk factors for CRS. (C) 2015 ARS-AAOA, LLC. C1 [Zhang, Zi] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Adappa, Nithin D.; Doghramji, Laurel J.; Cohen, Noam A.; Palmer, James N.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Chiu, Alexander G.] Univ Arizona, Dept Surg, Tucson, AZ USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Zhang, Z (reprint author), 8th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM zizhang@mail.med.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 38 TC 2 Z9 2 U1 0 U2 2 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 JUL PY 2015 VL 5 IS 7 BP 643 EP 649 DI 10.1002/alr.21505 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA CM7PT UT WOS:000357888100015 PM 25763837 ER PT J AU Jowett, N Hadlock, TA AF Jowett, Nate Hadlock, Tessa A. TI A Contemporary Approach to Facial Reanimation SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID QUALITY-OF-LIFE; GRACILIS MUSCLE TRANSFER; LYME-DISEASE; NERVE ANASTOMOSIS; PARALYZED FACE; BELLS-PALSY; MANAGEMENT; RECONSTRUCTION; SMILE; VALACICLOVIR AB The management of acute facial nerve insult may entail medical therapy, surgical exploration, decompression, or repair depending on the etiology. When recovery is not complete, facial mimetic function lies on a spectrum ranging from flaccid paralysis to hyperkinesis resulting in facial immobility. Through systematic assessment of the face at rest and with movement, one may tailor the management to the particular pattern of dysfunction. Interventions for long-standing facial palsy include physical therapy, injectables, and surgical reanimation procedures. The goal of the management is to restore facial balance and movement. This article summarizes a contemporary approach to the management of facial nerve insults. C1 [Jowett, Nate] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Jowett, N (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nathanjowett@meei.harvard.edu NR 46 TC 8 Z9 8 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD JUL-AUG PY 2015 VL 17 IS 4 BP 293 EP 300 DI 10.1001/jamafacial.2015.0399 PG 8 WC Surgery SC Surgery GA CN0CP UT WOS:000358080400011 PM 26042960 ER PT J AU Kremer, S Renard, F Achard, S Lana-Peixoto, MA Palace, J Asgari, N Klawiter, EC Tenembaum, SN Banwell, B Greenberg, BM Bennett, JL Levy, M Villoslada, P Saiz, A Fujihara, K Chan, KH Schippling, S Paul, F Kim, HJ de Seze, J Wuerfel, JT AF Kremer, Stephane Renard, Felix Achard, Sophie Lana-Peixoto, Marco A. Palace, Jacqueline Asgari, Nasrin Klawiter, Eric C. Tenembaum, Silvia N. Banwell, Brenda Greenberg, Benjamin M. Bennett, Jeffrey L. Levy, Michael Villoslada, Pablo Saiz, Albert Fujihara, Kazuo Chan, Koon Ho Schippling, Sven Paul, Friedemann Kim, Ho Jin de Seze, Jerome Wuerfel, Jens T. CA Guthy-Jackson Charitable Fdn GJCF TI Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder SO JAMA NEUROLOGY LA English DT Review ID BRAIN-LESION DISTRIBUTION; VOXEL-BASED MORPHOMETRY; APPEARING WHITE-MATTER; MULTIPLE-SCLEROSIS; COGNITIVE IMPAIRMENT; MRI ABNORMALITIES; FUNCTIONAL MRI; DIFFUSION; DAMAGE; MS AB Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder but the specific morphological and temporal patterns distinguishing them uneqtaivcally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR voltametry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MR I techniques may further our understanding of the pathogenic processes hi NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease. C1 [Kremer, Stephane] Univ Strasbourg, CNRS, ICube UMR 7357, Federat Med Translat Strasbourg,UdS, Strasbourg, France. [Kremer, Stephane] Hop Univ Strasbourg, Dept Radiol, Strasbourg, France. [Renard, Felix; Achard, Sophie] Grenoble Image Parole Signal Automat, CNRS, Grenoble, France. [Lana-Peixoto, Marco A.] Univ Fed Minas Gerais, CIEM MS Res Ctr, Belo Horizonte, MG, Brazil. [Palace, Jacqueline] Oxford Univ Hosp Trust, Dept Neurol, Oxford, England. [Asgari, Nasrin] Univ Southern Denmark, Inst Mol Med, Dept Neurobiol, Odense, Denmark. [Asgari, Nasrin] Vejle Hosp, Dept Neurol, Vejle, Denmark. [Klawiter, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Tenembaum, Silvia N.] Natl Pediat Hosp Dr Juan P Garrahan, Dept Neurol & Neurophysiol, Buenos Aires, DF, Argentina. [Banwell, Brenda] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Banwell, Brenda] Childrens Hosp Philadelphia, Dept Pediat, Div Child Neurol, Philadelphia, PA 19104 USA. [Greenberg, Benjamin M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Greenberg, Benjamin M.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Bennett, Jeffrey L.] Univ Colorado Denver, Dept Neurol, Aurora, CO USA. [Levy, Michael] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Villoslada, Pablo; Saiz, Albert] Hosp Clin Barcelona, Inst Biomed Res August Pi Sunyer, Barcelona, Spain. [Fujihara, Kazuo] Tohoku Univ, Grad Sch Med, Dept Multiple Sclerosis Therapeut, Sendai, Miyagi 980, Japan. [Chan, Koon Ho] Univ Hong Kong, Univ Dept Med, Li Ka Shing Fac Med, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China. [Schippling, Sven] Univ Zurich Hosp, Neuroimmunol & Multiple Sclerosis Res Sect, CH-8091 Zurich, Switzerland. [Schippling, Sven] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Schippling, Sven] Fed Tech High Sch Zurich, Neurosci Ctr Zurich, Zurich, Switzerland. [Schippling, Sven] Univ Zurich, Zurich, Switzerland. [Paul, Friedemann; Wuerfel, Jens T.] Charite, NeuroCure Clin Res Ctr, D-13353 Berlin, Germany. [Paul, Friedemann; Wuerfel, Jens T.] Charite, Clin & Expt Multiple Sclerosis Res Ctr, D-13353 Berlin, Germany. [Paul, Friedemann; Wuerfel, Jens T.] Charite, Dept Neurol, D-13353 Berlin, Germany. [Kim, Ho Jin] Res Inst, Dept Neurol, Goyang, South Korea. [Kim, Ho Jin] Natl Canc Ctr Hosp, Goyang, South Korea. [de Seze, Jerome] Hop Univ Strasbourg, Dept Neurol, Strasbourg, France. [de Seze, Jerome] Hop Univ Strasbourg, Clin Invest Ctr INSERM 1434, Strasbourg, France. [de Seze, Jerome] UMR INSERM 1119, Strasbourg, France. [de Seze, Jerome] Federat Med Translat, Strasbourg, France. [Wuerfel, Jens T.] Univ Med Gottingen, Inst Neuroradiol, Gottingen, Germany. RP Wuerfel, JT (reprint author), Univ Med Gottingen, Inst Neuroradiol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM jens.wuerfel@charite.de RI Aktas, Orhan/B-7623-2009; De Seze, Jerome/M-8316-2016; Sato, Douglas/F-2508-2013; OI Aktas, Orhan/0000-0002-2020-9210; De Seze, Jerome/0000-0002-7197-7578; paul, friedemann/0000-0002-6378-0070; Sato, Douglas/0000-0002-7695-6020; Hooper, Douglas/0000-0002-8578-5104 FU Bayer Schering Pharma; Biogen Idec; Genzyme; Kael-GemVax; Merck Serono; Novartis; Teva-Handok; UCB; German Research Council; German Ministry of Education and Research (Competence Network Multiple Sclerosis [KKNMS]); GJCF; Bayer; Teva; Merck; Sanofi; Chugai Pharma; Bayer Schering; National MS Society; Roche; Bayer Healthcare; Genzyme Corp; Teva Neuroscience; Ministry of Education, Culture, Sports, Science and Technology in Japan; Ichiro Kanehara Foundation; German Ministry of Science (BMBF/KKNMS); Canadian MS Research Foundation; Canadian MS Society; Canadian Institutes of Health Research; Multiple Sclerosis Association of America; DioGenix; Amplimmune; Biogen; National Institutes of Health; Patient-Centered Outcomes Research Institute; Acorda Therapeutics; Viropharma; Acorda; NeuralStem; Genentech; European Commission; Instituto Salud Carlos III; Marato TV3; Eisai; Mitsubishi Tanabe Pharma Corp; Novartis Pharma; Astellas Pharma; Takeda Pharmaceutical Company Limited; Asahi Kasei Medical; Daiichi Sankyo; Nihon Pharmaceutical; Biogen Idec Japan; Chemo-Sero-Therapeutic Research Institute; Teva Pharmaceutical; Mitsubishi Tanabe Pharma; Teijin Pharma; Chugai Pharmaceutical; Ono Pharmaceutical; Genzyme Japan; Ministry of Education, Science and Technology in Japan [22229008]; Ministry of Health, Welfare and Labour of Japan; Teva Pharmaceuticals; Opexa Therapeutics; US Department of Veterans Affairs; German Research Council (DFG); German Ministry of Education and Research (BMBF-EDEN); Alexion; Terumo BCT FX Dr Kim has given talks, consulted, and received honoraria and/or research support from Bayer Schering Pharma, Biogen Idec, Genzyme, Kael-GemVax, Merck Serono, Novartis, Teva-Handok, and UCB. He serves on a steering committee for MedImmune. Dr Paul has received funding from the German Research Council, the German Ministry of Education and Research (Competence Network Multiple Sclerosis [KKNMS]), and the GJCF. He has received travel compensation, speaker honoraria, and research support from Biogen Idec, Bayer, Teva, Merck, Novartis, and Sanofi and has served as a steering committee member of the OCTIMS study sponsored by Novartis. Dr Tenembaum has provided consulting services to Genzyme Corp and Biogen Idec and has received lecture fees from Merck Serono. Dr Palace is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honoraria for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma, and Bayer Schering and unrestricted grants from Merck Serono, Novartis, Biogen Idec, and Bayer Schering. Her hospital trust receives funds for her role as clinical leader for the RSS, and she has received grants from the National MS Society and the GJCF for unrelated research studies. Dr Klawiter has received research funding from Roche. He has received consulting fees and/or speaking honoraria from Biogen Idec, Bayer Healthcare, Genzyme Corp, and Teva Neuroscience. Dr Sato receives a scholarship from the Ministry of Education, Culture, Sports, Science and Technology in Japan and has received research support from the Ichiro Kanehara Foundation. Dr de Seze has received honoraria from Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi, and Teva. He serves as a consultant for Alexion and Chugai. DrWuerfel serves on advisory boards for Novartis and Biogen Idec. He received a research grant from Novartis and speaker honoraria from Bayer, Novartis, and Biogen Idec. He is supported by the German Ministry of Science (BMBF/KKNMS). Dr Banwell serves as a senior editor for Multiple Sclerosis and Related Disorders and on the editorial board of Neurology. She serves as a consultant for Biogen Idec, Novartis, Teva Neuroscience, and Merck Serono. She has been funded by the Canadian MS Research Foundation, the Canadian MS Society, and the Canadian Institutes of Health Research. Dr Greenberg serves as a section editor for JAMA Neurology. He has received consulting fees or honoraria from the Multiple Sclerosis Association of America, DioGenix, Amplimmune, Novartis, and Biogen. He has received grant funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, the GJCF, Acorda Therapeutics, and Biogen Idec. Dr Bennett serves as a consultant for Novartis Pharmaceuticals, Alnaylam Pharmaceuticals, MedImmune, Chugai Pharmaceuticals, EMD Serono, AbbVie, Genentech, Genzyme, Apsara Therapeutics, and Questcor Pharmaceuticals; receives license royalties for a patent regarding "Compositions and Methods for the Treatment of Neuromyelitis Optica"; and serves on the editorial boards of the Multiple Sclerosis Journal and the Journal of Neuro-Ophthalmology. Dr Levy receives research support from the National Institutes of Health, the GJCF, Viropharma, Acorda, Sanofi, NeuralStem, and Genentech and serves as a consultant for Chugai Pharmaceuticals, GlaxoSmithKline, and MedImmune.; Dr Villoslada serves as a board member for Roche, Novartis, Neurotec Pharma, and Bionure Farma and as a consultant for Novartis, Roche, TFS, Heidelberg Engineering, MedImmune, Digna Biotec, and Neurotec Pharma. He has received research support from the European Commission, the Instituto Salud Carlos III, Marato TV3, Novartis, and Roche and travel expenses from Novartis. He holds patents with Digna Biotec and Bionure Farma and stock/stock options of Bionure Farma. Dr Saiz has received compensation for consulting services and speaking from Bayer Schering, Merck Serono, Biogen Idec, Sanofi, Teva Pharmaceutical Industries, and Novartis. Dr Fujihara serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corp, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, MedImmune, and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai, Mitsubishi Tanabe Pharma Corp, Novartis Pharma, Astellas Pharma, Takeda Pharmaceutical Company Limited, Asahi Kasei Medical, Daiichi Sankyo, and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009 to the present) and an advisory board member of the Sri Lanka Journal of Neurology; has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan; and is funded as the secondary investigator (grant 22229008, 2010-2015) by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology in Japan and as the secondary investigator by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labour of Japan (2010 to the present). Dr Stuve serves on the editorial boards of JAMA Neurology, the Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders. He has received grant support from Teva Pharmaceuticals and Opexa Therapeutics. Dr. Steve has served on data monitoring committees for Pfizer and Sanofi without monetary compensation. He is funded by a Merit grant from the US Department of Veterans Affairs. Dr Aktas receives research support from the German Research Council (DFG), the German Ministry of Education and Research (BMBF-EDEN), Bayer, Biogen Idec, Merck Serono, Novartis, and Teva and serves on an advisory board for MedImmune. He is an academic editor for PLOS ONE. Dr Wingerchuk has received research support from Alexion, Terumo BCT, and the GJCF; receives financial compensation for participation in a relapse adjudication panel for MedImmune; and has served as a consultant to Alexion, MedImmune, and Chugai Pharmaceuticals. No other disclosures are reported. NR 57 TC 10 Z9 11 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUL PY 2015 VL 72 IS 7 BP 815 EP 822 DI 10.1001/jamaneurol.2015.0248 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CM8EP UT WOS:000357931000016 PM 26010909 ER PT J AU Sloane, JA Mainero, C Kinkel, RP AF Sloane, Jacob A. Mainero, Caterina Kinkel, R. Philip TI No Evidence of Disease Activity in Multiple Sclerosis SO JAMA NEUROLOGY LA English DT Letter C1 [Sloane, Jacob A.] Beth Israel Deaconess Med Ctr, Multiple Sclerosis Ctr, Boston, MA 02115 USA. [Mainero, Caterina] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kinkel, R. Philip] Univ Calif San Diego, Multiple Sclerosis Ctr, San Diego, CA 92103 USA. RP Sloane, JA (reprint author), Beth Israel Deaconess Med Ctr, Multiple Sclerosis Ctr, 330 Brookline Ave,Ks212, Boston, MA 02115 USA. EM jsloane@bidmc.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUL PY 2015 VL 72 IS 7 BP 835 EP 836 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CM8EP UT WOS:000357931000024 PM 26167901 ER PT J AU Goldstein, JE Jackson, ML Fox, SM Deremeik, JT Massof, RW AF Goldstein, Judith E. Jackson, Mary Lou Fox, Sandra M. Deremeik, James T. Massof, Robert W. CA Low Vision Res Network Study Grp TI Clinically Meaningful Rehabilitation Outcomes of Low Vision Patients Served by Outpatient Clinical Centers SO JAMA OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; VISUAL DISABILITY VARIABLES; RANDOMIZED CONTROLLED-TRIAL; MACULAR DEGENERATION; INTERVENTION TRIAL; SERVICE; QUESTIONNAIRE; PARTICIPATION; DIFFICULTY; PEOPLE AB IMPORTANCE To facilitate comparative clinical outcome research in low vision rehabilitation, we must use patient-centered measurements that reflect clinically meaningful changes in visual ability. OBJECTIVE To quantify the effects of currently provided low vision rehabilitation (LVR) on patients who present for outpatient LVR services in the United States. DESIGN, SETTING, AND PARTICIPANTS Prospective, observational study of new patients seeking outpatient LVR services. From April 2008 through May 2011, 779 patients from 28 clinical centers in the United States were enrolled in the Low Vision Rehabilitation Outcomes Study. The Activity Inventory, a visual function questionnaire, was administered to measure overall visual ability and visual ability in 4 functional domains (reading, mobility, visual motor function, and visual information processing) at baseline and 6 to 9 months after usual LVR care. The Geriatric Depression Scale, Telephone Interview for Cognitive Status, and Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning questionnaires were also administered to measure patients' psychological, cognitive, and physical health states, respectively, and clinical findings of patients were provided by study centers. MAIN OUTCOMES AND MEASURES Mean changes in the study population and minimum clinically important differences in the individual in overall visual ability and in visual ability in 4 functional domains as measured by the Activity Inventory. RESULTS Baseline and post-rehabilitation measures were obtained for 468 patients. Minimum clinically important differences (95% CIs) were observed in nearly half (47%[95% CI, 44%-50%]) of patients in overall visual ability. The prevalence rates of patients with minimum clinically important differences in visual ability in functional domains were reading (44%[95% CI, 42%-48%]), visual motor function (38%[95% CI, 36%-42%]), visual information processing (33%[95% CI, 31%-37%]), and mobility (27%[95% CI, 25%-31%]). The largest average effect size (Cohen d = 0.87) for the population was observed in overall visual ability. Age (P = .006) was an independent predictor of changes in overall visual ability, and logMAR visual acuity (P = .002) was predictive of changes in visual information processing. CONCLUSIONS AND RELEVANCE Forty-four to fifty percent of patients presenting for outpatient LVR show clinically meaningful differences in overall visual ability after LVR, and the average effect sizes in overall visual ability are large, close to 1 SD. C1 [Goldstein, Judith E.; Deremeik, James T.; Massof, Robert W.] Johns Hopkins Univ, Wilmer Eye Inst, Lions Vis Res & Rehabil Ctr, Sch Med, Baltimore, MD 21287 USA. [Jackson, Mary Lou] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear, Boston, MA USA. [Fox, Sandra M.] South Texas Vet Hlth Care Syst, San Antonio Polytrauma Rehabil Ctr, San Antonio, TX USA. [Fox, Sandra M.] Univ Texas Hlth Sci Ctr San Antonio, Lions Low Vis Ctr Texas, San Antonio, TX 78229 USA. RP Goldstein, JE (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Lions Vis Res & Rehabil Ctr, Sch Med, 600 N Wolfe St,Wilmer 317, Baltimore, MD 21287 USA. EM jgolds28@jhmi.edu FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [EY012045, EY018696]; Reader's Digest Partners for Sight Foundation FX This work was supported by grants EY012045 and EY018696 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, and a grant from Reader's Digest Partners for Sight Foundation. NR 35 TC 6 Z9 6 U1 2 U2 12 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 JUL PY 2015 VL 133 IS 7 BP 762 EP 769 DI 10.1001/jamaophthalmol.2015.0693 PG 8 WC Ophthalmology SC Ophthalmology GA CM6TO UT WOS:000357823100008 PM 25856370 ER PT J AU Fay, A Nallasamy, N Bernardini, F Wladis, EJ Durand, ML Devoto, MH Meyer, D Hartstein, M Honavar, S Osaki, MH Osaki, TH Santiago, YM Sales-Sanz, M Vadala, G Verity, D AF Fay, Aaron Nallasamy, Nambi Bernardini, Francesco Wladis, Edward J. Durand, Marlene L. Devoto, Martin H. Meyer, Dale Hartstein, Morris Honavar, Santosh Osaki, Midori H. Osaki, Tammy H. Santiago, Yvette M. Sales-Sanz, Marco Vadala, Giuseppe Verity, David TI Multinational Comparison of Prophylactic Antibiotic Use for Eyelid Surgery SO JAMA OPHTHALMOLOGY LA English DT Article ID ANTIMICROBIAL PROPHYLAXIS; INFECTION; RISK; ARTHROPLASTY; HIP AB IMPORTANCE Antibiotic stewardship is important in controlling resistance, adverse reactions, and cost. The literature regarding antibiotic use for eyelid surgery is lacking. OBJECTIVES To determine standard care and assess factors influencing antibiotic prescribing practices for eyelid surgery. DESIGN, SETTING, AND PARTICIPANTS A survey study was conducted from February 2, 2014, to March 24, 2014. The survey was distributed to 2397 oculoplastic surgeons in private and academic oculoplastic surgery practices in 43 countries. All surgeons were members of ophthalmic plastic and reconstructive surgery societies. Data were analyzed by geographic location. Linear regression was performed to quantify contributions to rates of prescribing postoperative antibiotics for routine eyelid surgical procedures. MAIN OUTCOMES AND MEASURES Rates of prescribing prophylactic intravenous, oral, and topical antibiotics as well as factors that influence surgeons' prescribing practices. RESULTS A total of 782 responses were received from 2397 surgeons (average response rate, 36.7%; 2.5% margin of error) from 43 countries. Topical antibiotic use was common in all regions (85.2%). Perioperative intravenous antibiotic use was uncommon in all regions (13.5%). Geographic location was the greatest predictor of antibiotic prescribing practices (range, 2.9% in the United Kingdom to 86.7% in India; mean, 24%). Within Europe, Italy had the highest rate of antibiotic prescriptions for eyelid surgery (41.7%) and the United Kingdom had the lowest rate (2.9%.) In South America, Venezuela had the highest rate of antibiotic prescriptions for eyelid surgery (83.3%) and Chile had the lowest rate (0%). The practice locations that were associated with routinely prescribing postoperative oral antibiotics were India (odds ratio [OR], 15.83; 95% CI, 4.85-51.68; P < .001), Venezuela (OR, 13.47; 95% CI, 1.43-127.19; P = .02), and Southeast Asia (OR, 2.80; 95% CI, 1.15-6.84; P = .02). Conversely, practice location in the United Kingdom (OR, 0.048; 95% CI, 0.0063-0.37; P = .004), Australia and New Zealand (OR, 0.15; 95% CI, 0.033-0.67; P = .01), and the United States and Canada (OR, 0.41; 95% CI, 0.23-0.72; P = .002) were associated with decreased rates of postoperative oral antibiotic use. Surgeons' concern for allergic reactions was associated with decreased rates of prescribing antibiotics (OR, 0.34; 95% CI, 0.23-0.49; P < .001), while surgeons' concern for infection was associated with increased rates of prescribing antibiotics (OR 1.80; 95% CI, 1.45-2.23; P < .001). CONCLUSIONS AND RELEVANCE These results from members of ophthalmic plastic and reconstructive surgery societies confirm that antibiotic prescribing practices for routine eyelid surgical procedures vary widely throughout the world. No standard of care has been established that would require the routine use of postoperative prophylactic antibiotics following eyelid surgery. C1 [Fay, Aaron] Harvard Univ, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. [Nallasamy, Nambi] Duke Univ, Ctr Eye, Durham, NC USA. [Bernardini, Francesco] Oculoplast Bernardini, Genoa, Italy. [Wladis, Edward J.; Meyer, Dale] Albany Med Coll, Dept Ophthalmol, Lions Eye Inst, Slingerlands, NY USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. [Durand, Marlene L.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02114 USA. [Devoto, Martin H.] Consultores Oftalmol, Buenos Aires, DF, Argentina. [Hartstein, Morris] Tel Aviv Univ, Sackler Sch Med, Assaf Harofeh Med Ctr, Dept Ophthalmol, IL-69978 Tel Aviv, Israel. [Honavar, Santosh] Ophthalm & Facial Plast Surg & Ocular Oncol Ctr S, Hyderabad, Andhra Pradesh, India. [Osaki, Midori H.; Osaki, Tammy H.] Univ Fed Sao Paulo, Dept Ophthalmol, Ophthalm Plast Surg Div, Sao Paulo, Brazil. [Santiago, Yvette M.] St Lukes Med Ctr, Inst Eye, Quezon City, Philippines. [Sales-Sanz, Marco] Hosp Univ Ramon y Cajal, Dept Ophthalmol, Oculoplast & Orbital Surg Unit, Madrid, Spain. [Vadala, Giuseppe] Ivrea Hosp, Dept Ophthalmol, Turin, Italy. [Verity, David] Moorfields Eye Hosp, Ophthalm Plast & Reconstruct Surg, London, England. RP Fay, A (reprint author), Harvard Univ, Dept Ophthalmol, Sch Med, Zero Emerson Pl,Ste 2A, Boston, MA 02114 USA. EM aaronfay@gmail.com RI Osaki, Tammy /G-1539-2016; Menezes, Isabel/D-9281-2012 NR 30 TC 2 Z9 3 U1 1 U2 5 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 JUL PY 2015 VL 133 IS 7 BP 778 EP 784 DI 10.1001/jamaophthalmol.2015.0789 PG 7 WC Ophthalmology SC Ophthalmology GA CM6TO UT WOS:000357823100010 PM 25905446 ER PT J AU Lane, AM Kim, IK Gragoudas, ES AF Lane, Anne Marie Kim, Ivana K. Gragoudas, Evangelos S. TI Long-term Risk of Melanoma-Related Mortality for Patients With Uveal Melanoma Treated With Proton Beam Therapy SO JAMA OPHTHALMOLOGY LA English DT Article ID COLLABORATIVE OCULAR MELANOMA; CHOROIDAL MELANOMA; SURVIVAL RATES; IODINE-125 BRACHYTHERAPY; FOLLOW-UP; ENUCLEATION; TRIAL; DEATH; PLAQUE AB IMPORTANCE Little is known about the long-term risk of dying of uveal melanoma after treatment with radiotherapy. OBJECTIVE To determine the long-term risk of dying of this disease, we evaluated melanoma-related mortality rates up to 25 years after proton beam therapy in a large series of patients with uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS In this analysis, we included 3088 patients with uveal melanoma, identified from a hospital-based cohort and treated with proton irradiation between January 1975 and December 2005. Vital status and cause of death were ascertained through active follow-up and searches of government databases (the Social Security Death Index and the National Death Index) through December 31, 2008. Cumulative rates of melanoma-related mortality were calculated using the Kaplan-Meier method. Patient and tumor characteristics of known prognostic significance for melanoma-associated death were evaluated, including patient age and tumor dimensions. MAIN OUTCOMES AND MEASURES The primary outcome measure was cumulative rates of melanoma-specific mortality, and secondary measures included annual melanoma-specific mortality hazard rates and cumulative all-cause mortality rates. RESULTS Of 1490 deceased patients, 620 (41.6%) died of ocular melanoma. In addition, 19 patients were alive, but their melanoma metastasized, by the end of the observation period (mean follow-up after diagnosis of metastasis, 5.3 years). All-cause mortality rates in this cohort were 49.0% (95% CI, 47.0-51.1) at 15 years, 58.6% (95% CI, 56.4%-60.8%) at 20 years, and 66.8% (95% CI, 64.2%-69.4%) at 25 years. Melanoma-related mortality rates were 24.6% (95% CI, 22.8-26.4) at 15 years after treatment, 25.8% (95% CI, 24.0-27.8) at 20 years after treatment, and 26.4% (95% CI, 24.5-28.5) at 25 years after treatment. The 20-year mortality rate was 8.6% (95% CI, 6.2-11.9) for younger patients (<= 60 years) with small tumors (<= 11 mm) and 40.1% (95% CI, 36.1-44.3) for older patients (>60 years) with large tumors (>11 mm). CONCLUSIONS AND RELEVANCE In this large series of patients with ocular melanoma treated conservatively with proton beam irradiation, the cumulative melanoma-related mortality rates continued to increase up to 23 years after treatment. Annual rates decreased considerably (to <1%) 14 years after treatment. Information regarding the long-term risk of dying of uveal melanoma may be useful to clinicians when counseling patients. C1 [Lane, Anne Marie; Kim, Ivana K.; Gragoudas, Evangelos S.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM evangelos_gragoudas@meei.harvard.edu FU MEEI Melanoma Research Fund FX The MEEI Melanoma Research Fund provided financial support only. NR 19 TC 5 Z9 6 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 JUL PY 2015 VL 133 IS 7 BP 792 EP 796 DI 10.1001/jamaophthalmol.2015.0887 PG 5 WC Ophthalmology SC Ophthalmology GA CM6TO UT WOS:000357823100012 PM 25905597 ER PT J AU Reddy, AK Gonzalez, MA Henry, CR Yeh, S Sobrin, L Albini, TA AF Reddy, Ashvini K. Gonzalez, Marco A. Henry, Christopher R. Yeh, Steven Sobrin, Lucia Albini, Thomas A. TI Diagnostic Sensitivity of Indocyanine Green Angiography for Birdshot Chorioretinopathy SO JAMA OPHTHALMOLOGY LA English DT Article ID RETINOCHOROIDITIS AB IMPORTANCE To describe a cohort of patients with birdshot chorioretinopathy who did not manifest birdshot lesions on clinical examination but had retinal vasculitis, low-grade to moderate vitritis, and hypocyanescent lesions on indocyanine green angiography (ICGA). OBSERVATIONS Case series of 3 patients with mild to moderate vitritis and retinal vasculitis without definite birdshot lesions on clinical examination evaluated from January 2007 to December 2014 at 4 academic ophthalmology centers. All patients' results were positive for human leukocyte antigen-A29. All cases had hypocyanescent lesions visible on ICGA but not detectable on fluorescein angiography. CONCLUSIONS AND RELEVANCE Patients with retinal vasculitis and low-grade vitritis with or without macular edema may have birdshot chorioretinopathy evident on ICGA before lesions are visible on clinical examination or fluorescein angiography. Expanding birdshot chorioretinopathy diagnostic criteria to include the presence of hypocyanescent lesions on ICGA could improve the sensitivity of diagnosis. C1 [Reddy, Ashvini K.] Univ Virginia, Dept Ophthalmol, Charlottesville, VA USA. [Gonzalez, Marco A.; Henry, Christopher R.; Albini, Thomas A.] Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Yeh, Steven] Emory Univ, Atlanta, GA 30322 USA. [Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Albini, TA (reprint author), Univ Miami, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA. EM talbini@med.miami.edu OI Albini, Thomas/0000-0003-2199-9047 FU Santen FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sobrin reported receiving personal fees from Santen outside of this work. No other disclosures were reported. NR 14 TC 1 Z9 1 U1 0 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 JUL PY 2015 VL 133 IS 7 BP 840 EP 843 DI 10.1001/jamaophthalmol.2015.0822 PG 4 WC Ophthalmology SC Ophthalmology GA CM6TO UT WOS:000357823100019 PM 25906054 ER PT J AU Schatz, M Zeiger, RS Yang, SJ Chen, WS Sajjan, S Allen-Ramey, F Camargo, CA AF Schatz, Michael Zeiger, Robert S. Yang, Su-Jau Chen, Wansu Sajjan, Shiva Allen-Ramey, Felicia Camargo, Carlos A., Jr. TI Prospective Study on the Relationship of Obesity to Asthma Impairment and Risk SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Asthma; BMI; Overweight; Obesity; Asthma control; Asthma risk; Asthma impairment; Asthma exacerbations; Short-acting beta-agonists ID BODY-MASS INDEX; PERSISTENT ASTHMA; BARIATRIC SURGERY; WEIGHT-LOSS; ADULTS; SEVERITY; PHENOTYPE; DISEASE; AGE; EXACERBATIONS AB BACKGROUND: Although studies consistently show an association between obesity and increased asthma incidence, the role of obesity in asthma control is less clear. OBJECTIVE: The objective of this study was to evaluate the association between baseline body mass index (BMI) and measures of subsequent asthma control in a large real-world cohort of adults with persistent asthma. METHODS: In Kaiser Permanente Southern California (KPSC), a large managed care organization, we identified adults with persistent asthma in 2006, continuous health plan enrollment in 2007 and 2008, and a BMI measurement in 2006 or 2007. Each patient's last BMI measure in 2006 or 2007 was categorized into a BMI group: normal (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (>= 30 kg/m(2)). Asthma control outcomes in 2008 included asthma hospitalizations or emergency department visits (EDHO), oral corticosteroid dispensings linked to an asthma encounter (OCS), and dispensing of >= 7 short-acting beta-agonist canisters (SABA7). Multivariable analyses were conducted to assess the relationships of BMI categories with the risk of the asthma control outcomes after controlling for potential confounders. RESULTS: In the 10,233 eligible adults-after adjusting for potential demographic, comorbidity, and prior utilization confounders-we found an increased relative risk (RR) of EDHO in overweight and obese (RR 1.40, 95% CI 1.10-1.78) individuals. Only obesity was associated in adjusted analyses with a significant increased relative risk of SABA7 (RR 1.27, 95% CI 1.15-1.40). CONCLUSIONS: Elevated BMI, particularly obesity, is associated with subsequent poor asthma control, especially in the risk domain (exacerbations). These findings further support the importance of facilitating weight loss in overweight and obese adults with asthma. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Schatz, Michael; Zeiger, Robert S.] Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA 92111 USA. [Schatz, Michael; Zeiger, Robert S.] Kaiser Permanente Med Ctr, Dept Allergy, Los Angeles, CA 90034 USA. [Yang, Su-Jau; Chen, Wansu] Kaiser Permanente Med Ctr, Dept Res & Evaluat, San Diego, CA 92111 USA. [Yang, Su-Jau; Chen, Wansu] Kaiser Permanente Med Ctr, Dept Res & Evaluat, Los Angeles, CA 90034 USA. [Sajjan, Shiva; Allen-Ramey, Felicia] Merck & Co Inc, Dept Global Hlth Outcomes, West Point, PA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Schatz, M (reprint author), Kaiser Permanente Med Ctr, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. EM michael.x.schatz@kp.org FU Merck and Co., Inc. FX This study was supported by a research grant from Merck and Co., Inc. NR 40 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JUL-AUG PY 2015 VL 3 IS 4 BP 560 EP + DI 10.1016/j.jaip.2015.03.017 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA CM4XX UT WOS:000357690800014 PM 25975622 ER PT J AU Teodorescu, M Broytman, O Curran-Everett, D Sorkness, RL Crisafi, G Bleecker, ER Erzurum, S Gaston, BM Wenzel, SE Jarjour, NN AF Teodorescu, Mihaela Broytman, Oleg Curran-Everett, Douglas Sorkness, Ronald L. Crisafi, Gina Bleecker, Eugene R. Erzurum, Serpil Gaston, Benjamin M. Wenzel, Sally E. Jarjour, Nizar N. CA Natl Inst Hlth Natl Heart Lung Blood Inst Severe Asthma Res Program SARP Inv TI Obstructive Sleep Apnea Risk, Asthma Burden, and Lower Airway Inflammation in Adults in the Severe Asthma Research Program (SARP) II SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Asthma; Sleep apnea; Obstructive; Airway inflammation ID QUALITY-OF-LIFE; TO-CONTROL ASTHMA; BODY-MASS INDEX; DAYTIME SLEEPINESS; PERSISTENT ASTHMA; NOCTURNAL ASTHMA; TREAT ASTHMA; QUESTIONNAIRE; ASSOCIATION; PHENOTYPE AB BACKGROUND: Obstructive sleep apnea (OSA) may worsen asthma, but large studies are lacking and the underlying mechanisms are unknown. OBJECTIVE: The objective of this study was to determine the prevalence of OSA risk among patients with asthma of different severity compared with normal controls (NC), and among asthmatics, to test the relationship of OSA risk with asthma burden and airway inflammation. METHODS: Subjects with severe (SA, n = 94) and nonsevere asthma (NSA, n = 161), and NC (n = 146) were recruited in an add-on substudy, to the observational Severe Asthma Research Program (SARP) II; subjects completed sleep quality, sleepiness and OSA risk (Sleep Apnea scale of the Sleep Disorders Questionnaire [SA-SDQ]) questionnaires, and clinical assessments. Sputum was induced in a subset of asthmatics. RESULTS: Relative to NC, despite similar sleep duration, the subjects with SA and NSA had worse sleep quality, were sleepier, and had higher SA-SDQ scores. Among asthmatics, higher SA-SDQ was associated with increased asthma symptoms, beta-agonist use, health care utilization, and worse asthma quality of life. A significant association of SA-SDQ with sputum polymorphonuclear cells% was noted: each increase in SA-SDQ by its standard deviation (6.85 units) was associated with a rise in % sputum neutrophils of 7.78 (95% CI 2.33-13.22, P = .0006), independent of obesity and other confounders. CONCLUSIONS: OSA symptoms are more prevalent among asthmatics, in whom they are associated with higher disease burden. OSA risk is associated with a neutrophilic airway inflammation in asthma, which suggests that OSA may be an important contributor to the neutrophilic asthma. Further studies are necessary to confirm these findings and better understand the mechanistic underpinnings of this relationship. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology C1 [Teodorescu, Mihaela; Broytman, Oleg] William S Middleton Mem Vet Adm Med Ctr, Med Serv, James B Skatrud Pulm Sleep Res Lab, Madison, WI USA. [Teodorescu, Mihaela; Broytman, Oleg; Sorkness, Ronald L.; Crisafi, Gina; Jarjour, Nizar N.] Univ Wisconsin, Sch Med & Publ Hlth, Div Allergy Pulm & Crit Care Med, Madison, WI 53792 USA. [Teodorescu, Mihaela] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Sleep Med & Sleep Res Wisconsin Sleep, Madison, WI 53792 USA. [Curran-Everett, Douglas] Natl Jewish Hlth, Div Biostat & Bioinformat, Denver, CO USA. [Curran-Everett, Douglas] Univ Colorado, Colorado Sch Publ Hlth, Dept Biostat & Informat, Denver, CO 80202 USA. [Bleecker, Eugene R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA. [Erzurum, Serpil] Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44106 USA. [Gaston, Benjamin M.] Univ Virginia, Sch Med, Dept Pediat, Div Resp Med, Charlottesville, VA 22908 USA. [Wenzel, Sally E.] Univ Pittsburgh, Sch Med, Asthma Inst, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. RP Teodorescu, M (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, K4-910 CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM mt3@medicine.wisc.edu FU National Institutes of Health (NIH) [HL069170, HL069174, HL069167, HL069116, UL1RR025011]; Department of Medicine and University of Wisconsin School of Medicine and Public Health; Medical Education and Research Committee-New Investigator Award; University of Wisconsin; Department of Veterans Affairs for asthma-sleep apnea research FX National Institutes of Health (NIH) HL069170, HL069174, HL069167, HL069116, UL1RR025011; and additional resources from the William S. Middleton Memorial Veterans Hospital, Madison, Wis. Dr. Teodorescu received funding from the Department of Medicine and University of Wisconsin School of Medicine and Public Health, Medical Education and Research Committee-New Investigator Award, University of Wisconsin, and Department of Veterans Affairs for asthma-sleep apnea research. Mrs. Crisafi, Drs. Broytman, Curran-Everett, Sorkness, Bleecker, Erzurum, Gaston, Wenzel, and Jarjour report no conflicts of interest related to this work. The content of this article is solely the responsibility of the authors and does not represent the views of the Department of Veterans Affairs, NIH, or the United States Government. NR 61 TC 10 Z9 10 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JUL-AUG PY 2015 VL 3 IS 4 BP 566 EP + DI 10.1016/j.jaip.2015.04.002 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA CM4XX UT WOS:000357690800015 PM 26004304 ER PT J AU Waseem, M Leber, MJ Wasserman, EJ Sullivan, AF Camargo, CA Hasegawa, K AF Waseem, Muhammad Leber, Mark J. Wasserman, Eric J. Sullivan, Ashley F. Camargo, Carlos A., Jr. Hasegawa, Kohei TI Factors associated with concordance with the nonlevel-A guideline recommendations for emergency department patients with acute asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter ID CARE C1 [Waseem, Muhammad] Lincoln Med & Mental Hlth Ctr, Dept Emergency Med, New York, NY USA. [Leber, Mark J.] Brooklyn Med Ctr, Dept Emergency Med, New York, NY USA. [Wasserman, Eric J.] Newark Beth Israel Med Ctr, Dept Emergency Med, Newark, NJ USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 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 NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JUL-AUG PY 2015 VL 3 IS 4 BP 618 EP + DI 10.1016/j.jaip.2015.03.007 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA CM4XX UT WOS:000357690800028 PM 25869584 ER PT J AU Zharikov, AD Cannon, JR Tapias, V Bai, Q Horowitz, MP Shah, V El Ayadi, A Hastings, TG Greenamyre, JT Burton, EA AF Zharikov, Alevtina D. Cannon, Jason R. Tapias, Victor Bai, Qing Horowitz, Max P. Shah, Vipul El Ayadi, Amina Hastings, Teresa G. Greenamyre, J. Timothy Burton, Edward A. TI shRNA targeting alpha-synuclein prevents neurodegeneration in a Parkinson's disease model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GENOME-WIDE ASSOCIATION; TRANSGENIC MICE; IN-VIVO; DOPAMINE NEURONS; LEWY BODIES; LOCUS TRIPLICATION; OXIDATIVE STRESS; ROTENONE MODEL; GENE-THERAPY; DOUBLE-BLIND AB Multiple convergent lines of evidence implicate both alpha-synuclein (encoded by SCNA) and mitochondrial dysfunction in the pathogenesis of sporadic Parkinson's disease (PD). Occupational exposure to the mitochondrial complex I inhibitor rotenone increases PD risk; rotenone-exposed rats show systemic mitochondrial defects but develop specific neuropathology, including alpha-synuclein aggregation and degeneration of substantia nigra dopaminergic neurons. Here, we inhibited expression of endogenous alpha-synuclein in the adult rat substantia nigra by adeno-associated virus-mediated delivery of a short hairpin RNA (shRNA) targeting the endogenous rat Snca transcript. Knockdown of alpha-synuclein by similar to 35% did not affect motor function or cause degeneration of nigral dopaminergic neurons in control rats. However, in rotenone-exposed rats, progressive motor deficits were substantially attenuated contralateral to alpha-synuclein knockdown. Correspondingly, rotenone-induced degeneration of nigral dopaminergic neurons, their dendrites, and their striatel terminals was decreased ipsilateral to alpha-synuclein knockdown. These data show that alpha-synuclein knockdown is neuroprotective in the rotenone model of PD and indicate that endogenous alpha-synuclein contributes to the specific vulnerability of dopaminergic neurons to systemic mitochondrial inhibition. Our findings are consistent with a model in which genetic variants influencing alpha-synuclein expression modulate cellular susceptibility to environmental exposures in PD patients. shRNA targeting the SNCA transcript should be further evaluated as a possible neuroprotective therapy in PD. C1 [Zharikov, Alevtina D.; Cannon, Jason R.; Tapias, Victor; Bai, Qing; Horowitz, Max P.; Shah, Vipul; El Ayadi, Amina; Hastings, Teresa G.; Greenamyre, J. Timothy; Burton, Edward A.] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15213 USA. [Zharikov, Alevtina D.; Cannon, Jason R.; Tapias, Victor; Bai, Qing; Horowitz, Max P.; Shah, Vipul; El Ayadi, Amina; Hastings, Teresa G.; Greenamyre, J. Timothy; Burton, Edward A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zharikov, Alevtina D.; Cannon, Jason R.; Greenamyre, J. Timothy; Burton, Edward A.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Burton, Edward A.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15213 USA. RP Burton, EA (reprint author), Univ Pittsburgh, 7015 BST 3,3501 Fifth Ave, Pittsburgh, PA 15213 USA. EM eab25@pitt.edu OI Burton, Edward/0000-0002-8072-4636 FU BLRD VA [I01 BX000548]; NIEHS NIH HHS [R01 ES022644, ES018058, ES019879, ES020327, ES020718, ES022644, K99 ES019879, R00 ES019879, R01 ES020327, R01 ES020718, RC1 ES018058]; NINDS NIH HHS [NS059806, P01 NS059806] NR 71 TC 12 Z9 12 U1 3 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2015 VL 125 IS 7 BP 2721 EP 2735 DI 10.1172/JCI64502 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CM3AK UT WOS:000357553300020 PM 26075822 ER PT J AU Li, H Fu, YX Wu, Q Zhou, Y Crossman, DK Yang, PA Li, J Luo, B Morel, LM Kabarowski, JH Yagita, H Ware, CF Hsu, HC Mountz, JD AF Li, Hao Fu, Yang-Xin Wu, Qi Zhou, Yong Crossman, David K. Yang, PingAr Li, Jun Luo, Bao Morel, Laurence M. Kabarowski, Janusz H. Yagita, Hideo Ware, Carl F. Hsu, Hui-Chen Mountz, John D. TI Interferon-induced mechanosensing defects impede apoptotic cell clearance in lupus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SPLENIC MARGINAL ZONE; AUTOIMMUNE BXD2 MICE; PRECURSOR B-CELLS; DENDRITIC CELLS; I INTERFERON; T-CELL; PATHOGENIC AUTOANTIBODIES; ADAPTIVE IMMUNITY; LYMPHOID-TISSUES; ACTIN DYNAMICS AB Systemic lupus erythematosus (SLE) is a severe autoimmune disease that is associated with increased circulating apoptotic cell autoantigens (AC-Ags) as well as increased type I IFN signaling. Here, we describe a pathogenic mechanism in which follicular translocation of marginal zone (MZ) B cells in the spleens of BXD2 lupus mice disrupts marginal zone macrophages (MZMs), which normally clear AC debris and prevent follicular entry of AC-Ags. Phagocytosis of ACs by splenic MZMs required the megakaryoblastic leukemia 1 (MKL1) transcriptional coactivator-mediated mechanosensing pathway, which was maintained by MZ B cells through expression of membrane lymphotoxin-alpha 1 beta 2 (mLT). Specifically, type I IFN-induced follicular shuttling of mLT-expressing MZ B cells disengaged interactions between these MZ B cells and up receptor-expressing MZMs, thereby downregulating MKL1 in MZMs. Loss of MKL1 expression in MZMs led to defective F-actin polymerization, inability to clear ACs, and, eventually, MZM dissipation. Aggregation of plasmacytoid DCs in the splenic perifollicular region, follicular translocation of MZ B cells, and loss of MKL1 and MZMs were also observed in an additional murine lupus model and in the spleens of patients with SLE. Collectively, the results suggest that lupus might be interrupted by strategies that maintain or enhance mechanosensing signaling in the MZM barrier to prevent follicular entry of AC-Ags. C1 [Li, Hao; Wu, Qi; Yang, PingAr; Li, Jun; Luo, Bao; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Fu, Yang-Xin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Zhou, Yong] UAB, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Crossman, David K.] UAB, Heflin Ctr Genom Sci, Birmingham, AL USA. [Crossman, David K.] UAB, Dept Genet, Div Genet Res, Birmingham, AL USA. [Morel, Laurence M.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Kabarowski, Janusz H.; Mountz, John D.] UAB, Dept Microbiol, Birmingham, AL USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. [Ware, Carl F.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Hsu, HC (reprint author), Shelby Rm 311,1825 Univ Blvd, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu RI Li, Hao/N-7406-2015; OI Li, Hao/0000-0002-2171-8826; fu, yang-xin/0000-0001-8441-6617; Crossman, David/0000-0002-0981-169X FU NIH [R01-AI-071110, R01-AI-083705, R01-A1058150, R01-HL-124076, 5 R01-AI048073, P30-AR-048311, P30-AI-027767]; Department of Veterans Affairs [1I01BX000600-01]; Lupus Research Institute; Rheumatology Research Foundation; American Heart Association [14GRNT20180023]; American Thoracic Society Recognition Award; UAB RDCC [P30-AR-048311]; Cancer Center [CA-013148]; Center for AIDS Research grant [AI-027767] FX This worked was supported by grants from the NIH (R01-AI-071110, to J.D. Mountz; R01-AI-083705, to H.C. Hsu; R01-A1058150, to L.M. Morel; R01-HL-124076, to Y. Zhou; 5 R01-AI048073, to C.F. Ware; P30-AR-048311, to the UAB Rheumatic Diseases Core Centers [RDCC], including the Comprehensive Flow Cytometry Core and the Analytic Imaging and Immunore-agent Core; and P30-AI-027767, to the UAB Center for AIDS Research Comprehensive Flow Cytometry Core). Support was also provided by a Merit Review grant from the Department of Veterans Affairs (1I01BX000600-01, to J.D. Mountz); Novel Research grants from the Lupus Research Institute (to J.H. Kabarowski and H.C. Hsu); the Rheumatology Research Foundation (to J.D. Mountz); the American Heart Association (14GRNT20180023, to Y. Zhou); an American Thoracic Society Recognition Award (to Y. Zhou); and the UAB RDCC P30 Pilot and Feasibility Project (P30-AR-048311, to J. Li). We thank Michael Crowley and Bing Xue, supported by a Cancer Center grant (CA-013148) and a Center for AIDS Research grant (AI-027767), for performing the GeneChip analysis. We thank UAB Tissue Procurement for providing normal and SLE splenic tissue sections. We also thank Fiona Hunter for careful review of the manuscript. NR 62 TC 9 Z9 9 U1 2 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2015 VL 125 IS 7 BP 2877 EP 2890 DI 10.1172/JCI81059 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CM3AK UT WOS:000357553300032 PM 26098211 ER PT J AU De Souza, A Carter, JB Harris, NL Ferry, JA Duncan, LM AF De Souza, Aieska Carter, Joi B. Harris, Nancy L. Ferry, Judith A. Duncan, Lyn M. TI Contribution of longitudinal follow up and clinical pathological correlation in the diagnosis CD30-positive skin infiltrates SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE anaplastic large cell lymphoma; CD30; CD30+lymphoproliferative disorder; lymphomatoid papulosis ID LARGE-CELL LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; CUTANEOUS LYMPHOMAS; PAPULOSIS; CLASSIFICATION; EXPRESSION; SPECTRUM; DISEASE AB The diagnosis of a CD30+ cutaneous infiltrate is often difficult and requires clinicopathologic correlation. To further evaluate this challenge, initial clinical and histopathologic diagnoses were correlated with final clinicopathologic diagnosis in 44 cases with CD30 immunopositivity. Dermatopathologic evaluation confirmed the initial clinical diagnosis in 65% of the suspected benign cases, all cases of suspected lymphomatoid papulosis (LyP), and 72% of clinically malignant cases. In the 25 patients with clinical suspicion for lymphoma, the histopathologic diagnoses included lymphoma in 18, LyP in 2, CD30+ lymphoproliferative disorder (CD30 LPD) in 3 and hypersensitivity reaction in 2 patients. Clinicopathologic correlation led to a change in three cases diagnosed histopathologically as anaplastic large cell lymphoma (ALCL) reclassified as LyP type C, and one patient diagnosed as CD30 LPD clinically evolved as herpes virus infection. Furthermore, five cases reported as CD30 LPD received more specific diagnoses after clinicopathologic correlation (LyP type C in three, and ALCL in two patients). Clinicopathologic correlation is essential in establishing the correct diagnosis of CD30 LPD, in particular the distinction of ALCL from LyP type C. In this setting, the histopathologic diagnosis of CD30 LPD is advisable in the absence of clinical data. C1 [De Souza, Aieska; Carter, Joi B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Harris, Nancy L.; Ferry, Judith A.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, Nancy L.; Ferry, Judith A.; Duncan, Lyn M.] Harvard Univ, Sch Med, Boston, MA USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit WRN 825, 55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUL PY 2015 VL 42 IS 7 BP 452 EP 458 DI 10.1111/cup.12510 PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA CN0RS UT WOS:000358121700003 PM 25931140 ER PT J AU Ronis, SD Baldwin, CD Blumkin, A Kuhlthau, K Szilagyi, PG AF Ronis, Sarah D. Baldwin, Constance D. Blumkin, Aaron Kuhlthau, Karen Szilagyi, Peter G. TI Patient-Centered Medical Home and Family Burden in Attention-Deficit Hyperactivity Disorder SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article ID HEALTH-CARE NEEDS; QUALITY-OF-LIFE; DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADHD; ADOLESCENTS; CHILDHOOD; DIAGNOSIS; PATTERNS; COSTS AB Objective: Attention-deficit hyperactivity disorder (ADHD) can impair child health and functioning, but its effects on the family's economic burden are not well understood. The authors assessed this burden in US families of children with ADHD, and the degree to which access to a patient-centered medical home (PCMH) might reduce this burden. Methods: We conducted cross-sectional analyses of 2005-2006 and 2009-2010 National Surveys of Children with Special Health Care Needs, focusing on families of children with ADHD. They defined family economic burden as (1) family financial problems (annual expenses for the child's health care or illness-related financial problems for the family) and/or (2) family employment problems (job loss, work time loss, or failure to change jobs to avoid insurance loss). Relative risk models assessed associations between PCMH and family economic burden, adjusted for child age, sex, ethnicity, ADHD severity, poverty status, caregiver education, and insurance. Results: In 2009, 26% of families reported financial problems because of the child's ADHD, 2.1% reported out-of-pocket expenses >5% of income, and 36% reported employment problems. Only 38% reported care that met all 5 criteria for a PCMH (similar to rates in 2005-2006). In multivariable analysis, care in a PCMH was associated with 48% lower relative risk (RR) of financial problems (RR = 0.52, p < .001) and 36% lower relative risk of employment problems (RR = 0.64, p < .001). Among PCMH components, family-centered care and care coordination were more strongly associated with lower burden. Conclusions: The economic burdens of families with ADHD are significant but may be alleviated by family-centered care and care coordination in a medical home. C1 [Ronis, Sarah D.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Div Gen Pediat & Adolescent Med, Cleveland, OH 44106 USA. [Baldwin, Constance D.; Blumkin, Aaron] Univ Rochester, Dept Pediat, Div Gen Pediat, Rochester, NY USA. [Kuhlthau, Karen] Massachusetts Gen Hosp, Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Szilagyi, Peter G.] Univ Calif Los Angeles, Dept Pediat, Div Gen Pediat, Los Angeles, CA 90024 USA. RP Ronis, SD (reprint author), Rainbow Babies & Childrens Hosp, Dept Pediat, 11100 Euclid Ave,Mailstop RBC 6019, Cleveland, OH 44106 USA. EM sarah.ronis@uhhospitals.org FU NRSA [T32HP12002-24-00] FX An NRSA training grant T32HP12002-24-00 supported S. D. Ronis for this study. NR 28 TC 0 Z9 0 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUL-AUG PY 2015 VL 36 IS 6 BP 417 EP 425 DI 10.1097/DBP.0000000000000161 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA CM9CA UT WOS:000358002400002 PM 26035140 ER PT J AU Uchida, M Spencer, AE Biederman, J Castro, VM Kenworthy, T Chan, J Rosales, AM Newton-Cheh, C Perlis, RH AF Uchida, Mai Spencer, Andrea E. Biederman, Joseph Castro, Victor M. Kenworthy, Tara Chan, James Rosales, Ana M. Newton-Cheh, Christopher Perlis, Roy H. TI A Systematic Evaluation of the QTc Interval and Antidepressants in Youth: An Electronic Health Record Study SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article ID CHILDREN; SUICIDE AB Objective: The US Food and Drug Administration announced that citalopram was associated with dose-related prolongation of the QTc interval in adults. This study aimed to assess how antidepressants affect QTc intervals in children. The authors hypothesized that some antidepressants would show an association with QTc prolongation. Methods: An electronic medical record review was conducted of children aged 5 to 18 years in the Partners Healthcare system with at least 1 prescription of an antidepressant or methadone between February 1990 and August 2011. The authors extracted lifetime diagnoses and QTc interval of patients who had received an electrocardiogram 14 to 90 days after antidepressant or methadone prescription (N = 297). The mean QTc per medication was calculated as compared with the mean of all QTc measurements across medications. The number of patients taking medications who had QTc values in normal, borderline, abnormal, or high were also calculated. Results: Mean QTc values for all medications were in the normal range. The highest mean QTc was in patients on escitalopram (436 milliseconds). The mean QTc for sertraline (416 milliseconds) was significantly lower than all other drugs measured (t(331) = -2.21, p < .05). After controlling for confounding effects, none of the differences in mean QTc compared with other study drugs reached statistical significance. The greatest percentages of abnormal and high QTc values were found among patients taking paroxetine (18.8%), followed by escitalopram (15.4%). None of the children had documented ventricular arrhythmia. Conclusion: The results suggest that most antidepressants are not associated with prolonged QTc at doses typically prescribed for children. C1 [Uchida, Mai; Spencer, Andrea E.; Biederman, Joseph; Kenworthy, Tara; Chan, James] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Uchida, Mai; Spencer, Andrea E.; Biederman, Joseph; Kenworthy, Tara; Chan, James] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Castro, Victor M.] Partners HealthCare Syst, Partners Res Comp, Boston, MA USA. [Rosales, Ana M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org FU Pediatric Psychopharmacology Council Fund, Massachusetts General Hospital FX Supported in part by the Pediatric Psychopharmacology Council Fund, Massachusetts General Hospital. NR 16 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUL-AUG PY 2015 VL 36 IS 6 BP 434 EP 439 DI 10.1097/DBP.0000000000000188 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA CM9CA UT WOS:000358002400006 PM 26154713 ER PT J AU Becker, SJE Ring, D AF Becker, Stephanie J. E. Ring, David TI Epidemiology of Trapeziometacarpal Arthrosis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter ID OSTEOARTHRITIS; PREVALENCE; JOINT; THUMB; HAND C1 [Becker, Stephanie J. E.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02163 USA. RP Becker, SJE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02163 USA. OI Ring, David/0000-0002-6506-4879 NR 7 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2015 VL 40 IS 7 BP 1506 EP 1506 DI 10.1016/j.jhsa.2015.04.038 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CM7YD UT WOS:000357911500040 PM 26095062 ER PT J AU Schiehser, DM Twamley, EW Liu, L Matevosyan, A Filoteo, JV Jak, AJ Orff, HJ Hanson, KL Sorg, SF Delano-Wood, L AF Schiehser, Dawn M. Twamley, Elizabeth W. Liu, Lin Matevosyan, Adelina Filoteo, J. Vincent Jak, Amy J. Orff, Henry J. Hanson, Karen L. Sorg, Scott F. Delano-Wood, Lisa TI The Relationship Between Postconcussive Symptoms and Quality of Life in Veterans With Mild to Moderate Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article ID WORLD-HEALTH-ORGANIZATION; WHOQOL-BREF; HEAD-INJURY; FATIGUE; COMPLAINTS; INSOMNIA; SWEDEN AB Objective: To assess the relationship between postconcussive symptoms and quality of life (QOL) in Veterans with mild to moderate traumatic brain injury (TBI). Methods: Sixty-one Operation Enduring Freedom/Operation Iraqi Freedom/Persian Gulf War Veterans with a history of mild or moderate TBI, more than 6 months postinjury, and 21 demographically matched Veteran controls were administered self-report measures of QOL (World Health Organization Quality of Life-BREF) and postconcussive symptom severity (Neurobehavioral Symptom Inventory). Results: Perceived QOL was significantly worse in Veterans with mild-moderate TBI than in controls. In the TBI group, QOL was predominantly associated with affective symptoms, and moderate to strong correlations with fatigue and depression were evident across all QOL areas. Multivariate analyses revealed depression and fatigue to be the best predictors of Psychological, Social, and Environmental QOL, whereas sleep difficulty best predicted Physical QOL in mild-moderate TBI. Conclusion: Veterans with post-acute mild-moderate TBI evidence worse QOL than demographically matched Veteran controls. Affective symptoms, and specifically those of fatigue, depression, and sleep difficulty, appear to be the most relevant postconcussive symptoms predicting QOL in this population. These findings underscore the importance of examining specific symptoms as they relate to post-acute TBI QOL and provide guidance for treatment and intervention studies. C1 [Schiehser, Dawn M.; Twamley, Elizabeth W.; Matevosyan, Adelina; Filoteo, J. Vincent; Jak, Amy J.; Hanson, Karen L.; Delano-Wood, Lisa] VA San Diego Healthcare Syst, San Diego, CA USA. [Schiehser, Dawn M.; Twamley, Elizabeth W.; Filoteo, J. Vincent; Jak, Amy J.; Orff, Henry J.; Hanson, Karen L.; Delano-Wood, Lisa] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Liu, Lin] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Twamley, Elizabeth W.; Jak, Amy J.; Orff, Henry J.; Hanson, Karen L.; Delano-Wood, Lisa] VASDHS, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Sorg, Scott F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Schiehser, DM (reprint author), VA San Diego Healthcare Syst 151B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM dschiehser@ucsd.edu FU VA Career Development award; Department of Defense award FX This study was supported by VA Career Development (D.M.S. and L.D-W.) and Department of Defense (L.D-W.) awards. The authors thank Russell Kim, Elisa Lanni, and Norman Luc for their help with data collection and compilation. They also thank the patients, staff, and volunteers associated with the VA San Diego Healthcare System for their involvement in this study. NR 31 TC 4 Z9 4 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JUL-AUG PY 2015 VL 30 IS 4 BP E21 EP E28 DI 10.1097/HTR.0000000000000065 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CM8JB UT WOS:000357944800003 PM 24922041 ER PT J AU Linnstaedt, SD Hu, JM Bortsov, AV Soward, AC Swor, R Jones, J Lee, D Peak, D Domeier, R Rathlev, N Hendry, P McLean, SA AF Linnstaedt, Sarah D. Hu, JunMei Bortsov, Andrey V. Soward, April C. Swor, Robert Jones, Jeffrey Lee, David Peak, David Domeier, Robert Rathlev, Niels Hendry, Phyllis McLean, Samuel A. TI mu-Opioid Receptor Gene A118 G Variants and Persistent Pain Symptoms Among Men and Women Experiencing Motor Vehicle Collision SO JOURNAL OF PAIN LA English DT Article DE Opioid-induced hyperalgesia; A118 G; mu-opioid receptor 1; motor vehicle collision; pain ID PERITRAUMATIC DISTRESS INVENTORY; SINGLE NUCLEOTIDE POLYMORPHISM; POSTTRAUMATIC-STRESS-DISORDER; INDUCED HYPERALGESIA; EMERGENCY-DEPARTMENT; ENDOGENOUS OPIOIDS; POSTOPERATIVE PAIN; SWIM STRESS; ANALGESIA; OPRM1 AB The mu-opioid receptor 1 (OPRM1) binds endogenous opioids. Increasing evidence suggests that endogenous OPRM1 agonists released at the time of trauma may contribute to the development of posttraumatic musculoskeletal pain (MSP). In this prospective observational study, we evaluated the hypothesis that individuals with an AG or GG genotype at the OPRM1 A118 G allele, which results in a reduced response to opioids, would have less severe MSP 6 weeks after motor vehicle collision (MVC). Based on previous evidence, we hypothesized that this effect would be sex-dependent and most pronounced among women with substantial peritraumatic distress. European American men and women >= 18 years of age presenting to the emergency department after MVC and discharged to home after evaluation (N = 948) were enrolled. Assessments included genotyping and 6-week evaluation of overall MSP severity (0-10 numeric rating scale). In linear regression modeling, a significant A118 G Allele x Sex interaction was observed: an AG/GG genotype predicted reduced MSP severity among women with substantial peritraumatic distress (beta = -.925, P = .014) but not among all women. In contrast, men with an AG/GG genotype experienced increased MSP severity at 6 weeks (beta = .827, P = .019). Further studies are needed to understand the biologic mechanisms mediating observed sex differences in A118 G effects. Perspective: These results suggest a sex-dependent mechanism by which an emotional response to trauma (distress) contributes to a biologic mechanism (endogenous opioid release) that increases MSP in the weeks after stress exposure. These results also support the hypothesis that endogenous opioids influence pain outcomes differently in men and women. (C) 2015 by the American Pain Society C1 [Linnstaedt, Sarah D.; Hu, JunMei; Bortsov, Andrey V.; Soward, April C.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, TRYUMPH Res Program, Chapel Hill, NC 27599 USA. [Linnstaedt, Sarah D.; Hu, JunMei; Bortsov, Andrey V.; Soward, April C.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA. [McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. [Swor, Robert] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Jones, Jeffrey] Spectrum Hlth, Dept Emergency Med, Grand Rapids, MI USA. [Lee, David] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Peak, David] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Domeier, Robert] St Joseph Mercy Hosp, Dept Emergency Med, Ann Arbor, MI 48104 USA. [Rathlev, Niels] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Hendry, Phyllis] Univ Florida, Coll Med, Dept Emergency Med, Jacksonville, FL USA. RP McLean, SA (reprint author), Univ N Carolina, Med Sch Wing C,CB 7010, Chapel Hill, NC 27599 USA. EM smclean@aims.unc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR056328] FX Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR056328. NR 50 TC 6 Z9 6 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUL PY 2015 VL 16 IS 7 BP 637 EP 644 DI 10.1016/j.jpain.2015.03.011 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CM5ZL UT WOS:000357767400005 PM 25842347 ER PT J AU Bolognini, N Spandri, V Ferraro, F Salmaggi, A Molinari, ACL Fregni, F Maravita, A AF Bolognini, Nadia Spandri, Viviana Ferraro, Francesco Salmaggi, Andrea Molinari, Alessandro C. L. Fregni, Felipe Maravita, Angelo TI Immediate and Sustained Effects of 5-Day Transcranial Direct Current Stimulation of the Motor Cortex in Phantom Limb Pain SO JOURNAL OF PAIN LA English DT Article DE Phantom limb pain; transcranial direct current stimulation; motor cortex; phantom movement; neuroplasticity ID CORTICAL REORGANIZATION; ELECTRICAL-STIMULATION; BRAIN-STIMULATION; NEUROPATHIC PAIN; VISUAL FEEDBACK; PARIETAL CORTEX; DC STIMULATION; DOUBLE-BLIND; AMPUTEES; AMPUTATION AB The study explored the analgesic effects of transcranial direct current stimulation (tDCS) over the motor cortex on postamputation phantom limb pain (PIP). Eight subjects with unilateral lower or upper limb amputation and chronic PLP were enrolled in a crossover, double-blind, sham-controlled treatment program. For 5 consecutive days, anodal (active or sham) tDCS was applied over the motor cortex for 15 minutes at an intensity of 1.5 mA. The 5-day treatment with active, but not sham, tDCS induced a sustained decrease in background PLP and in the frequency of PLP paroxysms, which lasted for 1 week after the end of treatment. Moreover, on each day of active tDCS, patients reported an immediate PLP relief, along with an increased ability to move their phantom limb. Patients' immediate responses to sham tDCS, on the contrary, were variable, marked by an increase or decrease of PLP levels from baseline. These results show that a 5-day treatment of motor cortex stimulation with tDCS can induce stable relief from PLP in amputees. Neuromodulation targeting the motor cortex appears to be a promising option for the management of this debilitating neuropathic pain condition, which is often refractory to classic pharmacologic and surgical treatments. Perspective: The study describes sustained and immediate effects of motor cortex stimulation by tDCS on postamputation PLP, whose analgesic action seems linked to the motor reactivation of the phantom limb. These results are helpful for the exploitation of tDCS as a therapeutic tool for the management of neuropathic pain. (C) 2015 by the American Pain Society C1 [Bolognini, Nadia; Spandri, Viviana; Maravita, Angelo] Univ Milano Bicocca, Dept Psychol, I-20126 Milan, Italy. [Bolognini, Nadia] IRCCS, Ist Auxol Italiano, Neuropsychol Lab, Milan, Italy. [Spandri, Viviana; Salmaggi, Andrea] Azienda Osped Alessandro Manzoni, Dept Neurosci, Lecce, Italy. [Ferraro, Francesco] Azienda Osped Carlo Poma, Dept Rehabil, Mantua, Italy. [Molinari, Alessandro C. L.] Azienda Osped Alessandro Manzoni, Vasc Surg Unit, Lecce, Italy. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Bolognini, N (reprint author), Univ Milano Bicocca, Dept Psychol, Bldg U6,Piazza Ateneo Nuovo 1, I-20126 Milan, Italy. EM nadia.bolognini@unimib.it RI BOLOGNINI, NADIA/J-5746-2016 OI BOLOGNINI, NADIA/0000-0002-2921-8658 FU ATE from the University of Milano-Bicocca [2009-ATE-0293] FX Supported by the institutional fund ATE (2009-ATE-0293) from the University of Milano-Bicocca to N.B. and A.M. NR 48 TC 12 Z9 12 U1 3 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUL PY 2015 VL 16 IS 7 BP 657 EP 665 DI 10.1016/j.jpain.2015.03.013 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CM5ZL UT WOS:000357767400007 PM 25863170 ER PT J AU Webel, AR Wantland, D Rose, CD Kemppainen, J Holzemer, WL Chen, WT Johnson, MO Nicholas, P Eller, LS Chaiphibalsarisdi, P Sefcik, E Nokes, K Corless, IB Tyer-Viola, L Kirksey, K Voss, J Sullivan, K Rivero-Mendez, M Brion, J Iipinge, S Phillips, JC Portillo, C AF Webel, Allison R. Wantland, Dean Rose, Carol Dawson Kemppainen, Jeanne Holzemer, William L. Chen, Wei-Ti Johnson, Mallory O. Nicholas, Patrice Eller, Lucille Sanzero Chaiphibalsarisdi, Puangtip Sefcik, Elizabeth Nokes, Kathleen Corless, Inge B. Tyer-Viola, Lynda Kirksey, Kenn Voss, Joachim Sullivan, Kathy Rivero-Mendez, Marta Brion, John Iipinge, Scholastika Phillips, J. Craig Portillo, Carmen TI A Cross-Sectional Relationship Between Social Capital, Self-Compassion, and Perceived HIV Symptoms SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Symptom; HIV; self-compassion; social capital ID SUB-SAHARAN AFRICA; PSYCHOLOGICAL SYMPTOMS; INTERNATIONAL SAMPLE; STRESS REDUCTION; CONTROLLED-TRIAL; MANAGEMENT; HIV/AIDS; CARE; ADHERENCE; DISEASE AB Context. Individual resources of social capital and self-compassion are associated with health behaviors and perceived symptoms, suggesting that both are positive resources that can be modified to improve a person's symptom experience. Objectives. The aim was to examine the relationship between self-compassion and social capital and its impact on current HIV symptom experience in adult people living with HIV (PLWH). We further explored the impact of age on this relationship. Methods. We conducted a cross-sectional analysis of 2182 PLWH at 20 sites in five countries. Social capital, self-compassion, and HIV symptom experience were evaluated using valid and reliable scales. To account for inflated significance associated with a large sample size, we took a random sample of 28% of subjects (n = 615) and conducted correlation analyses and zero-inflated Poisson regression, controlling for known medical and demographic variables impacting HIV symptom experience. Results. Controlling for age, sex at birth, year of HIV diagnosis, comorbid health conditions, employment, and income, our model significantly predicted HIV symptom experience (overall model z = 5.77, P < 0.001). Employment status and social capital were consistent, negative, and significant predictors of HIV symptom experience. Self-compassion did not significantly predict HIV symptom experience. For those reporting symptoms, an increase in age was significantly associated with an increase in symptoms. Conclusion. Employment and social capital modestly predicted current HIV symptom experience. Social capital can be incorporated into symptom management interventions, possibly as a way to reframe a person's symptom appraisal. This may be increasingly important as PLWH age. The relationship between employment status and HIV symptom experience was significant and should be explored further. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Webel, Allison R.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Wantland, Dean; Holzemer, William L.; Eller, Lucille Sanzero] Rutgers Sch Nursing, Newark, NJ USA. [Kemppainen, Jeanne] Univ North Carolina Wilmington, Wilmington, NC USA. [Chen, Wei-Ti] Yale Univ, New Haven, CT USA. [Johnson, Mallory O.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nicholas, Patrice; Corless, Inge B.; Tyer-Viola, Lynda] Brigham & Womens Hosp, Global Hlth & Acad Partnerships, Boston, MA 02115 USA. [Nicholas, Patrice; Corless, Inge B.; Tyer-Viola, Lynda] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Chaiphibalsarisdi, Puangtip] Suan Sunandha Rajabhat Univ, Bangkok, Thailand. [Sefcik, Elizabeth] Texas A&M Univ Corpus Christi, Corpus Christi, TX USA. [Nokes, Kathleen] CUNY Hunter Coll, New York, NY 10021 USA. [Nokes, Kathleen] Hunter Bellevue Sch Nursing, New York, NY USA. [Kirksey, Kenn] Seton Family Hosp, Ctr Nursing Res, Austin, TX USA. [Voss, Joachim] Univ Washington, Seattle, WA 98195 USA. [Sullivan, Kathy] Univ Hawaii Manoa, Sch Nursing & Dent Hyg, Honolulu, HI 96822 USA. [Rivero-Mendez, Marta] Univ Puerto Rico, San Juan, PR 00936 USA. [Brion, John] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Iipinge, Scholastika] Univ Namibia, Windhoek, Namibia. [Phillips, J. Craig] Univ Ottawa, Ottawa, ON, Canada. [Rose, Carol Dawson; Portillo, Carmen] Univ Calif Sch Nursing San Francisco, Community Hlth Syst, San Francisco, CA USA. RP Webel, AR (reprint author), Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM allison.webel@case.edu FU NIH [UL1 RR024131, T32NR007081, KL2RR024990, R15NR011130]; International Pilot Award, University of Washington Center for AIDS Research [P30 AI027757]; University of British Columbia School of Nursing Helen Shore Fund; Duke University School of Nursing Office of Research Affairs; MGH Institute of Health Professions; University of Washington School of Nursing Research and Intramural Funding Program; Rutgers College of Nursing; City University of New York; Irwin Belk Distinguished Professorship Fund-University of North Carolina Wilmington FX This project was supported in part by: NIH UL1 RR024131; NIH T32NR007081; NIH KL2RR024990; NIH R15NR011130; International Pilot Award, University of Washington Center for AIDS Research (P30 AI027757); University of British Columbia School of Nursing Helen Shore Fund; Duke University School of Nursing Office of Research Affairs; MGH Institute of Health Professions; University of Washington School of Nursing Research and Intramural Funding Program; Rutgers College of Nursing; City University of New York; and the Irwin Belk Distinguished Professorship Fund-University of North Carolina Wilmington. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or any other funders. These funding agencies had no role in the 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. The authors declare no conflicts of interest. NR 65 TC 1 Z9 1 U1 2 U2 12 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 JUL PY 2015 VL 50 IS 1 BP 59 EP 68 DI 10.1016/j.jpainsymman.2014.12.013 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CM3GM UT WOS:000357570100009 PM 25659523 ER PT J AU Howard, SA Krajewski, KM Weissman, BN Seltzer, SE Ramaiya, NH Van den Abbeele, AD AF Howard, Stephanie A. Krajewski, Katherine M. Weissman, Barbara N. Seltzer, Steven E. Ramaiya, Nikhil H. Van den Abbeele, Annick D. TI Cancer Imaging Training in the 21st Century: An Overview of Where We Are, and Where We Need To Be SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Cancer imaging; residency curriculum; oncoradiology ID GASTROINTESTINAL STROMAL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; IMATINIB MESYLATE; RESPONSE CRITERIA; COMPUTED-TOMOGRAPHY; TARGETED THERAPIES; LUNG-CANCER; IMMUNOTHERAPY; PROGRESSION; TOXICITIES AB Advances in cancer care over the past decade have significantly changed treatment algorithms and life expectancies. Time from cancer diagnosis to death is rapidly increasing, as new, targeted therapies are developed, many prolonging life even in advanced disease. Tumors are now genotyped at diagnosis, allowing personalization of treatment. The FDA is continually approving new drugs that quickly become the standard of care for common tumors; the impact of these drugs and their side effects is monitored with imaging, and accurate interpretation of imaging studies has become essential as these patients live longer. Oncologists rely on radiologists to understand new patterns of treatment response and novel drug side effects that are associated with new drug classes, increasing the knowledge required for accurate image interpretation. These factors have led to the demand for dedicated cancer imaging training for radiologists, who can integrate findings throughout the body on various imaging modalities. In addition, we need to expand radiology's focus beyond diagnosis, staging, and restaging of tumors, and include education about the influence of genomics on tumor characterization and guidance for cancer care, the spectrum of treatment response, and the imaging characteristics of adverse events associated with various therapies. The time has come, therefore, to formally incorporate, as part of radiology residency, a distinct cancer imaging curriculum that is standardized, tested, and will allow the new generation of radiologists to effectively communicate with and assist their oncologic colleagues and optimally contribute to the care of patients with cancer. C1 [Howard, Stephanie A.; Krajewski, Katherine M.; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Howard, Stephanie A.; Krajewski, Katherine M.; Weissman, Barbara N.; Seltzer, Steven E.; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Howard, Stephanie A.; Krajewski, Katherine M.; Weissman, Barbara N.; Seltzer, Steven E.; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Boston, MA USA. RP Howard, SA (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA. EM sahoward@parmers.org NR 31 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2015 VL 12 IS 7 BP 714 EP 720 DI 10.1016/j.jacr.2015.03.044 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CM8QR UT WOS:000357967200019 PM 26143565 ER PT J AU Perry, DJ Kwan, SW Bhargava, P AF Perry, Don J. Kwan, Sharon W. Bhargava, Puneet TI Patient-Centered Clinical Training in Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Perry, Don J.; Kwan, Sharon W.; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Diagnost Imaging Serv, Seattle, WA USA. RP Perry, DJ (reprint author), Univ Washington, Med Ctr, Dept Radiol, RR215,Mailbox 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM perrymed@gmail.com NR 12 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2015 VL 12 IS 7 BP 724 EP 727 DI 10.1016/j.jacr.2014.12.013 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CM8QR UT WOS:000357967200021 PM 26143566 ER PT J AU Pfister, DG Spencer, S Brizel, DM Burtness, B Busse, PM Caudell, JJ Cmelak, AJ Colevas, AD Dunphy, F Eisele, DW Foote, RL Gilbert, J Gillison, ML Haddad, RI Haughey, BH Hicks, WL Hitchcock, YJ Jimeno, A Kies, MS Lydiatt, WM Maghami, E McCaffrey, T Mell, LK Mittal, BB Pinto, HA Ridge, JA Rodriguez, CR Samant, S Shah, JR Weber, RS Wolf, GT Worden, F Yom, SS McMillian, N Hughes, M AF Pfister, David G. Spencer, Sharon Brizel, David M. Burtness, Barbara Busse, Paul M. Caudell, Jimmy J. Cmelak, Anthony J. Colevas, A. Dimitrios Dunphy, Frank Eisele, David W. Foote, Robert L. Gilbert, Jill Gillison, Maura L. Haddad, Robert I. Haughey, Bruce H. Hicks, Wesley L., Jr. Hitchcock, Ying J. Jimeno, Antonio Kies, Merrill S. Lydiatt, William M. Maghami, Ellie McCaffrey, Thomas Mell, Loren K. Mittal, Bharat B. Pinto, Harlan A. Ridge, John A. Rodriguez, Cristina R. Samant, Sandeep Shah, Jatin R. Weber, Randal S. Wolf, Gregory T. Worden, Frank Yom, Sue S. McMillian, Nicole Hughes, Miranda TI Head and Neck Cancers, Version 1.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PROTON-BEAM THERAPY; CARBON ION RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; SALIVARY-GLAND TUMORS; RANDOMIZED CLINICAL-TRIAL; SQUAMOUS-CELL CARCINOMA; FAST-NEUTRON THERAPY; QUALITY-OF-LIFE; HUMAN-PAPILLOMAVIRUS; RADIATION-THERAPY AB These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RI and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages. C1 [Pfister, David G.; Shah, Jatin R.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Spencer, Sharon] Univ Alabama Birmingham, Comprehens Canc Ctr, Birmingham, AL USA. [Brizel, David M.; Dunphy, Frank] Duke Canc Inst, Durham, NC USA. [Burtness, Barbara] Yale Canc Ctr, Smilow Canc Hosp, New Haven, CT USA. [Busse, Paul M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Caudell, Jimmy J.; McCaffrey, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Cmelak, Anthony J.; Gilbert, Jill] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Colevas, A. Dimitrios; Pinto, Harlan A.] Stanford Canc Inst, Stanford, CA USA. [Eisele, David W.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Foote, Robert L.] Mayo Clin, Ctr Canc, Rochester, NY USA. [Gillison, Maura L.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Gillison, Maura L.] Solove Res Inst, Columbus, OH USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Haughey, Bruce H.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Haughey, Bruce H.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Hicks, Wesley L., Jr.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hitchcock, Ying J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Jimeno, Antonio] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kies, Merrill S.; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Lydiatt, William M.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Maghami, Ellie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Mell, Loren K.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Mittal, Bharat B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Rodriguez, Cristina R.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Samant, Sandeep] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Wolf, Gregory T.; Worden, Frank] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Yom, Sue S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [McMillian, Nicole; Hughes, Miranda] Natl Comprehens Canc Network, New York, NY USA. RP Pfister, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. 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 72 TC 33 Z9 33 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUL PY 2015 VL 13 IS 7 BP 847 EP 856 PG 10 WC Oncology SC Oncology GA CM7UI UT WOS:000357901600005 PM 26150579 ER PT J AU Bevers, TB Ward, JH Arun, BK Colditz, GA Cowan, KH Daly, MB Garber, JE Gemignani, ML Gradishar, WJ Jordan, JA Korde, LA Kounalakis, N Krontiras, H Kumar, S Kurian, A Laronga, C Layman, RM Loftus, LS Mahoney, MC Merajver, SD Meszoely, IM Mortimer, J Newman, L Pritchard, E Pruthi, S Seewaldt, V Specht, MC Visvanathan, K Wallace, A Bergman, MA Kumar, R AF Bevers, Therese B. Ward, John H. Arun, Banu K. Colditz, Graham A. Cowan, Kenneth H. Daly, Mary B. Garber, Judy E. Gemignani, Mary L. Gradishar, William J. Jordan, Judith A. Korde, Larissa A. Kounalakis, Nicole Krontiras, Helen Kumar, Shicha Kurian, Allison Laronga, Christine Layman, Rachel M. Loftus, Loretta S. Mahoney, Martin C. Merajver, Sofia D. Meszoely, Ingrid M. Mortimer, Joanne Newman, Lisa Pritchard, Elizabeth Pruthi, Sandhya Seewaldt, Victoria Specht, Michelle C. Visvanathan, Kale Wallace, Anne Bergman, Mary Ann Kumar, Rashmi CA Clinical Practice TI Breast Cancer Risk Reduction, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BRCA2 MUTATION CARRIERS; REDUCING SALPINGO-OOPHORECTOMY; SURGICAL ADJUVANT BREAST; ESTROGEN-PLUS-PROGESTIN; HORMONE-REPLACEMENT THERAPY; BILATERAL PROPHYLACTIC MASTECTOMY; MENOPAUSAL HOT FLASHES; BONE-MINERAL DENSITY; STAR P-2 TRIAL AB Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction. C1 [Bevers, Therese B.; Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Colditz, Graham A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Colditz, Graham A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Cowan, Kenneth H.] Fred & Pamela Buffett Canc Ctr, New York, NY USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA USA. [Gemignani, Mary L.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Korde, Larissa A.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Kounalakis, Nicole] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Krontiras, Helen] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kumar, Shicha; Mahoney, Martin C.] Roswell Pk Canc Inst, Buffalo, NY USA. [Kurian, Allison] Stanford Canc Inst, Stanford, CA USA. [Laronga, Christine; Loftus, Loretta S.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Layman, Rachel M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Layman, Rachel M.] Solove Res Inst, Columbus, OH USA. [Merajver, Sofia D.; Newman, Lisa] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Meszoely, Ingrid M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Mortimer, Joanne] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Pritchard, Elizabeth] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Pruthi, Sandhya] Mayo Clin, Ctr Canc, Rochester, MN USA. [Seewaldt, Victoria] Duke Canc Inst, Durham, NC USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Visvanathan, Kale] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Wallace, Anne] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Bevers, TB (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 238 TC 4 Z9 4 U1 1 U2 12 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 JUL PY 2015 VL 13 IS 7 BP 880 EP 915 PG 36 WC Oncology SC Oncology GA CM7UI UT WOS:000357901600008 PM 26150582 ER PT J AU Kronish, DP Penson, RT AF Kronish, Daniel P. Penson, Richard T. TI Theorist's Toy: Equipoise SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Kronish, Daniel P.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Kronish, Daniel P.; Penson, Richard T.] Dana Farber Canc Inst, Inst Review Board, Boston, MA 02115 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Med, Hematol Oncol, Boston, MA 02114 USA. RP Kronish, DP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 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 JUL PY 2015 VL 13 IS 7 BP 936 EP 938 PG 3 WC Oncology SC Oncology GA CM7UI UT WOS:000357901600011 PM 26150585 ER PT J AU Levesque, MH Montesi, SB Sharma, A AF Levesque, Marie-Helene Montesi, Sydney B. Sharma, Amita TI Diffuse Parenchymal Abnormalities in Acutely Dyspneic Patients A Pattern-based Approach SO JOURNAL OF THORACIC IMAGING LA English DT Review DE acute respiratory failure; emergency thoracic imaging; computed tomography; pattern-based approach; airspace opacity; linear opacity; nodular opacity; cystic opacity; aspiration; incidental findings; CTPA ID HIGH-RESOLUTION CT; THIN-SECTION CT; CHRONIC EOSINOPHILIC PNEUMONIA; ACUTE INTERSTITIAL PNEUMONIA; RESPIRATORY-DISTRESS-SYNDROME; HYDROSTATIC PULMONARY-EDEMA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMPUTED-TOMOGRAPHY FINDINGS; CRAZY-PAVING APPEARANCE; HYPERSENSITIVITY PNEUMONITIS AB Acute dyspnea is a common presenting complaint in the Emergency Room. Evaluation with chest radiography is vital for initial assessment and may reveal diffuse parenchymal abnormalities that require further assessment with computed tomography (CT). The aim of this review is to outline a pattern-based approach for the analysis of diffuse pulmonary abnormalities in an acutely dyspneic patient with emphasis on CT appearances. Specific disease entities may be differentiated by their distribution in the lungs and by their radiologic findings. Recognition of the predominant finding and its distribution can generate an appropriate differential diagnosis that is further refined by the presence or absence of ancillary findings. Incorporation of the clinical history, laboratory data, and prior studies narrows the differential diagnosis, indicates the optimum modality for further evaluation, and, in some situations, provides important prognostic data. C1 [Levesque, Marie-Helene; Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Thorac Imaging Div, Boston, MA 02114 USA. [Montesi, Sydney B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Thorac Imaging Div, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM asharma2@partners.org NR 95 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD JUL PY 2015 VL 30 IS 4 BP 220 EP 232 DI 10.1097/RTI.0000000000000133 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL9RX UT WOS:000357316900002 PM 25730554 ER PT J AU Thomas, GM Brill, A Mezouar, S Crescence, L Gallant, M Dubois, C Wagner, DD AF Thomas, G. M. Brill, A. Mezouar, S. Crescence, L. Gallant, M. Dubois, C. Wagner, D. D. TI Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE cancer; cell-derived microparticles; neutrophils; tissue factor; venous thrombosis ID EXTRACELLULAR DNA TRAPS; HUMAN PANCREATIC-CANCER; VENOUS THROMBOEMBOLISM; P-SELECTIN; RISK-FACTORS; PLATELET-AGGREGATION; PULMONARY-EMBOLISM; TUMOR-CELLS; IN-VIVO; MODEL AB BackgroundThe risk of thrombotic complications such as deep vein thrombosis (DVT) during tumor development is well known. Tumors release into the circulation procoagulant microparticles (MPs) that can participate in thrombus formation following vessel injury. The importance of this MP tissue factor (TF) in the initiation of cancer-associated DVT remains uncertain. ObjectiveTo investigate how pancreatic cancer MPs promote DVT invivo. MethodsWe combined a DVT mouse model in which thrombosis is induced by flow restriction in the inferior vena cava with one of subcutaneous pancreatic cancer in C57BL/6J mice. We infused high-TF and low-TF tumor MPs to determine the importance of TF in experimental cancer-associated DVT. ResultsBoth tumor-bearing mice and mice infused with tumor MPs subjected to 3h of partial flow restriction developed an occlusive thrombus; fewer than one-third of the control mice did. We observed that MPs adhered to neutrophil extracellular traps (NETs), which are functionally important players during DVT, whereas neither P-selectin nor glycoproteinIb were required for MP recruitment in DVT. The thrombotic phenotype induced by MP infusion was suppressed by hirudin, suggesting the importance of thrombin generation. TF carried by tumor MPs was essential to promote DVT, as mice infused with low-TF tumor MPs had less thrombosis than mice infused with high-TF tumor MPs. ConclusionsTF expressed on tumor MPs contributes to the increased incidence of cancer-associated venous thrombosis in mice invivo. These MPs may adhere to NETs formed at the site of thrombosis. C1 [Thomas, G. M.; Brill, A.; Gallant, M.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Thomas, G. M.; Brill, A.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Thomas, G. M.; Mezouar, S.; Crescence, L.; Dubois, C.] Aix Marseille Univ, INSERM, VRCM, UMR S 1076, Marseille, France. [Brill, A.] Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Mailstop BCH3146,Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu OI Thomas, Grace/0000-0003-4502-7154 FU NHLBI NIH HHS [R01 HL102101] NR 66 TC 15 Z9 15 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2015 VL 13 IS 7 BP 1310 EP 1319 DI 10.1111/jth.13002 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CM2DB UT WOS:000357488900018 PM 25955268 ER PT J AU Melrose, RJ Brewster, P Marquine, MJ MacKay-Brandt, A Reed, B Farias, ST Mungas, D AF Melrose, Rebecca J. Brewster, Paul Marquine, Maria J. MacKay-Brandt, Anna Reed, Bruce Farias, Sarah T. Mungas, Dan TI Early Life Development in a Multiethnic Sample and the Relation to Late Life Cognition SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cognition; Longitudinal change; Minority and diverse populations ID NEUROPSYCHOLOGICAL ASSESSMENT SCALES; INCIDENT ALZHEIMERS-DISEASE; HEAD CIRCUMFERENCE; RISK-FACTORS; SOCIOECONOMIC POSITION; LEG LENGTH; OLD-AGE; MAXIMUM-LIKELIHOOD; MEXICAN-AMERICANS; AFRICAN-AMERICANS AB Objectives. Poor quality of early life conditions has been associated with poorer late life cognition and increased risk of dementia. Early life physical development can be captured using adult measures of height and head circumference. Availability of resources may be reflected by socioeconomic indicators, such as parental education and family size. We sought to determine the association between early life development and experience and late life semantic memory, episodic memory, and executive functioning abilities, as well as rate of cognitive decline. Method. This study was conducted using the UC Davis Aging Diversity cohort, an ethnically diverse sample of Caucasian, African American, and Hispanic individuals from northern California. We used latent variable modeling to measure growth and childhood socioeconomic environment (SES) and examine their associations with longitudinal cognitive outcomes using mixed effects modeling. Results. Growth was positively related to higher childhood SES. Higher childhood SES was associated with better semantic memory. Both low growth and low SES were associated with increased rate of cognitive decline. Discussion. These findings demonstrate that early life experiences influence the trajectory of cognitive aging. Early life development and experience appears to provide a distal basis upon which additional risk and protective factors interact in the development of dementia. C1 [Melrose, Rebecca J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Melrose, Rebecca J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brewster, Paul] Univ Victoria, Dept Psychol, Victoria, BC V8W 2Y2, Canada. [Marquine, Maria J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [MacKay-Brandt, Anna] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Reed, Bruce; Farias, Sarah T.; Mungas, Dan] Univ Calif Davis, Sch Med, Dept Neurol, Davis, CA 95616 USA. RP Melrose, RJ (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rebecca.melrose@va.gov FU National Institute on Aging at the National Institutes of Health [R13 AG030995, R01 AG10220, P30 AG10129, R01 AG AG031563, R01 AG021028, P50 CA098252]; VA Career Development Award; Canadian Institutes for Health Research; Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN) [T32DA031098]; [T32 MH02004] FX This work was supported by the National Institute on Aging at the National Institutes of Health (R13 AG030995 to D. Mungas, R01 AG10220 to D. Mungas, P30 AG10129 to DeCarli, R01 AG AG031563 to B. Reed, R01 AG021028 to S. Tomaszewski Farias, P50 CA098252); VA Career Development Award (R. J. Melrose); Doctoral Research Award from the Canadian Institutes for Health Research (P. Brewster); Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN, T32DA031098 to M. J. Marquine) and a T32 MH02004 (A. MacKay-Brandt). NR 71 TC 4 Z9 4 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2015 VL 70 IS 4 BP 519 EP 531 DI 10.1093/geronb/gbt126 PG 13 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CM7NC UT WOS:000357879600003 PM 24389122 ER PT J AU Schneider, BC Gross, AL Bangen, KJ Skinner, JC Benitez, A Glymour, MM Sachs, BC Shih, RA Sisco, S Manly, JJ Luchsinger, JA AF Schneider, Brooke C. Gross, Alden L. Bangen, Katherine J. Skinner, Jeannine C. Benitez, Andreana Glymour, M. Maria Sachs, Bonnie C. Shih, Regina A. Sisco, Shannon Manly, Jennifer J. Luchsinger, Jose A. TI Association of Vascular Risk Factors With Cognition in a Multiethnic Sample SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cardiovascular disease; Cognitive decline; Ethnic differences; Racial differences ID HIGH BLOOD-PRESSURE; OLDER-ADULTS; ALZHEIMERS-DISEASE; AFRICAN-AMERICANS; ETHNIC DISPARITIES; HEART-FAILURE; DIABETES-MELLITUS; METABOLIC DISEASE; IMPAIRMENT; DECLINE AB Objectives. To examine the relationship between cardiovascular risk factors (CVRFs) and cognitive performance in a multiethnic sample of older adults. Method. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project. A composite score including smoking, stroke, heart disease, diabetes, hypertension, and central obesity represented CVRFs. Multiple group parallel process multivariate random effects regression models were used to model cognitive functioning and examine the contribution of CVRFs to baseline performance and change in general cognitive processing, memory, and executive functioning. Results. Presence of each CVRF was associated with a 0.1 SD lower score in general cognitive processing, memory, and executive functioning in black and Hispanic participants relative to whites. Baseline CVRFs were associated with poorer baseline cognitive performances among black women and Hispanic men. CVRF increase was related to baseline cognitive performance only among Hispanics. CVRFs were not related to cognitive decline. After adjustment for medications, CVRFs were not associated with cognition in Hispanic participants. Discussion. CVRFs are associated with poorer cognitive functioning, but not cognitive decline, among minority older adults. These relationships vary by gender and medication use. Consideration of unique racial, ethnic, and cultural factors is needed when examining relationships between CVRFs and cognition. C1 [Schneider, Brooke C.] VA Greater Los Angeles Healthcare Syst, Psychol Serv, Los Angeles, CA USA. [Gross, Alden L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gross, Alden L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Bangen, Katherine J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Skinner, Jeannine C.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Benitez, Andreana] Med Univ S Carolina, Ctr Biomed Imaging, Dept Radiol & Radiol Sci, Charleston, SC USA. [Glymour, M. Maria] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Glymour, M. Maria] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Sachs, Bonnie C.] Virginia Commonwealth Univ, Sch Med, Dept Neurol, Richmond, VA 23284 USA. [Shih, Regina A.] RAND Corp, Arlington, VA USA. [Sisco, Shannon] North Florida South Georgia Vet Hlth Syst, Dept Vet Affairs, Gainesville, FL USA. [Manly, Jennifer J.] Columbia Univ Coll Phys & Surg, Dept Neurol, Cognit Neurosci Div, New York, NY 10032 USA. [Luchsinger, Jose A.] Columbia Univ, Med Ctr, Joseph P Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Luchsinger, Jose A.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. RP Luchsinger, JA (reprint author), Columbia Univ, Med Ctr, Dept Med, PH9 Ctr,Room 210,630 West 168th St, New York, NY 10032 USA. EM jal94@columbia.edu OI Glymour, M. Maria/0000-0001-9644-3081 FU National Institute on Aging [T32AG023480, R03 AG045494-01, T32AG000258, R21 AG03438501, R01 AG028786, 1R01AG037212-01]; National Institutes of Health [T32 MH1993417, UL1 TR000062, KL2 TR000060]; National Institute of Minority Health and Health Disparities [P60 MD000206] FX A. L. Gross was supported by a National Institute on Aging (T32AG023480 and R03 AG045494-01). K. J. Bangen was supported by the National Institutes of Health (T32 MH1993417). J. C. Skinner was supported by the National Institute on Aging (T32AG000258). A. Benitez was supported by the Litwin Foundation and National Institutes of Health grants (UL1 TR000062 and KL2 TR000060). M. M. Glymour was partially supported by a pilot grant from the National Institute on Aging-funded Harvard Program on the Global Development of Aging and by a National Institute on Aging grant (R21 AG03438501). J. J. Manly was supported by the National Institute on Aging (R01 AG028786). J. A. Luchsinger was supported by grants from the National Institute of Minority Health and Health Disparities (P60 MD000206) and National Institute on Aging (1R01AG037212-01). This content is solely the responsibility of the authors and does not necessarily represent the official view of the supporting institutions. NR 74 TC 3 Z9 3 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2015 VL 70 IS 4 BP 532 EP 544 DI 10.1093/geronb/gbu040 PG 13 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CM7NC UT WOS:000357879600004 PM 24821298 ER PT J AU Carvalho, JO Tommet, D Crane, PK Thomas, ML Claxton, A Habeck, C Manly, JJ Romero, HR AF Carvalho, Janessa O. Tommet, Doug Crane, Paul K. Thomas, Michael L. Claxton, Amy Habeck, Christian Manly, Jennifer J. Romero, Heather R. TI Deconstructing Racial Differences: The Effects of Quality of Education and Cerebrovascular Risk Factors SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE African American; Cognitive decline; Education quality; Latent growth curve modeling; Race; Vascular ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; ETHNICALLY DIVERSE ELDERS; OLDER AFRICAN-AMERICANS; ALZHEIMERS-DISEASE; ATRIAL-FIBRILLATION; CARDIOVASCULAR HEALTH; COGNITIVE DYSFUNCTION; MULTIETHNIC COHORT; BIFACTOR MODEL; READING LEVEL AB Objectives. To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults. Method. We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences. Results. On average, AAs had lower quality of education and more cerebrovascular risk factors including hypertension, diabetes, and obesity. AAs had lower mean EF and memory at baseline, but there were no group differences in rates of decline. Cross-sectional racial differences in EF and memory persisted after controlling for vascular disease, but disappeared when controlling for Shipley Vocabulary. Discussion. Quality of education appears to be more important than cerebrovascular risk factors in explaining cross-sectional differences in memory and EF performance between White and AA older adults. Further investigation is needed regarding the relative contribution of education quality and cerebrovascular risk factors to cognitive decline among ethnically/racially diverse older adults. C1 [Carvalho, Janessa O.; Tommet, Doug] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. [Carvalho, Janessa O.] Bridgewater State Univ, Dept Psychol, Bridgewater, MA USA. [Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA USA. [Thomas, Michael L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Claxton, Amy] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Claxton, Amy] Univ Washington, Sch Med, Seattle, WA USA. [Habeck, Christian; Manly, Jennifer J.] Columbia Univ, Dept Neurol, Cognit Neurosci Div, New York, NY USA. [Romero, Heather R.] Duke Univ, Med Ctr, Dept Psychiat, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27710 USA. [Romero, Heather R.] Univ Notre Dame, Dept Psychol, Indiana, PA USA. RP Romero, HR (reprint author), Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Box 3503, Durham, NC 27710 USA. EM heather.romero@duke.edu FU National Institute on Aging (NIA) [P30 AG028377, R13 AG030995]; National Institute of Health/NIA [5R01AG026114-02] FX Data provided by the Joseph and Kathleen Bryan Alzheimer's Disease Research Center were supported by National Institute on Aging (NIA) (P30 AG028377). This research project began at the 2012 Friday Harbor Advanced Psychometrics Workshop, which is supported by NIA (R13 AG030995). C. Habeck received support from National Institute of Health/NIA (5R01AG026114-02). The contents do not necessarily represent views of the funding entities. Funders had no deciding roles in the design and conduct of this study. NR 52 TC 3 Z9 3 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2015 VL 70 IS 4 BP 545 EP 556 DI 10.1093/geronb/gbu086 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CM7NC UT WOS:000357879600005 PM 25098527 ER PT J AU Sisco, S Gross, AL Shih, RA Sachs, BC Glymour, MM Bangen, KJ Benitez, A Skinner, J Schneider, BC Manly, JJ AF Sisco, Shannon Gross, Alden L. Shih, Regina A. Sachs, Bonnie C. Glymour, M. Maria Bangen, Katherine J. Benitez, Andreana Skinner, Jeannine Schneider, Brooke C. Manly, Jennifer J. TI The Role of Early-Life Educational Quality and Literacy in Explaining Racial Disparities in Cognition in Late Life SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cognition; Life events and contexts; Minority and diverse populations ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; DIVERSE OLDER PERSONS; AFRICAN-AMERICAN; ALZHEIMERS-DISEASE; WHITE ELDERS; DECLINE; MEMORY; ADULTS; SCORES; RACE AB Objectives. Racial disparities in late-life cognition persist even after accounting for educational attainment. We examined whether early-life educational quality and literacy in later life help explain these disparities. Method. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project (WHICAP). Educational quality (percent white students; urban/rural school; combined grades in classroom) was operationalized using canonical correlation analysis. Late-life literacy (reading comprehension and ability, writing) was operationalized using confirmatory factor analysis. We examined whether these factors attenuated race-related differences in late-life cognition. Results. The sample consisted of 1,679 U.S.-born, non-Hispanic, community-living adults aged 65-102 (71% black, 29% white; 70% women). Accounting for educational quality and literacy reduced disparities by 29% for general cognitive functioning, 26% for memory, and 32% for executive functioning but did not predict differences in rate of cognitive change. Discussion. Early-life educational quality and literacy in late life explain a substantial portion of race-related disparities in late-life cognitive function. C1 [Sisco, Shannon] North Florida South Georgia Vet Hlth Syst, Dept Vet Affairs, Gainesville, FL 32608 USA. [Gross, Alden L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gross, Alden L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Shih, Regina A.] RAND Corp, Arlington, VA USA. [Sachs, Bonnie C.] Virginia Commonwealth Univ, Dept Neurol, Sch Med, Richmond, VA 23284 USA. [Glymour, M. Maria] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Glymour, M. Maria] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangen, Katherine J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Benitez, Andreana] Med Univ S Carolina, Ctr Biomed Imaging, Dept Radiol & Radiol Sci, Charleston, SC USA. [Skinner, Jeannine] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Schneider, Brooke C.] VA Greater Los Angeles Healthcare Syst, Dept Psychol, Los Angeles, CA USA. [Manly, Jennifer J.] Columbia Univ Coll Phys & Surg, Dept Neurol, Cognit Neurosci Div, New York, NY 10032 USA. RP Sisco, S (reprint author), North Florida South Georgia Vet Hlth Syst, Dept Vet Affairs, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM Shannon.Sisco@va.gov OI Glymour, M. Maria/0000-0001-9644-3081 FU National Institute on Aging [T32 AG023480, R03 AG045494, R01 AG043960, R21 AG03438501, T32 AG000258, R01 AG028786]; National Institutes of Health [T32 MH1993417, UL1 TR000062, KL2 TR000060]; Litwin Foundation FX A. L. Gross was supported by the National Institute on Aging (T32 AG023480 and R03 AG045494). R. A. Shih was supported by the National Institute on Aging (R01 AG043960). M. M. Glymour was partially supported by a pilot grant from the National Institute on Aging-funded Harvard Program on the Global Demography of Aging and by a National Institute on Aging grant (R21 AG03438501). K. J. Bangen was supported by the National Institutes of Health (T32 MH1993417). A. Benitez was supported by the Litwin Foundation and National Institutes of Health (UL1 TR000062 and KL2 TR000060). J. Skinner was supported by the National Institute on Aging (T32 AG000258). J. J. Manly was supported by the National Institute on Aging (R01 AG028786). The content is solely the responsibility of the authors and does not necessarily represent the official views of the supporting institutions. NR 58 TC 9 Z9 9 U1 3 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2015 VL 70 IS 4 BP 557 EP 567 DI 10.1093/geronb/gbt133 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CM7NC UT WOS:000357879600006 PM 24584038 ER PT J AU Bhanot, H Reddy, MM Nonami, A Weisberg, EL Bonal, D Kirschmeier, PT Salgia, S Podar, K Galinsky, I Chowdary, TK Neuberg, D Tonon, G Stone, RM Asara, J Griffin, JD Sattler, M AF Bhanot, H. Reddy, M. M. Nonami, A. Weisberg, E. L. Bonal, D. Kirschmeier, P. T. Salgia, S. Podar, K. Galinsky, I. Chowdary, T. K. Neuberg, D. Tonon, G. Stone, R. M. Asara, J. Griffin, J. D. Sattler, M. TI Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells SO LEUKEMIA LA English DT Article ID ACTIVATED PROTEIN-KINASE; RABBIT SKELETAL-MUSCLE; PHOSPHORYLASE-KINASE; CANCER GENOMICS; GROWTH-FACTOR; PROLIFERATION; METABOLISM; LIVER; MICE; SITE AB The rapid proliferation of myeloid leukemia cells is highly dependent on increased glucose metabolism. Through an unbiased metabolomics analysis of leukemia cells, we found that the glycogenic precursor UDP-D-glucose is pervasively upregulated, despite low glycogen levels. Targeting the rate-limiting glycogen synthase 1 (GYS1) not only decreased glycolytic flux but also increased activation of the glycogen-responsive AMP kinase (AMPK), leading to significant growth suppression. Further, genetic and pharmacological hyper-activation of AMPK was sufficient to induce the changes observed with GYS1 targeting. Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a therapeutic entry point for targeting leukemia cell metabolism. C1 [Bhanot, H.; Reddy, M. M.; Nonami, A.; Weisberg, E. L.; Salgia, S.; Galinsky, I.; Stone, R. M.; Griffin, J. D.; Sattler, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bhanot, H.; Reddy, M. M.; Nonami, A.; Weisberg, E. L.; Stone, R. M.; Asara, J.; Griffin, J. D.; Sattler, M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bonal, D.; Kirschmeier, P. T.] Dana Farber Canc Inst, Ctr Biomed Imaging Oncol, Lurie Family Imaging Ctr, Boston, MA 02215 USA. [Podar, K.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Podar, K.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Chowdary, T. K.] Natl Inst Sci Educ & Res, Sch Biol Sci, Bhubaneswar, Orissa, India. [Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Tonon, G.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Asara, J.] Dana Farber Canc Inst, Oncol, Boston, MA 02215 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM martin_sattler@dfci.harvard.edu FU National Institutes of Health grant [CA134660, CA6696]; Gloria Spivak Faculty Advancement Fund FX This work is supported in part by National Institutes of Health grant CA134660 (MS), CA6696 (JDG) and by the Gloria Spivak Faculty Advancement Fund (MS). NR 63 TC 3 Z9 3 U1 3 U2 12 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 JUL PY 2015 VL 29 IS 7 BP 1555 EP 1563 DI 10.1038/leu.2015.46 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CM3ZE UT WOS:000357623100015 PM 25703587 ER PT J AU Elshahat, B Gill, HS Filipyev, I Shrestha, S Hesser, J Kumar, J Karellas, A Zygmanski, P Sajo, E AF Elshahat, Bassem Gill, Hardeep Singh Filipyev, Ilya Shrestha, Suman Hesser, Juergen Kumar, Jayant Karellas, Andrew Zygmanski, Piotr Sajo, Erno TI Technical Note: Nanometric organic photovoltaic thin film detectors for dose monitoring in diagnostic x-ray imaging SO MEDICAL PHYSICS LA English DT Article DE dose monitoring; x-ray; thin-film; photovoltaic; organic ID SOLAR-CELLS AB Purpose: To fabricate organic photovoltaic (OPV) cells with nanometric active layers sensitive to ionizing radiation and measure their dosimetric characteristics in clinical x-ray beams in the diagnostic tube potential range of 60-150 kVp. Methods: Experiments were designed to optimize the detector's x-ray response and find the best parameter combination by changing the active layer thickness and the area of the electrode. The OPV cell consisted of poly (3-hexylthiophene-2,5-diyl): [6,6]-phenyl C-61 butyric acid methyl ester photoactive donor and acceptor semiconducting organic materials sandwiched between an aluminum electrode as an anode and an indium tin oxide electrode as a cathode. The authors measured the radiation-induced electric current at zero bias voltage in all fabricated OPV cells. Results: The net OPV current as a function of beam potential (kVp) was proportional to kVp(-0.5) when normalized to x-ray tube output, which varies with kVp. Of the tested configurations, the best combination of parameters was 270 nm active layer thicknesses with 0.7 cm(2) electrode area, which provided the highest signal per electrode area. For this cell, the measured current ranged from approximately 0.7 to 2.4 nA/cm(2) for 60-150 kVp, corresponding to about 0.09 nA-0.06 nA/mGy air kerma, respectively. When compared to commercial amorphous silicon thin film photovoltaic cells irradiated under the same conditions, this represents 2.5 times greater sensitivity. An additional 40% signal enhancement was observed when a 1 mm layer of plastic scintillator was attached to the cells' beam-facing side. Conclusions: Since both OPVs can be produced as flexible devices and they do not require external bias voltage, they open the possibility for use as thin film in vivo detectors for dose monitoring in diagnostic x-ray imaging. (C) 2015 American Association of Physicists in Medicine. C1 [Elshahat, Bassem; Sajo, Erno] Univ Massachusetts Lowell, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. [Elshahat, Bassem] Vancouver Isl Hlth Author, Dept Med Imaging, Royal Jubilee Hosp, Victoria, BC V8R 1J8, Canada. [Gill, Hardeep Singh; Kumar, Jayant] Univ Massachusetts Lowell, Dept Phys & Appl Phys, Lowell, MA 01854 USA. [Filipyev, Ilya; Zygmanski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Filipyev, Ilya; Zygmanski, Piotr] Brigham & Womens Hosp, Boston, MA 02215 USA. [Shrestha, Suman; Karellas, Andrew] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Hesser, Juergen] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Radiat Oncol, D-68167 Mannheim, Germany. RP Sajo, E (reprint author), Univ Massachusetts Lowell, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. EM Erno_Sajo@uml.edu RI Shrestha, Suman/E-6979-2013 OI Shrestha, Suman/0000-0003-1378-9605 NR 12 TC 3 Z9 3 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2015 VL 42 IS 7 BP 4027 EP 4032 DI 10.1118/1.4922202 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CM4WN UT WOS:000357686400024 PM 26133603 ER PT J AU Dutta, J Huang, C Li, QZ El Fakhri, G AF Dutta, Joyita Huang, Chuan Li, Quanzheng El Fakhri, Georges TI Pulmonary imaging using respiratory motion compensated simultaneous PET/MR SO MEDICAL PHYSICS LA English DT Article DE PET/MR; motion compensation; multimodal imaging; pulmonary; gating; MAP reconstruction ID POSITRON-EMISSION-TOMOGRAPHY; ATTENUATION CORRECTION; LUNG-CANCER; LESION DETECTION; SPATIAL-RESOLUTION; 4-DIMENSIONAL PET; OPTICAL-FLOW; CT IMAGES; GATED PET; 3-D PET AB Purpose: Pulmonary positron emission tomography (PET) imaging is confounded by blurring artifacts caused by respiratory motion. These artifacts degrade both image quality and quantitative accuracy. In this paper, the authors present a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validate it through simulation and clinical patient studies. Methods: The authors have developed an MCIR framework based on maximum a posteriori or MAP estimation. For fast acquisition of high quality 4D MR images, the authors developed a novel Golden-angle RAdial Navigated Gradient Echo (GRANGE) pulse sequence and used it in conjunction with sparsity-enforcing k-t FOCUSS reconstruction. The authors use a 1D slice-projection navigator signal encapsulated within this pulse sequence along with a histogram-based gate assignment technique to retrospectively sort the MR and PET data into individual gates. The authors compute deformation fields for each gate via nonrigid registration. The deformation fields are incorporated into the PET data model as well as utilized for generating dynamic attenuation maps. The framework was validated using simulation studies on the 4D XCAT phantom and three clinical patient studies that were performed on the Biograph mMR, a simultaneous whole body PET/MR scanner. Results: The authors compared MCIR (MC) results with ungated (UG) and one-gate (OG) reconstruction results. The XCAT study revealed contrast-to-noise ratio (CNR) improvements for MC relative to UG in the range of 21%-107% for 14 mm diameter lung lesions and 39%-120% for 10 mm diameter lung lesions. A strategy for regularization parameter selection was proposed, validated using XCAT simulations, and applied to the clinical studies. The authors' results show that the MC image yields 19%-190% increase in the CNR of high-intensity features of interest affected by respiratory motion relative to UG and a 6%-51% increase relative to OG. Conclusions: Standalone MR is not the traditional choice for lung scans due to the low proton density, high magnetic susceptibility, and low T-2(*) relaxation time in the lungs. By developing and validating this PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging. (C) 2015 American Association of Physicists in Medicine. C1 [Dutta, Joyita; Huang, Chuan; Li, Quanzheng; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Dutta, Joyita; Huang, Chuan; Li, Quanzheng; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Huang, Chuan] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [Huang, Chuan] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. RP Li, QZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM li.quanzheng@mgh.harvard.edu OI Huang, Chuan/0000-0001-6052-0663 FU NCI NIH HHS [R01 CA165221, 1R01CA165221]; NHLBI NIH HHS [1R01HL110241, R01 HL110241]; NIBIB NIH HHS [1R01EB013293, R01 EB013293] NR 81 TC 4 Z9 4 U1 2 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2015 VL 42 IS 7 BP 4227 EP 4240 DI 10.1118/1.4921616 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CM4WN UT WOS:000357686400042 PM 26133621 ER PT J AU Zadra, G Batista, JL Loda, M AF Zadra, Giorgia Batista, Julie L. Loda, Massimo TI Dissecting the Dual Role of AMPK in Cancer: From Experimental to Human Studies SO MOLECULAR CANCER RESEARCH LA English DT Review ID ACTIVATED PROTEIN-KINASE; ACETYL-COA-CARBOXYLASE; RANDOMIZED CONTROLLED-TRIALS; PRACTICE RESEARCH DATALINK; POPULATION-BASED COHORT; NEGATIVE BREAST-CANCER; TUMOR-SUPPRESSOR LKB1; FATTY-ACID SYNTHESIS; LOW-DOSE ASPIRIN; GROWTH IN-VIVO AB The precise role of 5'AMP-activated kinase (AMPK) in cancer and its potential as a therapeutic target is controversial. Although it is well established that activation of this energy sensor inhibits the main anabolic processes that sustain cancer cell proliferation and growth, AMPK activation can confer on cancer cells the plasticity to survive under metabolic stress such as hypoxia and glucose deprivation, which are commonly observed in fast growing tumors. Thus, AMPK is referred to as both a "conditional" tumor suppressor and "contextual" oncogene. To add a further layer of complexity, AMPK activation in human cancer tissues and its correlation with tumor aggressiveness and progression appears to vary in different contexts. The current review discusses the different faces of this metabolic regulator, the therapeutic implications of its modulation, and provides an overview of the most relevant data available on AMPK activation and AMPK-activating drugs in human studies. (C) 2015 AACR. C1 [Zadra, Giorgia; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zadra, Giorgia; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Batista, Julie L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Batista, Julie L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Pathol, 450 Longwood Ave,D1536, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU NIH/NCI grant [2R01CA131945]; DF/HCC SPORE in Prostate Cancer [NIH/NCI P50 CA90381]; Prostate Cancer Foundation; DOD synergist idea development award [PC130716]; Department of Defense Prostate Cancer Research Program [W81XWH-12-1-0072]; Dana-Farber Cancer Institute Mazzone Awards Program FX This work was supported by the NIH/NCI grant 2R01CA131945, the DF/HCC SPORE in Prostate Cancer (NIH/NCI P50 CA90381), the Prostate Cancer Foundation, the DOD synergist idea development award (PC130716) to M. Loda. J.L. Batista is supported, in part, by the Department of Defense Prostate Cancer Research Program (W81XWH-12-1-0072) and the Dana-Farber Cancer Institute Mazzone Awards Program. NR 144 TC 25 Z9 25 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUL PY 2015 VL 13 IS 7 BP 1059 EP 1072 DI 10.1158/1541-7786.MCR-15-0068 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CM9WF UT WOS:000358059500001 PM 25956158 ER PT J AU Talekar, M Ouyang, Q Goldberg, MS Amiji, MM AF Talekar, Meghna Ouyang, Qijun Goldberg, Michael S. Amiji, Mansoor M. TI Cosilencing of PKM-2 and MDR-1 Sensitizes Multidrug-Resistant Ovarian Cancer Cells to Paclitaxel in a Murine Model of Ovarian Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PYRUVATE-KINASE; DRUG-RESISTANCE; TARGETED DELIVERY; LUNG-CANCER; IN-VIVO; SIRNA; COMBINATION; GROWTH; M2; IDENTIFICATION AB Tumor multidrug resistance (MDR) is a serious clinical challenge that significantly limits the effectiveness of cytotoxic chemotherapy. As such, complementary therapeutic strategies are being explored to prevent relapse. The altered metabolic state of cancer cells, which perform aerobic glycolysis, represents an interesting target that can enable discrimination between healthy cells and cancer cells. We hypothesized that cosilencing of genes responsible for aerobic glycolysis and for MDR would have synergistic antitumor effect. In this study, siRNA duplexes against pyruvate kinase M2 and multidrug resistance gene-1 were encapsulated in hyaluronic acid-based self-assembling nanoparticles. The particles were characterized for morphology, size, charge, encapsulation efficiency, and transfection efficiency. In vivo studies included biodistribution assessment, gene knockdown confirmation, therapeutic efficacy, and safety analysis. The benefit of active targeting of cancer cells was confirmed by modifying the particles' surface with a peptide targeted to epidermal growth factor receptor, which is overexpressed on the membranes of the SKOV-3 cancer cells. To augment the studies involving transplantation of a paclitaxel-resistant cell line, an in vivo paclitaxel resistance model was developed by injecting repeated doses of paclitaxel following tumor inoculation. The nanoparticles accumulated significantly in the tumors, hindering tumor volume doubling time (P < 0.05) upon combination therapy in both the wild-type (2-fold) and resistant (8-fold) xenograft models. Although previous studies indicated that silencing of MDR-1 alone sensitized MDR ovarian cancer to paclitaxel only modestly, these data suggest that concurrent silencing of PKM-2 improves the efficacy of paclitaxel against MDR ovarian cancer. (C) 2014 AACR. C1 [Talekar, Meghna; Ouyang, Qijun; Amiji, Mansoor M.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Amiji, MM (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. EM michael_goldberg1@dfci.harvard.edu; m.amiji@neu.edu FU National Cancer Institute's (NCI) Cancer Nanotechnology Platform Partnership (CNPP) grant [U01-CA151452]; Dana-Farber Cancer Institute-Northeastern University Collaborative Grant on Development of Cancer Therapeutics; Ovarian Cancer Research Fund FX This study was partially supported by the National Cancer Institute's (NCI) Cancer Nanotechnology Platform Partnership (CNPP) grant U01-CA151452, the Dana-Farber Cancer Institute-Northeastern University Collaborative Grant on Development of Cancer Therapeutics, and the Ovarian Cancer Research Fund. NR 23 TC 5 Z9 5 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2015 VL 14 IS 7 BP 1521 EP 1531 DI 10.1158/1535-7163.MCT-15-0100 PG 11 WC Oncology SC Oncology GA CM9UZ UT WOS:000358055900001 PM 25964202 ER PT J AU Grabiner, B Wagle, N Van Allen, E Garraway, L Lorch, J Sabatini, D AF Grabiner, Brian Wagle, Nikhil Van Allen, Eliezer Garraway, Levi Lorch, Jochen Sabatini, David TI mTOR mutations in cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Grabiner, Brian; Sabatini, David] Whitehead Inst, Cambridge, MA 02142 USA. [Wagle, Nikhil; Van Allen, Eliezer; Garraway, Levi; Lorch, Jochen] 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 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2015 VL 14 IS 7 SU S MA PR04 DI 10.1158/1538-8514.PI3K14-PR04 PG 2 WC Oncology SC Oncology GA CN1EF UT WOS:000358159200111 ER PT J AU Papageorgiou, A Tamayo, P Mesirov, J Avruch, J Rapley, J AF Papageorgiou, Angela Tamayo, Pablo Mesirov, Jill Avruch, Joseph Rapley, Joseph TI A genome-wide siRNA screen in mammalian cells for regulators of S6 phosphorylation SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Papageorgiou, Angela; Tamayo, Pablo; Avruch, Joseph; Rapley, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mesirov, Jill] MIT, Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2015 VL 14 IS 7 SU S MA A30 DI 10.1158/1538-8514.PI3K14-A30 PG 2 WC Oncology SC Oncology GA CN1EF UT WOS:000358159200025 ER PT J AU Wulf, GM Juvekar, A Lyssiotis, CM Hu, H Baek, K Yadegarynia, S Scully, R Winer, E Asara, J Cantley, LC Matulonis, U AF Wulf, Gerburg M. Juvekar, Ashish Lyssiotis, Costas M. Hu, Hai Baek, Kim Yadegarynia, Sina Scully, Ralph Winer, Eric Asara, John Cantley, Lewis C. Matulonis, Ursula TI Combination treatments that include PI3K-inhibitors for the treatment of triple-negative breast cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Wulf, Gerburg M.; Juvekar, Ashish; Hu, Hai; Yadegarynia, Sina; Scully, Ralph; Asara, John] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lyssiotis, Costas M.; Cantley, Lewis C.] Weill Cornell Canc Ctr, New York, NY USA. [Baek, Kim] Emory Sch Med, Atlanta, GA USA. [Winer, Eric; Matulonis, Ursula] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 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 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2015 VL 14 IS 7 SU S MA IA21 DI 10.1158/1538-8514.PI3K14-IA21 PG 2 WC Oncology SC Oncology GA CN1EF UT WOS:000358159200104 ER PT J AU Zhao, JJ AF Zhao, Jean J. TI Targeting PI3K isoforms in cancer: From mouse genetics to human therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Zhao, Jean J.] 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 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2015 VL 14 IS 7 SU S MA IA13 DI 10.1158/1538-8514.PI3K14-IA13 PG 1 WC Oncology SC Oncology GA CN1EF UT WOS:000358159200097 ER PT J AU Krom, RJ Bhargava, P Lobritz, MA Collins, JJ AF Krom, Russell J. Bhargava, Prerna Lobritz, Michael A. Collins, James J. TI Engineered Phagemids for Nonlytic, Targeted Antibacterial Therapies SO NANO LETTERS LA English DT Article DE Antimicrobial peptides; phagemids; targeted bacterial killing; bacterial toxins; synthetic gene networks; bacteriophage resistance ID ESCHERICHIA-COLI; BACTERIOPHAGE RESISTANCE; ANTIMICROBIAL PEPTIDE; GUT MICROBIOTA; MECHANISMS; PROTEINS; GYRASE; HEALTH; TOXIN AB The increasing incidence of antibiotic-resistant bacterial infections is creating a global public health threat. Because conventional antibiotic drug discovery has failed to keep pace with the rise of resistance, a growing need exists to develop novel antibacterial methodologies. Replication-competent bacteriophages have been utilized in a limited fashion to treat bacterial infections. However, this approach can result in the release of harmful endotoxins, leading to untoward side effects. Here, we engineer bacterial phagemids to express antimicrobial peptides (AMPs) and protein toxins that disrupt intracellular processes, leading to rapid, nonlytic bacterial death. We show that this approach is highly modular, enabling one to readily alter the number and type of AMPs and toxins encoded by the phagemids. Furthermore, we demonstrate the effectiveness of engineered phagemids in an in vivo murine peritonitis infection model. This work shows that targeted, engineered phagemid therapy can serve as a viable, nonantibiotic means to treat bacterial infections, while avoiding the health issues inherent to lytic and replicative bacteriophage use. C1 [Krom, Russell J.; Bhargava, Prerna; Lobritz, Michael A.; Collins, James J.] MIT, Dept Biol Engn, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Krom, Russell J.; Bhargava, Prerna; Lobritz, Michael A.; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Krom, Russell J.; Collins, James J.] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA. [Bhargava, Prerna; Lobritz, Michael A.; Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Krom, Russell J.; Bhargava, Prerna; Lobritz, Michael A.; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Krom, Russell J.] Boston Univ, Dept Mol & Translat Med, Boston, MA 02215 USA. [Lobritz, Michael A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Collins, JJ (reprint author), MIT, Dept Biol Engn, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jimjc@mit.edu FU Defense Threat Reduction Agency [HDTRA1-14-1-0006]; Howard Hughes Medical Institute; Wyss Institute for Biologically Inspired Engineering FX This work was supported by supported by the Defense Threat Reduction Agency Grant HDTRA1-14-1-0006, the Howard Hughes Medical Institute, and the Wyss Institute for Biologically Inspired Engineering. Additionally, we would like to thank Caleb Bashor for his help in figure layout and design. NR 29 TC 7 Z9 7 U1 4 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD JUL PY 2015 VL 15 IS 7 BP 4808 EP 4813 DI 10.1021/acs.nanolett.5b01943 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CM8PM UT WOS:000357964100084 PM 26044909 ER PT J AU Bigelow, CA Bryant, AS AF Bigelow, Catherine A. Bryant, Allison S. TI Short Interpregnancy Intervals: An Evidence-Based Guide for Clinicians SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Article ID WOMEN DELAYING INITIATION; LOW-BIRTH-WEIGHT; PERINATAL OUTCOMES; UTERINE RUPTURE; INTERDELIVERY INTERVAL; SUBSEQUENT PREGNANCY; METHOTREXATE TREATMENT; MATERNAL MORBIDITY; ECTOPIC PREGNANCY; INDUCED-ABORTION AB The interpregnancy interval (IPI) is the period of time between one birth outcome (live birth, miscarriage, stillbirth, or abortion) and conception of a subsequent pregnancy. Short IPI has been associated with obstetric, fetal, and maternal morbidity. While the literature has largely supported an ideal IPI of 18 to 23 months after live birth to minimize morbidity in a subsequent pregnancy, there are few references that can guide clinicians counseling patients about IPI after other pregnancy outcomes. In this article, we attempt to review, synthesize, and provide evidence-based IPI recommendations using the available literature. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner will be better able to discuss the definition of the interpregnancy interval, identify risk factors for short interpregnancy intervals, and interpret the available evidence for perinatal and maternal morbidity associated with short interpregnancy intervals. C1 [Bigelow, Catherine A.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Bigelow, Catherine A.] Harvard Univ, Sch Med, Boston, MA USA. [Bryant, Allison S.] Harvard Univ, Sch Med, Obstet Gynecol & Reprod Biol, Boston, MA USA. RP Bigelow, CA (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. EM cbigelow@partners.org NR 49 TC 3 Z9 3 U1 0 U2 6 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 JUL PY 2015 VL 70 IS 7 BP 458 EP 464 DI 10.1097/OGX.0000000000000195 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CM5OO UT WOS:000357737800017 PM 26185917 ER PT J AU Mounir, Z Lin, F Lin, VG Korn, JM Yu, Y Valdez, R Aina, OH Buchwalter, G Jaffe, AB Korpal, M Zhu, P Brown, M Cardiff, RD Rocnik, JL Yang, Y Pagliarini, R AF Mounir, Z. Lin, F. Lin, V. G. Korn, J. M. Yu, Y. Valdez, R. Aina, O. H. Buchwalter, G. Jaffe, A. B. Korpal, M. Zhu, P. Brown, M. Cardiff, R. D. Rocnik, J. L. Yang, Y. Pagliarini, R. TI TMPRSS2: ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation SO ONCOGENE LA English DT Article ID ANDROGEN RECEPTOR; MOLECULAR CHARACTERIZATION; GENOME BROWSER; GENE FUSIONS; IN-VIVO; PROGRESSION; EXPRESSION; TRANSDIFFERENTIATION; ADENOCARCINOMA; HYBRIDIZATION AB The biological outcome of TMPRSS2: ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2: ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2: ERG-positive PC cell line. This reveals that ERG represses the expression of a previously unreported set of androgen receptor (AR)-independent neuronal genes that are indicative of neuroendocrine (NE) cell differentiation-in addition to previously reported AR-regulated luminal genes. Cell sorting and proliferation assays performed after sustained ERG knockdown indicate that ERG drives proliferation and blocks the differentiation of prostate cells to both NE and luminal cell types. Inhibition of ERG expression in TMPRSS2: ERG-positive PC cells through blockade of AR signaling is tracked with increased NE gene expression. We also provide evidence that these NE cells are resistant to pharmacological AR inhibition and can revert to the phenotype of parental cells upon restoration of AR/ERG signaling. Our findings highlight an ERG-regulated mechanism capable of repopulating the parent tumor through the transient generation of an anti-androgen therapy-resistant cell population, suggesting that ERG may have a direct role in preventing resistance to anti-androgen therapy. C1 [Mounir, Z.; Lin, F.; Lin, V. G.; Korn, J. M.; Yu, Y.; Valdez, R.; Jaffe, A. B.; Korpal, M.; Zhu, P.; Rocnik, J. L.; Yang, Y.; Pagliarini, R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. [Aina, O. H.; Cardiff, R. D.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Buchwalter, G.; Brown, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Buchwalter, G.; Brown, M.] Harvard Univ, Sch Med, Boston, MA USA. [Buchwalter, G.; Brown, M.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. RP Pagliarini, R (reprint author), Novartis Inst BioMed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM raymond.pagliarini@novartis.com OI Brown, Myles/0000-0002-8213-1658 FU Novartis Institutes for Biomedical Research; Novartis FX ZM is the recipient of presidential postdoctoral fellowship from the Novartis Institutes for Biomedical Research. ZM, FL, VGL, JMK, YY, RV, ABJ, YY and RP are all employees of Novartis Institutes for Biomedical Research. MK and PZ are employees of H3 Biomedicine. MB is a consultant to Novartis and the recipient of sponsored research support from Novartis. JLR is an employee of Sanofi. The other authors declare no conflict of interest. NR 46 TC 10 Z9 11 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUL PY 2015 VL 34 IS 29 BP 3815 EP 3825 DI 10.1038/onc.2014.308 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CM9BV UT WOS:000358001600007 PM 25263440 ER PT J AU Boucher, J Lucca, J Hooper, C Pedulla, L Berry, DL AF Boucher, Jean Lucca, Joan Hooper, Catherine Pedulla, Lillian Berry, Donna L. TI A Structured Nursing Intervention to Address Oral Chemotherapy Adherence in Patients With Non-Small Cell Lung Cancer SO ONCOLOGY NURSING FORUM LA English DT Article DE lung cancer; oral chemotherapy; adherence; knowledge; oncology nursing ID MEDICATION ADHERENCE; PREDICTIVE-VALIDITY; FOLLOW-UP; THERAPIES; EDUCATION; AGENTS; PEOPLE; SAFETY AB Purpose/Objectives: To evaluate a nurse-led intervention to enhance medication knowledge and adherence using the Multinational Association for Supportive Care in Cancer Oral Agent Teaching Tool (MOATT). Design: Longitudinal, descriptive feasibility study. Setting: An ambulatory thoracic oncology disease center located at the Dana-Farber Cancer Institute in Boston, MA. Sample: 30 adult patients with lung cancer who received the oral agent erlotinib. Methods: Structured, nurse-led education sessions using the MOATT were provided, with a 72-hour follow-up telephone contact. Participants completed a Knowledge Rating Scale (KRS) and adapted Morisky Medication Adherence Scale-8 (MMAS-8) at the end of the first cycle of oral chemotherapy. Main Research Variables: Knowledge and adherence; feasibility. Findings: Twenty-seven participants completed the study outcome measures reporting high knowledge levels and MMAS-8 scores. Structured, nurse-led education and follow-up monitoring sessions ranged from 14-30 minutes. Several participants also initiated contact for assistance with prescription procurement and symptom management. Participants reported a median of two side effects. Conclusions: The structured, nurse-led teaching, using the MOATT tool, and follow-up nurse contacts were feasible as integrated into the thoracic oncology setting. Adherence and knowledge outcomes were encouraging. Additional studies should include objective adherence measures and strategies for delivering supportive care to patients at home. Implications for Nursing: Structured teaching with patients is important to enhance proper oral anticancer medication knowledge and adherence, including follow-up monitoring of administration and side effects at 72 hours. C1 [Boucher, Jean; Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. [Boucher, Jean] Univ Massachusetts, Worcester Grad Sch Nursing, Amherst, MA 01003 USA. [Lucca, Joan; Hooper, Catherine] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Pedulla, Lillian] Dana Farber Canc Inst, Nursing Care Serv, Boston, MA 02115 USA. [Pedulla, Lillian] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Boucher, J (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. EM donna_berry@dfci.harvard.edu NR 48 TC 4 Z9 4 U1 6 U2 18 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2015 VL 42 IS 4 BP 383 EP 389 DI 10.1188/15.ONF.383-389 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA CM7UH UT WOS:000357901500006 PM 26148317 ER PT J AU Sarris, J Price, LH Carpenter, LL Tyrka, AR Ng, CH Papakostas, GI Jaeger, A Fava, M Mischoulon, D AF Sarris, J. Price, L. H. Carpenter, L. L. Tyrka, A. R. Ng, C. H. Papakostas, G. I. Jaeger, A. Fava, M. Mischoulon, D. TI Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial SO PHARMACOPSYCHIATRY LA English DT Article DE S-adenosyl methionine; SAMe; antidepressant; gender; depression; RCT; one-carbon cycle ID DOUBLE-BLIND; SAM-E; DISORDER; ADENOSYLMETHIONINE; AUGMENTATION; ESCITALOPRAM; PLACEBO AB Objective: The aim of this study was to examine whether gender differences may have affected treatment response to S-adenosyl methionine (SAMe) in a recent failed randomized clinical trial (RCT) for adults with major depressive disorder. Methods: Data from a 2-site, 12-week, double-blind RCT (n = 189) assessing the efficacy of SAMe vs. placebo and a comparator selective serotonin reuptake inhibitor (escitalopram) were subjected to post-hoc analyses to evaluate effects of patient gender on treatment response. Results: When assessing the efficacy outcomes within each gender separately, SAMe was superior to placebo among males (n = 51), but not among females (n = 62). Males showed a significant reduction of depression severity from baseline to study endpoint on the 17-item Hamilton Depression Rating Scale (4.3 point difference; p = 0.034; d = 0.95), while females did not show significant change. This finding emerged despite equivalence on baseline measures of depression severity between the gender groups. Conclusion: Results of this secondary data analysis suggest that gender might impact the antidepressant efficacy of SAMe, with greater therapeutic effect found in males. The underlying mechanism is still relatively unknown. Further work is needed to replicate this observation in independent samples. C1 [Sarris, J.; Ng, C. H.] Univ Melbourne, Dept Psychiat, Melbourne Clin, Melbourne, Vic, Australia. [Sarris, J.] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic, Australia. [Price, L. H.; Carpenter, L. L.; Tyrka, A. R.] Brown Univ, Mood Disorders Res Program, Providence, RI 02912 USA. [Price, L. H.; Carpenter, L. L.; Tyrka, A. R.] Brown Univ, Dept Psychiat & Human Behav, Lab Clin & Translat Neurosci, Butler Hosp,Alpert Med Sch, Providence, RI 02912 USA. [Papakostas, G. I.; Jaeger, A.; Fava, M.; Mischoulon, D.] Harvard Univ, Sch Med, Dept Psychiat, Depress Clin & Res Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne Clin, 2 Salisbury St, Melbourne, Vic, Australia. EM jsarris@unimelb.edu.au FU NIH; National Center for Complementary Added Alternative Medicine (NCCAM), R01 grant [R01AT001638]; CR Roper Fellowship FX The study was supported by the NIH and the National Center for Complementary Added Alternative Medicine (NCCAM), R01 grant R01AT001638. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, National Institutes of Health. SAMe tosylate and matching placebo were supplied by Pharmavite LLC, California. Dr. Jerome Sarris is supported by a CR Roper Fellowship. NR 16 TC 4 Z9 4 U1 3 U2 9 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 EI 1439-0795 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JUL PY 2015 VL 48 IS 4-5 BP 141 EP 144 DI 10.1055/s-0035-1549928 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA CM8HH UT WOS:000357939300003 PM 26011569 ER PT J AU Figlewicz, DP AF Figlewicz, Dianne P. TI Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective SO PSYCHOSOMATIC MEDICINE LA English DT Review ID NUCLEUS-ACCUMBENS DOPAMINE; CONDITIONED PLACE PREFERENCE; STRESS-INDUCED REINSTATEMENT; OPIOID RECEPTOR STIMULATION; HIGH-FAT DIET; REINFORCING EFFICACY; INTRAVENTRICULAR INSULIN; SUBTHALAMIC NUCLEUS; METABOLIC SYNDROME; PROGRESSIVE RATIO AB Objective Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. Methods A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. Results The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. Conclusions High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention. C1 [Figlewicz, Dianne P.] VA Puget Sound Hlth Care Syst, BSR&D Program, Seattle, WA 98108 USA. [Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 South Columbian Way, Seattle, WA 98108 USA. EM latte@uw.edu FU National Institutes of Health [DK40963]; American Recovery and Reinvestment Act FX The author's research described in this article is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, WA, and was supported by National Institutes of Health Grant DK40963 and by the American Recovery and Reinvestment Act. The author declared no conflicts of interest. NR 98 TC 3 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2015 VL 77 IS 6 BP 664 EP 670 DI 10.1097/PSY.0000000000000146 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CM5KI UT WOS:000357726300007 PM 25738439 ER PT J AU Silva, PS Aiello, LP AF Silva, Paolo S. Aiello, Lloyd Paul TI Untitled Reply SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Letter C1 [Silva, Paolo S.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUL PY 2015 VL 35 IS 7 BP E37 EP E38 DI 10.1097/IAE.0000000000000640 PG 2 WC Ophthalmology SC Ophthalmology GA CM2AD UT WOS:000357481000006 PM 26057398 ER PT J AU Seidman, LJ Nordentoft, M AF Seidman, Larry J. Nordentoft, Merete TI New Targets for Prevention of Schizophrenia: Is It Time for Interventions in the Premorbid Phase? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical high risk; family high risk; prodrome; premorbid; prenatal; perinatal; primary prevention; endop henotype; critical period; early intervention ID RANDOMIZED CONTROLLED-TRIAL; ULTRA-HIGH RISK; YOUNG-PEOPLE; 1ST-EPISODE PSYCHOSIS; FUTURE-DIRECTIONS; BRAIN-DEVELOPMENT; CLINICAL-TRIAL; FAMILIAL RISK; FOLLOW-UP; PSYCHIATRY AB A number of influences have converged that make this Special Theme Issue timely: "A New Direction: Considering Developmentally Sensitive Targets for Very Early Intervention in Schizophrenia". These factors include: 1. the substantial knowledge about premorbid developmental vulnerabilities to psychosis, especially regarding schizophrenia; 2. the promising results emerging from interventions during the clinical high-risk (CHR) phase of psychosis and; 3. the recognition that the CHR period is a relatively late phase of developmental derailment. These factors have together led to a perspective that even earlier intervention is warranted. This paper briefly summarizes the articles comprising the Special Theme including new data on early neurocognitive development, proposed potential targets for psychosocial and psychopharmacological interventions during the premorbid period as early as pregnancy, and ethical challenges. These thought experiments must be empirically tested, and the ethical challenges overcome as posed by the various interventions, which range from relatively low risk, supportive, psychosocial to higher risk, experimental, pharmacological interventions. All of the interventions proposed require careful study of ethics, safety, potential stigma, feasibility, efficacy and tolerability, and the meaning to the people involved. C1 [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat,Med Sch, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Nordentoft, Merete] Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark. [Nordentoft, Merete] Mental Hlth Ctr Copenhagen, Mental Hlth Serv Capital Reg Denmark, Copenhagen, Denmark. RP Seidman, LJ (reprint author), Massachusetts Mental Hlth Ctr, Commonwealth Res Ctr, Room 542,75 Fenwood Rd, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu FU Commonwealth Research Center [SCDMH82101008006]; NIMH [R21 MH092840] FX Supported by the Commonwealth Research Center (SCDMH82101008006) and NIMH R21 MH092840. NR 59 TC 8 Z9 8 U1 8 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2015 VL 41 IS 4 BP 795 EP 800 DI 10.1093/schbul/sbv050 PG 6 WC Psychiatry SC Psychiatry GA CM7QV UT WOS:000357891500007 PM 25925393 ER PT J AU Liu, CH Keshavan, MS Tronick, E Seidman, LJ AF Liu, Cindy H. Keshavan, Matcheri S. Tronick, Ed Seidman, Larry J. TI Perinatal Risks and Childhood Premorbid Indicators of Later Psychosis: Next Steps for Early Psychosocial Interventions SO SCHIZOPHRENIA BULLETIN LA English DT Article DE psychosis; schizophrenia; early intervention; prevention; stress; psychological; parenting ID SEVERE MENTAL-ILLNESS; SCHIZOPHRENIA-SPECTRUM DISORDERS; GENOTYPE-ENVIRONMENT INTERACTION; COGNITIVE REMEDIATION THERAPY; JERUSALEM INFANT DEVELOPMENT; NEW-ENGLAND FAMILY; CLINICAL HIGH-RISK; 1966 BIRTH COHORT; ADULT SCHIZOPHRENIA; OBSTETRIC COMPLICATIONS AB Schizophrenia and affective psychoses are debilitating disorders that together affect 2%-3% of the adult population. Approximately 50%-70% of the offspring of parents with schizophrenia manifest a range of observable difficulties including socioemotional, cognitive, neuromotor, speech-language problems, and psychopathology, and roughly 10% will develop psychosis. Despite the voluminous work on pre-morbid vulnerabilities to psychosis, especially on schizophrenia, the work on premorbid intervention approaches is scarce. While later interventions during the clinical high-risk (CHR) phase of psychosis, characterized primarily by attenuated positive symptoms, are promising, the CHR period is a relatively late phase of developmental derailment. This article reviews and proposes potential targets for psychosocial interventions during the premorbid period, complementing biological interventions described by others in this Special Theme issue. Beginning with pregnancy, parents with psychoses may benefit from enhanced prenatal care, social support, parenting skills, reduction of symptoms, and programs that are family-centered. For children at risk, we propose preemptive early intervention and cognitive remediation. Empirical research is needed to evaluate these interventions for parents and determine whether interventions for parents and children positively influence the developmental course of the offspring. C1 [Liu, Cindy H.; Keshavan, Matcheri S.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Psychiat, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Liu, Cindy H.; Tronick, Ed] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Tronick, Ed] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Newborn Med, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Liu, CH (reprint author), 75 Fenwood Rd, Boston, MA 02115 USA. EM cliu@bidmc.harvard.edu FU Commonwealth Research Center [SCDMH82101008006]; NIMH [R21 MH092840] FX Commonwealth Research Center (SCDMH82101008006) and NIMH (R21 MH092840). NR 247 TC 6 Z9 6 U1 19 U2 35 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2015 VL 41 IS 4 BP 801 EP 816 DI 10.1093/schbul/sbv047 PG 16 WC Psychiatry SC Psychiatry GA CM7QV UT WOS:000357891500008 PM 25904724 ER PT J AU Agnew-Blais, JC Buka, SL Fitzmaurice, GM Smoller, JW Goldstein, JM Seidman, LJ AF Agnew-Blais, Jessica C. Buka, Stephen L. Fitzmaurice, Garrett M. Smoller, Jordan W. Goldstein, Jill M. Seidman, Larry J. TI Early Childhood IQ Trajectories in Individuals Later Developing Schizophrenia and Affective Psychoses in the New England Family Studies SO SCHIZOPHRENIA BULLETIN LA English DT Article DE IQ; cognition; schizophrenia; affective psychosis; cognitive development ID ADULT SCHIZOPHRENIA; STANFORD-BINET; BIRTH COHORT; RISK-FACTORS; PERFORMANCE; DISORDER; CHILDREN; DECLINE; UPDATE; DEFECT AB Individuals who develop schizophrenia in adulthood exhibit, on average, deficits in childhood cognition relative to healthy controls. However, it remains unclear when in childhood such deficits emerge and whether they are stable across childhood or change (increase or decrease) across development. Importantly, whether the trajectory of childhood cognition differs among youth who later develop affective psychoses (AP) vs schizophrenia as adults remains unresolved. Subjects in the Collaborative Perinatal Project were administered the Stanford-Binet IQ test at age 4 and the Wechsler Intelligence Scale for Children at age 7. A total of 9809 (54.7%) participants in the New England Study sites were tested at both ages, including 37 who later developed schizophrenia spectrum psychoses (SSP) and 39 who later developed AP. Logistic regression models examined the association of level of and change in childhood IQ and later SSP or AP. Lower overall childhood IQ was associated with higher risk of SSP. Additionally, there was a small mean increase in IQ in the SSP group relative to a mean decrease in the control group from age 4 to 7 such that positive change in IQ was significantly associated with a higher risk of SSP. Neither overall level nor change in IQ was associated with risk of AP. The results are consistent with neurocognitive impairment throughout early childhood specifically for children who later develop schizophrenia, affirming the theory of atypical neurodevelopment in premorbid schizophrenia. C1 [Agnew-Blais, Jessica C.] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Buka, Stephen L.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Fitzmaurice, Garrett M.] Harvard Univ, McLean Hosp, Sch Med, Lab Psychiat Biostat, Belmont, MA USA. [Fitzmaurice, Garrett M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Sch Med,Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med,Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill M.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02115 USA. RP Agnew-Blais, JC (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, 16 De Crespigny Pk,Denmark Hill, London SE5 8AF, England. EM jessica.agnew-blais@kcl.ac.uk RI Agnew-Blais, Jessica/L-9236-2015 OI Agnew-Blais, Jessica/0000-0002-0755-6867 FU National Institute of Mental Health [T32MH017119, R21 MH091461, RO1 MH56956, R01MH63951]; Commonwealth of Massachusetts [SCDMH82101008006]; Stanley Medical Research Institute FX J.C.A.-B. was supported during work on this manuscript by National Institute of Mental Health (T32MH017119). L.J.S. is supported by the Commonwealth of Massachusetts (SCDMH82101008006) and National Institute of Mental Health (R21 MH091461). Ascertainment and assessment of subjects were originally funded under National Institute of Mental Health (RO1 MH56956 to J.M.G., P.I., Stanley Medical Research Institute [S.L.B. and J.M.G., 1994-1997]) and National Institute of Mental Health (R01MH63951 to L.J.S., P.I.). The funders played 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. NR 38 TC 7 Z9 8 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2015 VL 41 IS 4 BP 817 EP 823 DI 10.1093/schbul/sbv027 PG 7 WC Psychiatry SC Psychiatry GA CM7QV UT WOS:000357891500009 PM 25904723 ER PT J AU Karambelkar, A Kasekar, R Palevsky, PM AF Karambelkar, Ameet Kasekar, Riyaj Palevsky, Paul M. TI Perioperative Pharmacologic Management of Patients with End Stage Renal Disease SO SEMINARS IN DIALYSIS LA English DT Article ID SUCCINYLCHOLINE-INDUCED HYPERKALEMIA; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; PHARMACOKINETICS; FAILURE; MORPHINE; HYDROMORPHONE; INSUFFICIENCY; SUXAMETHONIUM; METABOLISM AB The pharmacokinetics of numerous medications used in the perioperative period are altered in patients with end-stage renal disease. Clearance of drugs, or their metabolites, that are normally excreted by the kidney is markedly reduced in ESRD. In addition, patients with ESRD may also have alterations in gastrointestinal absorption, volume of distribution, protein binding, and metabolic clearance of pharmacologic agents. Finally, drug removal may be augmented during dialysis. All of these factors contribute to the need for dose adjustment of medications, including analgesics, anesthetics, neuromuscular blockers, and antimicrobial agents, which may be used in the perioperative management of the ESRD patient. C1 [Karambelkar, Ameet; Kasekar, Riyaj; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Med Serv, Renal Sect, Pittsburgh, PA 15240 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 54 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 JUL-AUG PY 2015 VL 28 IS 4 BP 392 EP 396 DI 10.1111/sdi.12384 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CM4WZ UT WOS:000357687800012 PM 25876523 ER PT J AU Austin, JH Mieure, KD Weber, LM McCarthy, BC AF Austin, Jennifer H. Mieure, Katherine D. Weber, Lynn M. McCarthy, Bryan C., Jr. TI National characteristics of residency program interview processes SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter ID MULTIPLE MINI-INTERVIEWS C1 [Austin, Jennifer H.] Univ Chicago Med, Dept Pharm Serv, Internal Med, Chicago, IL 60637 USA. [Mieure, Katherine D.] Massachusetts Gen Hosp, Dept Pharm, Pharm, Clin Serv, Boston, MA 02114 USA. [Weber, Lynn M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [McCarthy, Bryan C., Jr.] Univ Chicago Med, Dept Pharm Serv, Ambulatory Care Pharm Serv & Clin, Chicago, IL USA. [McCarthy, Bryan C., Jr.] Univ Chicago Med, Dept Pharm Serv, Qual Outcomes & Utilizat, Chicago, IL USA. RP Austin, JH (reprint author), Univ Chicago Med, Dept Pharm Serv, Internal Med, Chicago, IL 60637 USA. EM jennifer.austin@uchospitals.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 2015 VL 72 IS 13 BP 1085 EP 1086 DI 10.2146/ajhp150052 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CM1LJ UT WOS:000357442100004 PM 26092955 ER PT J AU Reddy, A Shea, JA Canamucio, A Werner, RM AF Reddy, Ashok Shea, Judy A. Canamucio, Anne Werner, Rachel M. TI The Effect of Organizational Climate on Patient-Centered Medical Home Implementation SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE medical home; organizational climate; veterans; primary care delivery ID HEALTH-CARE; PERFORMANCE; READINESS; SERVICES; CULTURE; SAFETY; MODEL AB Organizational climate is a key determinant of successful adoption of innovations; however, its relation to medical home implementation is unknown. This study examined the association between primary care providers' (PCPs') perception of organization climate and medical home implementation in the Veterans Health Administration. Multivariate regression was used to test the hypothesis that organizational climate predicts medical home implementation. This analysis of 191 PCPs found that higher scores in 2 domains of organizational climate (communication and cooperation, and orientation to quality improvement) were associated with a statistically significantly higher percentage (from 7 to 10 percentage points) of PCPs implementing structural changes to support the medical home model. In addition, some aspects of a better organizational climate were associated with improved organizational processes of care, including a higher percentage of patients contacted within 2 days of hospital discharge (by 2 to 3 percentage points) and appointments made within 3 days of a patient request (by 2 percentage points). C1 [Reddy, Ashok; Shea, Judy A.; Canamucio, Anne; Werner, Rachel M.] Philadelphia VA Med Ctr, VISN Ctr Evaluat PACT 4, Philadelphia, PA USA. [Reddy, Ashok; Shea, Judy A.; Werner, Rachel M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Reddy, Ashok; Shea, Judy A.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Reddy, Ashok] Univ Penn, Robert Wood Johnson Clin Scholar Program, Philadelphia, PA 19104 USA. RP Reddy, A (reprint author), Univ Penn, Perelman Sch Med, Blockley Hall 1303,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ashokr@upenn.edu FU Veterans Administration's PACT (Patient-Aligned Care Team) Demonstration Laboratory initiative; VA Office of Patient Care Services FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was undertaken as part of the Veterans Administration's PACT (Patient-Aligned Care Team) Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. Ashok Reddy MD, is a Robert Wood Johnson Foundation Clinical Scholar at University of Pennsylvania. NR 20 TC 1 Z9 1 U1 2 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD JUL-AUG PY 2015 VL 30 IS 4 BP 309 EP 316 DI 10.1177/1062860614532516 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CM5AQ UT WOS:000357698700001 PM 24788252 ER PT J AU Palen, BN Kapur, VK AF Palen, Brian N. Kapur, Vishesh K. TI Tailoring Therapy for Obesity Hypoventilation Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID POSITIVE-PRESSURE VENTILATION; NONINVASIVE VENTILATION; RANDOMIZED-TRIAL; SLEEP; SUPPORT; MANAGEMENT; EFFICACY; IMPACT C1 [Palen, Brian N.; Kapur, Vishesh K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Palen, Brian N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Palen, BN (reprint author), Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. OI Kapur, Vishesh/0000-0002-5417-1097 NR 14 TC 1 Z9 1 U1 0 U2 2 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 JUL 1 PY 2015 VL 192 IS 1 BP 8 EP 10 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CM6YY UT WOS:000357838800006 PM 26131989 ER PT J AU Giordano, S Hage, FG Xing, DQ Chen, YF Allon, S Chen, CJ Oparil, S AF Giordano, Samantha Hage, Fadi G. Xing, Dongqi Chen, Yiu-Fai Allon, Steven Chen, Chongjia Oparil, Suzanne TI Estrogen and Cardiovascular Disease: Is Timing Everything? SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; RAT CAROTID-ARTERY; ADVENTITIAL FIBROBLAST MIGRATION; PROTEIN TRANSGENIC MICE; SMOOTH-MUSCLE-CELLS; REPLACEMENT THERAPY; NEOINTIMA FORMATION; BALLOON INJURY C1 [Giordano, Samantha; Hage, Fadi G.; Xing, Dongqi; Chen, Yiu-Fai; Allon, Steven; Chen, Chongjia; Oparil, Suzanne] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Giordano, S (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, 703 19th St South,Zeigler Res Bldg,Room 1047, Birmingham, AL 35294 USA. EM sgiordan@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU National Heart, Lung and Blood Institute [R01 HL087980, T32 HL07457]; Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award OMB [4040-0001] FX Supported, in part, by National Heart, Lung and Blood Institute Grant R01 HL087980 (S.O.) and T32 HL07457 (S.O. and S.G.) and by Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award OMB 4040-0001 (F.G.H.). NR 58 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD JUL PY 2015 VL 350 IS 1 BP 27 EP 35 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CM2KA UT WOS:000357507400002 PM 26110752 ER PT J AU Khosroshahi, A Wallace, ZS Crowe, JL Akamizu, T Azumi, A Carruthers, MN Chari, ST Della-Torre, E Frulloni, L Goto, H Hart, PA Kamisawa, T Kawa, S Kawano, M Kim, MH Kodama, Y Kubota, K Lerch, MM Lohr, M Masaki, Y Matsui, S Mimori, T Nakamura, S Nakazawa, T Ohara, H Okazaki, K Ryu, JH Saeki, T Schleinitz, N Shimatsu, A Shimosegawa, T Takahashi, H Takahira, M Tanaka, A Topazian, M Umehara, H Webster, GJ Witzig, TE Yamamoto, M Zhang, W Chiba, T Stone, JH AF Khosroshahi, A. Wallace, Z. S. Crowe, J. L. Akamizu, T. Azumi, A. Carruthers, M. N. Chari, S. T. Della-Torre, E. Frulloni, L. Goto, H. Hart, P. A. Kamisawa, T. Kawa, S. Kawano, M. Kim, M. H. Kodama, Y. Kubota, K. Lerch, M. M. Lohr, M. Masaki, Y. Matsui, S. Mimori, T. Nakamura, S. Nakazawa, T. Ohara, H. Okazaki, K. Ryu, J. H. Saeki, T. Schleinitz, N. Shimatsu, A. Shimosegawa, T. Takahashi, H. Takahira, M. Tanaka, A. Topazian, M. Umehara, H. Webster, G. J. Witzig, T. E. Yamamoto, M. Zhang, W. Chiba, T. Stone, J. H. TI International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; IGG4-POSITIVE PLASMA-CELLS; CHURG-STRAUSS-SYNDROME; SERUM IGG4 LEVELS; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; CORTICOSTEROID-TREATMENT; DIAGNOSTIC-CRITERIA; CLINICOPATHOLOGICAL-ENTITY; RETROSPECTIVE MULTICENTER C1 [Khosroshahi, A.] Emory Univ, Sch Med, Atlanta, GA USA. [Wallace, Z. S.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crowe, J. L.] Univ Tennessee, Coll Med, Chattanooga, TN USA. [Akamizu, T.] Wakayama Med Univ, Tokyo, Japan. [Azumi, A.] Kobe Kaisei Hosp, Kobe, Hyogo, Japan. [Carruthers, M. N.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Chari, S. T.; Ryu, J. H.; Topazian, M.; Witzig, T. E.] Mayo Clin, Rochester, MN USA. [Della-Torre, E.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Frulloni, L.] Univ Verona, I-37100 Verona, Italy. [Goto, H.] Tokyo Med Univ, Tokyo 1608402, Japan. [Hart, P. A.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Hart, P. A.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Kamisawa, T.] Tokyo Metropolitan Komagome Hosp, Tokyo, Japan. [Kawa, S.] Shinshu Univ, Matsumoto, Nagano 390, Japan. [Kawano, M.; Takahira, M.] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. [Kawano, M.; Takahira, M.] Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan. [Kim, M. H.] Univ Ulsan, Coll Med, Ulsan 680749, South Korea. [Kim, M. H.] Asan Med Ctr, Ulsan, South Korea. [Kodama, Y.; Mimori, T.; Chiba, T.] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Kubota, K.] Yokohama City Univ, Yokohama, Kanagawa 232, Japan. [Kubota, K.] Yokohama City Univ Med, Yokohama, Kanagawa, Japan. [Lerch, M. M.] Ernst Moritz Arndt Univ Greifswald, Sch Med, Greifswald, Germany. [Lohr, M.] Karolinska Inst, Stockholm, Sweden. [Masaki, Y.; Umehara, H.] Kanazawa Med Univ, Kanazawa, Ishikawa, Japan. [Matsui, S.] Toyama Univ, Toyama 930, Japan. [Nakamura, S.] Kyushu Univ, Fukuoka 812, Japan. [Nakamura, S.] Kyushu Univ, Dent Hosp, Fukuoka 812, Japan. [Nakazawa, T.; Ohara, H.] Nagoya City Univ, Grad Sch Med, Nagoya, Aichi, Japan. [Okazaki, K.] Kansai Med Univ, Hirakata, Osaka, Japan. [Saeki, T.] Nagaoka Red Cross Hosp, Nagaoka, Niigata, Japan. [Schleinitz, N.] Aix Marseille Univ, Assistance Publ Hop Marseille, Marseille, France. [Shimatsu, A.] Natl Hosp Org Kyoto Med Ctr, Kyoto, Japan. [Shimosegawa, T.] Tohoku Univ, Tokyo, Japan. [Takahashi, H.; Yamamoto, M.] Sapporo Med Univ, Sch Med, Sapporo, Hokkaido, Japan. [Tanaka, A.] Teikyo Univ, Sch Med, Tokyo 173, Japan. [Webster, G. J.] UCL, London, England. [Webster, G. J.] Univ Coll London Hosp, London, England. [Zhang, W.] Chinese Acad Med Sci, Beijing 100730, Peoples R China. [Zhang, W.] Beijing Union Med Coll Hosp, Beijing, Peoples R China. RP Chiba, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan. EM chiba@kuhp.kyoto-u.ac.jp; jhstone@mgh.harvard.edu RI Lerch, Markus M./E-2206-2016; Hart, Phil/A-9842-2016; OI Lerch, Markus M./0000-0002-9643-8263; Hart, Phil/0000-0003-4346-6196; Della Torre, Emanuel/0000-0002-9192-4270; Lohr, Matthias/0000-0002-7647-198X; Frulloni, Luca/0000-0001-7417-2655 FU Chiesi Pharmaceuticals; Genentech; Japanese Ministry of Health, Labor, and Welfare; Amgen FX The Second International Symposium on IgG4-Related Disease was funded by the Japanese Ministry of Health, Labor, and Welfare, Amgen, and Genentech.Dr. Frulloni has received consulting fees, speaking fees, and/or honoraria from Chiesi Pharmaceuticals (less than $10,000). Dr. Stone has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000). NR 78 TC 74 Z9 83 U1 5 U2 12 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 JUL PY 2015 VL 67 IS 7 BP 1688 EP 1699 DI 10.1002/art.39132 PG 12 WC Rheumatology SC Rheumatology GA CL5QA UT WOS:000357013500002 PM 25809420 ER PT J AU Baker, JF Billig, E Michaud, K Ibrahim, S Caplan, L Cannon, GW Stokes, A Majithia, V Mikuls, TR AF Baker, Joshua F. Billig, Erica Michaud, Kaleb Ibrahim, Said Caplan, Liron Cannon, Grant W. Stokes, Andrew Majithia, Vikas Mikuls, Ted R. TI Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID BODY-MASS INDEX; DISEASE-ACTIVITY; US VETERANS; MORTALITY-RISKS; OLDER-ADULTS; HEALTH; ASSOCIATION; POPULATION; CATEGORIES; OVERWEIGHT AB ObjectiveIn contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether weight loss might explain these seemingly paradoxical observations. MethodsOur study included patients identified from the Veterans Affairs (VA) RA Registry. Dates of death were abstracted from VA electronic medical records. The BMI at each study visit and the change from the previous visit were determined. The maximum BMI of each patient was also obtained from medical records. The annualized rate of BMI loss was determined from the slope of change (per year) in BMI over visits within the preceding 13 months. Cox multivariable proportional hazards models were used to assess associations between BMI measures and mortality. ResultsIn a sample of 1,674 patients, 312 deaths occurred over 9,183 person-years. A loss in BMI of 1 kg/m(2) was associated with a greater risk of death, after adjustment for demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio [HR] 1.99, 95% confidence interval [95% CI] 1.53-2.59, P<0.001). This association remained significant in a subsample analysis adjusting for C-reactive protein and physical function (HR 1.81, 95% CI 1.36-2.41, P<0.001). Weight loss at an annualized rate of 3 kg/m(2) was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P<0.001). Low BMI (<20 kg/m(2)) in patients with a history of obesity (>30 kg/m(2)) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P<0.001). ConclusionWeight loss is a strong predictor of death in patients with RA. These observations may explain the observed obesity paradox and do not support a biologically protective role of obesity. C1 [Baker, Joshua F.; Ibrahim, Said] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Baker, Joshua F.; Billig, Erica; Ibrahim, Said] Univ Penn, Philadelphia, PA 19104 USA. [Michaud, Kaleb; Mikuls, Ted R.] Nebraska Western Iowa VA Med Ctr, Omaha, NE USA. [Michaud, Kaleb; Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Cannon, Grant W.] Salt Lake City VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Stokes, Andrew] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Majithia, Vikas] GV Sonny Montgomery VA Med Ctr, Montgomery, MS USA. [Majithia, Vikas] Univ Mississippi, Med Ctr, Jackson, MS USA. RP Baker, JF (reprint author), Hosp Univ Penn, Div Rheumatol, Dept Med, 8 Penn Tower Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu OI Stokes, Andrew/0000-0002-8502-3636 FU VA Clinical Science Research and Development Career Development Award [IK2 CX000955]; Rheumatology Research Foundation; NIH from National Institute of Arthritis and Musculoskeletal and Skin Diseases [1-K24-AR-055259-01]; VA Health Service Research and Development Career Development Award [07-221]; VA Merit Award; Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; VA Health Services Research and Development Program of the Veterans Health Administration FX Dr. Baker's work was supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Dr. Michaud's work was supported by a Rheumatology Research Foundation Investigator Award. Dr. Ibrahim's work was supported by the NIH (grant 1-K24-AR-055259-01 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases). Dr. Caplan's work was supported by a VA Health Service Research and Development Career Development Award (07-221). Dr. Mikuls' work was supported by a VA Merit Award. The VA Rheumatoid Arthritis Registry is supported by the Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center and by the VA Health Services Research and Development Program of the Veterans Health Administration. NR 33 TC 14 Z9 14 U1 1 U2 5 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 JUL PY 2015 VL 67 IS 7 BP 1711 EP 1717 DI 10.1002/art.39136 PG 7 WC Rheumatology SC Rheumatology GA CL5QA UT WOS:000357013500005 PM 25940140 ER PT J AU Grayson, PC Carmona-Rivera, C Xu, LJ Lim, N Gao, Z Asare, AL Specks, U Stone, JH Seo, P Spiera, RF Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, NK Ytterberg, SR Phippard, DJ Merkel, PA Kaplan, MJ Monach, PA AF Grayson, Peter C. Carmona-Rivera, Carmelo Xu, Lijing Lim, Noha Gao, Zhong Asare, Adam L. Specks, Ulrich Stone, John H. Seo, Philip Spiera, Robert F. Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Tchao, Nadia K. Ytterberg, Steven R. Phippard, Deborah J. Merkel, Peter A. Kaplan, Mariana J. Monach, Paul A. CA Rituximab ANCA-Associated TI Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SMALL-VESSEL VASCULITIS; ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; TREATMENT RESISTANCE; NETTING NEUTROPHILS; EXTRACELLULAR TRAPS; RELAPSE; TRANSCRIPTION; PROTEINASE-3; PREDICTORS AB ObjectiveTo discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to determine whether low-density granulocytes (LDGs) contribute to gene expression signatures in AAV. MethodsThe source of clinical data and linked biologic specimens was a randomized controlled treatment trial in AAV. RNA sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit and during remission 6 months later. Gene expression was compared between patients who met versus those who did not meet the primary trial outcome of clinical remission at 6 months (responders versus nonresponders). Measurement of neutrophil-related gene expression was confirmed in peripheral blood mononuclear cells (PBMCs) to validate the findings in whole blood. A negative-selection strategy isolated LDGs from PBMC fractions. ResultsDifferential expression between responders (n=77) and nonresponders (n=35) was detected in 2,346 transcripts at the baseline visit (P<0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multigene composite score was significantly higher in nonresponders than in responders (P<0.01) and during active disease than during remission (P<0.01). This signature strongly overlapped an LDG signature identified previously in lupus (false discovery rate by gene set enrichment analysis <0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (P<0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO. ConclusionIn AAV, increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV. C1 [Grayson, Peter C.; Carmona-Rivera, Carmelo; Kaplan, Mariana J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Xu, Lijing; Lim, Noha; Gao, Zhong; Asare, Adam L.; Tchao, Nadia K.; Phippard, Deborah J.] Immune Tolerance Network, Bethesda, MD USA. [Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin Fdn, Rochester, MN USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. [Monach, Paul A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Grayson, PC (reprint author), NIAMSD, NIH, 10 Ctr Dr,Bldg 10,Room 216G, Bethesda, MD 20892 USA. EM peter.grayson@nih.gov FU Immune Tolerance Network (NIH), an international clinical research consortium headquartered at the University of California San Francisco [N01-AI-15416]; NIH through National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program; National Center for Advancing Translational Sciences (Boston University-Clinical and Translational Science Institute) [KL2-TR-000158]; Rheumatology Scientist Development Award from Rheumatology Research Foundation; Genentech; ChemoCentryx; GlaxoSmithKline; Eli Lilly; MedImmune FX The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed with the support of the Immune Tolerance Network (NIH contract N01-AI-15416, protocol number ITN-21AI), an international clinical research consortium headquartered at the University of California San Francisco. Additional support was provided by the NIH through the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program and the National Center for Advancing Translational Sciences (Boston University-Clinical and Translational Science Institute grant KL2-TR-000158). Dr. Grayson's work was supported by a Rheumatology Scientist Development Award from the Rheumatology Research Foundation.; Drs. Specks and Stone have received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000). Dr. Kallenberg has received consulting fees from ChemoCentryx, GlaxoSmithKline, Eli Lilly, and MedImmune (less than $10,000 each). NR 38 TC 19 Z9 20 U1 1 U2 1 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 JUL PY 2015 VL 67 IS 7 BP 1922 EP 1932 DI 10.1002/art.39153 PG 11 WC Rheumatology SC Rheumatology GA CL5QA UT WOS:000357013500028 PM 25891759 ER PT J AU Da Silva, N Smith, TB AF Da Silva, Nicolas Smith, Tegan B. TI Exploring the role of mononuclear phagocytes in the epididymis SO ASIAN JOURNAL OF ANDROLOGY LA English DT Review DE antigen-presenting cells; autoimmunity; dendritic cells; epididymis; macrophages; peripheral tolerance; sperm maturation; spermatozoa ID CD103(+) DENDRITIC CELLS; SPERM QUALITY-CONTROL; REGULATORY T-CELLS; MOUSE EPIDIDYMIS; RAT EPIDIDYMIS; BASAL-CELLS; IN-VIVO; MURINE EPIDIDYMIS; GENE-EXPRESSION; LUMINAL FACTORS AB The onslaught of foreign antigens carried by spermatozoa into the epididymis, an organ that has not demonstrated immune privilege, a decade or more after the establishment of central immune tolerance presents a unique biological challenge. Historically, the physical confinement of spermatozoa to the epididymal tubule enforced by a tightly interwoven wall of epithelial cells was considered sufficient enough to prevent cross talk between gametes and the immune system and, ultimately, autoimmune destruction. The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment. This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa. Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility. C1 [Da Silva, Nicolas] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Nephrol, Ctr Syst Biol, Boston, MA USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU National Institutes of Health [5R01HD069623] FX Our research is supported by National Institutes of Health grant 5R01HD069623. We thank Claire R Barton for her help in proofing this manuscript. NR 73 TC 3 Z9 3 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD JUL PY 2015 VL 17 IS 4 BP 591 EP 596 DI 10.4103/1008-682X.153540 PG 6 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CL9HR UT WOS:000357288800011 PM 25966624 ER PT J AU Leuchter, AF Cook, IA Feifel, D Goethe, JW Husain, M Carpenter, LL Thase, ME Krystal, AD Philip, NS Bhati, MT Burke, WJ Howland, RH Sheline, YI Aaronson, ST Iosifescu, DV O'Reardon, JP Gilmer, WS Jain, R Burgoyne, KS Phillips, B Manberg, PJ Massaro, J Hunter, AM Lisanby, SH George, MS AF Leuchter, Andrew F. Cook, Ian A. Feifel, David Goethe, John W. Husain, Mustafa Carpenter, Linda L. Thase, Michael E. Krystal, Andrew D. Philip, Noah S. Bhati, Mahendra T. Burke, William J. Howland, Robert H. Sheline, Yvette I. Aaronson, Scott T. Iosifescu, Dan V. O'Reardon, John P. Gilmer, William S. Jain, Rakesh Burgoyne, Karl S. Phillips, Bill Manberg, Paul J. Massaro, Joseph Hunter, Aimee M. Lisanby, Sarah H. George, Mark S. TI Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression SO BRAIN STIMULATION LA English DT Article DE Synchronized Transcranial Magnetic Stimulation (sTMS); Low-intensity magnetic field; Static magnet; Major Depressive Disorder; Clinical treatment trial; Neuromodulation; Individual Alpha Frequency (IAF); Alpha oscillations; Electroencephalogram (EEG); Oscillatory synchrony ID SHAM-CONTROLLED TRIALS; ALPHA-FREQUENCY; RATING-SCALE; DOUBLE-BLIND; METAANALYSIS; RTMS; TMS; MEDICATION; MULTISITE; EEG AB Background: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events. Objective/Hypothesis: To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD. Methods: Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD(17)) >= 17. Results: 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD(17) than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naive subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS. Conclusions: Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended. (C) 2015 Elsevier Inc. All rights reserved. C1 [Leuchter, Andrew F.; Cook, Ian A.; Hunter, Aimee M.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Leuchter, Andrew F.; Cook, Ian A.; Hunter, Aimee M.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Neuromodulat Div, Los Angeles, CA 90024 USA. [Feifel, David] UCSD Sch Med, Dept Psychiat, San Diego, CA USA. [Goethe, John W.] Hartford Hosp, Inst Living, Hartford, CT 06115 USA. [Husain, Mustafa] UT Southwestern Med Sch, Dept Psychiat, Dallas, TX USA. [Carpenter, Linda L.; Philip, Noah S.] Brown Univ, Alpert Med Sch, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Thase, Michael E.; Bhati, Mahendra T.; Sheline, Yvette I.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Husain, Mustafa; Krystal, Andrew D.; Lisanby, Sarah H.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Burke, William J.] Univ Nebraska, Sch Med, Dept Psychiat, Omaha, NE 68198 USA. [Howland, Robert H.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. [Sheline, Yvette I.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Aaronson, Scott T.] Sheppard Pratt Hlth Syst, Baltimore, MD USA. [Iosifescu, Dan V.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [O'Reardon, John P.] Rowan Univ, Sch Osteopath Med, Dept Psychiat, Stratford, NJ USA. [Gilmer, William S.] Chicago TMS Specialists, Chicago, IL USA. [Jain, Rakesh] RD Clin Res, Lake Jackson, TX USA. [Burgoyne, Karl S.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Phillips, Bill; Manberg, Paul J.] NeoSync Inc, Waltham, MA USA. [Manberg, Paul J.] NeoSync Inc, Newport Beach, CA USA. RP Leuchter, AF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav,Neuromodulat Di, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM afl@ucla.edu RI Philip, Noah/C-3714-2016; Burke, William/C-1203-2012; Howland, Robert/K-6937-2015 OI Philip, Noah/0000-0002-4889-8775; Howland, Robert/0000-0002-6533-6010 FU NeoSync, Inc. FX Sponsorship of and financial support for the conduct of this research was provided by NeoSync, Inc. As the study sponsor, the company was involved in study design, as well in the collection, analysis, and interpretation of data. The authors of this article have final authority and responsibility for the data analyses and interpretation of the results presented here. All individuals who participated in the writing of this report and in the decision to submit the article for publication are listed as co-authors on this manuscript. Because this was an industry-sponsored study, most of the authors have some financial relationship to the study sponsor. NR 48 TC 7 Z9 7 U1 1 U2 10 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 JUL-AUG PY 2015 VL 8 IS 4 BP 787 EP 794 DI 10.1016/j.brs.2015.05.005 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CM2WD UT WOS:000357542100014 PM 26143022 ER PT J AU Nagashima, M Sasakawa, T Schaller, SJ Martyn, JAJ AF Nagashima, M. Sasakawa, T. Schaller, S. J. Martyn, J. A. J. TI Block of postjunctional muscle-type acetylcholine receptors in vivo causes train-of-four fade in mice SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE acetylcholine; neuromuscular monitoring; neuromuscular block; neuromuscular transmission; receptors; nicotinic ID NEUROMUSCULAR-JUNCTION; TETANIC FADE; ALPHA-CONOTOXINS; MYASTHENIA-GRAVIS; POSITIVE FEEDBACK; RELEASE; MOUSE; ALPHA-3-BETA-2; HEMIDIAPHRAGM; BUNGAROTOXIN AB Background: Train-of-four (TOP) fade during nerve-mediated muscle contraction is postulated to be attributable to inhibition of prejunctional nicotinic alpha 3 beta 2 acetylcholine receptors (nAChRs), while decrease of twitch tension is attributable to block of postjunctional muscle nAChRs. The validity of these presumptions was tested using specific prejunctional and postjunctional nAChR antagonists, testing the hypothesis that fade is not always a prejunctional phenomenon. Methods: Pentobarbital anaesthetized mice had TOP fade measured after administration of: either 0.9% saline; the prejunctional alpha 3 beta 2 nAChR antagonist, dihydro-beta-erythroidine (DH beta E); the postjunctional nAChR antagonists, alpha-bungarotoxin (alpha-BTX) or alpha-conotoxin GI; and a combination of alpha-BTX and DH beta E; or a combination of alpha-conotoxin GI and DHOE. Results: Saline caused no neuromuscular changes. Administration of muscle nAChR antagonists, alpha-BTX or alpha-conotoxin GI caused significant decrease of twitch tension and TOP fade compared with baseline (P<0.01). DH beta E alone caused no change of twitch tension or fade even after 90 min, but its coadministration with alpha-BTX or alpha-conotoxin GI significantly accelerated the onset of paralysis and degree of fade compared with alpha-BTX or alpha-conotoxin GI alone (P<0.01). Conclusions: Occupation of postjunctional nAChRs alone by alpha-BTX or alpha-conotoxin GI causes fade. As the prejunctional effects of DH beta E on fade became manifest only when co-administered with alpha-BTX or alpha-conotoxin GI, specific inhibition of prejunctional nAChR alone is not necessary and sufficient to cause fade. Fade observed during repetitive nerve stimulation can be because of block of either postjunctional nAChRs alone, or block of prejunctional and postjunctional nAChRs together. C1 [Nagashima, M.; Sasakawa, T.; Schaller, S. J.; Martyn, J. A. J.] Massachusetts Gen Hosp, Shriners Hosp Children Boston, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Nagashima, M.; Sasakawa, T.; Schaller, S. J.; Martyn, J. A. J.] Harvard Univ, Sch Med, Boston, MA USA. [Schaller, S. J.] Tech Univ Munich, Klin Anaesthesiol, Klinikum Rechts Isar, D-80290 Munich, Germany. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children Boston, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jmartyn@mgh.harvard.edu OI Schaller, Stefan/0000-0002-6683-9584; Nagashima, Michio/0000-0001-7416-5367 FU National Institutes of Health, Bethesda, Maryland [GM P50-21500]; Shriners Hospitals Research Philantrophy, Tampa, Florida FX National Institutes of Health (GM P50-21500) (Project I), Bethesda, Maryland, and from Shriners Hospitals Research Philantrophy, Tampa, Florida to J.A.J. Martyn. NR 35 TC 0 Z9 1 U1 0 U2 1 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 JUL PY 2015 VL 115 IS 1 BP 122 EP 127 DI 10.1093/bja/aev037 PG 6 WC Anesthesiology SC Anesthesiology GA CM0EG UT WOS:000357350600021 PM 25835024 ER PT J AU Hazelton, WD Curtius, K Inadomi, JM Vaughan, TL Meza, R Rubenstein, JH Hur, C Luebeck, EG AF Hazelton, William D. Curtius, Kit Inadomi, John M. Vaughan, Thomas L. Meza, Rafael Rubenstein, Joel H. Hur, Chin Luebeck, E. Georg TI The Role of Gastroesophageal Reflux and Other Factors during Progression to Esophageal Adenocarcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; INTERNATIONAL BEACON CONSORTIUM; BARRETTS-ESOPHAGUS; HELICOBACTER-PYLORI; UNITED-STATES; RISK-FACTORS; GENETIC POLYMORPHISMS; CIGARETTE-SMOKING; CANCER INCIDENCE; POOLED ANALYSIS AB Background: U.S. esophageal adenocarcinoma (EAC) incidence increased over 5-fold between 1975 and 2009. Symptomatic gastroesophageal reflux disease (sGERD) elevates the risk for EAC. However, a simple calculation suggests that changes in sGERD prevalence can explain at most approximately 16% of this trend. Importantly, a mechanistic understanding of the influence of sGERD and other factors (OF) on EAC is lacking. Methods: A multiscale model was developed to estimate temporal trends for sGERD and OF, and their mechanistic role during carcinogenesis. Model calibration was to Surveillance, Epidemiology, and End Results (SEER) incidence and age-dependent sGERD data using maximum likelihood and Markov chain Monte Carlo (MCMC) methods. Results: Among men, 77.8% [ 95% credibility interval (CI), 64.9%-85.6%] of the incidence trend is attributable to OF, 13.4% (95% CI, 11.4%-17.3%) to sGERD, and 8.8% (95% CI, 4.2%-13.7%) to sGERD-OF interactions. Among women, 32.6% (95% CI, 27.0%-39.9%) of the trend is attributable to OF, 13.6%(95% CI, 12.5%-15.9%) to sGERD, and 47.4% (95% CI, 30.7%-64.6%) to interactions. The predicted trends were compared with historical trends for obesity, smoking, and proton pump inhibitor use. Interestingly, predicted OF cohort trends correlated most highly with median body mass index (BMI) at age 50 (r = 0.988 for men; r = 0.998 for women). Conclusions: sGERD and OF mechanistically increase premalignant cell promotion, which increases EAC risk exponentially with exposure duration. Impact: Surveillance should target individuals with long-duration sGERD and OF exposures. (C) 2015 AACR. C1 [Hazelton, William D.; Luebeck, E. Georg] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98109 USA. [Hazelton, William D.; Vaughan, Thomas L.; Luebeck, E. Georg] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Curtius, Kit] Univ Washington, Dept Appl Math, Seattle, WA 98195 USA. [Inadomi, John M.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Vaughan, Thomas L.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98195 USA. [Meza, Rafael] Univ Michigan, Sch Publ Hlth, Sch Med, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Rubenstein, Joel H.] Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. [Rubenstein, Joel H.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. RP Hazelton, WD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M2-B500, Seattle, WA 98109 USA. EM hazelton@fhcrc.org OI Hur, Chin/0000-0002-2819-7576 FU National Cancer Institute (NCI) [UO1 CA152926, UO1 CA182940]; National Science Foundation [DGE-0718124] FX This research was supported by the National Cancer Institute (NCI) under grant nos. UO1 CA152926 and UO1 CA182940 (to W.D. Hazelton, J.M. Inadomi, C. Hur, and E.G. Luebeck), and by a Graduate Research Fellowship from the National Science Foundation, DGE-0718124 (to K. Curtius). NR 60 TC 5 Z9 5 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2015 VL 24 IS 7 BP 1012 EP 1023 DI 10.1158/1055-9965.EPI-15-0323-T PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CM1FF UT WOS:000357425700002 PM 25931440 ER PT J AU Thrift, AP Gong, J Peters, U Chang-Claude, J Rudolph, A Slattery, ML Chan, AT Locke, A Kahali, B Justice, AE Pers, TH Gallinger, S Hayes, RB Baron, JA Caan, BJ Ogino, S Berndt, SI Chanock, SJ Casey, G Haile, RW Du, MM Harrison, TA Thornquist, M Duggan, DJ Le Marchand, L Lindor, NM Seminara, D Song, MY Wu, K Thibodeau, SN Cotterchio, M Win, AK Jenkins, MA Hopper, J Ulrich, CM Potter, JD Newcomb, PA Hoffmeister, M Brenner, H White, E Hsu, L Campbell, PT AF Thrift, Aaron P. Gong, Jian Peters, Ulrike Chang-Claude, Jenny Rudolph, Anja Slattery, Martha L. Chan, Andrew T. Locke, Adame. Kahali, Bratati Justice, Anne E. Pers, Tune H. Gallinger, Steven Hayes, Richard B. Baron, John A. Caan, Bette J. Ogino, Shuji Berndt, Sonja I. Chanock, Stephen J. Casey, Graham Haile, Robert W. Du, Mengmeng Harrison, Tabitha A. Thornquist, Mark Duggan, David J. Le Marchand, Loic Lindor, Noralane M. Seminara, Daniela Song, Mingyang Wu, Kana Thibodeau, Stephen N. Cotterchio, Michelle Win, Aung Ko Jenkins, Mark A. Hopper, Johnl. Ulrich, Cornelia M. Potter, John D. Newcomb, Polly A. Hoffmeister, Michael Brenner, Hermann White, Emily Hsu, Li Campbell, Peter T. TI Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; INSTRUMENTAL VARIABLES; MICROSATELLITE INSTABILITY; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; COLON-CANCER; OBESITY; DESIGN; HEALTH AB Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer. Methods: Weused data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Results: Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk[ per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92). Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer. (C) 2015 AACR. C1 [Thrift, Aaron P.; Gong, Jian; Peters, Ulrike; Du, Mengmeng; Harrison, Tabitha A.; Thornquist, Mark; Potter, John D.; Newcomb, Polly A.; White, Emily; Hsu, Li] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA. [Thrift, Aaron P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Thrift, Aaron P.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Peters, Ulrike; Du, Mengmeng; Potter, John D.; Newcomb, Polly A.; White, Emily] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.; Du, Mengmeng] Harvard Univ, Sch Med, Boston, MA USA. [Locke, Adame.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kahali, Bratati] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Kahali, Bratati] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Justice, Anne E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol & Genet, Boston, MA USA. [Pers, Tune H.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA. [Pers, Tune H.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Pers, Tune H.] Harvard Univ, Cambridge, MA 02138 USA. [Pers, Tune H.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Gallinger, Steven] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Caan, Bette J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Song, Mingyang] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Casey, Graham] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Haile, Robert W.] Stanford Univ, Div Oncol, Dept Med, Stanford, CA 94305 USA. [Duggan, David J.] Translat Genom Res Inst, Phoenix, AZ USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Song, Mingyang; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Win, Aung Ko; Jenkins, Mark A.; Hopper, Johnl.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Ulrich, Cornelia M.] Populat Sci Huntsman Canc Inst, Salt Lake City, UT USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Hsu, Li] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. RP Thrift, AP (reprint author), Baylor Coll Med, Dan L Duncan Canc Ctr, 1 Baylor Plaza, Houston, TX 77030 USA. EM aaron.thrift@bcm.edu RI Hoffmeister, Michael/B-5745-2012; Song, Mingyang/M-6701-2013; Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Song, Mingyang/0000-0002-1324-0316; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Locke, Adam/0000-0001-6227-198X; Hayes, Richard/0000-0002-0918-661X; Win, Aung Ko/0000-0002-2794-5261 FU Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24 CA074800]; University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; NIH [R01 CA151993, R01 CA137178, P01 CA53996, R01 AG14358, 1U54CA155626-01, R25 CA094880, R01 DK062370, UM1 CA167551, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, P50 CA 127003, U01 CA074783, U01 HG004446, R01 CA076366, K05 CA154337]; National Cancer Institute, NIH, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; National Cancer Institute, NIH [U01 CA122839, R01 CA143237]; NIH: Australasian Colorectal Cancer Family Registry [U01 CA074778, U01/U24 CA097735]; Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]; Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; 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]; NHS by the NIH [R01 CA151993, R01 CA137178, P50 CA 127003, P01 CA 087969]; PHS by the NIH [R01 CA042182]; 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; NIH, Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX N.M. Lindor was supported through the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800). L. Le Marchand was supported through the University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). J.A. Baron was supported through the Familial Colorectal Neoplasia Collaborative Group (U01 CA074799). This work was supported by grants from the NIH (R01 CA151993 to S. Ogino; R01 CA137178 to A.T. Chan; P01 CA53996 and R01 AG14358 to L. Hsu). M. Song was supported by a grant from the NIH (1U54CA155626-01). M. Du was supported by a grant from the NIH (R25 CA094880). A.E. Locke was supported by a grant from the NIH (R01 DK062370).; GECCO is supported by National Cancer Institute, NIH, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; CCFR is supported by NIH (UM1 CA167551) and through cooperative agreements with members of the Colon Cancer Family Registry and PIs. This genome-wide scan was supported by the National Cancer Institute, NIH by U01 CA122839 and R01 CA143237 to Graham Casey. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the CCFR. The following CCFR centers contributed data to this article and were supported by NIH: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794).; DACHS is supported by 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 is supported by NIH (R01 CA48998 to M.L. Slattery).; HPFS is supported by the NIH (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, and P50 CA 127003), NHS by the NIH (R01 CA137178, P01 CA 087969, R01 CA151993, and P50 CA 127003), and PHS by the NIH (R01 CA042182).; OFCCR is supported by NIH, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. In addition, a subset of control samples was genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M. and colleagues. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 2007 May;39(5):64-59), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L. and colleagues. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986-90, and Petersen, G.M. and colleagues. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224-8), and the Lung Cancer and Smoking study (Landi M.T., and colleagues. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;85(5):679-91). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207. v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by 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.; PMH is supported by NIH (R01 CA076366 to P.A. Newcomb).; VITAL is supported by NIH (K05 CA154337).; The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 33 TC 13 Z9 14 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2015 VL 24 IS 7 BP 1024 EP 1031 DI 10.1158/1055-9965.EPI-14-1309 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CM1FF UT WOS:000357425700003 PM 25976416 ER PT J AU Tan, ASL Nagler, RH Hornik, RC DeMichele, A AF Tan, Andy S. L. Nagler, Rebekah H. Hornik, Robert C. DeMichele, Angela TI Evolving Information Needs among Colon, Breast, and Prostate Cancer Survivors: Results from a Longitudinal Mixed-Effects Analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID QUALITY-OF-LIFE; CARE PLANS; HEALTH; RECURRENCE; FEAR; POPULATION; PREVENTION; BEHAVIORS; DIAGNOSIS; DISTRESS AB Background: This study describes how cancer survivors' information needs about recurrence, late effects, and family risks of cancer evolve over the course of their survivorship period. Methods: Three annual surveys were conducted from 2006 to 2008 in a cohort of Pennsylvania cancer survivors diagnosed with colon, breast, or prostate cancer in 2005 (round 1, N = 2,013; round 2, N = 1,293; round 3, N = 1,128). Outcomes were information seeking about five survivorship topics. Key predictors were survey round, cancer diagnosis, and the interaction between these variables. Mixed-effects logistic regression analyses were performed to predict information seeking about each topic, adjusting for demographic variables, clinical characteristics, and clustering of repeated observations within individuals. Results: Information seeking about reducing risks of cancer recurrence was the most frequently reported topic across survivors and over time. Breast cancer survivors were more likely to seek about survivorship topics at round 1 compared with other survivors. In general, information seeking declined over time, but cancer-specific patterns emerged: the decline was sharpest for breast cancer survivors, whereas in later years female colon cancer survivors actually sought more information (about how to reduce the risk of family members getting colon cancer or a different cancer). Conclusion: Cancer survivors' information needs varied over time depending on the topic, and these trends differed by cancer type. Impact: Clinicians may need to intervene at distinct points during the survivorship period with information to address concerns about cancer recurrence, late effects, and family members' risks. (C) 2015 AACR. C1 [Tan, Andy S. L.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. [Tan, Andy S. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Nagler, Rebekah H.] Univ Minnesota, Sch Journalism & Mass Commun, Minneapolis, MN USA. [Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [DeMichele, Angela] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Tan, ASL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave LW662, Boston, MA 02215 USA. EM andy_tan@dfci.harvard.edu FU NCI [P20CA095856, P50CA095856] FX This study is supported by P20CA095856 and P50CA095856 from the NCI (PI: R.C. Hornik). A.S.L. Tan conducted this work while being a CECCR postdoctoral research fellow at the Annenberg School for Communication (supported by P20CA095856). NR 37 TC 7 Z9 7 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2015 VL 24 IS 7 BP 1071 EP 1078 DI 10.1158/1055-9965.EPI-15-0041 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CM1FF UT WOS:000357425700009 PM 25979968 ER PT J AU Farvid, MS Eliassen, AH Cho, E Chen, WY Willett, WC AF Farvid, Maryam S. Eliassen, A. Heather Cho, Eunyoung Chen, Wendy Y. Willett, Walter C. TI Adolescent and Early Adulthood Dietary Carbohydrate Quantity and Quality in Relation to Breast Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TOTAL-ENERGY-INTAKE; GLYCEMIC INDEX; INSULIN INDEX; UNITED-STATES; PROSPECTIVE COHORT; COLORECTAL-CANCER; C-PEPTIDE; LOAD; HEALTH; WOMEN AB Background: We investigated quantity and quality of dietary carbohydrate as well as insulin load and insulin index during adolescence and also early adulthood in relation to risk of breast cancer in the Nurses' Health Study II. Methods: During 20 years of follow-up of 90,534 premenopausal women who completed a diet questionnaire in 1991, 2,833 invasive breast cancer cases were documented. In 1998, 44,263 of these women also completed a questionnaire about their diet during high school; among these women, we documented 1,118 cases of breast cancer. Multivariable-adjusted Cox proportional hazards regression was used to model relative risks (RR) and 95% confidence intervals (95% CI) for breast cancer across categories of dietary carbohydrate, glycemic index (GI), glycemic load (GL), as well as insulin load and insulin index scores. Results: Adolescent or early adult intakes of GI or GL were not associated with risk of breast cancer. Comparing women in the highest versus lowest quintile, the multivariable-adjusted RRs were 1.14 (0.95-1.38) for adolescent GI scores and 1.03 (0.91-1.16) for early adulthood GI scores. We also did not observe associations with insulin index and insulin load scores in adolescence or early adulthood and breast cancer risk. Conclusions: We found that diets high in GI, GL, insulin index, and insulin load during adolescence or early adulthood were not associated with an increased risk of breast cancer in this cohort study. Impact: Diets with a high glucose or insulin response in adolescence or early adulthood were not significant predictors of breast cancer incidence. (C) 2015 AACR. C1 [Farvid, Maryam S.; Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Farvid, Maryam S.] Shahid Beheshti Univ Med Sci, Fac Nutr Sci & Food Technol, Dept Community Nutr, Tehran, Iran. [Eliassen, A. Heather; Cho, Eunyoung; Chen, Wendy Y.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Eliassen, A. Heather; Cho, Eunyoung; Chen, Wendy Y.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Eliassen, A. Heather; Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Farvid, MS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM mfarvid@hsph.harvard.edu FU NIH [R01 CA050385, UM1 CA176726]; Breast Cancer Research Foundation; Japan Pharmaceutical Manufacturers Association FX The study was supported by the NIH grants (R01 CA050385, UM1 CA176726) and a grant from The Breast Cancer Research Foundation. M.S. Farvid was supported by the Japan Pharmaceutical Manufacturers Association. NR 47 TC 1 Z9 1 U1 4 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2015 VL 24 IS 7 BP 1111 EP 1120 DI 10.1158/1055-9965.EPI-14-1401 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CM1FF UT WOS:000357425700014 PM 25805068 ER PT J AU Singh, I Ozturk, N Cordero, J Mehta, A Hasan, D Cosentino, C Sebastian, C Kruger, M Looso, M Carraro, G Bellusci, S Seeger, W Braun, T Mostoslavsky, R Barreto, G AF Singh, Indrabahadur Ozturk, Nihan Cordero, Julio Mehta, Aditi Hasan, Diya Cosentino, Claudia Sebastian, Carlos Krueger, Marcus Looso, Mario Carraro, Gianni Bellusci, Saverio Seeger, Werner Braun, Thomas Mostoslavsky, Raul Barreto, Guillermo TI High mobility group protein-mediated transcription requires DNA damage marker gamma-H2AX SO CELL RESEARCH LA English DT Article DE HMGA2; gamma-H2AX; TGF beta 1; ATM; Gata6; transcription; chromatin-associated proteins; DNA damage ID GENERATION SEQUENCING DATA; CELL-CYCLE ARREST; HISTONE H1; ATAXIA-TELANGIECTASIA; CANCER-CELLS; H2AX PHOSPHORYLATION; LUNG DEVELOPMENT; GENE-EXPRESSION; HMG PROTEINS; CHROMATIN AB The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying transcription regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of transcription regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; gamma-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGF beta 1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of transcription initiation. Our results link H2AXS139ph to transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome. C1 [Singh, Indrabahadur; Ozturk, Nihan; Cordero, Julio; Mehta, Aditi; Hasan, Diya; Barreto, Guillermo] Max Planck Inst Heart & Lung Res, LOEWE Res Grp Lung Canc Epigenet, D-61231 Bad Nauheim, Germany. [Krueger, Marcus] Max Planck Inst Heart & Lung Res, Div Biomol Mass Spectrometry, D-61231 Bad Nauheim, Germany. [Looso, Mario] Max Planck Inst Heart & Lung Res, Grp Bioinformat, D-61231 Bad Nauheim, Germany. [Seeger, Werner] Max Planck Inst Heart & Lung Res, Dept Lung Dev & Remodeling, D-61231 Bad Nauheim, Germany. [Braun, Thomas] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, D-61231 Bad Nauheim, Germany. [Cosentino, Claudia; Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02118 USA. [Carraro, Gianni] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Bellusci, Saverio] Univ Giessen, Excellence Cluster Cardio Pulm Syst, Lung Matrix Remodeling, D-35932 Giessen, Germany. [Bellusci, Saverio; Barreto, Guillermo] Kazan Volga Reg Fed Univ, Inst Fundamental Med & Biol, Kazan 420008, Russia. [Bellusci, Saverio; Seeger, Werner; Braun, Thomas; Barreto, Guillermo] German Ctr Lung Res, Giessen, Germany. RP Barreto, G (reprint author), Max Planck Inst Heart & Lung Res, LOEWE Res Grp Lung Canc Epigenet, Pk Str 1, D-61231 Bad Nauheim, Germany. EM guillermo.barreto@mpi-bn.mpg.de FU "LOEWE-Initiative der Landesforderung" [III L4-18/15.004 2009]; DFG [BA 4036/1-1]; NIH [R01GM093072-01]; Fondazione Umberto Veronesi; ECCPS; [HL086322]; [HL074832] FX We thank Bender R and Goth K for technical support; Bessler M, Kwon J for reagents; and Dimmeler S, Renkawitz R and Schaprian A for helpful discussions. Barreto G is funded by the "LOEWE-Initiative der Landesforderung" (III L4-18/15.004 2009) and the DFG grant BA 4036/1-1. R. Mostoslavsky is supported by NIH grants R01GM093072-01. Cosentino C receives a Fellowship from the Fondazione Umberto Veronesi. Bellusci S is supported by HL086322, HL074832 and the ECCPS. This work was done according to the program of competitive growth of the Kazan Federal University and the Russian Government. NR 58 TC 12 Z9 12 U1 2 U2 8 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JUL PY 2015 VL 25 IS 7 BP 837 EP 850 DI 10.1038/cr.2015.67 PG 14 WC Cell Biology SC Cell Biology GA CM2MZ UT WOS:000357516000010 PM 26045162 ER PT J AU Tan, TC Neilan, TG Francis, S Plana, JC Scherrer-Crosbie, M AF Tan, Timothy C. Neilan, Tomas G. Francis, Sanjeev Plana, Juan Carlos Scherrer-Crosbie, Marielle TI Anthracycline-Induced Cardiomyopathy in Adults SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CARDIOVASCULAR-MAGNETIC-RESONANCE; ACUTE LYMPHOBLASTIC-LEUKEMIA; CONGESTIVE-HEART-FAILURE; HIGH-DOSE CHEMOTHERAPY; DOXORUBICIN-INDUCED CARDIOTOXICITY; CHILDHOOD-CANCER SURVIVORS; COLLEGE-OF-CARDIOLOGY; TERM-FOLLOW-UP; TRASTUZUMAB-INDUCED CARDIOTOXICITY AB Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well-recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines-induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors. The mechanisms involved in anthracycline-induced cardiotoxicity involve myocyte loss by apoptosis in the presence of a limited regenerative capacity. Once symptomatic, anthracycline-induced cardiotoxicity is associated with markedly decreased survival. Left ventricular ejection fraction (LVEF), mostly determined using echocardiography, is used to monitor patients treated with anthracyclines. As more than 1/3 of patients treated with anthracyclines do not recover their baseline LVEF once it is decreased, more sensitive echocardiographic indices of LV function such as myocardial deformation or biomarkers have been studied in patients monitoring. Cardioprotective treatments such as angiotensin-converting enzyme inhibitors, beta-blockers, iron chelators, statins, and metformin are also the topic of research efforts. (C) 2015 American Physiological Society. C1 [Tan, Timothy C.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Tan, Timothy C.] Univ Western Sydney, Blacktown Hosp, Div Cardiol, Penrith, NSW 1797, Australia. [Neilan, Tomas G.; Francis, Sanjeev; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Cardiooncol Program, Boston, MA 02114 USA. [Neilan, Tomas G.; Francis, Sanjeev] Massachusetts Gen Hosp, Div Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Plana, Juan Carlos] Baylor Coll Med, Div Cardiol, Houston, TX 77030 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM marielle@crosbie.com NR 218 TC 3 Z9 3 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD JUL PY 2015 VL 5 IS 3 BP 1517 EP 1540 DI 10.1002/cphy.c140059 PG 24 WC Physiology SC Physiology GA CM3PY UT WOS:000357596400019 PM 26140726 ER PT J AU Lu, DF Wu, Y Harris, G Cai, WL AF Lu, Difei Wu, Yin Harris, Gordon Cai, Wenli TI Iterative mesh transformation for 3D segmentation of livers with cancers in CT images SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Image segmentation; Mesh deformation; Dynamic-programming; Liver segmentation ID STATISTICAL SHAPE MODEL; AUTOMATED SEGMENTATION; PROBABILISTIC ATLAS; LEVEL-SET AB Segmentation of diseased liver remains a challenging task in clinical applications due to the high interpatient variability in liver shapes, sizes and pathologies caused by cancers or other liver diseases. In this paper, we present a multi-resolution mesh segmentation algorithm for 3D segmentation of livers, called iterative mesh transformation that deforms the mesh of a region-of-interest (ROI) in a progressive manner by iterations between mesh transformation and contour optimization. Mesh transformation deforms the 3D mesh based on the deformation transfer model that searches the optimal mesh based on the affine transformation subjected to a set of constraints of targeting vertices. Besides, contour optimization searches the optimal transversal contours of the ROI by applying the dynamic-programming algorithm to the intersection polylines of the 3D mesh on 2D transversal image planes. The initial constraint set for mesh transformation can be defined by a very small number of targeting vertices, namely landmarks, and progressively updated by adding the targeting vertices selected from the optimal transversal contours calculated in contour optimization. This iterative 3D mesh transformation constrained by 2D optimal transversal contours provides an efficient solution to a progressive approximation of the mesh of the targeting ROI. Based on this iterative mesh transformation algorithm, we developed a semi-automated scheme for segmentation of diseased livers with cancers using as little as five user-identified landmarks. The evaluation study demonstrates that this semi-automated liver segmentation scheme can achieve accurate and reliable segmentation results with significant reduction of interaction time and efforts when dealing with diseased liver cases. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lu, Difei; Wu, Yin; Harris, Gordon; Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lu, Difei; Wu, Yin; Harris, Gordon; Cai, Wenli] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lu, Difei] Zhejiang Police Coll, Dept Informat, Hangzhou, Zhejiang, Peoples R China. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu FU NCI NIH HHS [R41 CA189637] NR 31 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 EI 1879-0771 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUL PY 2015 VL 43 BP 1 EP 14 DI 10.1016/j.compmedimag.2015.01.006 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CL8MW UT WOS:000357229800001 PM 25728595 ER PT J AU Davis, JS Weiss, ST Tantisira, KG AF Davis, Joshua S. Weiss, Scott T. Tantisira, Kelan G. TI Asthma Pharmacogenomics: 2015 Update SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review DE Asthma; Genes; Pharmacogenomics; Pharmacogenetics; GWAS; Systems biology ID GENOME-WIDE ASSOCIATION; IMPROVED LUNG-FUNCTION; SMOOTH-MUSCLE-CELLS; BETA(2)-ADRENERGIC RECEPTOR; INHALED CORTICOSTEROIDS; BRONCHODILATOR RESPONSE; BETA-AGONIST; PERSISTENT ASTHMA; CLINICAL-RESPONSE; ACTING BETA(2)-AGONISTS AB There is evidence that genetic factors are implicated in the observed differences in therapeutic responses to the common classes of asthma therapy such as beta 2-agonists, corticosteroids, and leukotriene modifiers. Pharmacogenomics explores the roles of genetic variation in drug response and continues to be a field of great interest in asthma therapy. Prior studies have focused on candidate genes and recently emphasized genome-wide association analyses. Newer integrative omics and system-level approaches have recently revealed novel understanding of drug response pathways. However, the current known genetic loci only account for a fraction of variability in drug response and ongoing research is needed. While the field of asthma pharmacogenomics is not yet fully translatable to clinical practice, ongoing research should hopefully achieve this goal in the near future buttressed by the recent precision medicine efforts in the USA and worldwide. C1 [Davis, Joshua S.; Weiss, Scott T.; Tantisira, Kelan G.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Davis, Joshua S.; Weiss, Scott T.; Tantisira, Kelan G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Davis, Joshua S.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Weiss, Scott T.; Tantisira, Kelan G.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Weiss, Scott T.] Partners HealthCare Syst, Partners Personalized Med, Boston, MA USA. RP Tantisira, KG (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM rejda@channing.harvard.edu; restw@channing.harvard.edu; rekgt@channing.harvard.edu FU NIH [U01 HL65899, R01 HL092197, R01 NR013391] FX This work was supported by NIH (U01 HL65899, R01 HL092197, and R01 NR013391). NR 100 TC 4 Z9 4 U1 2 U2 16 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 EI 1534-6315 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JUL PY 2015 VL 15 IS 7 AR 42 DI 10.1007/s11882-015-0544-y PG 12 WC Allergy; Immunology SC Allergy; Immunology GA CM1GL UT WOS:000357429200008 PM 26143396 ER PT J AU Wanner, M Mihm, MC Farinelli, WA Doukas, A Zurakowski, D Piris, A Avram, MM Klein, JA Anderson, RR AF Wanner, Molly Mihm, Martin C., Jr. Farinelli, William A. Doukas, Apostolos Zurakowski, David Piris, Adriano Avram, Mathew M. Klein, Jeffrey A. Anderson, R. Rox TI Use of Photodynamic Therapy and Sterile Water to Target Adipose Tissue SO DERMATOLOGIC SURGERY LA English DT Article ID ACID; FAT AB BACKGROUND Neither photodynamic therapy (PDT) nor sterile water has not been well studied for the treatment of adipose tissue. OBJECTIVE This investigation studied 2 different modalities, verteporfin PDT and sterile water, on adipose tissue compared with control. MATERIALS AND METHODS Four light-skinned pigs were used. Test sites received verteporfin PDT or sterile water injection. Control sites received injection of verteporfin without PDT, normal saline injection, no intervention, exposure to laser only, or insertion of a needle or cannula only. Sites were evaluated clinically, by ultrasound, and with histology 4 to 6 weeks after treatment. RESULTS There was a decrease in adipose tissue by ultrasound after verteporfin PDT (15%, p < .001) and sterile water (2%, p = .23). Verteporfin without PDT showed a decrease in adipose tissue (17%, p = .21). All other control sites showed an increase in adipose tissue. Histologically, verteporfin PDT and sterile water showed moderate damage (median Grade 2, p < .001) 4 to 6 weeks after intervention. CONCLUSION Verteporfin decreased adipose tissue after treatment. Sterile water injection had a statistically significant effect on adipose tissue histologically but did not substantially decrease the adipose tissue by ultrasound 4 to 6 weeks after intervention. Longer follow-up may be needed. C1 [Wanner, Molly; Avram, Mathew M.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mihm, Martin C., Jr.; Piris, Adriano] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wanner, Molly; Farinelli, William A.; Doukas, Apostolos; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Anesthesia, Boston Childrens Hosp, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Boston Childrens Hosp, Boston, MA 02115 USA. [Klein, Jeffrey A.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. RP Wanner, M (reprint author), 50 Staniford St,Suite 200, Boston, MA 02114 USA. EM mwanner@partners.org FU ASDS Cutting Edge Research Grant Program FX Supported by the ASDS Cutting Edge Research Grant Program. Equipment provided by Candela Corporation and HK Surgical. NR 18 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 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2015 VL 41 IS 7 BP 803 EP 811 DI 10.1097/DSS.0000000000000385 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA CM2AI UT WOS:000357481500006 PM 26079592 ER PT J AU Tirumani, SH Tirumani, H Jagannathan, JP Shinagare, AB Hornick, JL Ramaiya, NH Wagner, AJ AF Tirumani, S. H. Tirumani, H. Jagannathan, J. P. Shinagare, A. B. Hornick, J. L. Ramaiya, N. H. Wagner, A. J. TI Metastasis in dedifferentiated liposarcoma: Predictors and outcome in 148 patients SO EJSO LA English DT Article DE Dedifferentiated liposarcoma; Metastasis; Predictors; Survival ID SOFT-TISSUE SARCOMAS; RETROPERITONEAL; RECURRENCE; PATTERNS; GRADE AB Objective: To describe the pattern of dedifferentiated liposarcoma (DDLPS) metastases and to analyze their predictors and outcome. Materials and methods: In this retrospective study, we reviewed the imaging and clinical records of all consenting patients with histopathology-confirmed DDLPS seen from 2000 through 2012. The predictive value of clinical and histopathologic parameters for metastasis later in the disease course was analyzed using univariate and multivariate analyses. Survival of patients with and without metastasis was compared using Log-rank test. Results: Records of 148 patients (57 women, 91 men; mean age 59 years, range 30-87 years) were reviewed. Distant metastases were observed in 44/148 patients (29.7%), 9/44 (20.5%) at presentation and 35/44 (79.5%) developing them later at a median interval of 8 months (IQR = 0.80-26 months). Median duration of follow-up was 38 months (IQR = 18-74 months) with 77/148 patients (31 with metastases) deceased at the time of analysis. Median survival was 28 months (IQR = 10-56 months) for patients with metastases and 38 months (IQR, 17-65 months) for patients without metastases (p = 0.0123, Log-Rank test; Hazard ratio 1.79 [95% confidence interval 1.11-2.84]). Lung was the most common site of metastases (33 patients, 22.3%). On univariate analysis, grade and local recurrence were associated with subsequent risk of metastasis where as age, tumor size, site, de novo dedifferentiation, number of previous surgical resections, margin positivity and chemoradiation were not. On multivariate analysis, high tumor grade (p-value = 0.0005, OR 5.05; 95% CI 2.01-13.48) and local recurrence (p-value = 0.0025, OR 4.46; 95% CI 1.67-13.40) predicted metastasis. Conclusion: Lung was most frequent site of DDLPS metastases. Risk of developing metastatic disease was statistically associated with tumor grade and local recurrence. Metastatic disease was associated with decreased survival. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Tirumani, S. H.; Tirumani, H.; Jagannathan, J. P.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02215 USA. [Tirumani, S. H.; Jagannathan, J. P.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Hornick, J. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Wagner, A. J.] Harvard Univ, Sch Med, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Wagner, A. J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 16 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD JUL PY 2015 VL 41 IS 7 BP 899 EP 904 DI 10.1016/j.ejso.2015.01.012 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA CL8ME UT WOS:000357228000014 PM 25659772 ER PT J AU Duchemann, B Friboulet, L Besse, B AF Duchemann, Boris Friboulet, Luc Besse, Benjamin TI Therapeutic management of ALK(+) nonsmall cell lung cancer patients SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; TYROSINE KINASE; CRIZOTINIB RESISTANCE; CLINICAL-FEATURES; PULMONARY ADENOCARCINOMA; 1ST-LINE CRIZOTINIB; ACQUIRED-RESISTANCE; BRAIN METASTASES; GROWTH-FACTOR AB With therapeutic approaches based on oncogene addiction offering significant anticancer benefit, the identification of anaplastic lymphoma kinase (ALK) rearrangements is a key aspect of the management of lung cancers. The EML4-ALK gene fusion is detected in 4-8% of all lung cancers, predominantly in light smokers or nonsmokers. Crizotinib, the first agent to be approved in this indication, is associated with a median progression-free survival of 10.9 months when given as first-line treatment and 7.7 months when administered after chemotherapy. Median overall survival with crizotinib in the second-line setting is 20.3 months. Second-generation ALK inhibitors are currently being evaluated, with early studies giving impressive results, notably in patients resistant to crizotinib or with brain metastases. Among available chemotherapies, pemetrexed appears to be particularly active in this population. Despite this progress, several questions remain unanswered. What detection strategies should be favoured? What underlies the mechanisms of resistance and what options are available to overcome them? What are the best approaches for progressing patients? This review provides an overview of current data in the literature and addresses these questions. C1 [Duchemann, Boris] Hop Avicenne, Dept Med Oncol, F-93009 Bobigny, France. [Duchemann, Boris] Univ Paris 13, Paris, France. [Friboulet, Luc] Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Dept Med, Boston, MA USA. [Besse, Benjamin] Gustave Roussy, Dept Canc Med, Villejuif, France. [Besse, Benjamin] Univ Paris Sud, Paris, France. RP Besse, B (reprint author), Gustave Roussy, Dept Canc Med, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM benjamin.besse@gustaveroussy.fr NR 94 TC 4 Z9 4 U1 0 U2 7 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 JUL PY 2015 VL 46 IS 1 BP 230 EP 242 DI 10.1183/09031936.00236414 PG 13 WC Respiratory System SC Respiratory System GA CL7FG UT WOS:000357137300027 PM 25929953 ER PT J AU Dumas, O Matran, R Zerimech, F Decoster, B Huyvaert, H Ahmed, I Le Moual, N Nadif, R AF Dumas, Orianne Matran, Regis Zerimech, Farid Decoster, Brigitte Huyvaert, Helene Ahmed, Ismail Le Moual, Nicole Nadif, Rachel TI Occupational exposures and fluorescent oxidation products in 723 adults of the EGEA study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Letter ID IN-HOSPITAL WORKERS; CLEANING PRODUCTS; ASTHMA; FEMALES; STRESS C1 [Dumas, Orianne; Le Moual, Nicole; Nadif, Rachel] INSERM, U1168, VIMA, Aging & Chron Dis,Epidemiol & Publ Hlth Approache, F-94807 Villejuif, France. [Dumas, Orianne; Le Moual, Nicole; Nadif, Rachel] Univ Versailles, St Quentin En Yvelines, UMR S 1168, Montigny Le Bretonneux, France. [Dumas, Orianne] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Dumas, Orianne] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Matran, Regis; Decoster, Brigitte; Huyvaert, Helene] Univ Lille Nord France, Lille, France. [Zerimech, Farid; Huyvaert, Helene] CHRU, Ctr Biol Pathol, Biochim Lab, Lille, France. [Ahmed, Ismail] INSERM, UMR 1181, Biostat Biomath Pharmacoepidemiol & Infect Dis B2, Villejuif, France. [Ahmed, Ismail] Univ Versailles, St Quentin En Yvelines, UMR 1181, B2PHI, Montigny Le Bretonneux, France. RP Nadif, R (reprint author), INSERM, U1168, VIMA, Aging & Chron Dis,Epidemiol & Publ Hlth Approache, F-94807 Villejuif, France. EM rachel.nadif@inserm.fr RI Ahmed, Ismail/I-7106-2012; Nadif, Rachel/R-2876-2016; LeMoual, Nicole/R-8976-2016; OI Ahmed, Ismail/0000-0003-0468-6858; Nadif, Rachel/0000-0003-4938-9339; LeMoual, Nicole/0000-0002-2723-5569; Zerimech, Farid/0000-0003-2964-1031 NR 16 TC 2 Z9 2 U1 0 U2 3 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 JUL PY 2015 VL 46 IS 1 BP 258 EP 261 DI 10.1183/09031936.00177614 PG 5 WC Respiratory System SC Respiratory System GA CL7FG UT WOS:000357137300031 PM 25837036 ER PT J AU Daniels, TR Younger, ASE Penner, MJ Wing, KJ Le, ILD Russell, IS Lalonde, KA Evangelista, PT Quiton, JD Glazebrook, M DiGiovanni, CW AF Daniels, Timothy R. Younger, Alastair S. E. Penner, Murray J. Wing, Kevin J. Le, Ian L. D. Russell, Iain S. Lalonde, Karl-Andre Evangelista, Peter T. Quiton, Jovelyn D. Glazebrook, Mark DiGiovanni, Christopher W. TI Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a -TCP-Collagen Matrix SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE ankle fusion; autogenous bone graft; collagen; hindfoot fusion; nonunion; platelet derived growth factor; randomized controlled trial; rhPDGF-BB ID AUTOGENOUS BONE-GRAFT; GROWTH FACTOR-BB; ARTHRODESIS; BIOLOGY; COHORT; FOOT AB Background: Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. Methods: Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. Results: Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 8.9 weeks for rhPDGF-BB/-TCP-collagen patients versus 19.7 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. Conclusions: Application of rhPDGF-BB/-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. Level of Evidence: Level I, prospective randomized study. C1 [Daniels, Timothy R.] St Michaels Hosp, Div Orthopaed Surg, Toronto, ON M5C 1R6, Canada. [Daniels, Timothy R.] Univ Toronto, Toronto, ON M5C 1R6, Canada. [Younger, Alastair S. E.; Penner, Murray J.; Wing, Kevin J.] Univ British Columbia, Dept Orthopaed, Div Distal Extrem, Vancouver, BC V5Z 1M9, Canada. [Younger, Alastair S. E.] St Pauls Hosp, BCs Foot & Ankle Clin, Vancouver, BC V6Z 1Y6, Canada. [Le, Ian L. D.; Russell, Iain S.] Univ Calgary, Calgary Orthopaed Foot & Ankle Clin, Dept Surg, Sect Orthopaed Surg, Calgary, AB, Canada. [Le, Ian L. D.; Russell, Iain S.] Univ Calgary, Fac Med, Calgary, AB, Canada. [Lalonde, Karl-Andre] Ottawa Gen Hosp, Div Orthopaed Surg, Ottawa, ON K1H 8L6, Canada. [Lalonde, Karl-Andre] Univ Ottawa, Dept Surg, Ottawa, ON, Canada. [Evangelista, Peter T.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA. [Quiton, Jovelyn D.] Wright Med Technol Inc, Franklin, TN USA. [Glazebrook, Mark] Dalhousie Univ, Halifax, NS, Canada. [Glazebrook, Mark] Queen Elizabeth II Sci Ctr, Halifax, NS, Canada. [DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Daniels, TR (reprint author), St Michaels Hosp, Div Orthopaed Surg, 800-55 Queen St East, Toronto, ON M5C 1R6, Canada. EM DanielsT@smh.ca FU Wright Medical Technology, Inc, Franklin, Tennessee FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by BioMimetic Therapeutics, Inc. (now Wright Medical Technology, Inc, Franklin, Tennessee). Funds were used for salaries, supplies, imaging studies, laboratory procedures, data management activities, and other administrative fees. NR 20 TC 2 Z9 2 U1 0 U2 3 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 JUL PY 2015 VL 36 IS 7 BP 739 EP 748 DI 10.1177/1071100715576370 PG 10 WC Orthopedics SC Orthopedics GA CL9KA UT WOS:000357295900001 PM 25848134 ER PT J AU Larsen, PM Teerlink, JR AF Larsen, Paul M. Teerlink, John R. TI Team-based Care for Patients Hospitalized with Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Acute heart failure; Team-based; Hospitalized; Interdisciplinary; Therapeutics ID PRESERVED EJECTION FRACTION; ASSOCIATION TASK-FORCE; LOW-DOSE FUROSEMIDE; RELAX-AHF; EMERGENCY-DEPARTMENT; NATRIURETIC PEPTIDE; CARDIAC TROPONIN; RANDOMIZED-TRIAL; MANAGEMENT TEAM; OUTCOMES AB Hospitalizations for acute heart failure (HF) and subsequent readmissions have received increased attention because of the burden they place on patients, providers, and the health care system. These hospitalizations represent a significant portion of the total cost of HF care and health care in general. Although much of the care of the patient with HF occurs outside of the hospital, the genesis of the programs that attempt to limit repeat hospitalizations begin in the impatient setting. By using evidence-based guidelines, interdisciplinary teams, and comprehensive discharge planning, costly readmissions can be reduced and outcomes improved. C1 [Larsen, Paul M.] Univ Calif San Francisco, Div Internal Med, Sch Med, San Francisco, CA 94143 USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, Sch Med, San Francisco, CA 94121 USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, Sch Med, Cardiol 111C,Bldg 203 Room 2A49,4150 Clement St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu NR 66 TC 1 Z9 1 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2015 VL 11 IS 3 BP 359 EP + DI 10.1016/j.hfc.2015.03.002 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CM3GU UT WOS:000357570900004 PM 26142635 ER PT J AU Coetzee, SG Shen, HC Hazelett, DJ Lawrenson, K Kuchenbaecker, K Tyrer, J Rhie, SK Levanon, K Karst, A Drapkin, R Ramus, SJ Couch, FJ Offit, K Chenevix-Trench, G Monteiro, ANA Antoniou, A Freedman, M Coetzee, GA Pharoah, PDP Noushmehr, H Gayther, SA AF Coetzee, Simon G. Shen, Howard C. Hazelett, Dennis J. Lawrenson, Kate Kuchenbaecker, Karoline Tyrer, Jonathan Rhie, Suhn K. Levanon, Keren Karst, Alison Drapkin, Ronny Ramus, Susan J. Couch, Fergus J. Offit, Kenneth Chenevix-Trench, Georgia Monteiro, Alvaro N. A. Antoniou, Antonis Freedman, Matthew Coetzee, Gerhard A. Pharoah, Paul D. P. Noushmehr, Houtan Gayther, Simon A. CA Ovarian Canc Association Consortiu Consortium Investigators Modifiers TI Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GRADE SEROUS CARCINOMA; FALLOPIAN-TUBE; BREAST-CANCER; EPITHELIAL-CELLS; TRANSCRIPTION FACTORS; COMMON VARIANTS; PIK3CA MUTATION; IN-VITRO; ENDOMETRIOSIS AB Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 x 10(-30)), OSECs (P = 2.4 x 10(-23)) and HMECs (P = 6.7 x 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer. C1 [Coetzee, Simon G.; Noushmehr, Houtan] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP, Brazil. [Coetzee, Simon G.; Noushmehr, Houtan] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil. [Shen, Howard C.; Hazelett, Dennis J.; Lawrenson, Kate; Rhie, Suhn K.; Ramus, Susan J.; Coetzee, Gerhard A.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Hazelett, Dennis J.; Rhie, Suhn K.; Coetzee, Gerhard A.] Univ So Calif, Dept Urol, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Kuchenbaecker, Karoline; Tyrer, Jonathan; Antoniou, Antonis; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Dept Publ Hlth & Primary Care, Cambridge, England. [Levanon, Keren] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel. [Karst, Alison] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drapkin, Ronny; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Canc Biol & Genet Program, New York, NY 10021 USA. [Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. [Monteiro, Alvaro N. A.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Canc Epidemiol Program, Tampa, FL USA. [Freedman, Matthew] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02115 USA. [Noushmehr, Houtan] Univ Sao Paulo, NAP, CISBi, Ctr Integrat Syst Biol, BR-14051140 Ribeirao Preto, SP, Brazil. RP Gayther, SA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. EM simon.gayther@med.usc.edu RI Brinton, Louise/G-7486-2015; Hein, Alexander/F-6999-2010; Brooks-Wilson, Angela/E-9399-2012; Dork, Thilo/J-8620-2012; Drapkin, Ronny/E-9944-2016; salvesen, Helga/C-1187-2017; Coetzee, Simon/C-1218-2014; OI Krakstad, Camilla/0000-0002-0174-8139; Giles, Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Ramus, Susan/0000-0003-0005-7798; Brinton, Louise/0000-0003-3853-8562; Hein, Alexander/0000-0003-2601-3398; Brooks-Wilson, Angela/0000-0003-1009-6408; Drapkin, Ronny/0000-0002-6912-6977; salvesen, Helga/0000-0002-4438-8831; Coetzee, Simon/0000-0003-4267-5930; Glasspool, Rosalind/0000-0002-5000-1680; Kjaer, Susanne/0000-0002-8347-1398 FU Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative [U19-CA148112]; Program Project Development Grant from the Ovarian Cancer Research Fund; Clinical and Translational Science Institute at USC; K99/R00 grant from the National Cancer Institute [1K99CA184415-01]; National Cancer Institute [P30CA014089] FX This study was supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112), a Program Project Development Grant from the Ovarian Cancer Research Fund (to S.A.G. and A.M.) and a pilot award from the Clinical and Translational Science Institute at USC to K.L. and S.A.G. K.L. is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). The in vitro aspects of this project were performed within the Norris Cancer Centre at USC, which is supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 61 TC 9 Z9 9 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2015 VL 24 IS 13 BP 3595 EP 3607 DI 10.1093/hmg/ddv101 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CM2PO UT WOS:000357523900001 PM 25804953 ER PT J AU Kavanagh, D Yu, Y Schramm, EC Triebwasser, M Wagner, EK Raychaudhuri, S Daly, MJ Atkinson, JP Seddon, JM AF Kavanagh, David Yu, Yi Schramm, Elizabeth C. Triebwasser, Michael Wagner, Erin K. Raychaudhuri, Soumya Daly, Mark J. Atkinson, John P. Seddon, Johanna M. TI Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; COMPLEMENT FACTOR-I; FACTOR-H; HIGH-RISK; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; CLINICAL PHENOTYPE; SYNDROME AHUS; MUTATIONS; ACTIVATION; CELLS AB To assess a potential diagnostic and therapeutic biomarker for age-related macular degeneration (AMD), we sequenced the complement factor I gene (CFI) in 2266 individuals with AMD and 1400 without, identifying 231 individuals with rare genetic variants. We evaluated the functional impact by measuring circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. The burden of very rare (frequency < 1/1000) variants in CFI was strongly associated with disease (P = 1.1 x 10(-8)). In addition, we examined eight coding variants with counts a parts per thousand yen5 and saw evidence for association with AMD in three variants. Individuals with advanced AMD carrying a rare CFI variant had lower mean FI compared with non-AMD subjects carrying a variant (P < 0.001). Further new evidence that FI levels drive AMD risk comes from analyses showing individuals with a CFI rare variant and low FI were more likely to have advanced AMD (P = 5.6 x 10(-5)). Controlling for covariates, low FI increased the risk of advanced AMD among those with a variant compared with individuals without advanced AMD with a rare CFI variant (OR 13.6, P = 1.6 x 10(-4)), and also compared with control individuals without a rare CFI variant (OR 19.0, P = 1.1 x 10(-5)). Thus, low FI levels are strongly associated with rare CFI variants and AMD. Enhancing FI activity may be therapeutic and measuring FI provides a screening tool for identifying patients who are most likely to benefit from complement inhibitory therapy. C1 [Kavanagh, David] Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Yu, Yi; Wagner, Erin K.; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA USA. [Schramm, Elizabeth C.; Triebwasser, Michael; Atkinson, John P.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Raychaudhuri, Soumya; Daly, Mark J.] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Raychaudhuri, Soumya; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. RP Kavanagh, D (reprint author), Tufts Med Ctr, 800 Washington St 450, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org RI Kavanagh, David/E-8498-2011 OI Kavanagh, David/0000-0003-4718-0072 FU National Institute of Health [R01-EY11309, K08AR055688, U01HG0070033, F30HL103072, R01-AI041592, U54 HL112303]; Edward N. & Della L. Thome Memorial Foundation; Doris Duke Clinical Scientist Development Award; Protein Core Facility of the Rheumatic Diseases Core by National Institute of Arthritis and Musculoskeletal and Skin Diseases part of the National Institutes of Health [P30 AR48335]; Massachusetts Lions Eye Research Fund, Inc.; Foundation Fighting Blindness; Research to Prevent Blindness; American Macular Degeneration Foundation; Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine; Fight for Sight; Wellcome Trust FX This work was supported in part by National Institute of Health grants R01-EY11309 (J.M.S.), K08AR055688 (S.R.), U01HG0070033 (S.R.), F30HL103072 (M.T.), R01-AI041592 (J.P.A.), U54 HL112303 (J.P.A.); Edward N. & Della L. Thome Memorial Foundation (J.P.A.); the Doris Duke Clinical Scientist Development Award; the Protein Core Facility of the Rheumatic Diseases Core supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under award number P30 AR48335 (J.P.A.), Massachusetts Lions Eye Research Fund, Inc. (J.M.S.); the Foundation Fighting Blindness (J.M.S.); Research to Prevent Blindness Challenge grant to the New England Eye Center, Department of Ophthalmology, Tufts University School of Medicine; American Macular Degeneration Foundation (J.M.S.); and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. D.K. is a Wellcome Trust Intermediate Clinical Fellow and is funded by Fight for Sight. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. NR 54 TC 16 Z9 16 U1 3 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2015 VL 24 IS 13 BP 3861 EP 3870 DI 10.1093/hmg/ddv091 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CM2PO UT WOS:000357523900021 PM 25788521 ER PT J AU Li, Z Allingham, RR Nakano, M Jia, LY Chen, YH Ikeda, Y Mani, B Chen, LJ Kee, C Garway-Heath, DF Sripriya, S Fuse, N Abu-Amero, KK Huang, CK Namburi, P Burdon, K Perera, SA Gharahkhani, P Lin, Y Ueno, M Ozaki, M Mizoguchi, T Krishnadas, SR Osman, EA Lee, MC Chan, ASY Tajudin, LSA Do, T Goncalves, A Reynier, P Zhang, H Bourne, R Goh, D Broadway, D Husain, R Negi, AK Su, DH Ho, CL Blanco, AA Leung, CKS Wong, TT Yakub, A Liu, YT Nongpiur, ME Han, JC Hon, DN Shantha, B Zhao, BW Sang, JH Zhang, NH Sato, R Yoshii, K Panda-Jonas, S Koch, AEA Herndon, LW Moroi, SE Challa, P Foo, JN Bei, JX Zeng, YX Simmons, CP Chau, TNB Sharmila, PF Chew, M Lim, B Tam, POS Chua, E Ng, XY Yong, VHK Chong, YF Meah, WY Vijayan, S Seongsoo, S Xu, W Teo, YY Bailey, JNC Kang, JH Haines, JL Cheng, CY Saw, SM Tai, ES Richards, JE Ritch, R Gaasterland, DE Pasquale, LR Liu, JJ Jonas, JB Milea, D George, R Al-Obeidan, SA Mori, K Macgregor, S Hewitt, AW Girkin, CA Zhang, MZ Sundaresan, P Vijaya, L Mackey, DA Wong, TY Craig, JE Sun, XH Kinoshita, S Wiggs, JL Khor, CC Yang, ZL Pang, CP Wang, NL Hauser, MA Tashiro, K Aung, T Vithana, EN AF Li, Zheng Allingham, R. Rand Nakano, Masakazu Jia, Liyun Chen, Yuhong Ikeda, Yoko Mani, Baskaran Chen, Li-Jia Kee, Changwon Garway-Heath, David F. Sripriya, Sarangapani Fuse, Nobuo Abu-Amero, Khaled K. Huang, Chukai Namburi, Prasanthi Burdon, Kathryn Perera, Shamira A. Gharahkhani, Puya Lin, Ying Ueno, Morio Ozaki, Mineo Mizoguchi, Takanori Krishnadas, Subbiah Ramasamy Osman, Essam A. Lee, Mei Chin Chan, Anita S. Y. Tajudin, Liza-Sharmini A. Do, Tan Goncalves, Aurelien Reynier, Pascal Zhang, Hong Bourne, Rupert Goh, David Broadway, David Husain, Rahat Negi, Anil K. Su, Daniel H. Ho, Ching-Lin Blanco, Augusto Azuara Leung, Christopher K. S. Wong, Tina T. Yakub, Azhany Liu, Yutao Nongpiur, Monisha E. Han, Jong Chul Hon, Do Nhu Shantha, Balekudaru Zhao, Bowen Sang, Jinghong Zhang, NiHong Sato, Ryuichi Yoshii, Kengo Panda-Jonas, Songhomita Koch, Allison E. Ashley Herndon, Leon W. Moroi, Sayoko E. Challa, Pratap Foo, Jia Nee Bei, Jin-Xin Zeng, Yi-Xin Simmons, Cameron P. Tran Nguyen Bich Chau Sharmila, Philomenadin Ferdinamarie Chew, Merwyn Lim, Blanche Tam, Pansy O. S. Chua, Elaine Ng, Xiao Yu Yong, Victor H. K. Chong, Yaan Fun Meah, Wee Yang Vijayan, Saravanan Seongsoo, Sohn Xu, Wang Teo, Yik Ying Bailey, Jessica N. Cooke Kang, Jae H. Haines, Jonathan L. Cheng, Ching Yu Saw, Seang-Mei Tai, E-Shyong Richards, Julia E. Ritch, Robert Gaasterland, Douglas E. Pasquale, Louis R. Liu, Jianjun Jonas, Jost B. Milea, Dan George, Ronnie Al-Obeidan, Saleh A. Mori, Kazuhiko Macgregor, Stuart Hewitt, Alex W. Girkin, Christopher A. Zhang, Mingzhi Sundaresan, Periasamy Vijaya, Lingam Mackey, David A. Wong, Tien Yin Craig, Jamie E. Sun, Xinghuai Kinoshita, Shigeru Wiggs, Janey L. Khor, Chiea-Chuen Yang, Zhenglin Pang, Chi Pui Wang, Ningli Hauser, Michael A. Tashiro, Kei Aung, Tin Vithana, Eranga N. CA ICAARE-Glaucoma Consortium NEIGHBORHOOD Consortium TI A common variant near TGFBR3 is associated with primary open angle glaucoma SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CENTRAL CORNEAL THICKNESS; SUSCEPTIBILITY LOCI; MULTIPLE-SCLEROSIS; RISK-FACTORS; IDENTIFICATION; GENE; NUMBER; POPULATION; WORLDWIDE AB Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 x 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, P-meta = 1.60 x 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis. C1 [Khor, Chiea-Chuen; Vithana, Eranga N.] Academia, Singapore 169856, Singapore. [Li, Zheng; Mani, Baskaran; Perera, Shamira A.; Lee, Mei Chin; Chan, Anita S. Y.; Wong, Tina T.; Nongpiur, Monisha E.; Chew, Merwyn; Lim, Blanche; Chua, Elaine; Ng, Xiao Yu; Yong, Victor H. K.; Chong, Yaan Fun; Cheng, Ching Yu; Saw, Seang-Mei; Milea, Dan; Wong, Tien Yin; Aung, Tin; Vithana, Eranga N.] Singapore Eye Res Inst, Singapore, Singapore. [Perera, Shamira A.; Chan, Anita S. Y.; Goh, David; Husain, Rahat; Su, Daniel H.; Ho, Ching-Lin; Wong, Tina T.; Foo, Jia Nee; Cheng, Ching Yu; Milea, Dan; Wong, Tien Yin; Aung, Tin] Singapore Natl Eye Ctr, Singapore, Singapore. [Li, Zheng; Foo, Jia Nee; Meah, Wee Yang; Teo, Yik Ying; Liu, Jianjun; Khor, Chiea-Chuen] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Allingham, R. Rand; Herndon, Leon W.; Challa, Pratap; Hauser, Michael A.] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA. [Nakano, Masakazu; Sato, Ryuichi; Mori, Kazuhiko; Tashiro, Kei] Kyoto Prefectural Univ Med, Dept Genom Med Sci, Kyoto, Japan. [Ikeda, Yoko; Ueno, Morio; Kinoshita, Shigeru] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan. [Yoshii, Kengo] Kyoto Prefectural Univ Med, Dept Med Stat, Kyoto, Japan. [Jia, Liyun; Zhao, Bowen; Sang, Jinghong; Zhang, NiHong; Wang, Ningli] Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China. [Chen, Yuhong; Sun, Xinghuai] Fudan Univ, Eye & ENT Hosp, Shanghai Med Sch, Dept Ophthalmol & Visual Sci, Shanghai, Peoples R China. [Sun, Xinghuai] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai, Peoples R China. [Mani, Baskaran; Nongpiur, Monisha E.; Cheng, Ching Yu; Wong, Tien Yin; Khor, Chiea-Chuen; Aung, Tin; Vithana, Eranga N.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Xu, Wang; Teo, Yik Ying; Saw, Seang-Mei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. [Mani, Baskaran; Perera, Shamira A.; Wong, Tina T.; Nongpiur, Monisha E.; Cheng, Ching Yu; Milea, Dan; Aung, Tin; Vithana, Eranga N.] Duke NUS Grad Med Sch, Singapore, Singapore. [Chen, Li-Jia; Leung, Christopher K. S.; Tam, Pansy O. S.; Pang, Chi Pui] Chinese Univ Hong Kong, Hosp Eye, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China. [Kee, Changwon; Han, Jong Chul; Seongsoo, Sohn] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea. [Garway-Heath, David F.] UCL, Nat Inst Hlth Res Biomed Res Ctr, Moorfields Eye Hosp NHS Fdn Trust, London, England. [Garway-Heath, David F.] UCL, Inst Ophthalmol, London, England. [Sripriya, Sarangapani; Sharmila, Philomenadin Ferdinamarie] SNONGC, Sankara Nethralaya, Dept Mol Biol & Genet, Vision Res Fdn, Madras, Tamil Nadu, India. [Fuse, Nobuo] Tohoku Med Megabank Org, Dept Integrat Genom, Sendai, Miyagi, Japan. [Abu-Amero, Khaled K.; Osman, Essam A.; Al-Obeidan, Saleh A.] King Saud Univ, Coll Med, Dept Ophthalmol, Riyadh, Saudi Arabia. [Abu-Amero, Khaled K.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL USA. [Huang, Chukai; Zhang, Mingzhi] Shantou Univ, Chinese Univ Hong Kong Joint Shantou Int Eye Ctr, Shantou, Peoples R China. [Namburi, Prasanthi; Vijayan, Saravanan; Sundaresan, Periasamy] Aravind Med Res Fdn, Dept Genet, Madurai, Tamil Nadu, India. [Burdon, Kathryn; Hewitt, Alex W.; Mackey, David A.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Burdon, Kathryn; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA, Australia. [Gharahkhani, Puya; Macgregor, Stuart] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Lin, Ying; Yang, Zhenglin] Hosp Univ Elect Sci & Technol China, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu, Peoples R China. [Lin, Ying; Yang, Zhenglin] Hosp Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Chengdu, Peoples R China. [Lin, Ying; Yang, Zhenglin] Univ Elect Sci & Technol China, Sch Med, Chengdu, Peoples R China. [Ozaki, Mineo] Ozaki Eye Hosp, Hyuga, Miyazaki 8830066, Japan. [Mizoguchi, Takanori] Mizoguchi Eye Hosp, Sasebo, Nagasaki 8570016, Japan. [Krishnadas, Subbiah Ramasamy] Aravind Eye Hosp, Glaucoma Serv, Madurai, Tamil Nadu, India. [Tajudin, Liza-Sharmini A.; Yakub, Azhany] Univ Sains Malaysia, Sch Med Sci, Dept Ophthalmol, Kota Baharu, Kelantan, Malaysia. [Do, Tan; Hon, Do Nhu] Vietnam Natl Inst Ophthalmol, Hanoi, Vietnam. [Goncalves, Aurelien] Angers Univ Hosp, Dept Ophthalmol, Angers, France. [Zhang, Hong] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Ophthalmol, Wuhan 430074, Peoples R China. [Bourne, Rupert] Hinchingbrooke Hosp, Huntingdon Glaucoma Diagnost & Res Ctr, Huntingdon, England. [Broadway, David] Norfolk & Norwich Univ Hosp NHS Trust, Norwich, Norfolk, England. [Negi, Anil K.] Heart UK NHS Fdn Trust, Birmingham, W Midlands, England. [Blanco, Augusto Azuara] Queens Univ Belfast, Ctr Med Expt, Sch Med Dent & Biomed Sci, Belfast BT7 1NN, Antrim, North Ireland. [Liu, Yutao; Koch, Allison E. Ashley; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Liu, Yutao] Georgia Regents Univ, Dept Cell Biol & Anat, Augusta, GA USA. [Shantha, Balekudaru; George, Ronnie; Vijaya, Lingam] Sankara Nethralaya, Med Res Fdn, Madras, Tamil Nadu, India. [Panda-Jonas, Songhomita; Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Heidelberg, Germany. [Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Bei, Jin-Xin; Zeng, Yi-Xin] State Key Lab Oncol Southern China, Guangzhou, Guangdong, Peoples R China. [Bei, Jin-Xin; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510275, Guangdong, Peoples R China. [Simmons, Cameron P.; Tran Nguyen Bich Chau] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam. [Simmons, Cameron P.] Univ Oxford, Ctr Trop Med, Nuffield Dept Clin Med, Oxford OX3 7LJ, England. [Bailey, Jessica N. Cooke; Haines, Jonathan L.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Kang, Jae H.; Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Tai, E-Shyong] Natl Univ Hlth Syst, Dept Med, Singapore, Singapore. [Tai, E-Shyong] Natl Univ Singapore, Singapore 117548, Singapore. [Ritch, Robert] New York Eye & Ear Infirm, Einhorn Clin Res Ctr, Dept Ophthalmol, New York, NY 10003 USA. [Ritch, Robert; Gaasterland, Douglas E.] Eye Doctors Washington DC, Washington, DC USA. [Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Hewitt, Alex W.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, CERA, Melbourne, Vic, Australia. [Girkin, Christopher A.; Wiggs, Janey L.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL USA. [Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia. [Sun, Xinghuai] Minist Hlth China, Myopia Key Lab, Shanghai, Peoples R China. [Yang, Zhenglin] Chinese Acad Sci, Sichuan Translat Med Hosp, Chengdu, Peoples R China. [Reynier, Pascal] Angers Univ Hosp, Dept Biochem, Angers, France. RP Vithana, EN (reprint author), Academia, 20 Coll Rd,Discovery Tower Level 6, Singapore 169856, Singapore. EM khorcc@gis.a-star.edu.sg; eranga.n.v@sericom.sg RI Reynier, Pascal/K-3677-2015; Macgregor, Stuart/C-6442-2009; Hewitt, Alex/D-1936-2013; Foo, Jia Nee/D-6069-2014; Chen, Li Jia/I-5078-2014; OI Simmons, Cameron P./0000-0002-9039-7392; Macgregor, Stuart/0000-0001-6731-8142; Hewitt, Alex/0000-0002-5123-5999; Foo, Jia Nee/0000-0001-9899-2308; Chen, Li Jia/0000-0003-3500-5840; Yaakub, Azhany/0000-0001-8047-1192; Gharahkhani, Puya/0000-0002-4203-5952; Perera, Shamira/0000-0002-1404-5096; Ashley-Koch, Allison/0000-0001-5409-9155; Khor, Chiea Chuen/0000-0002-1128-4729; Garway-Heath, David/0000-0003-2907-6992; Li , Zheng/0000-0002-7060-2213; Mackey, David/0000-0001-7914-4709; Tai, E Shyong/0000-0003-2929-8966 FU Biomedical Research Council (BMRC) grant in Singapore [BMRC 10/1/35/19/675]; Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme [NMRC/TCR/008-SERI/2013]; National Medical Research Council, Singapore [NMRC/TCR/002-SERI/2008, (R626/47/2008TCR), CSA R613/34/2008, NMRC 0796/2003, STaR/0003/2008]; National Research Foundation of Singapore; Biomedical Research Council, Singapore [BMRC 09/1/35/19/616, 08/1/35/19/550]; Genome Institute of Singapore [GIS/12-AR2105]; NIH [R01 EY023646, P30-EY005722, HHSN268200782096C, EY015543, EY006827, HL73042, HL073389, EY13315, EY023646, CA87969, CA49449, UM1 CA167552, EY009149]; Collaborative Development of Innovative Seeds of Japan Science and Technology Agency (JST); Ministry of Health, Labor and Welfare of Japan; Santen Pharmaceutical Co. Ltd.; National Natural Science Foundation of China [81030016, 81200723, 81170883, 81430008]; Special Scientific Research Project of Health Professions [201302015]; Health and Medical Research Fund (HMRF), Hong Kong [01122236, 11120801]; General Research Fund from the Research Grants Council, Hong Kong [468810]; National Health and Medical Research Council of Australia [535074, 1023911]; NHMRC [1031362, 1037838, 1048037, 1009844, 1031920]; Alcon Research Institute; BrightFocus Foundation; Ramaciotti Establishment Grant; Australian Research Council (ARC); Queensland Cancer Fund; National Health and Medical Research Council (NHMRC) of Australia [199600, 552429]; National Cancer Institute [5 RO1 CA 001833, R01 CA136725]; Glaucoma Research Chair at College of Medicine, King Saud University, Riyadh, Saudi Arabia; NEI [HG005259-01]; NEI through American Recovery and Reinvestment Act (ARRA) [3R01EY015872-05S1, 3R01EY019126-02S1]; Harvard Glaucoma Center for Excellence; Research to Prevent Blindness; NIH GEI [U01HG04424, U01HG004728]; Singapore Eye Research Institute; The NIH [EY022305, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, RR015574, EY015872, EY010886, EY009847, EY014104, EY011008, EY144428, EY144448, EY18660, T32 EY007157, T32 EY21453-2, P30 014104] FX We thank all the study participants, the staff from all involved studies and sites who contributed to this study. The authors J.E.C., K.P.B., D.A.M., and others acknowledge the support of Ms Bronwyn Usher-Ridge in patient recruitment and data collection, and Dr Patrick Danoy and Dr Johanna Hadler for genotyping of the ANZRAG cohort. They also acknowledge David C. Whiteman and Graham Radford-Smith for providing access to the control samples used with the ANZRAG glaucoma cases. The authors D.M. thank Dr Philippe Gohier and Dr Ghislaine Jallet for patient recruitment and data collection and acknowledge the technical assistance provided by the Centre de Recherche Biologique (Dr Odile Blanchet) and Centre de Recherche Clinique (Pr Marc-Antoine Custeau), University Hospital, Angers, France. The Singapore study of E.N.V., T.A. and C.C.K was supported by a Biomedical Research Council (BMRC) grant in Singapore, Ref: BMRC 10/1/35/19/675. This research was also partly supported by a grant (NMRC/TCR/008-SERI/2013) from the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council. We also acknowledge the following source of funding support for recruitment and genotyping of population-based cohorts SIMES and SCES: National Medical Research Council, Singapore (NMRC/TCR/002-SERI/2008, (R626/47/2008TCR), CSA R613/34/2008, NMRC 0796/2003, STaR/0003/2008), the National Research Foundation of Singapore, the Biomedical Research Council, Singapore (BMRC 09/1/35/19/616 and 08/1/35/19/550) and Genome Institute of Singapore (GIS/12-AR2105). The Singapore Tissue Network and the Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore provided services. The research of M.A.H. was supported by NIH R01 EY023646, EY13315 (MAH) and by P30-EY005722. The Japanese sample collection from Kyoto was supported by the grants from the Collaborative Development of Innovative Seeds of Japan Science and Technology Agency (JST) to M.K. and K.T., from the Ministry of Health, Labor and Welfare of Japan to M.N., K.M., K.T. and S.K., and from Santen Pharmaceutical Co. Ltd. to S.K. and K.T. The collection of Japanese POAG cases by N.F. was supported by a grant provided by the Ministry of Health, Labor and Welfare of Japan. The glaucoma research of WNL is supported by National Natural Science Foundation of China project (81030016). The research of Y. Chen was supported by National Natural Science Foundation of China (81200723) and glaucoma research of Xinghuai Sun was supported by Special Scientific Research Project of Health Professions (201302015). This research project was supported by the National Natural Science Foundation of China (81170883 (Z. Y.) and 81430008 (Z. Y.)). The glaucoma research of C.P.P. is supported by the Health and Medical Research Fund (HMRF, Ref: 01122236 and 11120801), Hong Kong and the General Research Fund from the Research Grants Council (grant number 468810), Hong Kong. Support for recruitment of Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) was provided by the Royal Australian and New Zealand College of Ophthalmology (RANZCO) Eye Foundation. Genotyping was funded by the National Health and Medical Research Council of Australia (#535074 and #1023911). This workwas also supported by funding from NHMRC #1031362 awarded to Jamie E. Craig, NHMRC #1037838 awarded to Alex W. Hewitt, NHMRC # 1048037 awarded to Stuart L. Graham, NHMRC # 1009844 awarded to Robert J.; Casson and Ivan Goldberg, NHMRC # 1031920 and an Alcon Research Institute grant awarded to David A. Mackey, an Allergan Unrestricted grant awarded to Andrew J. White, the BrightFocus Foundation and a Ramaciotti Establishment Grant. S.M. is supported by Australian Research Council (ARC) and Australian National Health & Medical Research Council (NHMRC) Fellowships. Controls for the ANZRAG discovery cohort were drawn from the Australian Cancer Study, the Study of Digestive Health, and from a study of inflammatory bowel diseases. The Australian Cancer Study was supported by the Queensland Cancer Fund and the National Health and Medical Research Council (NHMRC) of Australia (Program no. 199600, awarded to David C. Whiteman, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie and Penelope M. Webb, and program number 552429, awarded to David C. Whiteman). The Study of Digestive Health was supported by grant number 5 RO1 CA 001833 from the National Cancer Institute (awarded to David C. Whiteman). The Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS) sponsored the genotyping of oesophageal cancer and Barrett's oesophagus cases, which were used as unscreened controls in the ANZRAG discovery cohort. BEAGESS was funded by grant R01 CA136725 from the National Cancer Institute Collection of Saudi POAG cases and controls was supported by the Glaucoma Research Chair at College of Medicine, King Saud University, Riyadh, Saudi Arabia. NEI Glaucoma Human Genetics Collaboration (NEIGHBOR): genotyping services for the NEIGHBOR study were provided by the CIDR and were supported by the NEI through grant HG005259-01 (J.L.W.). Additionally, CIDR is funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268200782096C. Collecting and processing samples for the NEIGHBOR data set was supported by the NEI through American Recovery and Reinvestment Act (ARRA) grants 3R01EY015872-05S1 (J.L.W.) and 3R01EY019126-02S1 (M.A.H.). Genotype imputation and meta-analysis were supported by EY022305 (J.L.W.). Funding for the collection of cases and controls was provided by the following NIH grants: EY015543 (R.R. Allingham); EY006827 (D. Gaasterland); HL73042, HL073389, EY13315, EY023646 (M. A. H.); CA87969, CA49449, UM1 CA167552 (J.H. Kang); EY009149 (P.R. Lichter); HG004608 (C. McCarty); EY008208 (F.A. Medeiros); EY015473 (L.R.P.); EY012118 (M. Pericak-Vance); EY015682 (A. Realini); EY011671, EY09580 (J.E. Richards); EY013178 (J. S. Schuman); RR015574, EY015872, EY010886, EY009847, EY014104 (J.L.W.); EY011008, EY144428, EY144448 and EY18660 (K. Zhang). J.L.W. and L.R.P. are also supported by the Harvard Glaucoma Center for Excellence and Research to Prevent Blindness. J.N.C.B. is supported by NIH T32 EY007157 (CWRU) and T32 EY21453-2 (VUMC). MEEI case-control sample: genotyping for the Massachusetts Eye and Ear Infirmary (MEEI) case-control sample was performed at the Broad Institute of MIT and Harvard with funding support fromthe NIH GEI (Gene Environment Initiative) (U01HG04424 and U01HG004728). The GENEVA Coordinating Center (U01HG004446) assisted with genotype cleaning. Imputation was supported by NIH EY022305 (JLW). Collection of cases and controls was supported by NIH EY015872 (JLW) and NIH P30 014104 (JLW). Funding to pay the Open Access publication charges for this article was provided by Singapore Eye Research Institute. NR 54 TC 19 Z9 19 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2015 VL 24 IS 13 BP 3880 EP 3892 DI 10.1093/hmg/ddv128 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CM2PO UT WOS:000357523900023 PM 25861811 ER PT J AU Sullivan, CA Kahn, SE Fujimoto, WY Hayashi, T Leonetti, DL Boyko, EJ AF Sullivan, Catherine A. Kahn, Steven E. Fujimoto, Wilfred Y. Hayashi, Tomoshige Leonetti, Donna L. Boyko, Edward J. TI Change in Intra-Abdominal Fat Predicts the Risk of Hypertension in Japanese Americans SO HYPERTENSION LA English DT Article DE adiposity; Asian Americans; hypertension; intra-abdominal fat ID VISCERAL ADIPOSE-TISSUE; IMPAIRED GLUCOSE-TOLERANCE; METABOLIC SYNDROME; INCIDENT HYPERTENSION; INSULIN-RESISTANCE; LIPOPROTEIN LEVELS; MEN; ASSOCIATION; PREVALENCE; OBESITY AB In Japanese Americans, intra-abdominal fat area measured by computed tomography is positively associated with the prevalence and incidence of hypertension. Evidence in other populations suggests that other fat areas may be protective. We sought to determine whether a change in specific fat depots predicts the development of hypertension. We prospectively followed up 286 subjects (mean age, 49.5 years; 50.4% men) from the Japanese American Community Diabetes Study for 10 years. At baseline, subjects did not have hypertension (defined as blood pressure 140/90 mmHg) and were not taking blood pressure or glucose-lowering medications. Mid-thigh subcutaneous fat area, abdominal subcutaneous fat area, and intra-abdominal fat area were directly measured by computed tomography at baseline and 5 years. Logistic regression was used to estimate odds of incident hypertension over 10 years in relation to a 5-year change in fat area. The relative odds of developing hypertension for a 5-year increase in intra-abdominal fat was 1.74 (95% confidence interval, 1.28-2.37), after adjusting for age, sex, body mass index, baseline intra-abdominal fat, alcohol use, smoking status, and weekly exercise energy expenditure. This relationship remained significant when adjusted for baseline fasting insulin and 2-hour glucose levels or for diabetes mellitus and pre-diabetes mellitus classification. There were no significant associations between baseline and change in thigh or abdominal subcutaneous fat areas and incident hypertension. In conclusion, in this cohort of Japanese Americans, the risk of developing hypertension is related to the accumulation of intra-abdominal fat rather than the accrual of subcutaneous fat in either the thigh or the abdominal areas. C1 [Kahn, Steven E.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Gen Med & Hosp Serv, Seattle, WA USA. [Kahn, Steven E.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Specialty Med Serv, Seattle, WA USA. [Sullivan, Catherine A.; Kahn, Steven E.] Univ Washington, Dept Med, Div Endocrinol Metab & Nutr, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Hayashi, Tomoshige] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Boyko, EJ (reprint author), VA Puget Sound S 123 PCC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eboyko@uw.edu RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU Medical Research Service and Cooperative Studies Program of the Department of Veterans Affairs, Seattle, WA; National Institutes of Health [DK-031170, HL-049293, DK-002654, DK-017047, DK-035816, RR-000037] FX This study was supported, in part, by the Medical Research Service and Cooperative Studies Program of the Department of Veterans Affairs, Seattle, WA, as well as National Institutes of Health grants DK-031170, HL-049293, DK-002654, DK-017047, DK-035816, and RR-000037. NR 39 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUL PY 2015 VL 66 IS 1 BP 134 EP 140 DI 10.1161/HYPERTENSIONAHA.114.04990 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CL6MD UT WOS:000357080300021 PM 26063668 ER PT J AU Isganaitis, E Rifas-Shiman, SL Oken, E Dreyfuss, JM Gall, W Gillman, MW Patti, ME AF Isganaitis, E. Rifas-Shiman, S. L. Oken, E. Dreyfuss, J. M. Gall, W. Gillman, M. W. Patti, M-E TI Associations of cord blood metabolites with early childhood obesity risk SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID LOW-BIRTH-WEIGHT; ACID-METABOLISM; AMINO-ACIDS; FATTY-ACID; GROWTH; MICE; METABOLOMICS; INDIVIDUALS; PREGNANCY; DISEASE AB BACKGROUND/OBJECTIVE: Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. METHODS: We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n = 26) based on top quartile of change in weight-for-age 0-6 months and body mass index (BMI) >85th percentile in mid-childhood (median 7.7 years). Controls (n = 26) were age and sex matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 months) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted liquid chromatography-mass spectrometry; individual metabolites and pathways differing between cases and controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). RESULTS: Of 415 detected metabolites, 16 were altered in cases versus controls (t-test, nominal P<0.05). Three metabolites were related to tryptophan: serotonin, tryptophan betaine and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of two methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16%, respectively, P = 0.01). Moreover, the glutamine: glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case versus control status. CONCLUSIONS: Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study. C1 [Isganaitis, E.; Dreyfuss, J. M.; Patti, M-E] Harvard Univ, Div Res, Dept Genet & Epidemiol, Joslin Diabet Ctr,Med Sch, Boston, MA 02215 USA. [Rifas-Shiman, S. L.; Oken, E.; Gillman, M. W.] Harvard Univ, Obes Prevent Program, Dept Populat Med, Sch Med, Boston, MA 02215 USA. [Rifas-Shiman, S. L.; Oken, E.; Gillman, M. W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Dreyfuss, J. M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Gall, W.] Metabolon Inc, Durham, NC USA. RP Isganaitis, E (reprint author), Harvard Univ, Div Res, Dept Genet & Epidemiol, Joslin Diabet Ctr,Med Sch, One Joslin Pl,Room 607, Boston, MA 02215 USA. EM Elvira.Isganaitis@joslin.harvard.edu FU Joslin Bioinformatics Core - Diabetes Research Center [DK036836]; Pediatric Endocrine Society; Canadian Institutes of Health Research; American Diabetes Association; Graetz Foundation; [K99/R00 (HD064793)]; [K24 HD069408] FX We gratefully acknowledge the support of the Joslin Bioinformatics Core, funded by Diabetes Research Center grant DK036836. Grant support was provided by K99/R00 (HD064793), the Pediatric Endocrine Society, the Canadian Institutes of Health Research and the Graetz Foundation (to EI); by K24 HD069408 (to EO) and by the American Diabetes Association and the Graetz Foundation (to M-EP). NR 34 TC 4 Z9 4 U1 2 U2 10 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 JUL PY 2015 VL 39 IS 7 BP 1041 EP 1048 DI 10.1038/ijo.2015.39 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CM5LW UT WOS:000357730400002 PM 25804930 ER PT J AU Koren, D Chirinos, JA Katz, LEL Mohler, ER Gallagher, PR Mitchell, GF Marcus, CL AF Koren, D. Chirinos, J. A. Katz, L. E. L. Mohler, E. R. Gallagher, P. R. Mitchell, G. F. Marcus, C. L. TI Interrelationships between obesity, obstructive sleep apnea syndrome and cardiovascular risk in obese adolescents SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID INTIMA-MEDIA THICKNESS; PULSE-WAVE VELOCITY; ARTERIAL STIFFNESS; CAROTID-ARTERY; YOUNG-ADULTS; INSULIN-RESISTANCE; METABOLIC SYNDROME; UNITED-STATES; CHILDREN; ATHEROSCLEROSIS AB BACKGROUND/OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) may be a cardiovascular disease (CVD) risk factor independently of obesity in adults. Pediatric studies have associated OSAS with endothelial dysfunction, but few studies have examined relationships between OSAS and macrovascular sequelae. Our objective was to examine OSAS's independent contribution to macrovascular CVD risk measures in obese adolescents. SUBJECTS/METHODS: This cross-sectional observational study was conducted at Children's Hospital of Philadelphia Clinical Research and Academic Sleep Centers, and University of Pennsylvania Vascular Research Unit. Thirty-one obese non-diabetic adolescents underwent anthropometric measurements, overnight polysomnography, fasting laboratory draw and cardiovascular imaging. Cardiovascular outcome measures included maximal carotid intima-media thickness (cIMTmax), a measure of carotid structural changes, and carotid-femoral pulse wave velocity (CFPWV), an aortic stiffness measure whose relationship vis-a-vis OSAS in children has not been previously examined. Carotid diameter and augmentation index (AIx, measuring central pressure augmentation from wave reflections) were assessed. Potential confounding variables examined included blood pressure, lipoproteins, high-sensitivity C-reactive protein, insulin and glucose. RESULTS: The apnea hypopnea index, a primary OSAS measure, was not associated with cIMTmax, carotid diameter, CFPWV or AIx. body mass index (BMI) associated positively with cIMTmax (r = 0.52, P = 0.006) and CFPWV (r = 0.45, P = 0.01). Mean asleep end-tidal CO2 was negatively associated with carotid diameter (r = -0.63, P < 0.0005). Insulin levels were negatively associated with AIx (r = -0.53, P = 0.02). CONCLUSIONS: OSAS did not predict carotid structural changes or arterial stiffness independently of BMI in obese adolescents. Higher insulin levels associated with lower central pressure wave augmentation. Finally, long-term hypercapnia may predispose to carotid narrowing. C1 [Koren, D.] Univ Chicago, Sect Endocrinol Diabet & Metab, Pediat, Chicago, IL 60637 USA. [Chirinos, J. A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chirinos, J. A.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Katz, L. E. L.] Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Pediat, Philadelphia, PA USA. [Mohler, E. R.] Univ Penn, Perelman Sch Med, Vasc Med Sect, Dept Med,Cardiovasc Div, Philadelphia, PA USA. [Gallagher, P. R.] Childrens Hosp Philadelphia, Biostat Core, Clin & Translat Res Ctr, Philadelphia, PA 19104 USA. [Mitchell, G. F.] Cardiovasc Engn Inc, Norwood, MA USA. [Marcus, C. L.] Childrens Hosp Philadelphia, Sleep Ctr, Pediat, Philadelphia, PA 19104 USA. [Marcus, C. L.] Univ Penn, Philadelphia, PA 19104 USA. RP Koren, D (reprint author), Univ Chicago, Pediat & Med, Sect Adult & Pediat Endocrinol Diabet & Metab, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM dkoren@peds.bsd.uchicago.edu FU NIH [KL2 RR024132, RO1 HL58585] FX We would like to thank our research participants and their families for their time and efforts in participating in our study, the sleep technicians who oversaw and scored the polysomnography studies, and the research coordinators who helped with study recruitment. The study was supported by NIH KL2 RR024132 and NIH RO1 HL58585. NR 49 TC 10 Z9 10 U1 2 U2 5 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 JUL PY 2015 VL 39 IS 7 BP 1086 EP 1093 DI 10.1038/ijo.2015.67 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CM5LW UT WOS:000357730400008 PM 25913504 ER PT J AU Patil, SU Ogunniyi, AO Calatroni, A Tadigotla, VR Ruiter, B Ma, A Moon, J Love, JC Shreffler, WG AF Patil, Sarita U. Ogunniyi, Adebola O. Calatroni, Agustin Tadigotla, Vasisht R. Ruiter, Bert Ma, Alex Moon, James Love, J. Christopher Shreffler, Wayne G. TI Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated subjects SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Immunotherapy; antigen-specific B cells; peanut allergy; food allergy; antibody repertoire ID GRASS-POLLEN IMMUNOTHERAPY; DIAL TELEPHONE SURVEY; TREE NUT ALLERGY; RT-PCR; RESPONSES; IGE; CHILDREN; ANTIBODIES; PREVALENCE; SIGNATURES AB Background: Peanut oral immunotherapy (PNOIT) induces persistent tolerance to peanut in a subset of patients and induces specific antibodies that might play a role in clinical protection. However, the contribution of induced antibody clones to clinical tolerance in PNOIT is unknown. Objective: We hypothesized that PNOIT induces a clonal, allergen-specific B-cell response that could serve as a surrogate for clinical outcomes. Methods: We used a fluorescent Ara h 2 multimer for affinity selection of Ara h 2-specific B cells and subsequent single-cell immunoglobulin amplification. The diversity of related clones was evaluated by means of next-generation sequencing of immunoglobulin heavy chains from circulating memory B cells with 2x250 paired-end sequencing on the Illumina MiSeq platform. Results: Expression of class-switched antibodies from Ara h 2-positive cells confirms enrichment for Ara h 2 specificity. PNOIT induces an early and transient expansion of circulating Ara h 2-specific memory B cells that peaks at week 7. Ara h 2-specific sequences from memory cells have rates of nonsilent mutations consistent with affinity maturation. The repertoire of Ara h 2-specific antibodies is oligoclonal. Next-generation sequencing-based repertoire analysis of circulating memory B cells reveals evidence for convergent selection of related sequences in 3 unrelated subjects, suggesting the presence of similar Ara h 2-specific B-cell clones. Conclusions: Using a novel affinity selection approach to identify antigen-specific B cells, we demonstrate that the early PNOIT-induced Ara h 2-specific B-cell receptor repertoire is oligoclonal and somatically hypermutated and shares similar clonal groups among unrelated subjects consistent with convergent selection. C1 [Patil, Sarita U.; Ruiter, Bert; Ma, Alex; Moon, James; Shreffler, Wayne G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Patil, Sarita U.; Ruiter, Bert; Ma, Alex; Moon, James; Shreffler, Wayne G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Patil, Sarita U.; Ruiter, Bert; Shreffler, Wayne G.] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Patil, Sarita U.; Ruiter, Bert; Shreffler, Wayne G.] MassGen Hosp Children, Boston, MA USA. [Patil, Sarita U.; Ogunniyi, Adebola O.; Love, J. Christopher] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Calatroni, Agustin] Rho, Chapel Hill, NC USA. [Tadigotla, Vasisht R.] Boston Univ, Dept Phys, Boston, MA 02215 USA. [Love, J. Christopher] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Love, J. Christopher] Harvard Univ, Sch Med, Boston, MA USA. RP Patil, SU (reprint author), 55 Fruit St,Cox 201, Boston, MA 02114 USA. EM Sarita.patil@mgh.harvard.edu OI Shreffler, Wayne/0000-0001-6465-137X; Moon, James/0000-0001-8246-931X FU National Institute of Allergy and Infectious Diseases (NIAID) [U19 AI087881, U19 AI095261]; National Institutes of Health grant [1S10RR023440-01A1]; Koch Institute Support (core) grant [P30-CA14051]; Keck Foundation; Bill and Melinda Gates Foundation; NIAID [F32 AI104182]; AAAAI/Food Allergy Research & Education Howard Gittis Memorial Research Award; Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award) [UL1 TR001102]; Harvard University FX Supported by contracts with the National Institute of Allergy and Infectious Diseases (NIAID U19 AI087881 and NIAID U19 AI095261), National Institutes of Health grant 1S10RR023440-01A1, and in part by Koch Institute Support (core) grant P30-CA14051. Research was also supported by the Keck Foundation and the Bill and Melinda Gates Foundation. S.U.P. is supported by NIAID F32 AI104182 and 2013 AAAAI/Food Allergy Research & Education Howard Gittis Memorial Research Award. J.C.L is a Camile Dreyfus Teacher-Scholar. Clinical studies were supported in part by the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic health care centers. NR 47 TC 9 Z9 9 U1 0 U2 3 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 JUL PY 2015 VL 136 IS 1 BP 125 EP U253 DI 10.1016/j.jaci.2015.03.026 PG 22 WC Allergy; Immunology SC Allergy; Immunology GA CM2WE UT WOS:000357542200014 PM 25985925 ER PT J AU Townsend, RR Black, HR Chirinos, JA Feig, PU Ferdinand, KC Germain, M Rosendorff, C Steigerwalt, SP Stepanek, JA AF Townsend, Raymond R. Black, Henry R. Chirinos, Julio A. Feig, Peter U. Ferdinand, Keith C. Germain, Michael Rosendorff, Clive Steigerwalt, Susan P. Stepanek, Jan A. TI Clinical Use of Pulse Wave Analysis: Proceedings From a Symposium Sponsored by North American Artery SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID CENTRAL BLOOD-PRESSURE; CARDIOVASCULAR RISK-FACTORS; ASCENDING AORTIC PRESSURE; AUGMENTATION INDEX; REPRODUCIBILITY; AMPLIFICATION; VALIDATION; VELOCITY; FORM AB The use of pulse wave analysis may guide the provider in making choices about blood pressure treatment in prehypertensive or hypertensive patients. However, there is little clinical guidance on how to interpret and use pulse wave analysis data in the management of these patients. A panel of clinical researchers and clinicians who study and clinically use pulse wave analysis was assembled to discuss strategies for using pulse wave analysis in the clinical encounter. This manuscript presents an approach to the clinical application of pulse waveform analysis, howto interpret central pressure waveforms, and how to use existing knowledge about the pharmacodynamic effect of antihypertensive drug classes in combination with brachial and central pressure profiles in clinical practice. The discussion was supplemented by case-based examples provided by panel members, which the authors hope will provoke discussion on how to understand and incorporate pulse wave analysis into clinical practice. (C) 2015 Wiley Periodicals, Inc. C1 [Townsend, Raymond R.; Chirinos, Julio A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Black, Henry R.] NYU, Sch Med, Ctr Prevent Cardiovasc Dis, New York, NY USA. [Feig, Peter U.] Weill Cornell Med Coll, New York, NY USA. [Ferdinand, Keith C.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Germain, Michael] Baystate Med Ctr, Springfield, MA USA. [Germain, Michael] Tufts Univ, Springfield, MA USA. [Rosendorff, Clive] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY USA. [Steigerwalt, Susan P.] St Clair Specialty Phys, Detroit, MI USA. [Stepanek, Jan A.] Mayo Clin, Div Prevent Occupat & Aerosp Med, Scottsdale, AZ USA. RP Townsend, RR (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, 122 Founders Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM townsend@exchange.upennn.edu FU AtCor Medical; National Institutes of Health FX This symposium was supported by an unrestricted grant to North American Artery from AtCor Medical, which covered travel costs and a small stipend for attendees. RRT: National Institutes of Health grant in a relevant area; HRB, JAC, PUF, KCF, MG, CR, SPS, and JAS: nothing to declare. NR 14 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUL PY 2015 VL 17 IS 7 BP 503 EP 513 DI 10.1111/jch.12574 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CM1GI UT WOS:000357428900003 PM 26010834 ER PT J AU Normandin, PA Benotti, SA AF Normandin, Patricia A. Benotti, Stacey A. TI PEDIATRIC EMERGENCY UPDATE: LETHALITY OF LIQUID NICOTINE IN E-CIGARETTES SO JOURNAL OF EMERGENCY NURSING LA English DT Article C1 [Normandin, Patricia A.] Tufts Med Ctr, Boston, MA 02111 USA. [Normandin, Patricia A.] Northeastern Univ, Boston, MA 02115 USA. [Normandin, Patricia A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Normandin, Patricia A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Normandin, Patricia A.] Boston Childrens Hosp, Boston, MA USA. [Benotti, Stacey A.] Tufts Med Ctr, Pediat & Adult Emergency Dept, Boston, MA USA. RP Normandin, PA (reprint author), Tufts Med Ctr, Boston, MA 02111 USA. EM pnormandinrn@aol.com NR 6 TC 0 Z9 0 U1 1 U2 5 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 JUL PY 2015 VL 41 IS 4 BP 357 EP 359 DI 10.1016/j.jen.2015.04.001 PG 3 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA CM3GJ UT WOS:000357569800022 PM 25913384 ER PT J AU Gilden, D Lieberman, P AF Gilden, Don Lieberman, Paul TI Memories and Vignettes From Friends of Hilary Koprowski SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article C1 [Gilden, Don] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Lieberman, Paul] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, B-182,12700 E 19th Ave,Rm 5014, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu NR 5 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 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2015 VL 212 SU 1 BP S5 EP S11 DI 10.1093/infdis/jiv243 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CM6SI UT WOS:000357819700003 PM 26116733 ER PT J AU Blasi, F Oliveira, BL Rietz, TA Rotile, NJ Day, H Naha, PC Cormode, DP Izquierdo-Garcia, D Catana, C Caravan, P AF Blasi, Francesco Oliveira, Bruno L. Rietz, Tyson A. Rotile, Nicholas J. Day, Helen Naha, Pratap C. Cormode, David P. Izquierdo-Garcia, David Catana, Ciprian Caravan, Peter TI Radiation Dosimetry of the Fibrin-Binding Probe Cu-64-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE thrombosis; PET imaging; fibrin; DVT-PE; dosimetry ID VENOUS THROMBOEMBOLISM; COMPUTED-TOMOGRAPHY; CONTRAST AGENT; THROMBOLYSIS; MODEL; SUSCEPTIBILITY; ANGIOGRAPHY; DIAGNOSIS; TIME AB The diagnosis of deep venous thromboembolic disease is still challenging despite the progress of current thrombus imaging modalities and new diagnostic algorithms. We recently reported the high target uptake and thrombus imaging efficacy of the novel fibrin-specific PET probe Cu-64-FBP8. Here, we tested the feasibility of Cu-64-FBP8 PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE). To support clinical translation of Cu-64-FBP8, we performed a human dosimetry estimation using time-dependent biodistribution in rats. Methods: Sprague-Dawley rats (n = 7) underwent ferric chloride application on the femoral vein to trigger thrombosis. Pulmonary embolism was induced 30 min or 2 d after DVT by intrajugular injection of a preformed blood clot labeled with I-125-fibrinogen. PET imaging was performed to detect the clots, and SPECT was used to confirm in vivo the location of the pulmonary emboli. Ex vivo y counting and histopathology were used to validate the imaging findings. Detailed biodistribution was performed in healthy rats (n = 30) at different time points after Cu-64-FBP8 administration to estimate human radiation dosimetry. Longitudinal whole-body PET/MR imaging (n = 2) was performed after Cu-64-FBP8 administration to further assess radioactivity clearance. Results: Cu-64-FBP8 PET imaging detected the location of lung emboli and venous thrombi after DVT-PE, revealing significant differences in uptake between target and background tissues (P < 0.001). In vivo SPECT imaging and ex vivo y counting confirmed the location of the lung emboli. PET quantification of the venous thrombi revealed that probe uptake was greater in younger clots than in older ones, a result confirmed by ex vivo analyses (P < 0.001). Histopathology revealed an age-dependent reduction of thrombus fibrin content (P = 0.006), further supporting the imaging findings. Biodistribution and whole-body PET/MR imaging showed a rapid, primarily renal, body clearance of Cu-64-FBP8. The effective dose was 0.021 mSv/MBq for males and 0.027 mSv/MBq for females, supporting the feasibility of using Cu-64-FBP8 in human trials. Conclusion: We showed that Cu-64-FBP8 PET is a feasible approach to image DVT-PE and that radiogenic adverse health effects should not limit the clinical translation of Cu-64-FBP8. C1 [Blasi, Francesco; Oliveira, Bruno L.; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Izquierdo-Garcia, David; Catana, Ciprian; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Naha, Pratap C.; Cormode, David P.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Caravan, Peter] Massachusetts Gen Hosp, Inst Innovat Imaging, Boston, MA 02114 USA. RP Caravan, P (reprint author), Bldg 149,Rm 2301,13th St, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu OI Oliveira, Bruno/0000-0002-7687-4746 FU National Heart, Lung, and Blood Institute [HL109448]; National Center for Research Resources [RR029495] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported by HL109448 from the National Heart, Lung, and Blood Institute. The small-animal PET/SPECT/CT system was funded by RR029495 from the National Center for Research Resources. Dr. Caravan has equity in Factor 1A, LLC, the company that holds the patent rights of the fibrin-binding peptide used in this study. No other potential conflict of interest relevant to this article was reported. NR 38 TC 4 Z9 4 U1 1 U2 7 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 2015 VL 56 IS 7 BP 1088 EP 1093 DI 10.2967/jnumed.115.157982 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CM5UN UT WOS:000357754600042 PM 25977464 ER PT J AU Gu, C Yang, J Yuan, Y Yao, M Zhang, X AF Gu, Chuan Yang, Jun Yuan, Ying Yao, Min Zhang, Xiong TI The safety of photochemical tissue bonding for treating damaged corneal epithelium using limbal stem cells pre-cultured on human amniotic membrane SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article ID ROSE-BENGAL; RECONSTRUCTION; REPAIR; TRANSPLANTATION; POPULATION; SURFACE; MARKER; LABEL; BRDU AB We previously demonstrated the feasibility of treating limbal stem cell deficiency (LSCD) with limbal stem cells (LSCs) pre-cultured on human amniotic membrane (HAM), using a suture-free technique called photochemical tissue bonding (PTB). However, important issues regarding the safety and the influence of PTB on LSCs have not been elucidated. In this study, LSCs, isolated from rabbit eyes and identified by cell markers, were labeled with BrdU prior to cultivation on de-epithelialized HAM to fabricate grafts. Rabbit LSCD models were created and randomly divided into groups for transplantation of fabricated grafts using sutures or PTB (n = 10). Possible phototoxicity of PTB to LSCs was analyzed in vitro and in vivo. Restoration of corneal epithelium was evaluated at 28 days after grafting. Our results showed that phototoxicity did not occur in the LSCs cultured on HAM after PTB in vitro. Transplantation of grafts with PTB restored the damaged cornea epithelium effectively and no significant influences on LSC characteristics were found in both sutured and PTB groups. BrdU positive cells were tracked at 28 days post grafting suggesting that the restored epithelium was derived from the in vitro fabricated HAM/LSC graft. These data suggest that PTB is a safe and potential strategy for securing LSC/HAM grafts that produces with better outcomes than sutured attachment. (C) 2015 Published by Elsevier B.V. C1 [Gu, Chuan; Yao, Min; Zhang, Xiong] Shanghai Jiao Tong Univ, Peoples Hosp 3, Dept Burn & Plast Surg, Shanghai 201900, Peoples R China. [Gu, Chuan; Yao, Min] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gu, Chuan; Yang, Jun] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai 200011, Peoples R China. [Yuan, Ying] Chengyang Peoples Hosp, Dept Ophthalmol, Qingdao 266109, Shandong, Peoples R China. RP Zhang, X (reprint author), 280 Mohe Rd, Shanghai 201900, Peoples R China. EM xiong@medmail.co FU American Society for Laser Medicine and Surgery; Chinese National Natural Science Funds [81272113, 81101431] FX We sincerely appreciate Dr. Jenny Zhao for technical support, and Irene E. Kochevar for the manuscript preparation. This study was partially supported by a Grant from the American Society for Laser Medicine and Surgery to Min Yao (2009) and from the Chinese National Natural Science Funds to Min Yao and Chuan Gu (81272113, 81101431). NR 32 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD JUL PY 2015 VL 148 BP 59 EP 65 DI 10.1016/j.jphotobiol.2015.03.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CM0DN UT WOS:000357348700008 PM 25889946 ER PT J AU Huang, XC Dong, WJ Milewska, A Golda, A Qi, YH Zhu, QK Marasco, WA Baric, RS Sims, AC Pyrc, K Li, WH Sui, JH AF Huang, Xingchuan Dong, Wenjuan Milewska, Aleksandra Golda, Anna Qi, Yonghe Zhu, Quan K. Marasco, Wayne A. Baric, Ralph S. Sims, Amy C. Pyrc, Krzysztof Li, Wenhui Sui, Jianhua TI Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE RESPIRATORY SYNDROME; EPITHELIAL-CELL CULTURES; VIRUS; OC43; METABOLISM; PNEUMONIA; EVOLUTION; SEQUENCE; BINDING; TARGET AB Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity. IMPORTANCE Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity. C1 [Huang, Xingchuan; Dong, Wenjuan; Qi, Yonghe; Li, Wenhui; Sui, Jianhua] Natl Inst Biol Sci, Beijing, Peoples R China. [Dong, Wenjuan] China Agr Univ, Grad Program, Natl Inst Biol Sci, Beijing 100094, Peoples R China. [Milewska, Aleksandra; Golda, Anna; Pyrc, Krzysztof] Jagiellonian Univ, Dept Microbiol, Fac Biochem Biophys & Biotechnol, Krakow, Poland. [Qi, Yonghe] Beijing Normal Univ, Grad Program, Natl Inst Biol Sci, Beijing 100875, Peoples R China. [Zhu, Quan K.; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Zhu, Quan K.; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Baric, Ralph S.; Sims, Amy C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Pyrc, Krzysztof] Jagiellonian Univ, Malopolska Ctr Biotechnol, Krakow, Poland. RP Li, WH (reprint author), Natl Inst Biol Sci, Beijing, Peoples R China. EM liwenhui@nibs.ac.cn; suijianhua@nibs.ac.cn OI Li, Wenhui/0000-0003-1305-7404; Pyrc, Krzysztof/0000-0002-3867-7688; SUI, JIANHUA/0000-0002-1272-9662 FU Ministry of Science and Technology, China; Science and Technology Bureau of Beijing Municipal Government [2012CB837602, 2010CB530101]; Thousand Young Talents Program, China; National Centre for Research and Development, Poland [Lider/27/55/L-2/10/2011]; National Science Center, Poland [UMO-2012/07/E/NZ6/01712]; NIH [U19 AI109761, AI085524] FX This work was supported by grants from the Ministry of Science and Technology, China, to J.S. (2012CB837602) and to W.L. (2010CB530101), from the Science and Technology Bureau of Beijing Municipal Government to W.L. and J.S., from the Thousand Young Talents Program, China, to J.S., from the National Centre for Research and Development, Poland (Lider/27/55/L-2/10/2011),and from the National Science Center, Poland (UMO-2012/07/E/NZ6/01712), to K.P., and from NIH (U19 AI109761) to R.S.B. and NIH (AI085524) to W.A.M. and R.S.B. NR 42 TC 9 Z9 9 U1 1 U2 7 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 JUL PY 2015 VL 89 IS 14 BP 7202 EP 7213 DI 10.1128/JVI.00854-15 PG 12 WC Virology SC Virology GA CM3XU UT WOS:000357619500021 PM 25926653 ER PT J AU Kim, MK Park, HJ Kim, SR Choi, YK Bae, SK Bae, MK AF Kim, Mi-Kyoung Park, Hyun-Joo Kim, Su-Ryun Choi, Yoon Kyung Bae, Soo-Kyung Bae, Moon-Kyoung TI Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells SO KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY LA English DT Article DE Orexin-A; Heme oxygenase-1; Angiogenesis; Vascular endothelial cells ID CARBON-MONOXIDE; PROMOTES ANGIOGENESIS; EXPRESSION; PATHWAY; GENE; RATS; NEUROPEPTIDES; HYPOCRETINS; HIF-1-ALPHA; ACTIVATION AB The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin-A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis. C1 [Kim, Mi-Kyoung; Park, Hyun-Joo; Kim, Su-Ryun; Bae, Moon-Kyoung] Pusan Natl Univ, Sch Dent, Dept Oral Physiol, Yangsan 626770, South Korea. [Park, Hyun-Joo; Kim, Su-Ryun; Bae, Soo-Kyung] Pusan Natl Univ, Sch Dent, Dept Dent Pharmacol, Yangsan 626770, South Korea. [Choi, Yoon Kyung] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. [Choi, Yoon Kyung] Massachusetts Gen Hosp East, Dept Neurol, Charlestown, MA 02129 USA. [Choi, Yoon Kyung] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Bae, MK (reprint author), Pusan Natl Univ, Sch Dent, Dept Oral Physiol, 3-3 Beomeo Ri, Yangsan 626770, South Korea. EM mkbae@pusan.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0003750]; National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [1220080] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0003750) and by the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1220080). NR 35 TC 1 Z9 1 U1 0 U2 2 PU KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY PI SEOUL PA C/O EDITORIAL OFFICE, 448-13 SEOKYO-DONG, SEOUL, SOUTH KOREA SN 1226-4512 EI 2093-3827 J9 KOREAN J PHYSIOL PHA JI KOREAN J. PHYSIOL. PHARMACOL. PD JUL PY 2015 VL 19 IS 4 BP 327 EP 334 DI 10.4196/kjpp.2015.19.4.327 PG 8 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA CM5XE UT WOS:000357761500004 PM 26170736 ER PT J AU Yang, JCH Sequist, LV Geater, SL Tsai, CM Mok, TSK Schuler, M Yamamoto, N Yu, CJ Ou, SHI Zhou, CC Massey, D Zazulina, V Wu, YL AF Yang, James C-H Sequist, Lecia V. Geater, Sarayut Lucien Tsai, Chun-Ming Mok, Tony Shu Kam Schuler, Martin Yamamoto, Nobuyuki Yu, Chong-Jen Ou, Sai-Hong I. Zhou, Caicun Massey, Daniel Zazulina, Victoria Wu, Yi-Long TI Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6 SO LANCET ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; RANDOMIZED PHASE-3 TRIAL; 1ST-LINE TREATMENT; OPEN-LABEL; CARBOPLATIN-PACLITAXEL; PROLONGED SURVIVAL; GEFITINIB; CHEMOTHERAPY; ERLOTINIB AB Background Most patients with non-small-cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21, or both (ie, common mutations). However, a subset of patients (10%) with mutations in EGFR have tumours that harbour uncommon mutations. There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors. Here we present data for the activity of afatinib in patients with advanced non-small-cell lung cancer that have tumours harbouring uncommon EGFR mutations. Methods In this post-hoc analysis, we used prospectively collected data from tyrosine kinase inhibitor-naive patients with EGFR mutation-positive advanced (stage IIIb-IV) lung adenocarcinomas who were given afatinib in a single group phase 2 trial (LUX-Lung 2), and randomised phase 3 trials (LUX-Lung 3 and LUX-Lung 6). Analyses were done in the intention-to-treat population, including all randomly assigned patients with uncommon EGFR mutations. The type of EGFR mutation (exon 19 deletion [del19], Leu858Arg point mutation in exon 21, or other) and ethnic origin (LUX-Lung 3 only; Asian vs non-Asian) were pre-specified stratification factors in the randomised trials. We categorised all uncommon mutations as: point mutations or duplications in exons 18-21 (group 1); de-novo Thr790Met mutations in exon 20 alone or in combination with other mutations (group 2); or exon 20 insertions (group 3). We also assessed outcomes in patients with the most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, alone or in combination with other mutations. Response was established by independent radiological review. These trials are registered with ClinicalTrials.gov, numbers NCT00525148, NCT00949650, and NCT01121393. Findings Of 600 patients given afatinib across the three trials, 75 (12%) patients had uncommon EGFR mutations (38 in group 1, 14 in group 2, 23 in group 3). 27 (71.1%, 95% CI 54.1-84.6) patients in group 1 had objective responses, as did two (14.3%, 1.8-42.8) in group 2 and two (8.7%, 1.1-28.0) in group 3. Median progression-free survival was 10.7 months (95% CI 5.6-14. 7) in group 1, 2.9 months (1.2-8.3) in group 2; and 2.7 months (1.8-4.2) in group 3. Median overall survival was 19.4 months (95% CI 16.4-26.9) in group 1, 14.9 months (8.1-24.9) in group 2, and 9.2 months (4.1-14.2) in group 3. For the most frequent uncommon mutations, 14 (77.8%, 95% CI 52.4-93.6) patients with Gly719Xaa had an objective response, as did nine (56.3%, 29.9-80.2) with Leu861Gln, and eight (100.0%, 63.1-100.0) with Ser768Ile. Interpretation Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations. C1 [Yang, James C-H] Natl Taiwan Univ, Grad Inst Oncol, Taipei, Taiwan. [Yang, James C-H] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Geater, Sarayut Lucien] Prince Songkla Univ, Fac Med, Internal Med, Hat Yai, Songkhla, Thailand. [Tsai, Chun-Ming] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Dept Chest Med, Taipei 112, Taiwan. [Tsai, Chun-Ming] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Mok, Tony Shu Kam] Chinese Univ Hong Kong, Clin Oncol, Hong Kong, Hong Kong, Peoples R China. [Schuler, Martin] Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany. [Schuler, Martin] German Canc Consortium DKTK, Heidelberg, Germany. [Yamamoto, Nobuyuki] Wakayama Med Univ, Dept Internal Med 3, Wakayama, Wakayama Prefec, Japan. [Yu, Chong-Jen] Natl Taiwan Univ, Dept Internal Med, Taipei, Taiwan. [Yu, Chong-Jen] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Ou, Sai-Hong I.] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Zhou, Caicun] Shanghai Pulm Hosp, Shanghai, Peoples R China. [Zazulina, Victoria] Clin Dev & Med Affairs, Bracknell, Berks, England. [Massey, Daniel] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. [Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. RP Wu, YL (reprint author), Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou 510080, Guangdong, Peoples R China. EM syylwu@live.cn OI Yang, James Chih-Hsin/0000-0002-5586-5138; Yu, Chong-Jen/0000-0001-5664-9392 FU Boehringer Ingelheim FX Boehringer Ingelheim. NR 30 TC 62 Z9 63 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2015 VL 16 IS 7 BP 830 EP 838 DI 10.1016/S1470-2045(15)00026-1 PG 9 WC Oncology SC Oncology GA CL9CU UT WOS:000357273600056 PM 26051236 ER PT J AU Bernhard, J Luo, WX Ribi, K Colleoni, M Burstein, HJ Tondini, C Pinotti, G Spazzapan, S Ruhstaller, T Puglisi, F Pavesi, L Parmar, V Regan, MM Pagani, O Fleming, GF Francis, PA Price, KN Coates, AS Gelber, RD Goldhirsch, A Walley, BA AF Bernhard, Juerg Luo, Weixiu Ribi, Karin Colleoni, Marco Burstein, Harold J. Tondini, Carlo Pinotti, Graziella Spazzapan, Simon Ruhstaller, Thomas Puglisi, Fabio Pavesi, Lorenzo Parmar, Vani Regan, Meredith M. Pagani, Olivia Fleming, Gini F. Francis, Prudence A. Price, Karen N. Coates, Alan S. Gelber, Richard D. Goldhirsch, Aron Walley, Barbara A. TI Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials SO LANCET ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; CLINICAL-TRIALS; ENDOCRINE THERAPY; PREVENTION; SYMPTOMS; WORTHWHILE; INDICATORS; ARIMIDEX; IMPACT AB Background The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS. We present pat ient-reported outcomes from these trials. Methods Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5.7 years (IQR 3.7-6.9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov, as NCT00066703 (TEXT) and NCT00066690 (SOFT). Findings Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years. Interpretation Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually. C1 [Bernhard, Juerg; Ribi, Karin] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. [Bernhard, Juerg] Univ Hosp Bern, Inselspital, CH-3010 Bern, Switzerland. [Luo, Weixiu] Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. [Colleoni, Marco] European Inst Oncol, Div Med Senol, Milan, Italy. [Colleoni, Marco] Int Breast Canc Study Grp, Milan, Italy. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Alliance Clin Trials Oncol, Boston, MA USA. [Tondini, Carlo] Osp Papa Giovanni XXIII, Med Oncol, Bergamo, Italy. [Tondini, Carlo] Int Breast Canc Study Grp, Bergamo, Italy. [Pinotti, Graziella] Osped Circolo Varese, Med Oncol, Varese, Italy. [Pinotti, Graziella] Fdn Macchi, Varese, Italy. [Pinotti, Graziella] Int Breast Canc Study Grp, Varese, Italy. [Spazzapan, Simon] Ctr Riferimento Oncol, Med Oncol, Aviano, Italy. [Spazzapan, Simon] Int Breast Canc Study Grp, Aviano, Italy. [Ruhstaller, Thomas] Swiss Grp Clin Canc Res SAKK, Kantonsspital St Gallen, Breast Ctr, St Gallen, Switzerland. [Ruhstaller, Thomas] Int Breast Canc Study Grp, St Gallen, Switzerland. [Puglisi, Fabio] Univ Udine, Univ Hosp Udine, Dept Oncol, I-33100 Udine, Italy. [Puglisi, Fabio] Int Breast Canc Study Grp, Udine, Italy. [Pavesi, Lorenzo] Salvatore Maugeri Fdn, Oncol Unit, Pavia, Italy. [Pavesi, Lorenzo] Int Breast Canc Study Grp, Pavia, Italy. [Parmar, Vani] Tata Mem Hosp, Breast Serv, Surg Oncol, Bombay 400012, Maharashtra, India. [Parmar, Vani] Int Breast Canc Study Grp, Bombay, Maharashtra, India. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. [Pagani, Olivia] Swiss Grp Clin Canc Res, Inst Oncol Southern Switzerland, Lugano Viganello, Switzerland. [Pagani, Olivia] Int Breast Canc Study Grp, Lugano Viganello, Switzerland. [Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Fleming, Gini F.] Alliance Clin Trials Oncol, Chicago, IL USA. [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence A.] Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Francis, Prudence A.] Int Breast Canc Study Grp, Boston, MA USA. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Int Breast Canc Study Grp Stat Ctr, Boston, MA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Gelber, Richard D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Int Breast Canc Study Grp S, Harvard Sch Publ Hlth,Frontier Sci & Technol Res, Boston, MA 02115 USA. [Goldhirsch, Aron] European Inst Oncol, Program Breast Hlth Senol, Milan, Italy. [Goldhirsch, Aron] Int Breast Canc Study Grp, Bern, Switzerland. [Walley, Barbara A.] Tom Baker Canc Clin, Calgary, AB, Canada. [Walley, Barbara A.] Natl Canc Inst Canada Clin Trials Grp, Calgary, AB, Canada. RP Bernhard, J (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM juerg.bernhard@ibcsg.org OI Puglisi, Fabio/0000-0003-0573-4938 FU Pfizer; International Breast Cancer Study Group; US National Cancer Institute FX Pfizer, International Breast Cancer Study Group, and US National Cancer Institute. NR 29 TC 29 Z9 30 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2015 VL 16 IS 7 BP 848 EP 858 DI 10.1016/S1470-2045(15)00049-2 PG 11 WC Oncology SC Oncology GA CL9CU UT WOS:000357273600058 PM 26092816 ER PT J AU Zhu, AX Park, JO Ryoo, BY Yen, CJ Poon, R Pastorelli, D Blanc, JF Chung, HC Baron, AD Pfiffer, TEF Okusaka, T Kubackova, K Trojan, J Sastre, J Chau, I Chang, SC Abada, PB Yang, L Schwartz, JD Kudo, M AF Zhu, Andrew X. Park, Joon Oh Ryoo, Baek-Yeol Yen, Chia-Jui Poon, Ronnie Pastorelli, Davide Blanc, Jean-Frederic Chung, Hyun Cheol Baron, Ari D. Pfiffer, Tulio Eduardo Flesch Okusaka, Takuji Kubackova, Katerina Trojan, Jorg Sastre, Javier Chau, Ian Chang, Shao-Chun Abada, Paolo B. Yang, Ling Schwartz, Jonathan D. Kudo, Masatoshi CA REACH Trial Investigators TI Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ALPHA-FETOPROTEIN LEVELS; CANCER; ANGIOGENESIS; MONOTHERAPY; RECEPTOR-2; CIRRHOSIS; SURVIVAL; DESIGN AB Background VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. Methods In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. Findings Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9.2 months (95% CI 8.0-10.6) versus 7.6 months (6.0-9.3) for the placebo group (HR 0.87 [95% CI 0.72-1.05]; p=0.14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (>= 1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. Interpretation Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Park, Joon Oh] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Ryoo, Baek-Yeol] Univ Ulsan, Sch Med, Asan Med Ctr, Seoul, South Korea. [Yen, Chia-Jui] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Poon, Ronnie] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Pastorelli, Davide] Ist Oncol Veneto IRCCS, Padua, Italy. [Blanc, Jean-Frederic] Hop St Andre, Bordeaux, France. [Chung, Hyun Cheol] Yonsei Univ Hlth Syst, Yonsei Canc Ctr, Seoul, South Korea. [Baron, Ari D.] Calif Pacific Med Ctr, San Francisco, CA USA. [Pfiffer, Tulio Eduardo Flesch] Inst Canc Estado Sao Paulo, Sao Paulo, Brazil. [Okusaka, Takuji] Natl Canc Ctr, Tokyo, Japan. [Kubackova, Katerina] Univ Hosp Motol, Prague, Czech Republic. [Trojan, Jorg] Univ Hosp, Ctr Canc, Frankfurt, Germany. [Sastre, Javier] Hosp Clin San Carlos, Madrid, Spain. [Chau, Ian] Royal Marsden Hosp, Surrey, England. [Chang, Shao-Chun] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Yang, Ling] Eli Lilly & Co, Bridgewater, NJ USA. [Schwartz, Jonathan D.] Stemline Therapeut Inc, New York, NY USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM azhu@partners.org OI Ettrich, Thomas J./0000-0002-7654-2442; Kudo, Masatoshi/0000-0002-4102-3474 FU Eli Lilly and Co. FX Eli Lilly and Co. NR 31 TC 53 Z9 56 U1 5 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2015 VL 16 IS 7 BP 859 EP 870 DI 10.1016/S1470-2045(15)00050-9 PG 12 WC Oncology SC Oncology GA CL9CU UT WOS:000357273600059 PM 26095784 ER PT J AU Engelman, JA Oser, MG Niederst, MJ Sequist, LV AF Engelman, Jeffrey A. Oser, Matthew G. Niederst, Matthew J. Sequist, Lecia V. TI Transformation from NSCLC to SCLC: when did it happen? Reply SO LANCET ONCOLOGY LA English DT Letter ID CELL LUNG-CANCER; ADENOCARCINOMA C1 [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. EM jengelman@partners.org NR 6 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2015 VL 16 IS 7 BP E309 EP E310 PG 3 WC Oncology SC Oncology GA CL9CU UT WOS:000357273600002 PM 26149875 ER PT J AU Stone, JH Brito-Zeron, P Bosch, X Ramos-Casals, M AF Stone, John H. Brito-Zeron, Pilar Bosch, Xavier Ramos-Casals, Manuel TI Diagnostic Approach to the Complexity of IgG4-Related Disease SO MAYO CLINIC PROCEEDINGS LA English DT Review ID IMMUNOGLOBULIN G4-RELATED DISEASE; PRIMARY SCLEROSING CHOLANGITIS; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; TREATMENT RESPONSE; KIDNEY-DISEASE; RISK-FACTORS; IGG4; SIALADENITIS; FEATURES AB IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related. (C) 2015 Mayo Foundation for Medical Education and Research C1 [Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] CELLEX Inst Invest Biomed August Pi & Sunyer IDIB, Lab Autoimmune Dis, Barcelona, Spain. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] Univ Barcelona, Dept Autoimmune Dis, Hosp Clin, E-08007 Barcelona, Spain. [Bosch, Xavier] Univ Barcelona, Dept Internal Med ICMiD, Hosp Clin, E-08007 Barcelona, Spain. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org FU Josep Font Research Fellow Award, Hospital Clinic, Barcelona, Spain FX The work was supported by the Josep Font Research Fellow Award, Hospital Clinic, Barcelona, Spain (P.B.-Z.). NR 72 TC 21 Z9 25 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2015 VL 90 IS 7 BP 927 EP 939 DI 10.1016/j.mayocp.2015.03.020 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CM2PY UT WOS:000357525000013 PM 26141331 ER PT J AU Jamison, RN Mao, JR AF Jamison, Robert N. Mao, Jianren TI Opioid Analgesics SO MAYO CLINIC PROCEEDINGS LA English DT Article ID CHRONIC PAIN PATIENTS; CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PRIMARY-CARE PHYSICIANS; NONMEDICAL USE; HIGH-RISK; LONGITUDINAL OUTCOMES; PRESCRIPTION OPIOIDS; CROSS-VALIDATION; RANDOMIZED-TRIAL AB Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. (C) 2015 Mayo Foundation for Medical Education and Research C1 [Jamison, Robert N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Jamison, RN (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Pain Management Ctr, 850 Boylston St,Ste 320, Chestnut Hill, MA 02467 USA. EM rjamison@partners.org OI Jamison, Robert/0000-0003-1768-0906 FU NIDA NIH HHS [R01 DA036564] NR 94 TC 20 Z9 21 U1 4 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2015 VL 90 IS 7 BP 957 EP 968 DI 10.1016/j.mayocp.2015.04.010 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CM2PY UT WOS:000357525000016 PM 26141334 ER PT J AU Steensma, DP AF Steensma, David P. TI Myelodysplastic Syndromes: Diagnosis and Treatment SO MAYO CLINIC PROCEEDINGS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; STEM-CELL TRANSPLANTATION; CONVENTIONAL CARE REGIMENS; IRON CHELATION-THERAPY; BONE-MARROW FAILURE; SERUM FERRITIN; PHASE-III; LOW-RISK; ALLOGENEIC TRANSPLANTATION AB In the past few years, new biological insights into the myelodysplastic syndromes (MDS) resulting from molecular genetic analysis have improved pathologic understanding, but treatment advances have not kept pace. More than 40 genes are now known to be recurrently mutated in MDS. However, because most of these genes encode spliceosome components, chromatic remodeling factors, epigenetic pattern modulators, or transcription factors rather than more easily inhibited activated tyrosine kinases, there are as of yet few narrowly targeted therapies available for MDS. Three drugs-azacitidine, decitabine, and lenalidomide-were approved by the US Food and Drug Administration for MDS indications a decade ago, and these agents can improve hematopoiesis, delay disease progression, and improve survival and quality of life for a subset of patients. However, only a few patients with MDS respond to these agents, and their benefit is temporary. The only potentially curative therapy for MDS is allogeneic hematopoietic stem cell transplant, but owing to the advanced age of many patients with MDS and the frequency of serious comorbid conditions, less than 10% of patients currently undergo stem cell transplant. This narrative review summarizes the current understanding of MDS and treatment options for these challenging disorders. (C) 2015 Mayo Foundation for Medical Education and Research C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. RP Steensma, DP (reprint author), Brigham & Womens Hosp, Adult Leukemia Program, Div Hematol Malignancies, Dept Med Oncol,Dana Farber Canc Inst, 450 Brookline Ave,D2037, Boston, MA 02215 USA. EM David_Steensma@DFCI.harvard.edu NR 101 TC 12 Z9 13 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2015 VL 90 IS 7 BP 969 EP 983 DI 10.1016/j.mayocp.2015.04.001 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA CM2PY UT WOS:000357525000017 PM 26141335 ER PT J AU Gass, MLS Maki, PM Shifren, JL Schnatz, PF Kaunitz, AM Shapiro, M Sievert, LL AF Gass, Margery L. S. Maki, Pauline M. Shifren, Jan L. Schnatz, Peter F. Kaunitz, Andrew M. Shapiro, Marla Sievert, Lynnette Leidy TI NAMS supports judicious use of systemic hormone therapy for women aged 65 years and older SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID INAPPROPRIATE MEDICATION USE; EXPLICIT CRITERIA; BEERS CRITERIA; ADULTS C1 [Gass, Margery L. S.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, North Amer Menopause Soc,Ctr Specialized Womens H, Cleveland, OH 44106 USA. [Maki, Pauline M.] Univ Illinois, UIC Ctr Res Women & Gender, Womens Mental Hlth Res, Chicago, IL USA. [Shifren, Jan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Midlife Womens Hlth Ctr, Boston, MA USA. [Schnatz, Peter F.] Reading Hosp, Dept Obstet & Gynecol & Internal Med, Reading, PA USA. [Kaunitz, Andrew M.] Univ Florida, Coll Med, Dept Obstet & Gynecol, Jacksonville, FL USA. [Shapiro, Marla] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Sievert, Lynnette Leidy] Univ Massachusetts, Dept Anthropol, Amherst, MA 01003 USA. RP Gass, MLS (reprint author), Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, North Amer Menopause Soc,Ctr Specialized Womens H, Cleveland, OH 44106 USA. NR 10 TC 2 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL PY 2015 VL 22 IS 7 BP 685 EP 686 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CM1CE UT WOS:000357416700001 PM 26035151 ER PT J AU Mitchell, C AF Mitchell, Caroline TI A spoonful of sugar SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID VAGINAL FLORA; ATROPHY; WOMEN C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Mitchell, C (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL PY 2015 VL 22 IS 7 BP 689 EP 690 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CM1CE UT WOS:000357416700003 PM 25988801 ER PT J AU Duran-Pinedo, AE Frias-Lopez, J AF Duran-Pinedo, Ana E. Frias-Lopez, Jorge TI Beyond microbial community composition: functional activities of the oral microbiome in health and disease SO MICROBES AND INFECTION LA English DT Article DE Microbiome; Oral; Omics; Dysbiosis; Periododontitis; Caries ID EARLY-CHILDHOOD CARIES; PORPHYROMONAS-GINGIVALIS; PERIODONTITIS PATIENTS; METAPROTEOMIC ANALYSIS; BACTERIAL PROFILES; DENTAL PLAQUE; CANCER; EXPRESSION; DIVERSITY; MODEL AB The oral microbiome plays a relevant role in the health status of the host and is a key element in a variety of oral and non-oral diseases. Despite advances in our knowledge of changes in microbial composition associated with different health conditions the functional aspects of the oral microbiome that lead to dysbiosis remain for the most part unknown. In this review, we discuss the progress made towards understanding the functional role of the oral microbiome in health and disease and how novel technologies are expanding our knowledge on this subject. (C) 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Duran-Pinedo, Ana E.; Frias-Lopez, Jorge] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Frias-Lopez, Jorge] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Frias-Lopez, J (reprint author), 245 First St, Cambridge, MA 02142 USA. EM jfriaslopez@forsyth.org OI Frias-Lopez, Jorge/0000-0002-2097-3171 FU National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIDCR/NIH) [DE021553, DE021127] FX We are grateful to Rebecca Misra for reviewing the manuscript and her useful comments. This research was supported in part by the research grants DE021553 and DE021127 of the National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIDCR/NIH). NR 70 TC 17 Z9 17 U1 9 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2015 VL 17 IS 7 SI SI BP 505 EP 516 DI 10.1016/j.micinf.2015.03.014 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CM5TQ UT WOS:000357752100006 PM 25862077 ER PT J AU Weinberg, OK Pozdnyakova, O Campigotto, F DeAngelo, DJ Stone, RM Neuberg, D Hasserjian, RP AF Weinberg, Olga K. Pozdnyakova, Olga Campigotto, Federico DeAngelo, Daniel J. Stone, Richard M. Neuberg, Donna Hasserjian, Robert P. TI Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia SO MODERN PATHOLOGY LA English DT Article ID MYELODYSPLASIA-RELATED CHANGES; INTERMEDIATE-RISK CYTOGENETICS; MULTILINEAGE DYSPLASIA; TRILINEAGE MYELODYSPLASIA; AML; CLASSIFICATION; ABNORMALITIES; MUTATIONS; RELEVANCE; DIAGNOSIS AB The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia not evaluable showed significantly different event-free survival compared with acute myeloid leukemia not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors. C1 [Weinberg, Olga K.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Pozdnyakova, Olga] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [DeAngelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Weinberg, OK (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. EM Olga.Weinberg@childrens.harvard.edu NR 27 TC 1 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 2015 VL 28 IS 7 BP 965 EP 976 DI 10.1038/modpathol.2015.55 PG 12 WC Pathology SC Pathology GA CM0FX UT WOS:000357354900009 PM 25975285 ER PT J AU Vizoso, M Ferreira, HJ Lopez-Serra, P Carmona, FJ Martinez-Cardus, A Girotti, MR Villanueva, A Guil, S Moutinho, C Liz, J Portela, A Heyn, H Moran, S Vidal, A Martinez-Iniesta, M Manzano, JL Fernandez-Figueras, MT Elez, E Munoz-Couselo, E Botella-Estrada, R Berrocal, A Ponten, F van den Oord, J Gallagher, WM Frederick, DT Flaherty, KT McDermott, U Lorigan, P Marais, R Esteller, M AF Vizoso, Miguel Ferreira, Humberto J. Lopez-Serra, Paula Javier Carmona, F. Martinez-Cardus, Anna Girotti, Maria Romina Villanueva, Alberto Guil, Sonia Moutinho, Catia Liz, Julia Portela, Anna Heyn, Holger Moran, Sebastian Vidal, August Martinez-Iniesta, Maria Manzano, Jose L. Teresa Fernandez-Figueras, Maria Elez, Elena Munoz-Couselo, Eva Botella-Estrada, Rafael Berrocal, Alfonso Ponten, Fredrik van den Oord, Joost Gallagher, William M. Frederick, Dennie T. Flaherty, Keith T. McDermott, Ultan Lorigan, Paul Marais, Richard Esteller, Manel TI Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR SO NATURE MEDICINE LA English DT Article ID CUTANEOUS MELANOMA; CANCER-CELLS; BREAST-CANCER; INHIBITION; RECEPTOR; SENSITIVITY; METASTASIS; MEDICINE; INVASION; PROTEIN AB Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors. C1 [Vizoso, Miguel; Ferreira, Humberto J.; Lopez-Serra, Paula; Javier Carmona, F.; Martinez-Cardus, Anna; Guil, Sonia; Moutinho, Catia; Liz, Julia; Portela, Anna; Heyn, Holger; Moran, Sebastian] Bellvitge Biomed Res Inst, Canc Epigenet & Biol Program, Barcelona, Catalonia, Spain. [Girotti, Maria Romina; Marais, Richard] Canc Res UK Manchester Inst, Mol Oncol Grp, Manchester, Lancs, England. [Villanueva, Alberto; Martinez-Iniesta, Maria] Bellvitge Biomed Res Inst, Catalan Inst Oncol, Translat Res Lab, Barcelona, Catalonia, Spain. [Vidal, August] Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Pathol Anat, Barcelona, Catalonia, Spain. [Manzano, Jose L.] Germans Trias & Pujol Univ Hosp, Catalan Inst Oncol, Med Oncol Serv, Badalona, Catalonia, Spain. [Teresa Fernandez-Figueras, Maria] Germans Trias & Pujol Univ Hosp, Dept Pathol, Badalona, Catalonia, Spain. [Elez, Elena; Munoz-Couselo, Eva] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Catalonia, Spain. [Botella-Estrada, Rafael] Univ Valencia, Dermatol Serv, Hosp La Fe, Valencia, Spain. [Berrocal, Alfonso] Gen Hosp, Med Oncol Serv, Valencia, Spain. [Ponten, Fredrik] Univ Uppsala Hosp, Dept Pathol, S-75185 Uppsala, Sweden. [van den Oord, Joost] Katholieke Univ Leuven, Translat Cell & Tissue Pathol, Leuven, Belgium. [Gallagher, William M.] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 2, Ireland. [Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. [McDermott, Ultan] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Lorigan, Paul] Univ Manchester, Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England. [Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Catalonia, Spain. [Esteller, Manel] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. RP Esteller, M (reprint author), Bellvitge Biomed Res Inst, Canc Epigenet & Biol Program, Barcelona, Catalonia, Spain. EM mesteller@idibell.cat RI Lorigan, Paul/J-6898-2015; Esteller, Manel/L-5956-2014; Lopez-Serra, Paula/M-6835-2015; Guil, Sonia/M-8036-2015; Moran, Sebastian /G-5293-2013; Vidal, August/N-4662-2016 OI Heyn, Holger/0000-0002-3276-1889; Ferreira, Humberto/0000-0003-0834-2956; McDermott, Ultan/0000-0001-9032-4700; Lorigan, Paul/0000-0002-8875-2164; Esteller, Manel/0000-0003-4490-6093; Gallagher, William/0000-0002-4307-5999; Lopez-Serra, Paula/0000-0001-7231-3426; Guil, Sonia/0000-0002-2257-3331; Moran, Sebastian /0000-0003-4192-8983; Vidal, August/0000-0001-5727-2099 FU European Community's Seventh Framework Programme FP7 [PIAPP-GA-2009-230614]; Worldwide Cancer Research grant [15-0354]; European Research Council [268626-EPINORC]; Ministerio de Ciencia e Innovacion [SAF2011-22803, FIS PI13-01339]; CRUK Manchester Institute [C5759/A12328]; Wellcome Trust [100282/Z/12/Z]; Cellex Foundation; Health Department of the Catalan Government Generalitat de Catalunya [2005-SGR00727, 2014-SGR 633]; Science Department of the Catalan Government Generalitat de Catalunya [2005-SGR00727, 2014-SGR 633]; Formacion de Profesorado Universitario fellowship from the Spanish Ministry of Education FX We thank the patients and their families. The research leading to these results has received funding from the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement no. PIAPP-GA-2009-230614-Target-Melanoma project (F.P., J.O., W.M.G., M.E.), the Worldwide Cancer Research grant reference no. 15-0354 (M.E.), the European Research Council Advanced grant no. 268626-EPINORC project (M.E.), the Ministerio de Ciencia e Innovacion grant numbers SAF2011-22803 (M.E.) and FIS PI13-01339 (A. Villanueva), the CRUK Manchester Institute (C5759/A12328 to R.M.), the Wellcome Trust (100282/Z/12/Z to R.M.), the Cellex Foundation (M.E.) and the Health and Science Departments of the Catalan Government Generalitat de Catalunya 2005-SGR00727 (A. Villanueva) and 2014-SGR 633 (M.E.). M.V. was supported by a Formacion de Profesorado Universitario fellowship from the Spanish Ministry of Education. We thank the staff of the Animal Core Facility of Bellvitge Biomedical Research Institute for mouse care and maintenance. M.E. is an Institucio Catalana de Recerca i Estudis Avancats Research Professor. NR 43 TC 13 Z9 13 U1 2 U2 15 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 JUL PY 2015 VL 21 IS 7 BP 741 EP + DI 10.1038/nm.3863 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600015 PM 26030178 ER PT J AU Yates, LR Gerstung, M Knappskog, S Desmedt, C Gundem, G Van Loo, P Aas, T Alexandrov, LB Larsimont, D Davies, H Li, YL Ju, YS Ramakrishna, M Haugland, HK Lilleng, PK Nik-Zainal, S McLaren, S Butler, A Martin, S Glodzik, D Menzies, A Raine, K Hinton, J Jones, D Mudie, LJ Jiang, B Vincent, D Greene-Colozzi, A Adnet, PY Fatima, A Maetens, M Ignatiadis, M Stratton, MR Sotiriou, C Richardson, AL Lonning, PE Wedge, DC Campbell, PJ AF Yates, Lucy R. Gerstung, Moritz Knappskog, Stian Desmedt, Christine Gundem, Gunes Van Loo, Peter Aas, Turid Alexandrov, Ludmil B. Larsimont, Denis Davies, Helen Li, Yilong Ju, Young Seok Ramakrishna, Manasa Haugland, Hans Kristian Lilleng, Peer Kaare Nik-Zainal, Serena McLaren, Stuart Butler, Adam Martin, Sancha Glodzik, Dominic Menzies, Andrew Raine, Keiran Hinton, Jonathan Jones, David Mudie, Laura J. Jiang, Bing Vincent, Delphine Greene-Colozzi, April Adnet, Pierre-Yves Fatima, Aquila Maetens, Marion Ignatiadis, Michail Stratton, Michael R. Sotiriou, Christos Richardson, Andrea L. Lonning, Per Eystein Wedge, David C. Campbell, Peter J. TI Subclonal diversification of primary breast cancer revealed by multiregion sequencing SO NATURE MEDICINE LA English DT Article ID COPY-NUMBER ALTERATION; TUMOR TYPES; INTRATUMOR HETEROGENEITY; MUTATIONAL PROCESSES; MOLECULAR PORTRAITS; PANCREATIC-CANCER; DRIVER MUTATIONS; PROSTATE-CANCER; CLINICAL-TRIALS; EVOLUTION AB The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer. C1 [Gerstung, Moritz; Gundem, Gunes; Van Loo, Peter; Alexandrov, Ludmil B.; Davies, Helen; Li, Yilong; Ju, Young Seok; Ramakrishna, Manasa; Nik-Zainal, Serena; McLaren, Stuart; Butler, Adam; Martin, Sancha; Glodzik, Dominic; Menzies, Andrew; Raine, Keiran; Hinton, Jonathan; Jones, David; Mudie, Laura J.; Stratton, Michael R.; Wedge, David C.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England. [Yates, Lucy R.] Univ Cambridge, Dept Oncol, Cambridge, England. [Knappskog, Stian; Lonning, Per Eystein] Univ Bergen, Sect Oncol, Dept Clin Sci, Bergen, Norway. [Knappskog, Stian; Lonning, Per Eystein] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. [Desmedt, Christine; Larsimont, Denis; Vincent, Delphine; Adnet, Pierre-Yves; Maetens, Marion; Ignatiadis, Michail; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Brussels, Belgium. [Van Loo, Peter] Univ Leuven, Dept Human Genet, Leuven, Belgium. [Aas, Turid] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway. [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. [Haugland, Hans Kristian; Lilleng, Peer Kaare] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Lilleng, Peer Kaare] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway. [Jiang, Bing; Greene-Colozzi, April; Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England. EM pc8@sanger.ac.uk RI Ju, Young Seok/E-1324-2012; OI Ju, Young Seok/0000-0002-5514-4189; Gerstung, Moritz/0000-0001-6709-963X; Van Loo, Peter/0000-0003-0292-1949; Knappskog, Stian/0000-0002-4153-1655; Wedge, David/0000-0002-7572-3196; Alexandrov, Ludmil/0000-0003-3596-4515; Desmedt, Christine/0000-0002-5223-5579; Martin, Sancha/0000-0001-6213-5259 FU Wellcome Trust [077012/Z/05/Z]; Wellcome Trust Intermediate Clinical Research Fellowship [WT100183MA]; Belgian Cancer Plan-Ministry of Health; Breast Cancer Research Foundation; Brussels Region; Norwegian Cancer Society; Norwegian Health Region West; Bergen Research Foundation; European Community's Seventh Framework Programme (FP7) [242006]; Institut National du Cancer (INCa); National Nuclear Security Administration of the US Department of Energy FX This work is supported by the Wellcome Trust. P.J.C. is a Wellcome Trust Senior Clinical Fellow (103858/Z/14/Z). L.R.Y., Y.L. and L.B.A. are funded by Wellcome Trust PhD fellowships. S.N.-Z. is funded by a Wellcome Trust Intermediate Clinical Research Fellowship (WT100183MA). P.V.L. is a postdoctoral researcher at the Research Foundation Flanders (FWO). Work within the project is supported by the Belgian Cancer Plan-Ministry of Health, the Breast Cancer Research Foundation, the Brussels Region, the Norwegian Cancer Society, the Norwegian Health Region West and the Bergen Research Foundation. Some samples referenced in this publication will be included in the Breast Cancer Genome Analyses for the International Cancer Genome Consortium (ICGC) Working Group led by the Wellcome Trust Sanger Institute. BASIS is a part of the ICGC working group and is funded by the European Community's Seventh Framework Programme (FP7/2010-2014) under grant agreement number 242006. This working group also encompasses a triple-negative breast cancer project funded by the Wellcome Trust (grant 077012/Z/05/Z) and a HER2+ breast cancer project funded by Institut National du Cancer (INCa). We thank B. Leirvaag, D. Ekse, N.K. Duong and C. Eriksen for technical assistance. Research performed at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the US Department of Energy. NR 52 TC 86 Z9 88 U1 5 U2 35 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 JUL PY 2015 VL 21 IS 7 BP 751 EP + DI 10.1038/nm.3886 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600016 PM 26099045 ER PT J AU Xue, RD Lynes, MD Dreyfuss, JM Shamsi, F Schulz, TJ Zhang, HB Huang, TL Townsend, KL Li, YM Takahashi, H Weiner, LS White, AP Lynes, MS Rubin, LL Goodyear, LJ Cypess, AM Tseng, YH AF Xue, Ruidan Lynes, Matthew D. Dreyfuss, Jonathan M. Shamsi, Farnaz Schulz, Tim J. Zhang, Hongbin Huang, Tian Lian Townsend, Kristy L. Li, Yiming Takahashi, Hirokazu Weiner, Lauren S. White, Andrew P. Lynes, Maureen S. Rubin, Lee L. Goodyear, Laurie J. Cypess, Aaron M. Tseng, Yu-Hua TI Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes SO NATURE MEDICINE LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; ADIPOSE-TISSUE; ADULT HUMANS; FUNCTIONAL-CHARACTERIZATION; ENERGY-EXPENDITURE; COLD-EXPOSURE; IN-VIVO; FAT; ADIPOCYTES; IDENTIFICATION AB Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. However, both inter-and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here we generated clones of brown and white preadipocytes from human neck fat and characterized their adipogenic and thermogenic differentiation. We combined an uncoupling protein 1 (UCP1) reporter system and expression profiling to define novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes using CRISPR-Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using the cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer potential biomarkers for identifying thermogenically competent preadipocytes. C1 [Xue, Ruidan; Lynes, Matthew D.; Shamsi, Farnaz; Schulz, Tim J.; Zhang, Hongbin; Huang, Tian Lian; Townsend, Kristy L.; Takahashi, Hirokazu; Weiner, Lauren S.; Goodyear, Laurie J.; Cypess, Aaron M.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [Xue, Ruidan; Li, Yiming] Fudan Univ, Shanghai Med Coll, Huashan Hosp, Div Endocrinol & Metab, Shanghai 200433, Peoples R China. [Dreyfuss, Jonathan M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Bioinformat Core, Boston, MA 02115 USA. [Dreyfuss, Jonathan M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [White, Andrew P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthoped Surg, Boston, MA 02215 USA. [Lynes, Maureen S.; Rubin, Lee L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Lynes, Maureen S.; Rubin, Lee L.; Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cypess, Aaron M.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. EM yu-hua.tseng@joslin.harvard.edu OI Schulz, Tim/0000-0002-8413-3972 FU US National Institutes of Health (NIH) [R01DK077097, R01DK099511, K23DK081604, P30DK036836]; National Institute of Diabetes and Digestive and Kidney Diseases; Chugai Pharmaceutical Co.; American Diabetes Association [ADA 7-12-BS-191]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Harvard Stem Cell Institute; NIH [T32DK007260, F32DK102320] FX This work was supported in part by US National Institutes of Health (NIH) grants R01DK077097 (to Y.-H.T.), R01DK099511 (to L.J.G.), K23DK081604 (to A.M.C.) and P30DK036836 (to Joslin Diabetes Center's Diabetes Research Center, DRC) from the National Institute of Diabetes and Digestive and Kidney Diseases, a sponsored research grant from Chugai Pharmaceutical Co. (to Y.-H.T. and A.M.C.), a research grant from the American Diabetes Association (ADA 7-12-BS-191, to Y.-H.T.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and by funding from the Harvard Stem Cell Institute (to Y.-H.T.). M.D.L. was supported by NIH fellowships (T32DK007260 and F32DK102320). We thank M.-E. Patti and K. Hughes of the Advanced Genomics and Genetics Core of Joslin's DRC for advice and expert technical assistance. The authors thank Stryker Regenerative Medicine (Hopkinton, Massachusetts) for the generous gift of recombinant BMP7. NR 51 TC 33 Z9 33 U1 3 U2 23 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 JUL PY 2015 VL 21 IS 7 BP 760 EP + DI 10.1038/nm.3881 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600017 PM 26076036 ER PT J AU Siravegna, G Mussolin, B Buscarino, M Corti, G Cassingena, A Crisafulli, G Ponzetti, A Cremolini, C Amatu, A Lauricella, C Lamba, S Hobor, S Avallone, A Valtorta, E Rospo, G Medico, E Motta, V Antoniotti, C Tatangelo, F Bellosillo, B Veronese, S Budillon, A Montagut, C Racca, P Marsoni, S Falcone, A Corcoran, RB Di Nicolantonio, F Loupakis, F Siena, S Sartore-Bianchi, A Bardelli, A AF Siravegna, Giulia Mussolin, Benedetta Buscarino, Michela Corti, Giorgio Cassingena, Andrea Crisafulli, Giovanni Ponzetti, Agostino Cremolini, Chiara Amatu, Alessio Lauricella, Calogero Lamba, Simona Hobor, Sebastijan Avallone, Antonio Valtorta, Emanuele Rospo, Giuseppe Medico, Enzo Motta, Valentina Antoniotti, Carlotta Tatangelo, Fabiana Bellosillo, Beatriz Veronese, Silvio Budillon, Alfredo Montagut, Clara Racca, Patrizia Marsoni, Silvia Falcone, Alfredo Corcoran, Ryan B. Di Nicolantonio, Federica Loupakis, Fotios Siena, Salvatore Sartore-Bianchi, Andrea Bardelli, Alberto TI Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients SO NATURE MEDICINE LA English DT Article ID DROPLET DIGITAL PCR; FREE TUMOR DNA; KRAS MUTATIONS; ACQUIRED-RESISTANCE; SENSITIVE DETECTION; DRUG-RESISTANCE; NUCLEIC-ACIDS; HETEROGENEITY; MELANOMA; THERAPY AB Colorectal cancers (CRCs) evolve by a reiterative process of genetic diversification and clonal evolution. The molecular profile of CRC is routinely assessed in surgical or bioptic samples(1). Genotyping of CRC tissue has inherent limitations; a tissue sample represents a single snapshot in time, and it is subjected to spatial selection bias owing to tumor heterogeneity. Repeated tissue samples are difficult to obtain and cannot be used for dynamic monitoring of disease progression and response to therapy. We exploited circulating tumor DNA (ctDNA) to genotype colorectal tumors and track clonal evolution during treatment with the epidermal growth factor receptor (EGFR)specific antibodies cetuximab or panitumumab. We identified alterations in ctDNA of patients with primary or acquired resistance to EGFR blockade in the following genes: KRAS, NRAS, MET, ERBB2, FLT3, EGFR and MAP2K1. Mutated KRAS clones, which emerge in blood during EGFR blockade, decline upon withdrawal of EGFR-specific antibodies, indicating that clonal evolution continues beyond clinical progression. Pharmacogenomic analysis of CRC cells that had acquired resistance to cetuximab reveals that upon antibody withdrawal KRAS clones decay, whereas the population regains drug sensitivity. ctDNA profiles of individuals who benefit from multiple challenges with anti-EGFR antibodies exhibit pulsatile levels of mutant KRAS. These results indicate that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of rechallenge therapies based on EGFR blockade. C1 [Siravegna, Giulia; Medico, Enzo; Di Nicolantonio, Federica; Bardelli, Alberto] Univ Turin, Dept Oncol, Turin, Italy. [Siravegna, Giulia; Mussolin, Benedetta; Buscarino, Michela; Corti, Giorgio; Crisafulli, Giovanni; Lamba, Simona; Hobor, Sebastijan; Rospo, Giuseppe; Medico, Enzo; Marsoni, Silvia; Di Nicolantonio, Federica; Bardelli, Alberto] Fdn Piemontese Oncol, Candiolo Canc Inst, IRCCS, Turin, Italy. [Siravegna, Giulia] Fdn Italiana Ric Canc, Inst Mol Oncol IFOM, Turin, Italy. [Cassingena, Andrea; Amatu, Alessio; Lauricella, Calogero; Valtorta, Emanuele; Motta, Valentina; Veronese, Silvio; Siena, Salvatore; Sartore-Bianchi, Andrea] Osped Niguarda Ca Granda, Niguarda Canc Ctr, Milan, Italy. [Ponzetti, Agostino; Racca, Patrizia] San Giovanni Battista Hosp, Colorectal Canc Unit, Div Med Oncol 1, AOU Citta Salute & Sci, Turin, Italy. [Cremolini, Chiara; Antoniotti, Carlotta; Falcone, Alfredo; Loupakis, Fotios] Azienda Osped Univ Pisana, Pisa, Italy. [Cremolini, Chiara; Antoniotti, Carlotta; Falcone, Alfredo; Loupakis, Fotios] Univ Pisa, Pisa, Italy. [Avallone, Antonio; Tatangelo, Fabiana; Budillon, Alfredo] Ist Nazl Tumori Fdn G Pascale IRCCS, Naples, Italy. [Bellosillo, Beatriz; Montagut, Clara] Inst Hosp Mar Invest Med IMIM, Barcelona, Spain. [Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Sartore-Bianchi, A (reprint author), Osped Niguarda Ca Granda, Niguarda Canc Ctr, Milan, Italy. EM andrea.sartorebianchi@ospedaleniguarda.it; alberto.bardelli@unito.it RI Loupakis, Fotios/I-7243-2012; Avallone, Antonio/K-4662-2016; Di Nicolantonio, Federica/A-2503-2011 OI VALTORTA, EMANUELE/0000-0002-5087-6233; /0000-0001-5396-3378; SIENA, SALVATORE/0000-0002-2681-2846; Loupakis, Fotios/0000-0001-9651-0395; Avallone, Antonio/0000-0001-6188-5664; Budillon, Alfredo/0000-0002-6330-6053; Corti, Giorgio/0000-0001-6379-4117; Di Nicolantonio, Federica/0000-0001-9618-2010 FU EU Seventh Framework Programme [259015 COLTHERES]; Associazione Italiana per la Ricerca sul Cancro (AIRC), IG [12812]; AIRC, MFAG [11349]; Fondazione Piemontese per la Ricerca sul Cancro ONLUS (FPRC), Italian Ministry of Education, Universities and Research (MIUR); AIRC [9970]; FPRC, Italian Ministry of Health; MIUR, grant PRIN; Italian Ministry of Health [RF2009-1539464]; Xarxa de Banc de Tumors de Catalunya; Fondazione Oncologia Niguarda Ca' Granda Onlus; Azioni, Ricerche e Cure in Oncologia (ARCO); [RD12/0036/0051]; [PI12/00989]; [PI12/00680]; [PT13/0010/0005]; [2014 SGR 740] FX The authors would like to thank all the patients that participated in the study and their families. We are grateful to the members of the Laboratory of Molecular Genetics at Candiolo Cancer Institute for critical reading and editing of this manuscript. We thank S. Destefanis for administrative support. We thank S. Lonardi and F. Bergamo (Istituto Oncologico Veneto) for clinical data collection. This work was supported by The EU Seventh Framework Programme under grant agreement no. 259015 COLTHERES (A. Bardelli); Associazione Italiana per la Ricerca sul Cancro (AIRC), IG grant no. 12812 (A. Bardelli); AIRC, MFAG grant no. 11349 (F.D.N.); Fondazione Piemontese per la Ricerca sul Cancro ONLUS (FPRC), 5 per mille 2009 Italian Ministry of Education, Universities and Research (MIUR) grant Farmacogenomica (F.D.N.); AIRC, 2010 Special Program Molecular Clinical Oncology 5 per mille, project no. 9970 (A. Bardelli); FPRC, 5 per mille 2010 and 2011 Italian Ministry of Health (A. Bardelli); and MIUR, grant PRIN (A. Bardelli). This work was partially supported by a grant to A. Avallone from the Italian Ministry of Health (RF2009-1539464). This work was supported by RD12/0036/0051, PI12/00989, PI12/00680, PT13/0010/0005 and 2014 SGR 740 grants and by the Xarxa de Banc de Tumors de Catalunya (C.M.). Investigators at Niguarda Cancer Center are supported by grant Terapia Molecolare Tumori by Fondazione Oncologia Niguarda Ca' Granda Onlus (A.S.-B. and S.S.). This work was also partially supported by Azioni, Ricerche e Cure in Oncologia (ARCO) (C.C., C.A., F.L., A.F.) NR 49 TC 88 Z9 92 U1 9 U2 79 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 JUL PY 2015 VL 21 IS 7 BP 795 EP + DI 10.1038/nm.3870 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600021 PM 26030179 ER PT J AU Bachhuber, T Katzmarski, N McCarter, JF Loreth, D Tahirovic, S Kamp, F Abou-Ajram, C Nuscher, B Serrano-Pozo, A Muller, A Prinz, M Steiner, H Hyman, BT Haass, C Meyer-Luehmann, M AF Bachhuber, Teresa Katzmarski, Natalie McCarter, Joanna F. Loreth, Desiree Tahirovic, Sabina Kamp, Frits Abou-Ajram, Claudia Nuscher, Brigitte Serrano-Pozo, Alberto Mueller, Alexandra Prinz, Marco Steiner, Harald Hyman, Bradley T. Haass, Christian Meyer-Luehmann, Melanie TI Inhibition of amyloid-beta plaque formation by alpha-synuclein SO NATURE MEDICINE LA English DT Article ID LEWY BODY VARIANT; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CEREBROSPINAL-FLUID; SYNAPSE DENSITY; MICE; DEMENTIA; PRECURSOR; PATHOLOGY AB Amyloid-beta (A beta) plaques and alpha-synuclein (alpha-syn)-rich Lewy bodies are the major neuropathological hallmarks of Alzheimer's disease (AD) and Parkinson's disease, respectively. An overlap of pathologies is found in most individuals with dementia with Lewy bodies (DLB) 1 and in more than 50% of AD cases(2). Their brains display substantial alpha-syn accumulation not only in Lewy bodies, but also in dystrophic neurites decorating A beta plaques(2-4). Several studies report binding and coaggregation of A beta and alpha-syn(5-7), yet the precise role of alpha-syn in amyloid plaque formation remains elusive. Here we performed intracerebral injections of alpha-syn-containing preparations into amyloid precursor protein (APP) transgenic mice (expressing APP695(KM670/671NL) and PSEN1(L166P) under the control of the neuron-specific Thy-1 promoter; referred to here as 'APPPS1'). Unexpectedly, alpha-syn failed to cross-seed A. plaques in vivo, but rather it inhibited plaque formation in APPPS1 mice coexpressing SNCA(A30P) (referred to here as 'APPPS1 x [A30P]aSYN' double-transgenic mice). This was accompanied by increased A beta levels in cerebrospinal fluid despite unchanged overall A beta levels. Notably, the seeding activity of A beta-containing brain homogenates was considerably reduced by alpha-syn, and A beta deposition was suppressed in grafted tissue from [A30P]aSYN transgenic mice. Thus, we conclude that an interaction between A beta and alpha-syn leads to inhibition of A. deposition and to reduced plaque formation. C1 [Bachhuber, Teresa; McCarter, Joanna F.; Abou-Ajram, Claudia; Meyer-Luehmann, Melanie] Univ Munich, Dept Biochem, Adolf Butenandt Inst, Munich, Germany. [Katzmarski, Natalie; Loreth, Desiree; Meyer-Luehmann, Melanie] Univ Freiburg, Dept Neurol, Neuroctr, Freiburg, Germany. [Katzmarski, Natalie] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany. [Tahirovic, Sabina; Steiner, Harald; Haass, Christian] German Ctr Neurodegenerat Dis DZNE, Munich, Germany. [Kamp, Frits; Nuscher, Brigitte; Steiner, Harald; Haass, Christian] Univ Munich, Dept Metab Biochem, Munich, Germany. [Serrano-Pozo, Alberto; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Serrano-Pozo, Alberto; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA USA. [Mueller, Alexandra; Prinz, Marco] Univ Freiburg, Inst Neuropathol, D-79106 Freiburg, Germany. [Prinz, Marco] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, D-79106 Freiburg, Germany. [Haass, Christian] Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Meyer-Luehmann, M (reprint author), Univ Munich, Dept Biochem, Adolf Butenandt Inst, Munich, Germany. EM melanie.meyer-luehmann@uniklinik-freiburg.de FU Emmy Noether Program of the Deutsche Forschungsgemeinschaft; European Research Council (ERC) under the EU's Seventh Framework Programme (FP7)/ERC [321366]; Kompetenznetz Degenerative Demenzen of the German Federal Ministry of Education and Research; Hans and Ilse Breuer Foundation; Graduate School of Systemic Neurosciences; International Max Planck Research School FX We thank A. Wenninger-Weinzierl, S. Diederich, S. Waldkirch and R. Ziegler for technical assistance. This work was supported by the Emmy Noether Program of the Deutsche Forschungsgemeinschaft (M.M.-L.), the European Research Council (ERC) under the EU's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 321366-Amyloid (advanced grant to C.H.), the Kompetenznetz Degenerative Demenzen of the German Federal Ministry of Education and Research (C.H. and H.S.), the Hans and Ilse Breuer Foundation (M.M.-L.), the Graduate School of Systemic Neurosciences (J.F.M.) and the International Max Planck Research School (J.F.M.). We also would like to thank T. Iwatsubo (University of Tokyo) for the phospho-Ser129 antibody, E. Kremmer (Ludwig-Maximilians University, Munich) for the 3552 and 15G7 antibodies, N. Exner (Ludwig-Maximilians University, Munich) for the a-synuclein cDNA constructs and M. Jucker (University of Tubingen) for generously providing the APPPS1 transgenic mice. NR 41 TC 17 Z9 17 U1 8 U2 34 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 JUL PY 2015 VL 21 IS 7 BP 802 EP + DI 10.1038/nm.3885 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600023 PM 26099047 ER PT J AU Wong, SL Demers, M Martinod, K Gallant, M Wang, YM Goldfine, AB Kahn, CR Wagner, DD AF Wong, Siu Ling Demers, Melanie Martinod, Kimberly Gallant, Maureen Wang, Yanming Goldfine, Allison B. Kahn, C. Ronald Wagner, Denisa D. TI Diabetes primes neutrophils to undergo NETosis, which impairs wound healing SO NATURE MEDICINE LA English DT Article ID EXTRACELLULAR TRAP FORMATION; DNASE-I GENE; POLYMORPHONUCLEAR LEUKOCYTES; MICE; THROMBOSIS; MELLITUS; RELEASE; PAD4; SUSCEPTIBILITY; ASSOCIATION AB Wound healing is impaired in diabetes, resulting in significant morbidity and mortality. Neutrophils are the main leukocytes involved in the early phase of healing. As part of their antimicrobial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins(1). NETs, however, can also induce tissue damage. Here we show that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis). Expression of peptidylarginine deiminase 4 (PAD4, encoded by Padi4 in mice), an enzyme important in chromatin decondensation, was elevated in neutrophils from individuals with diabetes. When subjected to excisional skin wounds, wild-type (WT) mice produced large quantities of NETs in wounds, but this was not observed in Padi4(-/-) ice. In diabetic mice, higher levels of citrullinated histone H3 (H3Cit, a NET marker) were found in their wounds than in normoglycemic mice and healing was delayed. Wound healing was accelerated in Padi4(-/-) ice as compared to WT mice, and it was not compromised by diabetes. DNase 1, which disrupts NETs, accelerated wound healing in diabetic and normoglycemic WT mice. Thus, NETs impair wound healing, particularly in diabetes, in which neutrophils are more susceptible to NETosis. Inhibiting NETosis or cleaving NETs may improve wound healing and reduce NET-driven chronic inflammation in diabetes. C1 [Wong, Siu Ling; Demers, Melanie; Martinod, Kimberly; Gallant, Maureen; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wong, Siu Ling; Demers, Melanie; Martinod, Kimberly; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Yanming] Penn State Univ, Ctr Eukaryot Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02115 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM Denisa.Wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU Harvard Clinical and Translational Science Center, US National Institutes of Health (NIH) [UL1 TR001102]; American Diabetes Association [7-13-IN-44]; National Heart, Lung, and Blood Institute of the NIH [R01HL102101]; National Cancer Institute [R01CA136856]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK031036]; GlaxoSmithKline/Immune Disease Institute Alliance Fellowship FX We thank H. Ferris for advice on diabetes protocols; L. DeVita for selection of diabetic patients; P. Forbes (The Harvard Clinical and Translational Science Center, US National Institutes of Health (NIH) Award UL1 TR001102) for statistical advice; J.E. Cabral and S. Cifuni for valuable technical support; and L. Cowan for manuscript preparation assistance. This study was supported by the American Diabetes Association (Innovation Award 7-13-IN-44 to D.D.W.), the National Heart, Lung, and Blood Institute of the NIH (R01HL102101 to D.D.W.), the National Cancer Institute (R01CA136856 to Y.W.), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031036 to C.R.K.) and a GlaxoSmithKline/Immune Disease Institute Alliance Fellowship (S.L.W.). NR 40 TC 69 Z9 72 U1 8 U2 32 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 JUL PY 2015 VL 21 IS 7 BP 815 EP + DI 10.1038/nm.3887 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM3SO UT WOS:000357604600025 PM 26076037 ER PT J AU Sarioglu, AF Aceto, N Kojic, N Donaldson, MC Zeinali, M Hamza, B Engstrom, A Zhu, H Sundaresan, TK Miyamoto, DT Luo, X Bardia, A Wittner, BS Ramaswamy, S Shioda, T Ting, DT Stott, SL Kapur, R Maheswaran, S Haber, DA Toner, M AF Sarioglu, A. Fatih Aceto, Nicola Kojic, Nikola Donaldson, Maria C. Zeinali, Mahnaz Hamza, Bashar Engstrom, Amanda Zhu, Huili Sundaresan, Tilak K. Miyamoto, David T. Luo, Xi Bardia, Aditya Wittner, Ben S. Ramaswamy, Sridhar Shioda, Toshi Ting, David T. Stott, Shannon L. Kapur, Ravi Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet TI A microfluidic device for label-free, physical capture of circulating tumor cell clusters SO NATURE METHODS LA English DT Article ID BREAST-CANCER; MOLECULAR CHARACTERIZATION; PERIPHERAL-BLOOD; TISSUE INHIBITOR; LUNG-CANCER; METASTASIS; TIMP-1; MARKER; PROGRESSION; PLATELETS AB Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis. C1 [Sarioglu, A. Fatih; Kojic, Nikola; Zeinali, Mahnaz; Hamza, Bashar; Stott, Shannon L.; Kapur, Ravi; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Sarioglu, A. Fatih; Aceto, Nicola; Kojic, Nikola; Donaldson, Maria C.; Zeinali, Mahnaz; Hamza, Bashar; Engstrom, Amanda; Zhu, Huili; Sundaresan, Tilak K.; Miyamoto, David T.; Luo, Xi; Bardia, Aditya; Wittner, Ben S.; Ramaswamy, Sridhar; Shioda, Toshi; Ting, David T.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Haber, Daniel A.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA USA. [Sarioglu, A. Fatih; Aceto, Nicola; Donaldson, Maria C.; Zeinali, Mahnaz; Engstrom, Amanda; Zhu, Huili; Sundaresan, Tilak K.; Miyamoto, David T.; Luo, Xi; Bardia, Aditya; Wittner, Ben S.; Ramaswamy, Sridhar; Shioda, Toshi; Ting, David T.; Stott, Shannon L.; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sarioglu, A. Fatih; Kojic, Nikola; Maheswaran, Shyamala; Toner, Mehmet] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Aceto, Nicola; Bardia, Aditya; Ramaswamy, Sridhar; Ting, David T.; Stott, Shannon L.; Haber, Daniel A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Miyamoto, David T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM mtoner@mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Swiss National Science Foundation; Human Frontiers Science Program; US National Institutes of Health (NIH) P41 Resource Center; NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant; Stand Up to Cancer; Howard Hughes Medical Institute; Prostate Cancer Foundation; Charles Evans Foundation; Johnson and Johnson FX We express our gratitude to all patients and healthy volunteers who participated in this study and contributed blood samples. We thank O. Hurtado, A.J. Aranyosi and L. Libby for coordination of the research laboratories; D.M. Lewis for his help in instrumentation; and L. Nieman, J. Walsh and T.N. Lewis for their help with microscopy. N.A. was supported by the Swiss National Science Foundation and the Human Frontiers Science Program. This work was supported by the US National Institutes of Health (NIH) P41 Resource Center (M.T.); an NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant (M.T. and D.A.H.); Stand Up to Cancer (D.A.H., M.T. and S.M.); the Howard Hughes Medical Institute (D.A.H.); the Prostate Cancer Foundation and the Charles Evans Foundation (D.A.H. and M.T.); and Johnson and Johnson (M.T. and S.M.). NR 37 TC 89 Z9 96 U1 47 U2 210 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JUL PY 2015 VL 12 IS 7 BP 685 EP + DI 10.1038/NMETH.3404 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CM0YH UT WOS:000357405700029 PM 25984697 ER PT J AU Tian, Y Wang, T Liu, WY Xin, HL Li, HL Ke, YG Shih, WM Gang, O AF Tian, Ye Wang, Tong Liu, Wenyan Xin, Huolin L. Li, Huilin Ke, Yonggang Shih, William M. Gang, Oleg TI Prescribed nanoparticle cluster architectures and low-dimensional arrays built using octahedral DNA origami frames SO NATURE NANOTECHNOLOGY LA English DT Article ID GOLD NANOPARTICLES; NANOSCALE SHAPES; STRANDED-DNA; FOLDING DNA; NANOCLUSTERS; CRYSTALLIZATION; ENHANCEMENT; MOLECULES AB Three-dimensional mesoscale clusters that are formed from nanoparticles spatially arranged in pre-determined positions can be thought of as mesoscale analogues of molecules. These nanoparticle architectures could offer tailored properties due to collective effects, but developing a general platform for fabricating such clusters is a significant challenge. Here, we report a strategy for assembling three-dimensional nanoparticle clusters that uses a molecular frame designed with encoded vertices for particle placement. The frame is a DNA origami octahedron and can be used to fabricate clusters with various symmetries and particle compositions. Cryo-electron microscopy is used to uncover the structure of the DNA frame and to reveal that the nanoparticles are spatially coordinated in the prescribed manner. We show that the DNA frame and one set of nanoparticles can be used to create nanoclusters with different chiroptical activities. We also show that the octahedra can serve as programmable interparticle linkers, allowing one-and two-dimensional arrays to be assembled with designed particle arrangements. C1 [Tian, Ye; Liu, Wenyan; Xin, Huolin L.; Gang, Oleg] Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA. [Wang, Tong; Li, Huilin] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. [Li, Huilin] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. [Ke, Yonggang; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ke, Yonggang; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ke, Yonggang; Shih, William M.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. RP Tian, Y (reprint author), Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA. EM ogang@bnl.gov RI Xin, Huolin/E-2747-2010 OI Xin, Huolin/0000-0002-6521-868X FU US Department of Energy, Office of Basic Energy Sciences [DE-SC0012704]; National Institutes of Health R01 grant [AG029979]; National Science Foundation Expeditions grant [1317694]; Designing Materials to Revolutionize and Engineer Our Future grant [1435964] FX The authors thank J. Li for help with tomography analysis and D. Chen for assistance with schematic drawing. Research carried out at the Centre for Functional Nanomaterials, Brookhaven National Laboratory, was supported by the US Department of Energy, Office of Basic Energy Sciences (contract no. DE-SC0012704). H.L. was supported by a National Institutes of Health R01 grant (AG029979) and W.M.S. was supported by a National Science Foundation Expeditions grant (1317694) and Designing Materials to Revolutionize and Engineer Our Future grant (1435964). NR 45 TC 37 Z9 37 U1 25 U2 97 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 EI 1748-3395 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD JUL PY 2015 VL 10 IS 7 BP 637 EP + DI 10.1038/NNANO.2015.105 PG 9 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA CM2BW UT WOS:000357485600020 PM 26005999 ER PT J AU Ahmed, SU Zhang, Y Chen, L St Hillary, K Cohen, A Vo, T Houghton, M Mao, JR AF Ahmed, Shihab U. Zhang, Yi Chen, Lucy St Hillary, Kristin Cohen, Abigail Trang Vo Houghton, Mary Mao, Jianren TI Effects of Spinal Cord Stimulation on Pain Thresholds and Sensory Perceptions in Chronic Pain Patients SO NEUROMODULATION LA English DT Article DE Pain; quantitative sensory testing (QST); spinal cord stimulation (SCS) ID DORSAL COLUMN STIMULATION; GAMMA-AMINOBUTYRIC-ACID; MONONEUROPATHIC RATS; RECEPTOR ACTIVATION; NEUROPATHIC PAIN; HORN; MECHANISMS; RELEASE; TRIAL; SUPPRESSION AB Objective: Spinal cord stimulation (SCS) has been in clinical use for nearly four decades. In earliest observations, researchers found a significant increase in pain threshold during SCS therapy without changes associated with touch, position, and vibration sensation. Subsequent studies yielded diverse results regarding how SCS impacts pain and other sensory thresholds. This pilot study uses quantitative sensory testing (QST) to objectively quantify the impact of SCS on warm sensation, heat pain threshold, and heat pain tolerance. Materials and Methods: Nineteen subjects with an indwelling SCS device for chronic pain were subjected to QST with heat stimuli. QST was performed on an area of pain covered with SCS-induced paresthesia and an area without pain and without paresthesia, while the SCS was turned off and on. The temperature at which the patient detected warm sensation, heat pain, and maximal tolerable heat pain was used to define the thresholds. Results: We found that all three parameters, the detection of warm sensation, heat pain threshold, and heat pain tolerance, were increased during the period when SCS was on compared with when it was off. This increase was observed in both painful and non-painful sites. Conclusion: The observed pain relief during SCS therapy seems to be related to its impact on increased sensory threshold as detected in this study. The increased sensory threshold on areas without pain and without the presence of SCS coverage may indicate a central (spinal and/or supra-spinal) influence from SCS. C1 [Ahmed, Shihab U.; Zhang, Yi; Chen, Lucy; St Hillary, Kristin; Cohen, Abigail; Trang Vo; Houghton, Mary; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Ahmed, SU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, 101 Merrimac St,Suite 610, Boston, MA 02114 USA. EM sahmed@partners.org NR 32 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 EI 1525-1403 J9 NEUROMODULATION JI Neuromodulation PD JUL PY 2015 VL 18 IS 5 BP 355 EP 360 DI 10.1111/ner.12316 PG 6 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA CM0SI UT WOS:000357388400003 PM 26033205 ER PT J AU Hayek, SM Hanes, MC Wang, C Veizi, IE AF Hayek, Salim M. Hanes, Michael C. Wang, Connie Veizi, I. Elias TI Ziconotide Combination Intrathecal Therapy for Noncancer Pain Is Limited Secondary to Delayed Adverse Effects: A Case Series With a 24-Month Follow-Up SO NEUROMODULATION LA English DT Article DE Adverse effects; intrathecal drug delivery; nonmalignant pain; ziconotide ID NEUROPATHIC PAIN; OPEN-LABEL; PLASMA PHARMACOKINETICS; COMBINING ZICONOTIDE; CEREBROSPINAL-FLUID; CHEMICAL-STABILITY; EPIDURAL OPIOIDS; DOUBLE-BLIND; MULTICENTER; MORPHINE AB Objectives: The efficacy and safety of ziconotide as a single agent has been evaluated in few short-term clinical trials and open-label studies. Ziconotide use is challenging given its adverse effect (AE) profile. The objective of this study is to describe the long-term efficacy and AEs of ziconotide used as an adjunct to other intrathecal (IT) agents in chronic noncancer pain patients. Materials and Methods: A case series of chronic noncancer pain patients who had suboptimal pain control from IT therapy. Ziconotide was introduced in the IT infusion mixture after a successful ziconotide trial. Pain scores, IT doses, as well as AEs were recorded and analyzed from trial to initial ziconotide infusion and up to 24 months. Results: Fifteen patients underwent ziconotide trials. Four subjects failed the trial, and 11 proceeded to continuous ziconotide treatment. Seven out of 11 patients experienced AEs resulting in ziconotide discontinuation. Two of the seven subjects who required discontinuation of ziconotide had improved pain. Four subjects were able to continue IT ziconotide through 24 months. Conclusions: A high incidence of AEs limits the usefulness of IT ziconotide as adjunct therapy. Our results are limited by the size of our patient population; however, they represent a long follow-up period, which is limited in most current publications on this IT peptide. While ziconotide is a needed IT agent, more studies are necessary to better understand the factors that would improve the treatment to trial ratio as well as the long-term efficacy of IT ziconotide treatment. C1 [Hayek, Salim M.; Hanes, Michael C.; Veizi, I. Elias] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Pain Med, Dept Anesthesiol, Cleveland, OH 44106 USA. [Wang, Connie] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Veizi, I. Elias] Louis Stokes Vet Adm Med Ctr, Pain Med & Spine Care, Cleveland, OH USA. RP Hanes, MC (reprint author), Univ Hosp Case Med Ctr, Case Western Reserve Sch Med, Div Pain Med, Dept Anesthesiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Michael.Hanes@uhhospitals.org NR 25 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 EI 1525-1403 J9 NEUROMODULATION JI Neuromodulation PD JUL PY 2015 VL 18 IS 5 BP 397 EP 403 DI 10.1111/ner.12270 PG 7 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA CM0SI UT WOS:000357388400009 PM 25655991 ER PT J AU Apovian, CM Garvey, WT Ryan, DH AF Apovian, Caroline M. Garvey, W. Timothy Ryan, Donna H. TI Challenging Obesity: Patient, Provider, and Expert Perspectives on the Roles of Available and Emerging Nonsurgical Therapies SO OBESITY LA English DT Article ID LIFE-STYLE INTERVENTION; WEIGHT CONTROL REGISTRY; CARDIOVASCULAR RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; CLINICAL ENDOCRINOLOGISTS; AMERICAN ASSOCIATION; BARIATRIC SURGERY; POSITION STATEMENT; CONTROLLED-RELEASE; SEROTONIN SYNDROME AB Objective: Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient's disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. Design and Methods: This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. Results: This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. Conclusions: This supplement provides a topical update of obesity management, including clinical practice examples, for healthcare professionals who treat or provide care for adults with obesity. C1 [Apovian, Caroline M.] Boston Univ, Sch Med, Nutr & Weight Management Ctr, Dept Med, Boston, MA 02215 USA. [Apovian, Caroline M.] Boston Univ, Sch Med, Nutr & Weight Management Ctr, Dept Pediat, Boston, MA 02215 USA. [Apovian, Caroline M.] Boston Med Ctr, Nutr Support Serv, Boston, MA USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] UAB Diabet Res Ctr, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Apovian, CM (reprint author), Boston Univ, Sch Med, Nutr & Weight Management Ctr, Dept Med, Boston, MA 02215 USA. EM Caroline.apovian@bmc.org FU Novo Nordisk Inc. FX This activity is supported by an educational grant from Novo Nordisk Inc. NR 102 TC 6 Z9 6 U1 2 U2 6 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 JUL PY 2015 VL 23 SU 2 BP S1 EP S26 DI 10.1002/oby.21140 PG 26 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CM6RW UT WOS:000357818500001 PM 26154880 ER PT J AU Wirostko, B Rafii, M Sullivan, DA Morelli, J Ding, J AF Wirostko, Barbara Rafii, MaryJane Sullivan, David A. Morelli, Julia Ding, Juan TI Novel Therapy to Treat Corneal Epithelial Defects: A Hypothesis with Growth Hormone SO OCULAR SURFACE LA English DT Article DE corneal epithelial defect; growth factors; human growth hormone; insulin-like growth factor-1; persistent corneal epithelial defects (PCED); wound healing ID AMNIOTIC MEMBRANE TRANSPLANTATION; LARGE CUTANEOUS BURNS; STEM-CELL DEFICIENCY; P-DERIVED PEPTIDE; FACTOR-I; SUBSTANCE-P; NEUROTROPHIC KERATOPATHY; AUTOLOGOUS SERUM; DRUG-DELIVERY; DIABETIC-RATS AB Impaired corneal wound healing that occurs with ocular surface disease, trauma, systemic disease, or surgical intervention can lead to persistent corneal epithelial defects (PCED), which result in corneal scarring, ulceration, opacification, corneal neovascularization, and, ultimately, visual compromise and vision loss. The current standard of care can include lubricants, ointments, bandage lenses, amniotic membranes, autologous serum eye drops, and corneal transplants. Various inherent problems exist with application and administration of these treatments, which often may not result in a completely healed surface. A topically applicable compound capable of promoting corneal epithelial cell proliferation and/or migration would be ideal to accelerate healing. We hypothesize that human growth hormone (HGH) is such a compound. In a recent study, HGH was shown to activate signal transducer and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial migration in a co-culture system of corneal epithelial cells and fibroblasts. These effects require an intact communication between corneal epithelia and fibroblasts. Further, HGH promotes corneal wound healing in a rabbit debridement model, thus demonstrating the effectiveness of HGH in vivo as well. In conclusion, HGH may represent an exciting and effective topical therapeutic to promote corneal wound healing. C1 [Wirostko, Barbara; Rafii, MaryJane; Morelli, Julia] Jade Therapeut Inc, Salt Lake City, UT USA. [Sullivan, David A.; Ding, Juan] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Sullivan, David A.; Ding, Juan] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wirostko, Barbara] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. RP Wirostko, B (reprint author), Massachusettes Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Juan_ding@meei.harvard.edu FU NIH [R01EY05612, 1K99EY023536-01A1]; Utah Governor's Office of Economic Development (GOED) FX This work was supported by NIH grant R01EY05612, 1K99EY023536-01A1 and the Margaret S. Sinon Scholar in Ocular Surface. Dr. Barbara Wirostko has received an unrestricted Technology Commercialization & Innovation Program (TCIP) grant from Utah Governor's Office of Economic Development (GOED) to help fund this work. NR 102 TC 2 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD JUL PY 2015 VL 13 IS 3 BP 204 EP + PG 10 WC Ophthalmology SC Ophthalmology GA CM3WP UT WOS:000357616200006 PM 26045234 ER PT J AU Aggarwal, S Kheirkhah, A Cavalcanti, BM Cruzat, A Colon, C Brown, E Borsook, D Pruss, H Hamrah, P AF Aggarwal, Shruti Kheirkhah, Ahmad Cavalcanti, Bernardo M. Cruzat, Andrea Colon, Clara Brown, Emma Borsook, David Pruess, Harald Hamrah, Pedram TI Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy SO OCULAR SURFACE LA English DT Article DE autologous serum tears; corneal neuropathy; laser in vivo confocal microscopy; light sensitivity; nerve growth factor; photoallodynia; regeneration ID RETINAL GANGLION-CELLS; SUBBASAL NERVE PLEXUS; DRY EYE; QUANTITATIVE-ANALYSIS; GROWTH-FACTOR; MYOPIC LASIK; BRIGHT LIGHT; PAIN; MORPHOLOGY; NEURONS AB Objective: Patients suffering from corneal neuropathy may present with photoallodynia; i. e., increased light sensitivity, frequently with a normal slit-lamp examination. This study aimed to evaluate the efficacy of autologous serum tears (AST) for treatment of severe photoallodynia in corneal neuropathy and to correlate clinical findings with corneal subbasal nerve alterations by in vivo confocal microscopy (IVCM). Methods: Retrospective case control study with 16 patients with neuropathyinduced severe photoallodynia compared to 16 normal controls. Symptom severity, clinical examination and bilateral corneal IVCM scans were recorded. Results: All patients suffered from extreme photoallodynia (8.8 +/- 1.1) with no concurrent ocular surface disease. Subbasal nerves were significantly decreased at baseline in patients compared to controls; total nerve length (9208 +/- 1264 vs 24714 +/- 1056 mu m/mm(2); P<.0001) and total nerve number (9.6 +/- 1.4 vs 28.6 +/- 2.0; P<.0001), respectively. Morphologically, significantly increased reflectivity (2.9 +/- 0.2 vs 1.8 +/- 0.1; P<.0001), beading (in 93.7%), and neuromas (in 62.5%) were seen. AST (3.6 +/- 2.1 months) resulted in significantly decreased symptom severity (1.6 +/- 1.7; P=.02). IVCM demonstrated significantly improved nerve parameters (P<.005), total nerve length (15451 +/- 1595 mu m/mm(2)), number (13.9 +/- 2.1), and reflectivity (1.9 +/- 0.1). Beading and neuromas were seen in only 56.2% and 7.6% of patients. Conclusion: Patients with corneal neuropathy-induced photoallodynia show profound alterations in corneal nerves. AST restores nerve topography through nerve regeneration, and this correlated with improvement in patient-reported photoallodynia. The data support the notion that corneal nerve damage results in alterations in afferent trigeminal pathways to produce photoallodynia. C1 [Aggarwal, Shruti; Kheirkhah, Ahmad; Cavalcanti, Bernardo M.; Cruzat, Andrea; Colon, Clara; Brown, Emma; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Surface Imaging Ctr,Cornea & Refract Surg, Boston, MA 02114 USA. [Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston Childrens Hosp,Dept Anesthesia,Pain Analge, Waltham, MA USA. [Pruess, Harald] Charite, Dept Neurol, Berlin, Germany. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU National Eye Institute (NIH) [K08-EY020575, R01-EY022695]; Research to Prevent Blindness Career Development Award; Falk Medical Research Trust; New England Corneal Transplant Research Fund FX National Eye Institute (NIH) K08-EY020575 (PH), National Eye Institute (NIH) R01-EY022695 (PH), Research to Prevent Blindness Career Development Award (PH), Falk Medical Research Trust (PH), and the New England Corneal Transplant Research Fund (PH). The funding organizations had no role in the design or conduct of this research. NR 68 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD JUL PY 2015 VL 13 IS 3 BP 250 EP 262 PG 13 WC Ophthalmology SC Ophthalmology GA CM3WP UT WOS:000357616200010 PM 26045233 ER PT J AU Kasinski, AL Kelnar, K Stahlhut, C Orellana, E Zhao, J Shimer, E Dysart, S Chen, X Bader, AG Slack, FJ AF Kasinski, A. L. Kelnar, K. Stahlhut, C. Orellana, E. Zhao, J. Shimer, E. Dysart, S. Chen, X. Bader, A. G. Slack, F. J. TI A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer SO ONCOGENE LA English DT Article ID MOUSE MODELS; CAENORHABDITIS-ELEGANS; MIR-34A; APOPTOSIS; ADENOCARCINOMA; ACTIVATION; EXPRESSION; INITIATION; ONCOGENE; DELIVERY AB Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to repress multiple oncogenic pathways at once. Here we treated the aggressive Kras; p53 non-small cell lung cancer mouse model and demonstrated efficacy with a combination of two tumor-suppressive microRNAs (miRNAs). Systemic nanodelivery of miR-34 and let-7 suppressed tumor growth leading to survival advantage. This combinatorial miRNA therapeutic approach engages numerous components of tumor cell-addictive pathways and highlights the ability to deliver multiple miRNAs in a safe and effective manner to target lung tissue. C1 [Kasinski, A. L.; Stahlhut, C.; Shimer, E.; Chen, X.; Slack, F. J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Kasinski, A. L.; Orellana, E.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Kelnar, K.; Zhao, J.; Dysart, S.; Bader, A. G.] Mirna Therapeut Inc, Austin, TX 78744 USA. [Slack, F. J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Slack, FJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, BIDMC, 3 Blackfan Circle CLS412, Boston, MA 02115 USA. EM abader@mirnarx.com; fslack@bidmc.harvard.edu RI Kasinski, Andrea/E-7951-2014; OI Stahlhut, Carlos/0000-0002-8472-7156; Slack, Frank/0000-0001-8263-0409; Orellana, Esteban/0000-0003-4369-9416 FU American Cancer Society [PF-11-244-01]; NIH [CA178091, CA131301]; Cancer Prevention Research Institute of Texas (CPRIT) FX ALK was supported by an American Cancer Society Fellowship (PF-11-244-01) and an NIH Pathway to Independence Award (CA178091). This work was supported by a grant to FJS from the NIH (CA131301) and by a commercialization grant from the Cancer Prevention Research Institute of Texas (CPRIT) to AGB. NR 34 TC 29 Z9 29 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUL PY 2015 VL 34 IS 27 BP 3547 EP 3555 DI 10.1038/onc.2014.282 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CM1IQ UT WOS:000357434900007 PM 25174400 ER PT J AU Jia, H Cong, Q Chua, JFL Liu, H Xia, X Zhang, X Lin, J Habib, SL Ao, J Zuo, Q Fu, C Li, B AF Jia, H. Cong, Q. Chua, J. F. L. Liu, H. Xia, X. Zhang, X. Lin, J. Habib, S. L. Ao, J. Zuo, Q. Fu, C. Li, B. TI p57Kip2 is an unrecognized DNA damage response effector molecule that functions in tumor suppression and chemoresistance SO ONCOGENE LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; IN MOUSE MODEL; CDK INHIBITORS; P57(KIP2) EXPRESSION; STEM-CELLS; CANCER; P38; P57; ATM; DIFFERENTIATION AB The DNA damage response (DDR) helps to maintain genome integrity, suppress tumorigenesis and mediate the radiotherapeutic and chemotherapeutic effects on cancer. Here we report that p57Kip2, a cyclin-dependent kinase (CDK) inhibitor implicated in the development of tumor-prone Beckwith-Wiedemann syndrome, is an effector molecule of the DNA-damage response. Genotoxic stress induces p57Kip2 expression via the bone morphogenetic protein-Smad1 and Atm-p38MAPK-Atf2 pathways in p53-proficient or -deficient cells and requires the Smad1-Atf2 complex that facilitates their recruitment to the p57Kip2 promoter. Elevated p57Kip2 induces G1/S phase cell cycle arrest but inhibits cell death in response to DNA damage and acts in parallel with p53 to suppress cell transformation and tumor formation. p57Kip2 is also upregulated in stage I and II clinical rectal tumor samples, likely due to genome instability of precancerous and/or early cancer cells. Targeting p57Kip2 in primary rectal cancer cells and tumor models resulted in increased sensitivity to doxorubicin, suggesting that p57Kip2 has a role in chemoresistance, which is consistent with its pro-survival function. These findings place p57Kip2 in DDR and uncover molecular mechanisms by which p57Kip2 suppresses tumorigenesis and causes chemoresistance. C1 [Jia, H.; Cong, Q.; Liu, H.; Xia, X.; Zhang, X.; Lin, J.; Li, B.] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai 200240, Peoples R China. [Chua, J. F. L.] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. [Habib, S. L.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Habib, S. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ao, J.] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Renji Hosp, Shanghai 200240, Peoples R China. [Zuo, Q.; Fu, C.] Second Mil Med Univ, Changhai Hosp, Dept Colorectal Surg, Shanghai, Peoples R China. RP Li, B (reprint author), Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Dongchuan Rd 800, Shanghai 200240, Peoples R China. EM libj@sjtu.edu.cn RI ASTAR, IMCB/E-2320-2012 FU Ministry of Science and Technology of China [2012CB966901]; National Natural Science Foundation of China [81130039, 31071229, 81121001] FX We thank Lina Gao, IH In, C Deyu, GC Hong, L Soh, J Lin and T Cheng for technical assistance and Boehringer Ingelheim, Novartis, Dr Michael D. Schneider, Dr Ye-Guang Chen, Dr Yibin Wang, Dr Nelson J Dusetti, Dr Olivier Delattre, Dr Philipp Kaldis and Dr Michael Kastan for providing constructs, reagents and mice. The work was supported by grants from the Ministry of Science and Technology of China (The National Key Scientific Program (2012CB966901 to BL) and the National Natural Science Foundation of China (81130039, 31071229 and 81121001). NR 62 TC 4 Z9 4 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUL PY 2015 VL 34 IS 27 BP 3568 EP 3581 DI 10.1038/onc.2014.287 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CM1IQ UT WOS:000357434900009 PM 25195859 ER PT J AU Shah, PV Kozin, ED Remenschneider, AK Dedmon, MM Nakajima, HH Cohen, MS Lee, DJ AF Shah, Parth V. Kozin, Elliott D. Remenschneider, Aaron K. Dedmon, Matthew M. Nakajima, Hideko Heidi Cohen, Michael S. Lee, Daniel J. TI Prolonged Radiant Exposure of the Middle Ear during Transcanal Endoscopic Ear Surgery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE endoscope; temperature; middle ear surgery; timing ID BONE AB Transcanal endoscopic ear surgery (EES) provides a high-resolution, wide-field view of the middle ear compared with the conventional operating microscope, reducing the need for a postauricular incision or mastoidectomy. Our group has shown in cadaveric human temporal bone studies that radiant energy from the endoscope tip can quickly elevate temperatures of the tympanic cavity. Elevated temperatures of the middle ear are associated with acute auditory brainstem response shifts in animal models. In EES, proposed methods to decrease middle ear temperature include frequent removal of the endoscope and the use of suction to rapidly dissipate heat; however, the routine application of such cooling techniques remains unknown. Herein, we aim to quantify the duration that the tympanic cavity is typically exposed to the endoscope during routine endoscopic middle ear surgery. We find that the tympanic cavity is exposed to the endoscope without a cooling mechanism for a prolonged period of time. C1 [Shah, Parth V.; Kozin, Elliott D.; Remenschneider, Aaron K.; Dedmon, Matthew M.; Nakajima, Hideko Heidi; Cohen, Michael S.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kozin, Elliott D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Kozin, ED (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Elliott_Kozin@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 NR 8 TC 4 Z9 4 U1 0 U2 0 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 JUL PY 2015 VL 153 IS 1 BP 102 EP 104 DI 10.1177/0194599815574842 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CL9KL UT WOS:000357297000016 PM 25779471 ER PT J AU Mansour, M Afzal, MR Gunda, S Pillarisetti, J Heist, K Acha, MR Heard, M Ruskin, J Lakkireddy, D AF Mansour, Moussa Afzal, Muhammad R. Gunda, Sampath Pillarisetti, Jayasree Heist, Kevin Acha, Moshe Rav Heard, Michael Ruskin, Jeremy Lakkireddy, Dhanunjaya TI Feasibility of Transseptal Puncture Using a Nonfluoroscopic Catheter Tracking System SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE MediGuide radiation reduction; three-dimensional mapping system; catheter visualization; TS puncture ID ATRIAL-FIBRILLATION ABLATION; INITIAL-EXPERIENCE; FLUTTER; NAVIGATION; MEDIGUIDE; IMPACT AB BackgroundRadiation exposure in the electrophysiology lab is a major occupational hazard to the electrophysiologists. A catheter localization system (MediGuide Technology, St. Jude Medical Inc., St. Paul, MN, USA) allows the integration of electroanatomical mapping and x-ray imaging, and has been shown to be effective in reducing radiation exposure during several electrophysiological procedures. We intended to evaluate the feasibility of this catheter tracking system to guide transseptal (TS) access. MethodsThe feasibility of performing TS puncture with MediGuide (MDG) was assessed in a prospective observational study in 16 patients undergoing radiofrequency ablation for atrial fibrillation. These patients were compared to 16 matched patients undergoing similar procedures during the same time frame using conventional approach. There were no differences in mean age, gender distribution, and body mass index between the two groups. Total duration of fluoroscopic exposure during TS puncture was compared between the two groups. ResultsAll patients underwent successful TS puncture. Fluoroscopy time for double TS puncture using the MDG system was significantly lower than the control group (0.48 0.17 minutes vs. 5.9 +/- 0.65 minutes; P < 0.0001). No major complications occurred during the procedures in either group. ConclusionsTS puncture can be successfully performed using MDG, and results in significant reduction in radiation exposure. C1 [Mansour, Moussa; Heist, Kevin; Acha, Moshe Rav; Ruskin, Jeremy] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Mansour, Moussa; Heist, Kevin; Acha, Moshe Rav; Ruskin, Jeremy] Harvard Univ, Sch Med, Boston, MA USA. [Afzal, Muhammad R.; Gunda, Sampath; Pillarisetti, Jayasree; Lakkireddy, Dhanunjaya] Univ Kansas Hosp & Med Ctr, Div Cardiovasc Dis, Cardiovasc Res Inst, Kansas City, KS USA. [Heard, Michael] St Jude Med Inc, Kansas City, KS USA. RP Lakkireddy, D (reprint author), Univ EP Res, Univ Kansas Hosp, Div Cardiovasc Dis,Mid Amer Cardiol, Res Inst KU Cardiovasc Res Inst,Bloch Heart Rhyth, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM dlakkireddy@kumc.edu NR 13 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2015 VL 38 IS 7 BP 791 EP 796 DI 10.1111/pace.12617 PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CL9TX UT WOS:000357322100004 PM 25712806 ER PT J AU Maan, A Refaat, MM Heist, EK Passeri, J Inglessis, I Ptaszek, L Vlahakes, G Ruskin, JN Palacios, I Sundt, T Mansour, M AF Maan, Abhishek Refaat, Marwan M. Heist, Edwin Kevin Passeri, Jonathan Inglessis, Ignacio Ptaszek, Leon Vlahakes, Gus Ruskin, Jeremy N. Palacios, Igor Sundt, Thoralf Mansour, Moussa TI Incidence and Predictors of Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE transcatheter aortic valve replacement; permanent pacemaker implantation ID COMPLETE HEART-BLOCK; HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; PERMANENT PACEMAKER; RISK-FACTORS; CONDUCTION DISTURBANCES; COREVALVE; OUTCOMES; BIOPROSTHESIS; REGURGITATION; STENOSIS AB BackgroundTranscatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement. The development of conduction abnormalities is a major complication in the postprocedural period of TAVR. ObjectivesThe objective of this study was to investigate the development of postprocedural conduction abnormalities and the requirement of permanent pacemaker (PPM) implantation in patients undergoing TAVR. MethodsData from 137 consecutive patients who underwent TAVR (Edwards SAPIEN valve, Edwards Lifesciences, Irvine, CA, USA) between June 2008 and October 2012 were reviewed. Patients with prior history of PPM (n = 27) were excluded. The role of various predictors for pacemaker implantation after TAVR, including the valve index (calculated as [valve size/left ventricular outflow tract diameter] x 100) was investigated. ResultsA total of 31/110 (28.2%) patients required implantation of a PPM after TAVR. The median time to implantation of a PPM was 5 days after the procedure. The development of postprocedural complete heart block was the most common indication for implantation of a PPM (16/31; 51.6%). On multivariate analysis, the presence of preexisting right bundle branch block (RBBB) was found to be a strong predictor of PPM implantation after TAVR (adjusted odds ratio: 4.87; 95% confidence interval: 1.29-18.46, P = 0.020). Using the receiver operated curve analysis, a cut-off value of valve index of 128 was found to be a strong predictor for PPM implantation with a sensitivity of 73% and specificity of 61% (c statistic = 0.68). ConclusionsThis study identified the presence of prior RBBB and a valve index of 128 as important risk factors for PPM implantation after TAVR. A larger implanted valve size relative to left ventricular outflow tract diameter leads to a greater compression of the intrinsic conduction system, increasing the need for pacemaker placement. C1 [Maan, Abhishek; Refaat, Marwan M.; Heist, Edwin Kevin; Passeri, Jonathan; Inglessis, Ignacio; Ptaszek, Leon; Vlahakes, Gus; Ruskin, Jeremy N.; Palacios, Igor; Sundt, Thoralf; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM mmansour@mgh.harvard.edu FU Deane Institute for Integrative Research in Atrial Fibrillation at Massachusetts General Hospital FX This work was supported in part by the Deane Institute for Integrative Research in Atrial Fibrillation at Massachusetts General Hospital. NR 36 TC 0 Z9 0 U1 1 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 JUL PY 2015 VL 38 IS 7 BP 878 EP 886 DI 10.1111/pace.12653 PG 9 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CL9TX UT WOS:000357322100014 PM 25940067 ER PT J AU Maleki, N Barmettler, G Moulton, EA Scrivani, S Veggeberg, R Spierings, ELH Burstein, R Becerra, L Borsook, D AF Maleki, Nasim Barmettler, Gabi Moulton, Eric A. Scrivani, Steven Veggeberg, Rosanna Spierings, Egilius L. H. Burstein, Rami Becerra, Lino Borsook, David TI Female migraineurs show lack of insular thinning with age SO PAIN LA English DT Article DE Migraine; Headache; Women; Aging; MRI; Imaging; Insula ID VOXEL-BASED MORPHOMETRY; MAGNETIC-RESONANCE IMAGES; BRAIN-STEM ACTIVATION; HUMAN CEREBRAL-CORTEX; GREY-MATTER CHANGES; TEMPORAL POLE; CHRONIC PAIN; GEOMETRICALLY ACCURATE; FMRI; HEADACHE AB Gray matter loss in cortical regions is a normal ageing process for the healthy brain. There have been few studies on the process of ageing of the brain in chronic neurological disorders. In this study, we evaluated changes in the cortical thickness by age in 92 female subjects (46 patients with migraine and 46 healthy controls) using high-field magnetic resonance imaging. The results indicate that in contrast to healthy subjects, migraineurs show a lack of thinning in the insula by age. The functional significance of the lack of thinning is unknown, but it may contribute to the overall cortical hyperexcitability of the migraine brain because the region is tightly involved in a number of major brain networks involved in interoception, salience, nociception, and autonomic function, including the default mode network. C1 [Maleki, Nasim; Barmettler, Gabi; Moulton, Eric A.; Veggeberg, Rosanna; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA 02215 USA. [Barmettler, Gabi; Moulton, Eric A.; Scrivani, Steven; Veggeberg, Rosanna; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston Childrens Hosp, Boston, MA 02215 USA. [Barmettler, Gabi; Moulton, Eric A.; Scrivani, Steven; Veggeberg, Rosanna; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, PAIN Grp, Boston Childrens Hosp, Boston, MA 02215 USA. [Scrivani, Steven] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Veggeberg, Rosanna; Becerra, Lino; Borsook, David] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat,PAIN Grp,Brain Imaging Ctr, Belmont, MA USA. [Spierings, Egilius L. H.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Anesthesia & Crit Care, Boston, MA USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Ctr Pain & Brain, Boston Childrens Hosp, Boston, MA 02215 USA. EM david.borsook@childrens.harvard.edu FU NINDS [R01-NS073997, K24-NS064050]; Boston Children's Hospital Office of Faculty Development Fellowship; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School FX The work was funded by Grants from NINDS (R01-NS073997 and K24-NS064050) to D. Borsook. Salary support in part to N. Maleki by Boston Children's Hospital Office of Faculty Development Fellowship and the Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School. NR 84 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUL PY 2015 VL 156 IS 7 BP 1232 EP 1239 DI 10.1097/j.pain.0000000000000159 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CM1FJ UT WOS:000357426200011 PM 25775358 ER PT J AU Egorova, N Yu, RJ Kaur, N Vangel, M Gollub, RL Dougherty, DD Kong, J Camprodon, JA AF Egorova, Natalia Yu, Rongjun Kaur, Navneet Vangel, Mark Gollub, Randy L. Dougherty, Darin D. Kong, Jian Camprodon, Joan A. TI Neuromodulation of conditioned placebo/nocebo in heat pain: anodal vs cathodal transcranial direct current stimulation to the right dorsolateral prefrontal cortex SO PAIN LA English DT Article DE tDCS; Placebo; Nocebo; Right dorsolateral prefrontal cortex; Conditioning; Pain ID NOCEBO PHENOMENON; BRAIN ACTIVITY; ANALGESIA; MECHANISMS; RESPONSES; TDCS; ANTICIPATION; MODULATION; ACTIVATION; NETWORK AB Placebo and nocebo play an important role in clinical practice and medical research. Modulating placebo/nocebo responses using noninvasive brain stimulation methods, such as transcranial direct current stimulation (tDCS), has the potential to harness these effects to therapeutic benefit in a clinical setting. In this study, we assessed the effect of anodal and cathodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on conditioned placebo/nocebo cue response to heat pain. Two matched groups of healthy volunteers were subjected to an identical session of conditioning, during which low and high cues (abstract images) were associated with low and high pain levels, respectively. Twenty-minute 2-mA tDCS (either anodal or cathodal) over the rDLPFC was applied. The influence of tDCS current polarity (anodel vs cathodal) on placebo and nocebo was assessed, using subjects' pain ratings in response to identical pain preceded by the conditioned high or low cues. The duration of cue presentation varied to allow either fully conscious or subliminal processing. Significant placebo and nocebo effects in the anodal but not the cathodal group were elicited with the conditioning paradigm. This study provides evidence of a possibility to modulate the conditioned placebo and nocebo effect by changing the excitability of the rDLPFC using tDCS. C1 [Egorova, Natalia; Yu, Rongjun; Kaur, Navneet; Gollub, Randy L.; Dougherty, Darin D.; Kong, Jian; Camprodon, Joan A.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Egorova, Natalia; Yu, Rongjun; Gollub, Randy L.; Dougherty, Darin D.; Kong, Jian; Camprodon, Joan A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Yu, Rongjun] Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore. [Vangel, Mark; Gollub, Randy L.; Kong, Jian; Camprodon, Joan A.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. RP Kong, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Bldg 120,2nd Ave,Suite 101C, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu RI Egorova, Natalia/N-9118-2015 OI Egorova, Natalia/0000-0002-9244-2900 FU NIH/NCCAM [R0AT006364, R01AT005280]; [P01 AT006663] FX This work was supported by R0AT006364 (NIH/NCCAM) to J. Kong, R01AT005280 (NIH/NCCAM) to R. L. Gollub, and P01 AT006663 to B. Rosen/R.L. Gollub. NR 58 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUL PY 2015 VL 156 IS 7 BP 1342 EP 1347 DI 10.1097/j.pain.0000000000000163 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CM1FJ UT WOS:000357426200021 PM 25806605 ER PT J AU Mull, HJ Brennan, CW Folkes, T Hermos, J Chan, J Rosen, AK Simon, SR AF Mull, Hillary J. Brennan, Caitlin W. Folkes, Tiffany Hermos, John Chan, Jeffrey Rosen, Amy K. Simon, Steven R. TI Identifying Previously Undetected Harm: Piloting the Institute for Healthcare Improvement's Global Trigger Tool in the Veterans Health Administration SO QUALITY MANAGEMENT IN HEALTH CARE LA English DT Article ID ADVERSE EVENTS; PATIENT SAFETY; HOSPITALIZED-PATIENTS; PERFORMANCE; QUALITY; PROGRAM; RATES AB Background: Adverse event (AE) surveillance may be enhanced by the Institute for Healthcare Improvement's Global Trigger Tool (GTT). A pilot study of the GTT was conducted in one Veterans Health Administration (VA) facility to assess the rates, types, and harm of AEs detected and to examine the overlap in AE detection between the GTT and existing surveillance mechanisms. Methods: GTT guidelines were followed and medical records were reviewed for 17 weeks of acute care hospitalizations. Investigators met monthly, first to adjudicate discordant reviewer categorizations of harm and later to categorize the AEs detected using standardized definitions. GTT-detected AEs were compared with incident reports, Patient Safety Indicators, and the VA Surgical Quality Improvement Program. Results: Medical records were reviewed for 273 of 1980 eligible cases. Using the GTT, a total of 109 AEs were identified. More than 1 of 5 hospitalizations (21%) were associated with an AE. The majority of AEs detected (60%) were minor harms; there were no deaths attributable to medical care. Ninety-six of the 109 AEs (88%) were not detected by other measures. Conclusions: The GTT identified previously undetected AEs at one VA. The GTT has the potential to track AEs and guide quality improvement efforts in conjunction with existing AE surveillance mechanisms. C1 [Mull, Hillary J.; Brennan, Caitlin W.; Chan, Jeffrey; Rosen, Amy K.; Simon, Steven R.] VA Boston Healthcare Syst, Patient Safety Ctr Inquiry, Measurement Assess Patient Safety, Boston, MA 02130 USA. [Mull, Hillary J.; Chan, Jeffrey; Rosen, Amy K.; Simon, Steven R.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Folkes, Tiffany] VA Boston Healthcare Syst, Dept Nursing, Boston, MA 02130 USA. [Hermos, John; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Mull, Hillary J.; Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Brennan, Caitlin W.] NIH, Ctr Clin, Dept Nursing, Res & Practice Dev Sect, Bethesda, MD 20892 USA. [Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM Hillary.mull@va.gov FU VA National Center for Patient Safety (NCPS) through the Patient Safety Center of Inquiry at VA Boston Healthcare System [VA NCPS XVA 68-023] FX This work was supported by the VA National Center for Patient Safety (NCPS) through the Patient Safety Center of Inquiry at VA Boston Healthcare System (VA NCPS XVA 68-023, Director: Amy Rosen, PhD). The authors acknowledge the contributions of Frank Federico, RPh, from the Institute for Healthcare Improvement, for guidance and support throughout our study. William O'Brien provided programming support to complete the analyses of our data. NR 28 TC 2 Z9 2 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1063-8628 EI 1550-5154 J9 QUAL MANAG HEALTH CA JI Qual. Manag. Health Care PD JUL-SEP PY 2015 VL 24 IS 3 BP 140 EP 146 DI 10.1097/QMH.0000000000000060 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CM8HY UT WOS:000357941400006 PM 26115062 ER PT J AU Bowman, C Luck, J Gale, RC Smith, N York, LS Asch, S AF Bowman, Candice Luck, Jeff Gale, Randall C. Smith, Nina York, Laura S. Asch, Steven TI A Qualitative Evaluation of Web-Based Cancer Care Quality Improvement Toolkit Use in the Veterans Health Administration SO QUALITY MANAGEMENT IN HEALTH CARE LA English DT Article ID IMPLEMENTATION; COLLABORATIVES; INNOVATION; DIFFUSION; LESSONS; PROGRAM; SYSTEM AB Background: Disease severity, complexity, and patient burden highlight cancer care as a target for quality improvement (QI) interventions. The Veterans Health Administration (VHA) implemented a series of disease-specific online cancer care QI toolkits. Objectives: To describe characteristics of the toolkits, target users, and VHA cancer care facilities that influenced toolkit access and use and assess whether such resources were beneficial for users. Methods: Deductive content analysis of detailed notes from 94 telephone interviews with individuals from 48 VHA facilities. We evaluated toolkit access and use across cancer types, participation in learning collaboratives, and affiliation with VHA cancer care facilities. Results: The presence of champions was identified as a strong facilitator of toolkit use, and learning collaboratives were important for spreading information about toolkit availability. Identified barriers included lack of personnel and financial resources and complicated approval processes to support tool use. Conclusions: Online cancer care toolkits are well received across cancer specialties and provider types. Clinicians, administrators, and QI staff may benefit from the availability of toolkits as they become more reliant on rapid access to strategies that support comprehensive delivery of evidence-based care. Toolkits should be considered as a complement to other QI approaches. C1 [Bowman, Candice; Luck, Jeff; Smith, Nina; York, Laura S.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Luck, Jeff] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. [Gale, Randall C.; Asch, Steven] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. [Asch, Steven] Stanford Univ, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. RP Gale, RC (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 790 Willow Rd, Menlo Pk, CA 94025 USA. EM randall.gale@va.gov FU VA Office of Analytics and Business Intelligence; VA Office of Systems Redesign FX This study was funded by VA Office of Analytics and Business Intelligence and VA Office of Systems Redesign with additional in-kind support from VA Center for Applied Systems Engineering. The authors thank the following for their contributions to this evaluation and the manuscript: Sangeeta Ahluwalia, PhD; Carla S. Alvarado, MPH; Jenny Barnard, BA; Bonnie Bruce, DrPH; Danielle Cohen, MPH; Marlin Elenes, MPH; Joya Golden, MSW; Christopher J. Koenig, PhD; Andrea Nevedal, PhD; and Sabine Oishi, PhD. NR 32 TC 0 Z9 0 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1063-8628 EI 1550-5154 J9 QUAL MANAG HEALTH CA JI Qual. Manag. Health Care PD JUL-SEP PY 2015 VL 24 IS 3 BP 147 EP 161 DI 10.1097/QMH.0000000000000063 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CM8HY UT WOS:000357941400007 PM 26115063 ER PT J AU Mumford, AD Frelinger, AL Gachet, C Gresele, P Noris, P Harrison, P Mezzano, D AF Mumford, Andrew D. Frelinger, Andrew L., III Gachet, Christian Gresele, Paolo Noris, Patrizia Harrison, Paul Mezzano, Diego TI A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders SO THROMBOSIS AND HAEMOSTASIS LA English DT Review DE Platelet pathology; inherited; acquired; secretion; exocytosis; diagnosis management ID LINKED-IMMUNOSORBENT-ASSAY; STORAGE POOL-DEFICIENCY; HERMANSKY-PUDLAK SYNDROME; PERFORMANCE LIQUID-CHROMATOGRAPHY; LIGHT TRANSMISSION AGGREGOMETRY; ADENOSINE-TRIPHOSPHATE RELEASE; CHEDIAK-HIGASHI-SYNDROME; DENSE GRANULE MEMBRANES; ALPHA-GRANULES; FACTOR-V AB Measurement of platelet granule release to detect inherited platelet secretion disorders (IPSDs) is essential for the evaluation of patients, with abnormal bleeding and is necessary to distinguish which granule sub-types are affected and whether there is abnormal granule biosynthesis or secretion. The radioactive serotonin incorporation and release assay, described before 1970, is still considered the "gold standard" test to assess platelet delta-granule release, although is unsuitable, for clinical diagnostic laboratories. Luciferin-based assays, such as lumiaggregometry, are the most widely performed alternatives, although these methods do not distinguish defects in delta-granule biosynthesis from defects in secretion. Platelet alpha-granule release is commonly evaluated using flow cytometry by measuring surface exposure of P-selectin after platelet activation. However, this assay has poor sensitivity for some a-granule disorders. Only few studies have been published with more recently developed assays and no critical reviews on these methods are available. In this review, we describe the rationale for developing robust and accurate laboratory tests of platelet granule release and describe the characteristics of the currently available tests. We identify an unmet need for further systematic evaluation of new assays and for standardisation of methodologies for clinical diagnostic laboratories. C1 [Mumford, Andrew D.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. [Frelinger, Andrew L., III] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Boston, Boston, MA 02115 USA. [Gachet, Christian] Univ Strasbourg, UMR INSERM S949, Etab Francais Sang Alsace, Strasbourg, France. [Gresele, Paolo] Univ Perugia, Dept Med, I-06100 Perugia, Italy. [Noris, Patrizia] Univ Pavia, IRCCS Policlin San Matteo Fdn, Dept Internal Med, I-27100 Pavia, Italy. [Harrison, Paul] Univ Birmingham, Sch Med, Sch Immun & Infect, Birmingham, W Midlands, England. [Mezzano, Diego] Pontificia Univ Catolica Chile, Sch Med, Santiago, Chile. [Mezzano, Diego] Conicyt 1130853, Budapest, Hungary. RP Mezzano, D (reprint author), Pontificia Univ Catolica Chile, Sch Med, Dept Hematol Oncol, Portugal 61,2nd Floor, Santiago, Chile. EM dmezzano@med.puc.cl RI Gachet, Christian/H-9156-2016; OI Harrison, Paul/0000-0003-4610-8909 NR 141 TC 14 Z9 14 U1 2 U2 11 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2015 VL 114 IS 1 BP 14 EP 25 DI 10.1160/TH14-11-0999 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CM2YH UT WOS:000357547800007 PM 25879272 ER PT J AU Kim, EJ Ozonoff, A Hylek, EM Berlowitz, DR Ash, AS Miller, DR Zhao, SB Reisman, JI Jasuja, GK Rose, AJ AF Kim, Eun-Jeong Ozonoff, Al Hylek, Elaine M. Berlowitz, Dan R. Ash, Arlene S. Miller, Donald R. Zhao, Shibei Reisman, Joel I. Jasuja, Guneet K. Rose, Adam J. TI Predicting outcomes among patients with atrial fibrillation and heart failure receiving anticoagulation with warfarin SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Anticoagulants; atrial fibrillation; heart failure; patient outcome assessment ID INTERNATIONAL NORMALIZED RATIO; ORAL ANTICOAGULATION; THERAPEUTIC RANGE; VETERANS AFFAIRS; SAME-TT2R2 SCORE; RISK; INHIBITION; VALIDATION; METOLAZONE; MORTALITY AB Among patients receiving oral anticoagulation for atrial fibrillation (AF), heart failure (HF) is associated with poor anticoagulation control. However, it is not known which patients with heart failure are at greatest risk of adverse outcomes. We evaluated 62,156 Veterans Health Administration (VA) patients receiving warfarin for AF between 10/1/06-9/30/08 using merged VA-Medicare dataset We predicted time in therapeutic range (TTR) and rates of adverse events by categorising patients into those with 0, 1, 2, or 3+ of five putative markers of HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline phosphatase> 150 U/l, serum sodium<130 mEq/l, any receipt of metolazone, and any inpatient admission for HF exacerbation. These risk categories predicted TTR: patients without HF (referent) had a mean, TTR of 65.0%, while HF patients with 0, 1, 2, 3 or more markers had mean TTRs of 62.2%, 57.2%, 53.5%, and 50.7%, respectively (p<0.001). These categories also discriminated for major haemorrhage well; compared to patients without HF, HF patients with increasing severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p<0.001). However, although patients with HF had an elevated hazard for bleeding compared to those without HF, these categories did not effectively discriminate risk of ischaemic stroke across HF. In conclusion, we developed a HF severity model using easily available clinical characteristics that performed well to risk-stratify patients with HF who are receiving anticoagulation for AF with regard to major haemorrhage. C1 [Kim, Eun-Jeong] Massachusetts Gen Hosp, Gen Internal Med Sect, Dept Med, Bedford, MA USA. [Ozonoff, Al; Hylek, Elaine M.; Berlowitz, Dan R.; Ash, Arlene S.; Miller, Donald R.; Zhao, Shibei; Reisman, Joel I.; Jasuja, Guneet K.; Rose, Adam J.] Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Hylek, Elaine M.; Berlowitz, Dan R.; Ash, Arlene S.; Rose, Adam J.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Ozonoff, Al] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA USA. [Berlowitz, Dan R.; Miller, Donald R.; Jasuja, Guneet K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Ash, Arlene S.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA. RP Kim, EJ (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Hosp Med Grp, 55 Fruit St Bulfinch 015, Boston, MA 02114 USA. EM ekim28@partners.org FU VA Health Services Research and Development Service [IIR-10-374] FX The first author conducted research during her internal medicine residency training at Boston Medical Center, Boston University School of Medicine, Boston MA. This study was supported by a grant from the VA Health Services Research and Development Service (IIR-10-374). The sponsor had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, and approval of the manuscript. The opinions expressed in this article are those of the authors, and do not necessarily represent the official views of the Department of Veterans Affairs. NR 32 TC 4 Z9 4 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2015 VL 114 IS 1 BP 70 EP 77 DI 10.1160/TH14-09-0754 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CM2YH UT WOS:000357547800013 PM 25948532 ER PT J AU Holcombe, H Parry, NM Rick, M Brown, DE Albers, TM Refsal, KR Morris, J Kelly, R Marko, ST AF Holcombe, H. Parry, N. M. Rick, M. Brown, D. E. Albers, T. M. Refsal, K. R. Morris, J. Kelly, R. Marko, S. T. TI Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus SO VETERINARY PATHOLOGY LA English DT Article DE guinea pigs; vitamin D; toxicity; metastatic calcification; cholecalciferol ID SOFT TISSUE CALCIFICATION; VITAMIN-D; RENAL-FAILURE; CALCIUM; PHOSPHORUS; METABOLISM; MAGNESIUM; DIET; SPERMATOZOA; HALIPHAGIA AB A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. C1 [Holcombe, H.; Parry, N. M.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Rick, M.; Refsal, K. R.] Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, Lansing, MI USA. [Brown, D. E.; Morris, J.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Brown, D. E.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Albers, T. M.] Res Models & Serv, Wilmington, MA USA. [Kelly, R.; Marko, S. T.] US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Holcombe, H (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hrh@mit.edu FU NIH HHS [R21 OD011193] NR 31 TC 0 Z9 0 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD JUL PY 2015 VL 52 IS 4 BP 741 EP 751 DI 10.1177/0300985814551423 PG 11 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA CM2MT UT WOS:000357515400022 PM 25281651 ER PT J AU de Vinck-Baroody, O Shui, A Macklin, EA Hyman, SL Leventhal, JM Weitzman, C AF de Vinck-Baroody, Oana Shui, Amy Macklin, Eric A. Hyman, Susan L. Leventhal, John M. Weitzman, Carol TI Overweight and Obesity in a Sample of Children With Autism Spectrum Disorder SO ACADEMIC PEDIATRICS LA English DT Article DE autism; obesity; overweight; macrocephaly; NHANES ID BODY-MASS INDEX; HEAD CIRCUMFERENCE; 1ST YEAR; GROWTH; PREVALENCE; DISABILITIES; LIFE; ADOLESCENTS; OVERGROWTH AB OBJECTIVE: To determine the prevalence of overweight/obese status in children with autism spectrum disorders (ASD), identify associated characteristics, and develop a model to predict weight status. METHODS: The prevalence of overweight and obesity was determined in 2769 children with ASD enrolled in the Autism Speaks Autism Treatment Network, a collaboration of 17 academic centers, and compared with a national sample matched for age, sex, and race. Associations in the ASD sample between weight status and demographic and clinical variables, such as age, race, head circumference, and adaptive functioning, were tested using ordinal logistic regression. The accuracy of a final model that predicted weight status based on early life variables was evaluated in a validation sample. RESULTS: The prevalence of overweight and obesity were 33.9% and 18.2%, respectively; ASD was associated with a higher risk of obesity (but not overweight) relative to the national sample (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.05-1.28; P = .003). In the adjusted analysis, overweight/obese status was significantly associated with Hispanic ethnicity (OR, 1.99; 95% CI, 1.37-2.89), parental high school education (OR, 1.56; 95% CI, 1.09-2.21), high birth weight (OR, 1.56; 95% CI, 1.11-2.18), macrocephaly (OR, 4.01; 95% CI, 2.96-5.43), and increased somatic symptoms (OR, 1.41; 95% CI, 1.01-1.95). A prediction model designed to have high sensitivity predicted low risk of overweight/obesity accurately, but had low positive predictive value. CONCLUSIONS: The prevalence of obesity in children with ASD was greater than a national sample. Independent associations with increased weight status included known risk factors and macrocephaly and increased level of somatic symptoms. A model based on early life variables accurately predicted low risk of overweight/obesity. C1 [de Vinck-Baroody, Oana; Leventhal, John M.; Weitzman, Carol] Yale Univ, Sch Med, Dev Behav Pediat, New Haven, CT USA. [Shui, Amy; Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. [Hyman, Susan L.] Univ Rochester, Dev Behav Pediat, Rochester, NY 14627 USA. RP de Vinck-Baroody, O (reprint author), 30 Prospect Ave, Hackensack, NJ 07601 USA. EM Odevinck-baroody@HackensackUMC.org FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054]; Maternal and Child Health Bureau [T77MC00024] FX Financial disclosure: Further support came from a cooperative agreement (UA3 MC 11054) from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. The Yale Developmental Behavioral Pediatrics Fellowship Program was supported by a grant from the Maternal and Child Health Bureau (T77MC00024). NR 37 TC 5 Z9 5 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JUL-AUG PY 2015 VL 15 IS 4 BP 396 EP 404 PG 9 WC Pediatrics SC Pediatrics GA CM0JE UT WOS:000357363400007 PM 25937610 ER PT J AU DiPasquale, DM Strangman, GE Harris, NS Muza, SR AF DiPasquale, Dana M. Strangman, Gary E. Harris, N. Stuart Muza, Stephen R. TI Hypoxia, Hypobaria, and Exercise Duration Affect Acute Mountain Sickness SO AEROSPACE MEDICINE AND HUMAN PERFORMANCE LA English DT Article DE normobaric; hypobaric; altitude; physical activity; severity; acute mountain sickness ID NORMOBARIC HYPOXIA; HIGH-ALTITUDE; VENTILATION; SATURATION; RESPONSES; HUMANS; SLEEP AB INTRODUCTION: This study simultaneously quantified the effects of normobaric hypoxia (NH), hypobaric hypoxia (HH), exercise duration, and exposure time on acute mountain sickness severity (AMS-C). METHODS: Thirty-six subjects (27.7 +/- 7.8 yr) participated in a partial repeated measures study, completing two of six conditions: normobaric normoxia (NN: 300 m/984 ft equivalent), NH or HH (PO2 = 91 mmHg; 4400 m/14,436 ft equivalent), combined with moderate intensity cycling for 10 or 60 min. Subjects completed the Environmental Symptoms Questionnaire and oxygen saturation (SpO2) was measured before, 1.5 h, 4 h, and 6.5 h into an 8-h exposure, and 1.5 h post-exposure. We fit multiple linear regression models with cluster adjusted standard errors on the exposure times using NH, HH, and long exercise as indicator variables, and AMS-C as the outcome variable. The SpO2 and pre-exposure AMS-C score were used as covariates. RESULTS: NH and HH led to substantial and progressively increasing AMS-C, but NN did not. The effect of HH on AMS-C was significantly different from NH, with AMS-C in HH being 1.6 times higher than in NH. HH led to significantly increasing AMS-C, regardless of the exercise duration, while NH only did so in combination with longer exercise. DISCUSSION: Increases in AMS-C were each independently related to NH, HH, and long duration exercise, with HH affecting AMS-C more severely. This suggests that hypobaria may affect AMS development above the level induced by hypoxia alone. This further suggests that NH and HH may not be interchangeable for studying AMS and that exercise duration may impact physiological responses. C1 [DiPasquale, Dana M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Wilderness Med, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. US Army Res Inst Environm Med, Environm Med & Mil Performance Div, Natick, MA USA. RP DiPasquale, DM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM dipasquale.dana@gmail.com FU DOD CDMRP program [W81-XWH1020199] FX We gratefully acknowledge the support of the DOD CDMRP program and grant W81-XWH1020199. We would also like to thank the following individuals for their assistance with this project: Andrea Gunn, Richard Goldstein, Janet Staab, Chuck Fulco, Beth Beidleman, Ingrid Sills, Vincent Forte, Marie Grunbeck, Sean Andrew, Katylin Guerriere, Myra Jones, Leslie Levine, SPC Bodunrin Shobayo, LTC James Persson, and all the USARIEM chamber operators. NR 22 TC 9 Z9 10 U1 0 U2 7 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 2375-6314 EI 2375-6322 J9 AEROSP MED HUM PERF JI Aerosp. Med.Hum. Perform. PD JUL PY 2015 VL 86 IS 7 BP 614 EP 619 DI 10.3357/AMHP.4266.2015 PG 6 WC Biophysics; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Biophysics; Public, Environmental & Occupational Health; Research & Experimental Medicine GA CM0RG UT WOS:000357385400004 PM 26102141 ER PT J AU Xu, K Kranzler, HR Sherva, R Sartor, CE Almasy, L Koesterer, R Zhao, HY Farrer, LA Gelernter, J AF Xu, Ke Kranzler, Henry R. Sherva, Richard Sartor, Carolyn E. Almasy, Laura Koesterer, Ryan Zhao, Hongyu Farrer, Lindsay A. Gelernter, Joel TI Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Maximum Drinks; Genomewide Association; African American; European American ID WIDE ASSOCIATION; NICOTINE DEPENDENCE; COCAINE DEPENDENCE; CONSUMPTION; RISK; GENES; LOCI; DEHYDROGENASE; METAANALYSIS; METABOLISM AB BackgroundWe conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24-hour period (MaxDrinks), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). MethodsThe samples included our GWAS samples (Yale-UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for similar to 890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. ResultsThe results confirmed significant associations of the well-known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p=5.96x10(-15)) and AAs (rs2066702 Arg370Cys, p=2.50x10(-10)). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale-UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00x10(-8)) and rs2309169 close to ANKRD36 on chromosome 2 (p=5.58x10(-9)). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p=1.99x10(-7)) and rs2309169 remained highly significant (2.12x10(-9)). ConclusionsThe results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs. C1 [Xu, Ke; Sartor, Carolyn E.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. VA CT Healthcare Ctr, West Haven, CT USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet & Neurobiol, West Haven, CT 06516 USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, VISN MIRECC 4, Philadelphia, PA USA. [Sherva, Richard; Koesterer, Ryan; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Almasy, Laura] Texas Biomed Res Inst, Dept Psychiat, San Antonio, TX USA. [Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA CT 116A2,950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health [RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, K12 DA000167, K01 AA017921]; Robert E. Leet and Clara Guthrie Patterson Trust; VA Connecticut and Philadelphia VA MIRECCs; AbbVie; Alkermes; Ethypharm; Lilly; Lundbeck; Pfizer FX This study was supported by National Institutes of Health grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, K12 DA000167, K01 AA017921, and the Robert E. Leet and Clara Guthrie Patterson Trust; and the VA Connecticut and Philadelphia VA MIRECCs.; Dr. Kranzler has been a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He is also a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trial Initiative, which is supported by AbbVie, Alkermes, Ethypharm, Lilly, Lundbeck, and Pfizer. NR 36 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2015 VL 39 IS 7 BP 1137 EP 1147 DI 10.1111/acer.12751 PG 11 WC Substance Abuse SC Substance Abuse GA CM0RW UT WOS:000357387000006 PM 26036284 ER PT J AU Ondersma, SJ Beatty, JR Svikis, DS Strickler, RC Tzilos, GK Chang, G Divine, GW Taylor, AR Sokol, RJ AF Ondersma, Steven J. Beatty, Jessica R. Svikis, Dace S. Strickler, Ronald C. Tzilos, Golfo K. Chang, Grace Divine, George W. Taylor, Andrew R. Sokol, Robert J. TI Computer-Delivered Screening and Brief Intervention for Alcohol Use in Pregnancy: A Pilot Randomized Trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Pregnancy; Fetal Alcohol Spectrum Disorder; Brief Intervention; Technology; Randomized Trial ID PRIMARY-CARE; DRUG-USE; METAANALYSIS; CONSUMPTION; WOMEN; KNOWLEDGE; RESPONSES AB BackgroundAlthough screening and brief intervention (SBI) for unhealthy alcohol use has demonstrated efficacy in some trials, its implementation has been limited. Technology-delivered approaches are a promising alternative, particularly during pregnancy when the importance of alcohol use is amplified. The present trial evaluated the feasibility and acceptability of an interactive, empathic, video-enhanced, and computer-delivered SBI (e-SBI) plus 3 tailored mailings, and estimated intervention effects. MethodsWe recruited 48 pregnant women who screened positive for alcohol risk at an urban prenatal care clinic. Participants were randomly assigned to the e-SBI plus mailings or to a control session on infant nutrition, and were re-evaluated during their postpartum hospitalization. The primary outcome was 90-day period prevalence abstinence as measured by timeline follow-back interview. ResultsParticipants rated the intervention as easy to use and helpful (4.7 to 5.0 on a 5-point scale). Blinded follow-up evaluation at childbirth revealed medium-size intervention effects on 90-day period prevalence abstinence (OR=3.4); similarly, intervention effects on a combined healthy pregnancy outcome variable (live birth, normal birthweight, and no neonatal intensive care unit stay) were also of moderate magnitude in favor of e-SBI participants (OR=3.3). As expected in this intentionally underpowered pilot trial, these effects were nonsignificant (p=0.19 and 0.09, respectively). ConclusionsThis pilot trial demonstrated the acceptability and preliminary efficacy of e-SBI plus tailored mailings for alcohol use in pregnancy. These findings mirror the promising results of other trials using a similar approach and should be confirmed in a fully powered trial. C1 [Ondersma, Steven J.; Beatty, Jessica R.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. [Ondersma, Steven J.; Beatty, Jessica R.] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI 48201 USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Dept Obstet Gynecol, Richmond, VA USA. [Strickler, Ronald C.; Divine, George W.; Taylor, Andrew R.] Henry Ford Hlth Syst, Detroit, MI USA. [Tzilos, Golfo K.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Chang, Grace] VA Boston Healthcare Syst, Boston, MA USA. [Chang, Grace] Harvard Univ, Sch Med, Boston, MA USA. [Sokol, Robert J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Ondersma, SJ (reprint author), Wayne State Univ, Dept Psychiat & Behav Neurosci, 3901 Chrysler Dr, Detroit, MI 48201 USA. EM s.ondersma@wayne.edu FU NIH [AA020056]; State of Michigan FX This research was supported by NIH award AA020056 to Dr. Ondersma, and by Helene Lycaki/Joseph Young, Sr. funds from the State of Michigan to Wayne State University. The authors wish to gratefully acknowledge Ms. Shetoya Rice and Ms. Amy Graham, the invaluable assistance of the women who participated in this study, Ms. Edith Combs and the medical staff from the Henry Ford Health System's New Center One Women's Health clinic, Ms. Linda McMath, and the Henry Ford Health System's delivery units in Detroit and West Bloomfield. Dr. Ondersma is part owner of Interva, Inc., the company that markets the intervention authoring tool used to develop the e-SBI used in this study. Interva had no role in study design, data analysis, or write-up of results. NR 51 TC 2 Z9 2 U1 5 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2015 VL 39 IS 7 BP 1219 EP 1226 DI 10.1111/acer.12747 PG 8 WC Substance Abuse SC Substance Abuse GA CM0RW UT WOS:000357387000015 PM 26010235 ER PT J AU Rochard, L Monica, S Kong, YW Grimaldi, M Liao, EC AF Rochard, Lucie Monica, Stefanie Kong, Yawei Grimaldi, Michael Liao, Eric C. TI Genetic analysis wls and wnt pathway in craniofacial convergence extension morphogenesis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Craniofacial-Genetics-and-Developmental-Biology (SCGDB) CY OCT 18, 2014 CL Sanford Consortium Regenerat Med, LaJolla, CA SP Soc Craniofacial Genet & Dev Biol HO Sanford Consortium Regenerat Med C1 [Rochard, Lucie; Monica, Stefanie; Kong, Yawei; Grimaldi, Michael; Liao, Eric C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 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 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL PY 2015 VL 167 IS 7 BP 1467 EP 1468 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA CL1BB UT WOS:000356676200039 ER PT J AU Mukherjee, K Grimaldi, MJ Talkowski, M Gusella, J Maas, R Morton, CC Liao, EC AF Mukherjee, Kusumika Grimaldi, Michael J. Talkowski, Michael Gusella, James Maas, Richard Morton, Cynthia C. Liao, Eric C. TI Requirement for actin capping protein CAPZB in cleft pathogenesis and lower jaw Extension SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Craniofacial-Genetics-and-Developmental-Biology (SCGDB) CY OCT 18, 2014 CL Sanford Consortium Regenerat Med, LaJolla, CA SP Soc Craniofacial Genet & Dev Biol HO Sanford Consortium Regenerat Med C1 [Mukherjee, Kusumika; Grimaldi, Michael J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Talkowski, Michael; Gusella, James] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. [Mukherjee, Kusumika; Talkowski, Michael; Gusella, James; Maas, Richard; Morton, Cynthia C.; Liao, Eric C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2015 VL 167 IS 7 BP 1468 EP 1468 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA CL1BB UT WOS:000356676200042 ER PT J AU Solanki, MH Chatterjee, PK Xue, XY Gupta, M Rosales, I Yeboah, MM Kohn, N Metz, CN AF Solanki, Malvika H. Chatterjee, Prodyot K. Xue, Xiangying Gupta, Madhu Rosales, Ivy Yeboah, Michael M. Kohn, Nina Metz, Christine N. TI Magnesium protects against cisplatin-induced acute kidney injury without compromising cisplatin-mediated killing of an ovarian tumor xenograft in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE hypomagnesemia; nephrotoxicity; renal protection ID DRINKING-WATER; INDUCED NEPHROTOXICITY; CANCER; CALCIUM; RISK; DEATH; ACCUMULATION; METASTASIS; METABOLISM; MECHANISMS AB Cisplatin, a commonly used chemotherapeutic for ovarian and other cancers, leads to hypomagnesemia in most patients and causes acute kidney injury (AKI) in 25-30% of patients. Previously, we showed that magnesium deficiency worsens cisplatin-induced AKI and magnesium replacement during cisplatin treatment protects against cisplatin-mediated AKI in non-tumor-bearing mice (Solanki MH, Chatterjee PK, Gupta M, Xue X, Plagov A, Metz MH, Mintz R, Singhal PC, Metz CN. Am J Physiol Renal Physiol 307: F369-F384, 2014). This study investigates the role of magnesium in cisplatin-induced AKI using a human ovarian tumor (A2780) xenograft model in mice and the effect of magnesium status on tumor growth and the chemotherapeutic efficacy of cisplatin in vivo. Tumor progression was unaffected by magnesium status in saline-treated mice. Cisplatin treatment reduced tumor growth in all mice, irrespective of magnesium status. In fact, cisplatin-treated magnesium-supplemented mice had reduced tumor growth after 3 wk compared with cisplatin-treated controls. While magnesium status did not interfere with tumor killing by cisplatin, it significantly affected renal function following cisplatin. Cisplatin-induced AKI was enhanced by magnesium deficiency, as evidenced by increased blood urea nitrogen, creatinine, and other markers of renal damage. This was accompanied by reduced renal mRNA expression of the cisplatin efflux transporter Abcc6. These effects were significantly reversed by magnesium replacement. On the contrary, magnesium status did not affect the mRNA expression of cisplatin uptake or efflux transporters by the tumors in vivo. Finally, magnesium deficiency enhanced platinum accumulation in the kidneys and renal epithelial cells, but not in the A2780 tumor cells. These findings demonstrate the renoprotective role of magnesium during cisplatin AKI, without compromising the chemotherapeutic efficacy of cisplatin in an ovarian tumor-bearing mouse model. C1 [Solanki, Malvika H.; Gupta, Madhu; Metz, Christine N.] Elmezzi Grad Sch Mol Med, Manhasset, NY USA. [Solanki, Malvika H.; Chatterjee, Prodyot K.; Xue, Xiangying; Gupta, Madhu; Metz, Christine N.] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Ctr Immunol & Inflammat, Manhasset, NY USA. [Metz, Christine N.] Hofstra North Shore LIJ Sch Med, Manhasset, NY USA. [Rosales, Ivy] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yeboah, Michael M.] Med Coll Wisconsin, Div Nephrol, Milwaukee, WI 53226 USA. [Kohn, Nina] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Biostat Unit, Manhasset, NY USA. RP Metz, CN (reprint author), Feinstein Inst Med Res, Ctr Immunol & Inflammat, 350 Community Dr, Manhasset, NY 11030 USA. EM cmetz@nshs.edu OI Christine, Metz/0000-0002-1013-1691 FU Feinstein Institute for Medical Research; International Society of Nephrology FX This work was supported by The Feinstein Institute for Medical Research. I. Rosales was supported by a Fellowship provided by the International Society of Nephrology. NR 43 TC 4 Z9 4 U1 2 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL 1 PY 2015 VL 309 IS 1 BP F35 EP F47 DI 10.1152/ajprenal.00096.2015 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CM2KB UT WOS:000357507500006 PM 25947343 ER PT J AU Hasegawa, K Ahn, J Brown, MA Press, VG Gabriel, S Herrera, V Bittner, JC Camargo, CA AF Hasegawa, Kohei Ahn, Jason Brown, Mark A. Press, Valerie G. Gabriel, Susan Herrera, Vivian Bittner, Jane C. Camargo, Carlos A., Jr. CA MARC- 37 Invest TI Underuse of guideline-recommended long-term asthma management in children hospitalized to the intensive care unit: a multicenter observational study SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID NEAR-FATAL ASTHMA; OUTCOMES; STATES; RACE/ETHNICITY; EXACERBATIONS; CHILDHOOD; TRENDS; YOUTH AB Background: Despite the significant burden of childhood asthma, little is known about prevention-oriented management before and after hospitalizations for asthma exacerbation. Objective: To investigate the proportion and characteristics of children admitted to the intensive care unit (ICU) for asthma exacerbation and the frequency of guideline-recommended outpatient management before and after the hospitalization. Methods: A 14-center medical record review study of children aged 2 to 17 years hospitalized for asthma exacerbation during 2012-2013. Primary outcome was admission to the ICU; secondary outcomes were 2 preventive factors: inhaled corticosteroid (ICS) use and evaluation by asthma specialists in the pre- and posthospitalization periods. Results: Among 385 children hospitalized for asthma, 130 (34%) were admitted to the ICU. Risk factors for ICU admission were female sex, having public insurance, a marker of chronic asthma severity (ICS use), and no prior evaluation by an asthma specialist. Among children with ICU admission, guideline-recommended outpatient management was suboptimal (eg, 65% were taking ICSs at the time of index hospitalization, and 19% had evidence of a prior evaluation by specialist). At hospital discharge, among children with ICU admission who had not previously used controller medications, 85% were prescribed ICSs. Furthermore, 62% of all children with ICU admission were referred to an asthma specialist during the 3-month post-hospitalization period. Conclusion: In this multicenter study of US children hospitalized with asthma exacerbation, one-third of children were admitted to the ICU. In this high-risk group, we observed suboptimal pre- and post-hospitalization asthma care. These findings underscore the importance of continued efforts to improve prevention-oriented asthma care at all clinical encounters. (C) 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Hasegawa, Kohei; Ahn, Jason; Bittner, Jane C.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Brown, Mark A.] Banner Univ, Med Ctr, Tucson, AZ USA. [Press, Valerie G.] Univ Chicago Med, Chicago, IL USA. [Gabriel, Susan; Herrera, Vivian] Nova Pharmaceut, E Hanover, NJ 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 This study was supported by Novartis Pharmaceuticals Corporation (Dr Camargo, principal investigator). The sponsor had no role in the conduct of the study or the collection, management, or analysis of the data. NR 41 TC 9 Z9 9 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUL PY 2015 VL 115 IS 1 BP 10 EP + DI 10.1016/j.anai.2015.05.004 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CL4YL UT WOS:000356964000004 PM 26123420 ER PT J AU Chasm, RM Pei, YV Pallin, DJ Shapiro, N Snyder, B Sullivan, AF Camargo, CA Hasegawa, K AF Chasm, Rose M. Pei, Y. Veronica Pallin, Daniel J. Shapiro, Nathan Snyder, Brian Sullivan, Ashley F. Camargo, Carlos A., Jr. Hasegawa, Kohei TI Sex differences in risk of hospitalization among emergency department patients with acute asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID ADULTS; CARE C1 [Chasm, Rose M.; Pei, Y. Veronica] Univ Maryland, Sch Med, Dept Emergency Med, Baltimore, MD 21201 USA. [Pallin, Daniel J.] Harvard Univ, Brigham & Womens Hosp, Dept Emergency Med, Sch Med, Boston, MA USA. [Shapiro, Nathan] Beth Israel Deaconess Med Sch, Dept Emergency Med, Boston, MA USA. [Snyder, Brian] Univ Calif San Diego, Dept Emergency Med, San Diego, CA 92103 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA USA. RP Chasm, RM (reprint author), Univ Maryland, Sch Med, Dept Emergency Med, Baltimore, MD 21201 USA. EM rchas001@umaryland.edu RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUL PY 2015 VL 115 IS 1 BP 70 EP + DI 10.1016/j.anai.2015.03.021 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA CL4YL UT WOS:000356964000015 PM 25956241 ER PT J AU Chauhan, SK Lee, HK Lee, HS Park, EY Jeong, E Dana, R AF Chauhan, Sunil K. Lee, Hyung Keun Lee, Hyun Soo Park, Eun Young Jeong, Eunae Dana, Reza TI PTK7(+) Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiopoietin-1; PTK7 protein; mouse; VEGFR2 protein; mouse ID ENDOTHELIAL PROGENITOR CELLS; HEMATOPOIETIC STEM-CELLS; MARROW-DERIVED CELLS; BONE-MARROW; TUMOR ANGIOGENESIS; PRECURSOR CELLS; MURAL CELLS; MIGRATION; GROWTH; MOBILIZATION AB Objective In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood. Approach and Results Here, we characterize the functional role of protein tyrosine kinase 7 (PTK7)-expressing CD11b(+) mononuclear cells in vitro and in vivo using a mouse model of angiogenesis. Although the frequencies of PTK7(+)CD11b(+) cells in the bone marrow remained similar after vascular endothelial growth factor-A-induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, vascular endothelial growth factor-A-induced chemotaxis of PTK7(+) cells was mediated by vascular endothelial growth factor receptor 2. In a coculture with endothelial cells, PTK7(+)CD11b(+) cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1. The enhanced vascular stability was abolished by knockdown of angiopoietin-1 in PTK7(+)CD11b(+) cells and could be restored by angiopoietin-1 treatment. Conclusions We conclude that PTK7 expression in perivascular mononuclear cells induces vascular endothelial growth factor receptor 2 and angiopoietin-1 expression and thus contributes to vascular stabilization in angiogenesis. C1 [Chauhan, Sunil K.; Lee, Hyung Keun; Lee, Hyun Soo; Park, Eun Young; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. [Lee, Hyung Keun; Jeong, Eunae] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul 13572, South Korea. [Lee, Hyun Soo] Catholic Univ Korea, Seoul St Marys Hosp, Dept Ophthalmol, Seoul, South Korea. RP Lee, HK (reprint author), Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, 211 Eonju Ro, Seoul 13572, South Korea. EM shadik@yuhs.ac; reza_dana@meei.harvard.edu FU National Institutes of Health [NIH/NEI RO1-12963]; Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Ministry of Health and Welfare, Republic of Korea [HI13C0055] FX This work was supported by grants from the National Institutes of Health (NIH/NEI RO1-12963), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI13C0055). NR 44 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2015 VL 35 IS 7 BP 1606 EP 1615 DI 10.1161/ATVBAHA.114.305228 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CL3RE UT WOS:000356867300009 PM 25997931 ER PT J AU Ghosh, S Vivar, J Nelson, CP Willenborg, C Segre, AV Maekinen, VP Nikpay, M Erdmann, J Blankenberg, S O'Donnell, C Maerz, W Laaksonen, R Stewart, AFR Epstein, SE Shah, SH Granger, CB Hazen, SL Kathiresan, S Reilly, MP Yang, X Quertermous, T Samani, NJ Schunkert, H Assimes, TL McPherson, R AF Ghosh, Sujoy Vivar, Juan Nelson, Christopher P. Willenborg, Christina Segre, Ayellet V. Maekinen, Ville-Petteri Nikpay, Majid Erdmann, Jeannette Blankenberg, Stefan O'Donnell, Christopher Maerz, Winfried Laaksonen, Reijo Stewart, Alexandre F. R. Epstein, Stephen E. Shah, Svati H. Granger, Christopher B. Hazen, Stanley L. Kathiresan, Sekar Reilly, Muredach P. Yang, Xia Quertermous, Thomas Samani, Nilesh J. Schunkert, Heribert Assimes, Themistocles L. McPherson, Ruth CA CARDIoGRAM Consortium TI Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary artery disease; pathway analysis ID SET ENRICHMENT ANALYSIS; GUIDANCE CUE NETRIN-1; EXPRESSION; IDENTIFICATION; PATHWAY; LOCI; ATHEROSCLEROSIS; SUSCEPTIBILITY; MACROPHAGES; INFERENCE AB Objective Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15502 cases/55730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. C1 [Ghosh, Sujoy] Duke NUS Grad Med Sch, Program Cardiovasc & Metab Disorders, Singapore, Singapore. [Ghosh, Sujoy] Duke NUS Grad Med Sch, Ctr Computat Biol, Singapore, Singapore. [Ghosh, Sujoy; Vivar, Juan] N Carolina Cent Univ, Biomed Biotechnol Res Inst, Dept Cardiovasc & Metab Res, Durham, NC USA. [Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Willenborg, Christina; Erdmann, Jeannette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Willenborg, Christina; Erdmann, Jeannette] DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany. [Segre, Ayellet V.; Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Maekinen, Ville-Petteri; Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA. [Nikpay, Majid; McPherson, Ruth] Univ Ottawa, Inst Heart, Atherogen Lab, Ottawa, ON K1Y 4W7, Canada. [Stewart, Alexandre F. R.; McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Res, Ottawa, ON K1Y 4W7, Canada. [McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1Y 4W7, Canada. [Blankenberg, Stefan] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Framingham, MA USA. [O'Donnell, Christopher] NHLBI, Framingham Heart Study, Boston, MA USA. [Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, D-69115 Heidelberg, Germany. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [Epstein, Stephen E.] Duke Univ, Washington Hosp Ctr, Med Ctr, Cardiovasc Res Inst, Durham, NC USA. [Shah, Svati H.; Granger, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Hazen, Stanley L.] Cleveland Clin, Cleveland, OH USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp,Ctr Human Genet Res, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. [Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Samani, Nilesh J.] Glenfield Hosp, Natl Inst Hlth Res NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Nelson, Christopher P.; Schunkert, Heribert] Partner Site Munich Heart Alliance, DZHK German Res Ctr Cardiovasc Res, Munich, Germany. RP McPherson, R (reprint author), Univ Ottawa, Inst Heart, Div Cardiol, 40 Ruskin St H4203, Ottawa, ON K1Y 4W7, Canada. EM sujoy.ghosh@duke-nus.edu.sg; rmcpherson@ottawaheart.ca RI Erdmann, Jeanette/P-7513-2014; OI Makinen, Ville-Petteri/0000-0002-7262-2656; Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231; GHOSH, SUJOY/0000-0002-7601-165X; Assimes, Themistocles/0000-0003-2349-0009 FU American Heart Association [AHA10SDG4230068, 13POST17240095, 13SDG17290032]; National Institutes of Health [1R21DK088319, 2P20MD000175-11, P01HL098055, P01HL076491, P20HL113452, R01-HL095987, K23DK088942]; Wellcome Trust [076113, 085475]; British Heart Foundation; European Union [201668]; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2); German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-plus); EU [LSHM-CT-2006-037593, 201413]; BMBF/ANR [01KU0908A]; Canadian Institutes of Health Research [MOP-2380941, MOP82810, MOP77682]; Canada Foundation for Innovation [11966]; Heart and Stroke Foundation of Canada [NA6001, NA6650] FX This work was supported by grants from the American Heart Association (AHA10SDG4230068 to S. Ghosh; 13POST17240095 to V.-P. Makinen; 13SDG17290032 to X. Yang); National Institutes of Health (1R21DK088319, 2P20MD000175-11 to S. Ghosh); (P01HL098055, P01HL076491, P20HL113452 to S.L. Hazen); (R01-HL095987 to S.H. Shah); (K23DK088942 to T.L. Assimes); Wellcome Trust (No. 076113 and No. 085475) British Heart Foundation (to N.J. Samani); European Union (No. 201668 to R. Laaksonen). Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus), the FP6 and FP7 EU funded integrated projects Cardiogenics (No. LSHM-CT-2006-037593) and ENGAGE (No. 201413), and the binational BMBF/ANR funded project CARDomics (No. 01KU0908A); Canadian Institutes of Health Research (No. MOP-2380941 to R. McPherson), (No. MOP82810, MOP77682 to A.F.R. Stewart and R. McPherson); Canada Foundation for Innovation (No. 11966 to A.F.R. Stewart and R. McPherson; Heart and Stroke Foundation of Canada (No. NA6001, No. NA6650 to R. McPherson). NR 46 TC 15 Z9 15 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2015 VL 35 IS 7 BP 1712 EP 1722 DI 10.1161/ATVBAHA.115.305513 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CL3RE UT WOS:000356867300021 PM 25977570 ER PT J AU Deng, B Brooks, DH Boas, DA Lundqvist, M Fang, QQ AF Deng, Bin Brooks, Dana H. Boas, David A. Lundqvist, Mats Fang, Qianqian TI Characterization of structural-prior guided optical tomography using realistic breast models derived from dual-energy x-ray mammography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID NEOADJUVANT CHEMOTHERAPY; IMAGE-RECONSTRUCTION; MRI; INFORMATION; TISSUE; QUANTIFICATION; REGULARIZATION; SPECTROSCOPY; RESOLUTION; ALGORITHM AB Multi-spectral near-infrared diffuse optical tomography (DOT) is capable of providing functional tissue assessment that can complement structural mammographic images for more comprehensive breast cancer diagnosis. To take full advantage of the readily available sub-millimeter resolution structural information in a multi-modal imaging setting, an efficient x-ray/optical joint image reconstruction model has been proposed previously to utilize anatomical information from a mammogram as a structural prior. In this work, we develop a complex digital breast phantom (available at http://openjd.sf.net/digibreast) based on direct measurements of fibroglandular tissue volume fractions using dual-energy mammographic imaging of a human breast. We also extend our prior-guided reconstruction algorithm to facilitate the recovery of breast tumors, and perform a series of simulation-based studies to systematically evaluate the impact of lesion sizes and contrasts, tissue background, mesh resolution, inaccurate priors, and regularization parameters, on the recovery of breast tumors using multi-modal DOT/x-ray measurements. Our studies reveal that the optical property estimation error can be reduced by half by utilizing structural priors; the minimum detectable tumor size can also be reduced by half when prior knowledge regarding the tumor location is provided. Moreover, our algorithm is shown to be robust to false priors on tumor location. (C) 2015 Optical Society of America C1 [Deng, Bin; Boas, David A.; Fang, Qianqian] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Brooks, Dana H.] Northeastern Univ, BSPIRAL Grp, Boston, MA 02115 USA. [Brooks, Dana H.] Northeastern Univ, ECE Dept, Boston, MA 02115 USA. [Lundqvist, Mats] Philips Healthcare, S-17141 Solna, Sweden. RP Deng, B (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU Massachusetts Life Sciences Center [2011D000334]; Massachusetts General Hospital Executive Committee on Research Interim Support Funding; NIH [R01-CA97305, R01-CA142575, R01-GM114365, 1S10RR023043] FX The authors acknowledge the Cooperative Research Matching Grand funding support, grand #2011D000334, from the Massachusetts Life Sciences Center, Massachusetts General Hospital Executive Committee on Research Interim Support Funding, and the NIH funding support under grants R01-CA97305, R01-CA142575, R01-GM114365 and 1S10RR023043. NR 40 TC 4 Z9 5 U1 1 U2 8 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 JUL 1 PY 2015 VL 6 IS 7 BP 2366 EP 2379 DI 10.1364/BOE.6.002366 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CM1IT UT WOS:000357435200007 PM 26203367 ER PT J AU Gala, MK Austin, T Ogino, S Chan, AT AF Gala, Manish K. Austin, Thomas Ogino, Shuji Chan, Andrew T. TI TFF2-CXCR4Axis Is Associated with BRAFV600E Colon Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID SESSILE SERRATED ADENOMAS; CXCR4 EXPRESSION; TREFOIL FACTOR-1; ACTIVATION; CELLS; SUSCEPTIBILITY; PROLIFERATION; PROGRESSION; SECRETION; CARCINOMA AB Oncogene-induced senescence (OIS), a tumor-suppressive mechanism that is induced by the replicative and metabolic stress of oncogene activation, is a key barrier in the development of BRAF V600E colon cancer. Inhibition of this mechanism has been observed through epigenetic changes observed in sporadic serrated polyps, as well as through the germline mutations associated with those who develop serrated polyposis. We hypothesize that upregulated autocrine factors exist that are specific to the serrated pathway and also promote bypass of oncogene-induced senescence. To identify such autocrine factors, we integrate analyses of microarrays of sessile serrated polyps and two large colon cancer cohorts, the Cancer Genome Atlas (TCGA; n = 153), and French national Cartes d'Identite des Tumeurs (CIT) program (n = 462), with enhanced gene annotation through natural language processing techniques of the existing medical corpus. We reproducibly associate higher expression of the ligand-receptor axis of TFF2 and CXCR4 with BRAF V600E-mutant colon cancer (P = 3.0 x 10(-3) and 0.077, respectively for TCGA; P = 3.0 x 10(-8) and 5.1 x 10(-7) for CIT). Given well-described oncogenic roles of TFF2 and CXCR4 in colon cancer, and availability of CXCR4 inhibitors for other clinical indications, this ligand-receptor axis may represent an actionable target for prevention and treatment of this molecular subtype of colorectal cancer. (C) 2015 AACR. C1 [Gala, Manish K.; Austin, Thomas; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Gala, Manish K.; Austin, Thomas; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Gala, Manish K.; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM achan@partners.org FU American College of Gastroenterology (Junior Faculty Career Development Award); NIH [K23 DK103119, K24 DK098311, R01 CA137178, R01 CA176272] FX M.K. Gala was supported by the American College of Gastroenterology (Junior Faculty Career Development Award) and the NIH (K23 DK103119). A.T. Chan was supported by the NIH (K24 DK098311, R01 CA137178, R01 CA176272). NR 30 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUL PY 2015 VL 8 IS 7 BP 614 EP 619 DI 10.1158/1940-6207.CAPR-14-0444 PG 6 WC Oncology SC Oncology GA CM1FY UT WOS:000357427800007 PM 25899003 ER PT J AU Song, MY Hu, FB Spiegelman, D Chan, AT Wu, KN Ogino, S Fuchs, CS Willett, WC Giovannucci, EL AF Song, Mingyang Hu, Frank B. Spiegelman, Donna Chan, Andrew T. Wu, Kana Ogino, Shuji Fuchs, Charles S. Willett, Walter C. Giovannucci, Edward L. TI Adulthood Weight Change and Risk of Colorectal Cancer in the Nurses' Health Study and Health Professionals Follow-up Study SO CANCER PREVENTION RESEARCH LA English DT Article ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; COLON-CANCER; LONGITUDINAL CHANGES; BARIATRIC SURGERY; PHYSICAL-ACTIVITY; CORONARY-DISEASE; RECTAL-CANCER; SEX-HORMONES; OBESITY AB We investigated the association between adulthood weight change and colorectal cancer risk in a prospective study with 24 to 34 years of follow-up among 90,988 women and 46,679 men. The primary exposures included weight change from early adulthood (age = 18 years for women, 21 years for men) to baseline enrollment (median age = 43 years for women, 52 years for men), and from baseline to present. In the secondary analyses, we also assessed 4-year weight change during follow-up, and during premenopausal (from age 18 years to menopause) and postmenopausal (from menopause to present) periods in women. Compared to men maintaining their weight from age 21 to baseline, those who gained 20 kg or more were at a higher risk of colorectal cancer (relative risk [RR], 1.64; 95% confidence interval [CI], 1.15-2.35, P-trend < 0.001), whereas those who lost 8 kg or more had a lower risk (RR, 0.61; 95% CI, 0.30-1.22, P-trend = 0.003). Similar but weaker associations were found in women and the corresponding RRs were 1.38 (95% CI, 1.13-1.69, P-trend < 0.001) and 0.80 (95% CI, 0.58-1.09, P-trend = 0.21). Weight change from baseline to present was not associated with colorectal cancer risk. Four-year weight change during follow-up was positively associated with colorectal cancer risk in men (P-trend = 0.03) but not in women (P-trend = 0.42). In addition, in women, weight change before, but not after, menopause was associated with colorectal cancer risk. Our findings provide further scientific rationale for recommendations to maintain a healthy body weight during adulthood. A potential differential association according to sex and timing of weight change warrants further investigation. (C) 2015 AACR. C1 [Song, Mingyang; Hu, Frank B.; Spiegelman, Donna; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Hu, Frank B.; Spiegelman, Donna; Ogino, Shuji; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Chan, Andrew T.; Ogino, Shuji; Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU National Institutes of Health [UM1 CA186107, P01 CA87969, UM1 CA167552, 1U54 CA155626, K24 DK098311] FX This work was supported by the National Institutes of Health (UM1 CA186107, P01 CA87969, UM1 CA167552, 1U54 CA155626, and K24 DK098311). NR 54 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUL PY 2015 VL 8 IS 7 BP 620 EP 627 DI 10.1158/1940-6207.CAPR-15-0061 PG 8 WC Oncology SC Oncology GA CM1FY UT WOS:000357427800008 PM 25930050 ER PT J AU Sullivan, RJ Flaherty, KT AF Sullivan, Ryan J. Flaherty, Keith T. TI Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RECOMBINANT INTERLEUKIN-2 THERAPY; METASTATIC MELANOMA; IMPROVED SURVIVAL; MEK INHIBITION; T-CELLS; BRAF; CANCER; SAFETY; IPILIMUMAB; BLOCKADE AB From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anticancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune-targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25% to 40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD- 1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of patients with melanoma. First, the optimal sequencing of therapy (first-line immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is a strong rationale to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies. (C) 2015 AACR. C1 [Sullivan, Ryan J.; Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org NR 32 TC 6 Z9 6 U1 4 U2 9 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 JUL 1 PY 2015 VL 21 IS 13 BP 2892 EP 2897 DI 10.1158/1078-0432.CCR-14-3061 PG 6 WC Oncology SC Oncology GA CL9ZF UT WOS:000357337200004 PM 25931451 ER PT J AU Giraldo, NA Becht, E Pages, F Skliris, G Verkarre, V Vano, Y Mejean, A Saint-Aubert, N Lacroix, L Natario, I Lupo, A Alifano, M Damotte, D Cazes, A Triebel, F Freeman, GJ Dieu-Nosjean, MC Oudard, S Fridman, WH Sautes-Fridman, C AF Giraldo, Nicolas A. Becht, Etienne Pages, Franck Skliris, Georgios Verkarre, Virginie Vano, Yann Mejean, Arnaud Saint-Aubert, Nicolas Lacroix, Laetitia Natario, Ivo Lupo, Audrey Alifano, Marco Damotte, Diane Cazes, Aurelie Triebel, Frederic Freeman, Gordon J. Dieu-Nosjean, Marie-Caroline Oudard, Stephane Fridman, Wolf H. Sautes-Fridman, Catherine TI Orchestration and Prognostic Significance of Immune Checkpoints in the Microenvironment of Primary and Metastatic Renal Cell Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TERTIARY LYMPHOID STRUCTURES; CD8(+) T-LYMPHOCYTES; DENDRITIC CELLS; HUMAN TUMORS; CARCINOMA PATIENTS; POOR-PROGNOSIS; GROWTH-FACTOR; LUNG-CANCER; EXPRESSION; B7-H1 AB Purpose: Clear cell renal cell carcinoma (ccRCC) has shown durable responses to checkpoint blockade therapies. However, important gaps persist in the understanding of its immune micro-environment. This study aims to investigate the expression and prognostic significance of immune checkpoints in primary and metastatic ccRCC, in relation with mature dendritic cells (DC) and T-cell densities. Experimental Design: We investigated the infiltration and the localization of CD8(+) T cells and mature DC, and the expression of immune checkpoints (PD-1, LAG-3, PD-L1, and PD-L2) in relation with prognosis, in 135 primary ccRCC tumors and 51 ccRCC lung metastases. RNA expression data for 496 primary ccRCC samples were used as confirmatory cohort. Results: We identify two groups of tumors with extensive CD8(+) T-cell infiltrates. One group, characterized by high expression of immune checkpoints in the absence of fully functional mature DC, is associated with increased risk of disease progression. The second group, characterized by low expression of immune checkpoints and localization of mature DC in peritumoral immune aggregates (tertiary lymphoid structures), is associated with good prognosis. Conclusions: The expression of the immune checkpoints and the localization of DC in the tumor microenvironment modulate the clinical impact of CD8(+) T cells in ccRCC. (C) 2015 AACR. C1 [Giraldo, Nicolas A.; Becht, Etienne; Lacroix, Laetitia; Natario, Ivo; Lupo, Audrey; Damotte, Diane; Dieu-Nosjean, Marie-Caroline; Fridman, Wolf H.; Sautes-Fridman, Catherine] INSERM, Cordeliers Res Ctr, UMRS 1138, Team Canc Immune Control & Escape 13, Paris, France. [Giraldo, Nicolas A.; Becht, Etienne; Pages, Franck; Lacroix, Laetitia; Natario, Ivo; Lupo, Audrey; Damotte, Diane; Dieu-Nosjean, Marie-Caroline; Oudard, Stephane; Fridman, Wolf H.; Sautes-Fridman, Catherine] Univ Paris 05, Sorbonne Paris Cite, UMRS 1138, Ctr Rech Cordeliers, Paris, France. [Giraldo, Nicolas A.; Becht, Etienne; Pages, Franck; Lacroix, Laetitia; Natario, Ivo; Lupo, Audrey; Damotte, Diane; Dieu-Nosjean, Marie-Caroline; Fridman, Wolf H.; Sautes-Fridman, Catherine] Univ Paris 06, Sorbonne Univ, UMRS 1138, Ctr Rech Cordeliers, Paris, France. [Pages, Franck] INSERM, UMRS 1138, Cordeliers Res Ctr, Team Integrat Canc Immunol 15, Paris, France. [Pages, Franck] Hop Europeen Georges Pompidou, Dept Immunol, Paris, France. [Skliris, Georgios] CoStim Pharmaceut, Boston, MA USA. [Verkarre, Virginie] Hop Necker Enfants Malad, Dept Pathol, Paris, France. [Vano, Yann; Oudard, Stephane] Hop Europeen Georges Pompidou, Dept Med Oncol, Paris, France. [Mejean, Arnaud; Saint-Aubert, Nicolas] Hop Europeen Georges Pompidou, Dept Urol, Paris, France. [Lupo, Audrey; Damotte, Diane] Hop Cochin, Dept Pathol, F-75674 Paris, France. [Alifano, Marco] Hop Cochin, Dept Thorac Surg, F-75674 Paris, France. [Cazes, Aurelie] Hop Europeen Georges Pompidou, Dept Pathol, Paris, France. [Triebel, Frederic] Immutep SA, Orsay, France. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sautes-Fridman, C (reprint author), INSERM, Ctr Rech Cordeliers, UMRS 1138, 15 Rue Ecole Med, F-75006 Paris, France. EM catherine.fridman@crc.jussieu.fr FU Institut National de la Sante et de la Recherche Medicale; University Paris-Descartes; University Pierre et Marie Curie; Institut National du Cancer [2011-1-PLBIO-06-INSERM 6-1, PLBIO09-088-IDF-KROEMER]; CARPEM (CAncer Research for PErsonalized Medicine); Labex Immuno-Oncology [LAXE62_9UMS872 FRIDMAN]; Universidad de los Andes School of Medicine; Colciencias; NIH [P50CA101942] FX This work was supported by the "Institut National de la Sante et de la Recherche Medicale," the University Paris-Descartes, the University Pierre et Marie Curie, the Institut National du Cancer (2011-1-PLBIO-06-INSERM 6-1 and PLBIO09-088-IDF-KROEMER), CARPEM (CAncer Research for PErsonalized Medicine), Labex Immuno-Oncology (LAXE62_9UMS872 FRIDMAN), Universidad de los Andes School of Medicine (to N.A. Giraldo), Colciencias (to N.A. Giraldo), and NIH (P50CA101942; to G.J. Freeman). NR 52 TC 30 Z9 30 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2015 VL 21 IS 13 BP 3031 EP 3040 DI 10.1158/1078-0432.CCR-14-2926 PG 10 WC Oncology SC Oncology GA CL9ZF UT WOS:000357337200020 PM 25688160 ER PT J AU Bui, E Mauro, C Robinaugh, DJ Skritskaya, NA Wang, YJ Gribbin, C Ghesquiere, A Horenstein, A Duan, NH Reynolds, C Zisook, S Simon, NM Shear, MK AF Bui, Eric Mauro, Christine Robinaugh, Donald J. Skritskaya, Natalia A. Wang, Yuanjia Gribbin, Colleen Ghesquiere, Angela Horenstein, Arielle Duan, Naihua Reynolds, Charles Zisook, Sidney Simon, Naomi M. Shear, M. Katherine TI THE STRUCTURED CLINICAL INTERVIEW FOR COMPLICATED GRIEF: RELIABILITY, VALIDITY, AND EXPLORATORY FACTOR ANALYSIS SO DEPRESSION AND ANXIETY LA English DT Article DE grief; bereavement; complicated grief; assessment; diagnosis; depression; anxiety; anxiety disorders; PTSD; posttraumatic stress disorder ID SCALE; IMPAIRMENT; DEPRESSION; PREVALENCE; INVENTORY; SYMPTOMS; DISORDER AB BackgroundComplicated grief (CG) has been recently included in the DSM-5, under the term persistent complex bereavement disorder, as a condition requiring further study. To our knowledge, no psychometric data on any structured clinical interview for CG (SCI-CG) is available to date. In this manuscript, we introduce the SCI-CG, a 31-item SCID-like clinician-administered instrument to assess the presence of CG symptoms. MethodsParticipants were 281 treatment-seeking adults with CG (77.9% [n = 219] women, mean age = 52.4, standard deviation [SD] = 17.8) who were assessed with the SCI-CG and measures of depression, posttraumatic stress, anxiety, functional impairment. ResultsThe SCI-CG exhibited satisfactory internal consistency ( = .78), good test-retest reliability (interclass correlation [ICC] 0.68, 95% CI [0.60-0.75]), and excellent interrater reliability (ICC = 0.95, 95% CI [0.89-0.98]). Exploratory factor analyses revealed that a five-factor structure, explaining 50.3% of the total variance, was the best fit for the data. ConclusionsThe clinician-rated SCI-CG demonstrates good internal consistency, reliability, and convergent validity in treatment-seeking individuals with CG and therefore can be a useful tool to assess CG. Although diagnostic criteria for CG have yet to be adequately validated, the SCI-CG may facilitate this process. The SCI-CG can now be used as a validated instrument in research and clinical practice. (C) 2015 Wiley Periodicals, Inc. C1 [Bui, Eric; Robinaugh, Donald J.; Horenstein, Arielle; Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. [Bui, Eric; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Mauro, Christine; Skritskaya, Natalia A.; Wang, Yuanjia; Gribbin, Colleen; Ghesquiere, Angela; Duan, Naihua; Shear, M. Katherine] Columbia Sch Social Work, Ctr Complicated Grief, New York, NY USA. [Reynolds, Charles] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Zisook, Sidney] VA San Diego Healthcare Syst, San Diego, CA USA. RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor,Suite 650, Boston, MA 02114 USA. EM tebui@mgh.harvard.edu RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU NIH [P30 MH90333, R01 MH085288, R01 MH060783, R01 MH085308, R01 MH085297]; American Foundation for Suicide Prevention; Highland Street Foundation FX Contract grant sponsor: NIH; Contract grant numbers: P30 MH90333, R01 MH085288, R01 MH060783, R01 MH085308, and R01 MH085297; Contract grant sponsor: American Foundation for Suicide Prevention; Contract grant sponsor: Highland Street Foundation. NR 30 TC 7 Z9 7 U1 6 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2015 VL 32 IS 7 BP 485 EP 492 DI 10.1002/da.22385 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CL9WZ UT WOS:000357330700003 PM 26061724 ER PT J AU Clark, CT Sit, DK Driscoll, K Eng, HF Confer, AL Luther, JF Wisniewski, SR Wisner, KL AF Clark, Crystal T. Sit, Dorothy K. Y. Driscoll, Kara Eng, Heather F. Confer, Andrea L. Luther, James F. Wisniewski, Stephen R. Wisner, Katherine L. TI DOES SCREENING WITH THE MDQ AND EPDS IMPROVE IDENTIFICATION OF BIPOLAR DISORDER IN AN OBSTETRICAL SAMPLE? SO DEPRESSION AND ANXIETY LA English DT Article DE postpartum; depression; bipolar; screening; manic-depressive; postnatal ID POSTNATAL DEPRESSION SCALE; POSTPARTUM DEPRESSION; PERINATAL DEPRESSION; QUESTIONNAIRE MDQ; SPECTRUM DISORDER; MOOD; VALIDATION; WOMEN; PREVALENCE; SYMPTOMS AB BackgroundWomen with bipolar disorder (BD) are at high risk for postpartum affective episodes and psychosis. Although validated screening tools are available for postpartum unipolar depression, few screening tools for hypomania/mania exist. Screening tools for BD in the postpartum period are essential for improving detection and planning appropriate treatment. We evaluated whether adding the Mood Disorders Questionnaire (MDQ) to the Edinburgh Postnatal Depression Scale (EPDS) increased the identification of BD in the early postpartum period. MethodsWomen (N = 1,279) who delivered a live infant and screened positive on the EPDS and/or MDQ at 4-6 weeks postbirth were invited to undergo an in-home Structured Clinical Interview for DSM-IV (SCID). ResultsPositive EPDS and/or MDQ screens occurred in 12% of the sample (n = 155). In home SCID diagnostic interviews were completed in 93 (60%) of the mothers with positive screens. BD was the primary diagnosis in 37% (n = 34). Women with BD screened positive on the EPDS and/or MDQ as follows: EPDS+/MDQ+ (n = 14), EPDS+/MDQ- (n = 17), and EPDS-/MDQ+ (n = 3). The MDQ identified 50% (17/34) of the women with BD and 6 additional cases of BD when the MDQ question regarding how impaired the mother perceived herself was excluded from the screen criterion. ConclusionAddition of the MDQ to the EPDS improved the distinction of unipolar depression from bipolar depression at the level of screening in 50% of women with traditional MDQ scoring and by nearly 70% when the MDQ was scored without the impairment criterion. (C) 2015 Wiley Periodicals, Inc. C1 [Clark, Crystal T.; Driscoll, Kara; Wisner, Katherine L.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat, Asher Ctr Study & Treatment Depress Disorders, Chicago, IL 60611 USA. [Sit, Dorothy K. Y.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Eng, Heather F.; Luther, James F.; Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Epidemiol Data Ctr, Pittsburgh, PA USA. [Confer, Andrea L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Clark, CT (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat, Asher Ctr Study & Treatment Depress Disorders, 676 St Clair,Suite 1000, Chicago, IL 60611 USA. EM crystal.clark@northwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU Eunice Kennedy Shriver National Institute of Child Health & Human Development [K12 HD055884]; [R01MH071825] FX This work was supported by R01MH071825, Identification and Therapy of Postpartum Depression, Katherine L. Wisner, P.I. Drs. Katherine L. Wisner and Steve Wisniewski, James Luther and Heather Eng had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Crystal Clark is supported in part by Grant Number K12 HD055884 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The authors would like to acknowledge Emily Pinheiro and Stephanie Schuette who arranged the references for this manuscript. NR 48 TC 7 Z9 7 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2015 VL 32 IS 7 BP 518 EP 526 DI 10.1002/da.22373 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CL9WZ UT WOS:000357330700007 PM 26059839 ER PT J AU Tomas, E Stanojevic, V McManus, K Khatri, A Everill, P Bachovchin, WW Habener, JF AF Tomas, Eva Stanojevic, Violeta McManus, Karen Khatri, Ashok Everill, Paul Bachovchin, William W. Habener, Joel F. TI GLP-1(32-36)amide Pentapeptide Increases Basal Energy Expenditure and Inhibits Weight Gain in Obese Mice SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; GLP-1 9-36 AMIDE; NEUTRAL ENDOPEPTIDASE-24.11; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; METABOLIC SYNDROME; HEPATIC STEATOSIS; CLEAVAGE PRODUCT; BETA-CELLS; GLUCOLIPOTOXICITY AB The prevalence of obesity-related diabetes is increasing worldwide. Here we report the identification of a pentapeptide, GLP-1(32-36)amide (LVKGRamide), derived from the glucoincretin hormone GLP-1, that increases basal energy expenditure and curtails the development of obesity, insulin resistance, diabetes, and hepatic steatosis in diet-induced obese mice. The pentapeptide inhibited weight gain, reduced fat mass without change in energy intake, and increased basal energy expenditure independent of physical activity. Analyses of tissues from peptide-treated mice reveal increased expression of UCP-1 and UCP-3 in brown adipose tissue and increased UCP-3 and inhibition of acetyl-CoA carboxylase in skeletal muscle, findings consistent with increased fatty acid oxidation and thermogenesis. In palmitate-treated C2C12 skeletal myotubes, GLP-1(32-36)amide activated AMPK and inhibited acetyl-CoA carboxylase, suggesting activation of fat metabolism in response to energy depletion. By mass spectroscopy, the pentapeptide is rapidly formed from GLP-1(9-36)amide, the major form of GLP-1 in the circulation of mice. These findings suggest that the reported insulin-like actions of GLP-1 receptor agonists that occur independently of the GLP-1 receptor might be mediated by the pentapeptide, and the previously reported nonapeptide (FIAWLVKGRamide). We propose that by increasing basal energy expenditure, GLP-1(32-36)amide might be a useful treatment for human obesity and associated metabolic disorders. C1 [Tomas, Eva; Stanojevic, Violeta; McManus, Karen; Khatri, Ashok; Habener, Joel F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02115 USA. [Tomas, Eva; Stanojevic, Violeta; McManus, Karen; Khatri, Ashok; Habener, Joel F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Everill, Paul; Bachovchin, William W.] Tufts Univ, Dept Biochem, Boston, MA 02111 USA. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02115 USA. EM jhabener@partners.org FU National Institutes of Health P30 Diabetes Endocrinology Research Center grant [DK-057521] FX This study was supported in part by a National Institutes of Health P30 Diabetes Endocrinology Research Center grant (DK-057521). NR 45 TC 6 Z9 6 U1 6 U2 13 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 JUL PY 2015 VL 64 IS 7 BP 2409 EP 2419 DI 10.2337/db14-1708 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4PA UT WOS:000356934000024 PM 25858562 ER PT J AU Begg, DP May, AA Mul, JD Liu, M D'Alessio, DA Seeley, RJ Woods, SC AF Begg, Denovan P. May, Aaron A. Mul, Joram D. Liu, Min D'Alessio, David A. Seeley, Randy J. Woods, Stephen C. TI Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin SO DIABETES LA English DT Article ID REDUCES FOOD-INTAKE; WITHIN-SUBJECT VARIABILITY; CENTRAL-NERVOUS-SYSTEM; WEIGHT-GAIN; INTRANASAL INSULIN; BRAIN-BARRIER; APOLIPOPROTEIN-E; GLYCEMIC CONTROL; BODY-WEIGHT; IN-VIVO AB Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. C1 [Begg, Denovan P.; May, Aaron A.; Mul, Joram D.; Liu, Min; D'Alessio, David A.; Seeley, Randy J.; Woods, Stephen C.] Univ Cincinnati, Metab Dis Inst, Cincinnati, OH 45221 USA. [Begg, Denovan P.] UNSW Australia, Sch Psychol, Sydney, NSW, Australia. [Mul, Joram D.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [D'Alessio, David A.] Duke Univ, Dept Med, Durham, NC USA. [Seeley, Randy J.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Woods, SC (reprint author), Univ Cincinnati, Metab Dis Inst, Cincinnati, OH 45221 USA. EM steve.woods@uc.edu RI Begg, Denovan/A-7969-2012; May, Aaron /A-3011-2017 OI Begg, Denovan/0000-0002-4551-2697; May, Aaron /0000-0002-9017-0657 FU National Institutes of Health [DK017844, DK095440, DK092779, DK57900, DK54080]; National Health and Medical Research Council of Australia [1013264] FX This work was supported by National Institutes of Health grants DK017844 and DK095440 to S.C.W., DK092779 to M.L. and S.C.W., DK57900 to D.A.D., and DK54080 to R.J.S. D.P.B. was supported by National Health and Medical Research Council of Australia Early Career Fellowship 1013264. NR 48 TC 6 Z9 7 U1 3 U2 7 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 JUL PY 2015 VL 64 IS 7 BP 2457 EP 2466 DI 10.2337/db14-1364 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4PA UT WOS:000356934000028 PM 25667307 ER PT J AU Prudente, S Shah, H Bailetti, D Pezzolesi, M Buranasupkajorn, P Mercuri, L Mendonca, C De Cosmo, S Niewczas, M Trischitta, V Doria, A AF Prudente, Sabrina Shah, Hetal Bailetti, Diego Pezzolesi, Marcus Buranasupkajorn, Patinut Mercuri, Luana Mendonca, Christine De Cosmo, Salvatore Niewczas, Monika Trischitta, Vincenzo Doria, Alessandro TI Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes SO DIABETES LA English DT Article ID CORONARY-HEART-DISEASE; GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; RISK; PATHOPHYSIOLOGY; METAANALYSIS; MANAGEMENT; THICKNESS AB Single nucleotide polymorphism (SNP) rs10911021 at the glutamate-ammonia ligase (GLUL) locus has been associated with an increased risk of coronary heart disease in individuals with type 2 diabetes. The effect of this SNP on mortality was investigated among 1,242 white subjects with type 2 diabetes from the Joslin Kidney Study (JKS) (n = 416) and the Gargano Mortality Study (GMS) (n = 826). During a mean follow-up of 12.8 +/- 5.8 and 7.5 +/- 2.2 years, respectively, a total of 215 and 164 deaths were observed in the two studies. In both cohorts, the all-cause mortality rate significantly increased with the number of rs10911021 risk alleles, with allelic hazard ratios (HRs) of 1.32 (95% CI 1.07-1.64, P = 0.01), 1.30 (1.10-1.69, P = 0.04), and 1.32 (1.12-1.55, P = 0.0011), respectively, in the JKS, the GMS, and the two studies combined. These associations were not affected by adjustment for possible confounders. In the JKS, for which data on causes of death were available, the HR for cardiovascular mortality was 1.51 (1.12-2.04, P = 0.0077) as opposed to 1.15 (0.84-1.55, P = 0.39) for mortality from noncardiovascular causes. These findings point to SNP rs10911021 as an independent modulator of mortality in patients with type 2 diabetes and, together with the previous observation, suggest that this results from an effect of this variant on cardiovascular risk. C1 [Prudente, Sabrina; Bailetti, Diego; Mercuri, Luana; Trischitta, Vincenzo] Ist Ricovero & Cura Carattere Sci, Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Shah, Hetal; Pezzolesi, Marcus; Buranasupkajorn, Patinut; Mendonca, Christine; Niewczas, Monika; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Shah, Hetal; Pezzolesi, Marcus; Buranasupkajorn, Patinut; Niewczas, Monika; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bailetti, Diego; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [De Cosmo, Salvatore] Ist Ricovero & Cura Carattere Sci, Casa Sollievo Sofferenza, Dept Med, San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Ist Ricovero & Cura Carattere Sci, Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Prudente, Sabrina/H-2886-2016; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016 OI Prudente, Sabrina/0000-0001-9220-8981; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X FU National Institutes of Health [R01-HL-073168, HL-110400, K01-DK-090125, P30-DK-036836]; Italian Ministry of Health (Ricerca Corrente) FX This work was supported by the National Institutes of Health (grants R01-HL-073168 and HL-110400 to A.D., K01-DK-090125 to M.P., and P30-DK-036836 to the Joslin Diabetes Research Center [Advanced Genomics and Genetics Core, and a Pilot and Feasibility Grant to M.N.]) and by the Italian Ministry of Health (Ricerca Corrente 2013 and 2014 to S.P. and V.T.). NR 19 TC 8 Z9 8 U1 0 U2 1 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 JUL PY 2015 VL 64 IS 7 BP 2658 EP 2663 DI 10.2337/db14-1653 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4PA UT WOS:000356934000047 PM 25677913 ER PT J AU Cefalu, WT Boulton, AJM Tamborlane, WV Moses, RG LeRoith, D Greene, EL Hu, FB Bakris, G Wylie-Rosett, J Rosenstock, J Weinger, K Blonde, L de Groot, M Riddle, MC Henry, R Golden, SH Rich, S Reynolds, L AF Cefalu, William T. Boulton, Andrew J. M. Tamborlane, William V. Moses, Robert G. LeRoith, Derek Greene, Eddie L. Hu, Frank B. Bakris, George Wylie-Rosett, Judith Rosenstock, Julio Weinger, Katie Blonde, Lawrence de Groot, Mary Riddle, Matthew C. Henry, Robert Golden, Sherita Hill Rich, Stephen Reynolds, Lyn TI Status of Diabetes Care: New Challenges, New Concepts, New MeasuresFocusing on the Future! SO DIABETES CARE LA English DT Article ID 1ST-LINE ADD-ON; POSITION STATEMENT; CARDIOVASCULAR-DISEASE; SULFONYLUREAS REMAIN; EUROPEAN ASSOCIATION; METFORMIN THERAPY; AMERICAN; INSULIN; COMPLICATIONS; DIRECTIONS C1 [Cefalu, William T.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Boulton, Andrew J. M.] Univ Manchester, Manchester Diabet Ctr, Manchester, Lancs, England. [Tamborlane, William V.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Moses, Robert G.] ISLHD, Wollongong, NSW, Australia. [LeRoith, Derek] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Greene, Eddie L.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Hu, Frank B.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Bakris, George] Univ Chicago Med, Dept Med, Div Endocrinol Diabet & Metab, ASH Comprehens Hypertens Ctr, Chicago, IL USA. [Wylie-Rosett, Judith] Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. [Rosenstock, Julio] Dallas Diabet & Endocrine Ctr Med City, Dallas, TX USA. [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Blonde, Lawrence] Ochsner Med Ctr, Dept Endocrinol, Frank Riddick Diabet Inst, Ochsner Diabet Clin Res Unit, New Orleans, LA USA. [de Groot, Mary] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Riddle, Matthew C.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. [Henry, Robert] VA San Diego Healthcare Syst, San Diego, CA USA. [Golden, Sherita Hill] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD USA. [Rich, Stephen] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Reynolds, Lyn] Amer Diabet Assoc, Indianapolis, IN USA. RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. EM cefaluwt@pbrc.edu FU NIDDK NIH HHS [P30 DK079637] NR 42 TC 2 Z9 2 U1 7 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2015 VL 38 IS 7 BP 1177 EP 1180 DI 10.2337/dc15-0875 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4OW UT WOS:000356933600009 PM 26312261 ER PT J AU Hosomura, N Goldberg, SI Shubina, M Zhang, M Turchin, A AF Hosomura, Naoshi Goldberg, Saveli I. Shubina, Maria Zhang, Mary Turchin, Alexander TI Electronic Documentation of Lifestyle Counseling and Glycemic Control in Patients With Diabetes SO DIABETES CARE LA English DT Article ID BONFERRONI PROCEDURE; GLUCOSE CONTROL; MULTIPLE TESTS; BLOOD-PRESSURE; HEALTH RECORDS; UNITED-STATES; CARE; INTERVENTION; PREVALENCE; MELLITUS AB OBJECTIVETo establish quantitative characteristics of lifestyle counseling documentation associated with improved glycemic control in patients with diabetes.RESEARCH DESIGN AND METHODSWe retrospectively studied 10,870 hyperglycemic (HbA(1c) 7.0% [53 mmol/mol]) adults with diabetes followed at primary care practices affiliated with two academic hospitals between 2000 and 2010. Documentation intensity was represented by the mean number of characters per note documenting lifestyle counseling. Heterogeneity was calculated as the normalized Levenshtein distance between lifestyle counseling sentences between consecutive notes. Cox proportional hazards model was constructed to assess association of heterogeneity and intensity of lifestyle counseling documentation to time to HbA(1c) <7.0% (53 mmol/mol) while adjusting for demographics, initial HbA(1c) level, insulin therapy, medication intensification, and frequency of lifestyle counseling.RESULTSComparing patients in the highest versus lowest tertile by documentation heterogeneity and documentation intensity, median time to HbA(1c) <7.0% (53 mmol/mol) was 26 vs. 39 months and 24 vs. 39 months, respectively (P < 0.001 for all). In multivariable analysis, an increase of documentation heterogeneity by 0.15 units and an increase of documentation intensity by 45 characters/note was associated with hazard ratios of 1.08 (95% CI 1.04-1.12; P < 0.001) and 1.27 (95% CI 1.23-1.31; P < 0.001) for time to HbA(1c) target, respectively.CONCLUSIONSHigher heterogeneity and intensity of lifestyle counseling documentation in provider notes were associated with better glycemic control. Further studies involving direct observation of patient care are needed to establish the nature of the relationship between documentation characteristics and patient outcomes. C1 [Hosomura, Naoshi; Shubina, Maria; Zhang, Mary; Turchin, Alexander] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Goldberg, Saveli I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Turchin, Alexander] Harvard Univ, Sch Med, Boston, MA USA. [Turchin, Alexander] Harvard Clin Res Inst, Boston, MA USA. RP Turchin, A (reprint author), Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA. EM aturchin@partners.org FU Agency for Healthcare Research and Quality [1R18HS017030] FX This study was supported in part by grant 1R18HS017030 from the Agency for Healthcare Research and Quality (to S.I.G., M.S., and A.T.). NR 33 TC 0 Z9 0 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2015 VL 38 IS 7 BP 1326 EP 1332 DI 10.2337/dc14-2016 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4OW UT WOS:000356933600028 PM 26070590 ER PT J AU Powers, MA Bardsley, J Cypress, M Duker, P Funnell, MM Fischl, AH Maryniuk, MD Siminerio, L Vivian, E AF Powers, Margaret A. Bardsley, Joan Cypress, Marjorie Duker, Paulina Funnell, Martha M. Fischl, Amy Hess Maryniuk, Melinda D. Siminerio, Linda Vivian, Eva TI Diabetes Self-management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CROSS-NATIONAL BENCHMARKING; GLYCEMIC CONTROL; CLINICAL-OUTCOMES; DECISION-MAKING; NEEDS 2ND; METAANALYSIS; CARE; PEOPLE C1 [Powers, Margaret A.] Int Diabet Ctr Pk Nicollet, Minneapolis, MN 55430 USA. [Bardsley, Joan] MedStar Hlth Res Inst, Hyattsville, MD USA. [Bardsley, Joan] MedStar Nursing, Hyattsville, MD USA. [Cypress, Marjorie] ABQ Hlth Partners, Albuquerque, NM USA. [Duker, Paulina] LifeScan, Dubai, U Arab Emirates. [Funnell, Martha M.] Univ Michigan Med Sch, Ann Arbor, MI USA. [Fischl, Amy Hess] Univ Chicago, Chicago, IL 60637 USA. [Maryniuk, Melinda D.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Siminerio, Linda] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Vivian, Eva] Univ Wisconsin, Madison, WI USA. RP Powers, MA (reprint author), Int Diabet Ctr Pk Nicollet, Minneapolis, MN 55430 USA. EM margaret.powers@parknicollet.com FU American Diabetes Association; American Association of Diabetes Educators; Academy of Nutrition and Dietetics FX The authors gratefully acknowledge the commitment and support of the collaborating organizations-the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics; their colleagues, including members of the Executive Committee of the National Diabetes Education Program, who participated in discussions and reviews about this inaugural position statement; and patients who teach and inspire them. The authors also thank Erika Gebel Berg (American Diabetes Association) for her invaluable editorial contribution. NR 81 TC 32 Z9 33 U1 4 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2015 VL 38 IS 7 BP 1372 EP 1382 DI 10.2337/dc15-0730 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4OW UT WOS:000356933600034 PM 26048904 ER PT J AU Dodge, LE Williams, PL Williams, MA Missmer, SA Toth, TL Calafat, AM Hauser, R AF Dodge, Laura E. Williams, Paige L. Williams, Michelle A. Missmer, Stacey A. Toth, Thomas L. Calafat, Antonia M. Hauser, Russ TI Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to Reproductive Outcomes among Couples from a Fertility Clinic SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BISPHENOL-A CONCENTRATIONS; IN-VITRO FERTILIZATION; SPERM DNA-DAMAGE; SPERMATOZOAL RNA; HUMAN EXPOSURE; SEMEN QUALITY; CANNED FOODS; MEN; WOMEN; PREGNANCY AB Background: Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. Objectives: We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. Methods: Male-female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males' specific gravity-adjusted urinary phenol concentrations measured before females' cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. Results: Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). Conclusions: To our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. C1 [Dodge, Laura E.; Williams, Paige L.; Williams, Michelle A.; Missmer, Stacey A.; 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. [Missmer, Stacey A.; Toth, Thomas L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Boston, MA 02114 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Hauser, R (reprint author), 665 Huntington Ave,Bldg 1,Room 1409, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu FU National Institute of Environmental Health Sciences [ES009718, ES022955]; [T32 ES 07069] FX This work was supported by National Institute of Environmental Health Sciences grants ES009718 and ES022955 and training grant T32 ES 07069, which supported L.E.D. NR 50 TC 7 Z9 7 U1 2 U2 18 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2015 VL 123 IS 7 BP 665 EP 671 DI 10.1289/ehp.1408605 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CL9KQ UT WOS:000357297500016 PM 25767892 ER PT J AU Tan, TC Dudzinski, DM Hung, J Mehta, V AF Tan, Timothy C. Dudzinski, David M. Hung, Judy Mehta, Vipin TI Peri-operative assessment of right heart function: role of echocardiography SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE Echocardiography; peri-operative assessment; right heart function ID RIGHT-VENTRICULAR-FUNCTION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; PULMONARY ARTERIAL-HYPERTENSION; ATRIAL SEPTAL-DEFECTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CARDIOVASCULAR ANESTHESIOLOGISTS; EJECTION FRACTION; AMERICAN SOCIETY; 2-DIMENSIONAL STRAIN; MAGNETIC-RESONANCE AB The right heart contributes significantly to overall cardiac function. Right ventricular (RV) haemodynamics and function have been defined to be physiologically different from the left ventricle, and yet independently associated with outcomes in a spectrum of conditions. In particular, RV function has been shown to influence prognosis of patients undergoing surgery. The assessment of right heart function during the intra-operative and immediate postoperative periods plays an important role in the clinical management of patients having surgery. While a number of techniques are available for the assessment of the right heart intra-operatively, echocardiography remains the prime choice being least invasive, relatively safe, readily accessible and cost-effective. Advancements in the field of echocardiographic have improved ability to assess right heart function. This review examines the role echocardiography and advances in this imaging modality in the assessment of right heart function within the peri-operative setting. C1 [Tan, Timothy C.; Dudzinski, David M.; Hung, Judy] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Tan, Timothy C.; Dudzinski, David M.; Hung, Judy] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Mehta, Vipin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mehta, V (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 55 Fruit St, Boston, MA 02114 USA. EM vmehta@partners.org NR 70 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD JUL PY 2015 VL 45 IS 7 BP 755 EP 766 DI 10.1111/eci.12462 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CL5VY UT WOS:000357031700012 PM 25989109 ER PT J AU Blum, K Thanos, PK Badgaiyan, RD Febo, M Oscar-Berman, M Fratantonio, J Demotrovics, Z Gold, MS AF Blum, Kenneth Thanos, Peter K. Badgaiyan, Rajendra D. Febo, Marcelo Oscar-Berman, Marlene Fratantonio, James Demotrovics, Zsolt Gold, Mark S. TI Neurogenetics and gene therapy for reward deficiency syndrome: are we going to the Promised Land? SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE antisense; gene therapy; gene transfer; hypodopaminergic; neurogenetics; neuroimaging; reward deficiency syndrome ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; D2R DNA TRANSFER; DRUG-ADDICTION; EPIGENETIC MECHANISMS; ALCOHOL DEPENDENCE; NUCLEUS-ACCUMBENS; ENVIRONMENT INTERACTIONS; SUBSTANCE ADDICTION; OPIATE ADDICTION AB Introduction: Addiction is a substantial health issue with limited treatment options approved by the FDA and as such currently available. The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies. Areas Covered: Through candidate and genome-wide association studies approaches, many gene polymorphisms and clusters have been implicated in drug, food and behavioral dependence linked by the common rubric reward deficiency syndrome (RDS). The results of selective studies that include the role of epigenetics, noncoding micro RNAs in RDS behaviors especially drug abuse involving alcohol, opioids, cocaine, nicotine, pain and feeding are reviewed in this article. New targets for addiction treatment and relapse prevention, treatment alternatives such as gene therapy in animal models, and pharmacogenomics and nutrigenomics methods to manipulate transcription and gene expression are explored. Expert Opinion: The recognition of the clinical benefit of early genetic testing to determine addiction risk stratification and dopaminergic agonistic, rather than antagonistic therapies are potentially the genomic-based wave of the future. In addition, further development, especially in gene transfer work and viral vector identification, could make gene therapy for RDS a possibility in the future. C1 [Blum, Kenneth; Febo, Marcelo; Gold, Mark S.] Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. [Blum, Kenneth; Febo, Marcelo; Gold, Mark S.] Univ Florida, Coll Med, McKnight Brain Inst, Gainesville, FL USA. [Blum, Kenneth; Fratantonio, James] Domin Diagnost LLC, Div Appl Clin Res & Educ, North Kingstown, RI USA. [Blum, Kenneth] Univ Vermont, Dept Psychiat, Burlington, VT USA. [Blum, Kenneth] Malibu Beach Recovery Ctr, Dept Addict Res & Therpy, Malibu Beach, CA USA. [Thanos, Peter K.] SUNY Stony Brook, Dept Psychol, Behav Neuropharmacol & Neuroimaging Lab, Stony Brook, NY 11794 USA. [Badgaiyan, Rajendra D.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. [Oscar-Berman, Marlene] VA Boston Healthcare Syst, Boston, MA USA. [Demotrovics, Zsolt] Eotvos Lorand Univ, Inst Psychol, Dept Clin Psychol & Addict, H-1064 Budapest, Hungary. [Gold, Mark S.] Rivermend LLC, New York, NY USA. [Gold, Mark S.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Gold, Mark S.] Univ So Calif, Keck Sch Med, Dept Behav Sci, Los Angeles, CA 90033 USA. [Gold, Mark S.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Blum, K (reprint author), Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. EM drd2gene@aol.com RI Febo, Marcelo/G-5718-2011; OI Febo, Marcelo/0000-0001-8981-4163 FU Rivermend; Life Extension Foundation, Ft. Lauderdale, FL, USA; NIH [R01HD70888-01A1, DA019946]; National Institutes of Health, NIAAA [R01-AA07112, K05-AA00219]; Medical Research Service of the US Department of Veterans Affairs; National Institutes of Health [1R01NS073884, 1R21MH073624]; VA Merit Review Awards [CX000479, CX000780]; McKnight Brain Institute Foundation FX K Blum is 100% owner of Synaptamine Inc. holding a number of nutrigenomic patents worldwide including genetic testing of RDS. Both K Blum and MS Gold are paid consultants of Rivermend. Kenneth Blum is the recipient of a grant from The Life Extension Foundation, Ft. Lauderdale, FL, USA to Path Foundation, NY, USA. Panayotis Thanos is the recipient of NIH grant R01HD70888-01A1. The preparation and review of the manuscript was supported in part by funds from the National Institutes of Health, NIAAA (R01-AA07112 and K05-AA00219) and the Medical Research Service of the US Department of Veterans Affairs (Marlene Oscar-Berman). Dr. Badgaiyan is supported by the National Institutes of Health grants 1R01NS073884 and 1R21MH073624, and VA Merit Review Awards CX000479 and CX000780. Marcelo Febo is the recipient of NIH DA019946 and is funded by the McKnight Brain Institute Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. NR 125 TC 3 Z9 3 U1 3 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUL PY 2015 VL 15 IS 7 BP 973 EP 985 DI 10.1517/14712598.2015.1045871 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CL5JH UT WOS:000356995700007 PM 25974314 ER PT J AU Zhen, DB Rabe, KG Gallinger, S Syngal, S Schwartz, AG Goggins, MG Hruban, RH Cote, ML McWilliams, RR Roberts, NJ Cannon-Albright, LA Li, DH Moyes, K Wenstrup, RJ Hartman, AR Seminara, D Klein, AP Petersen, GM AF Zhen, David B. Rabe, Kari G. Gallinger, Steven Syngal, Sapna Schwartz, Ann G. Goggins, Michael G. Hruban, Ralph H. Cote, Michele L. McWilliams, Robert R. Roberts, Nicholas J. Cannon-Albright, Lisa A. Li, Donghui Moyes, Kelsey Wenstrup, Richard J. Hartman, Anne-Renee Seminara, Daniela Klein, Alison P. Petersen, Gloria M. TI BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study SO GENETICS IN MEDICINE LA English DT Article DE BRCA1; BRCA2; PALB2; CDKN2A; familial pancreatic cancer ID GERMLINE MUTATIONS; HIGH-RISK; ADENOCARCINOMA; PREVALENCE; SUSCEPTIBILITY; CONSORTIUM; VARIANTS; CARRIERS; KINDREDS; PARTNER AB Purpose: Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing. Methods: Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma. Results: Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer. Conclusion: Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer. C1 [Zhen, David B.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Rabe, Kari G.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Gallinger, Steven] Univ Toronto, Div Gen Surg, Toronto, ON, Canada. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Schwartz, Ann G.; Cote, Michele L.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Detroit, MI USA. [Goggins, Michael G.; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Univ, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Roberts, Nicholas J.] Johns Hopkins Univ, Ludwig Ctr Canc Genet, Baltimore, MD USA. [Cannon-Albright, Lisa A.] Univ Utah, Sch Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Moyes, Kelsey; Wenstrup, Richard J.; Hartman, Anne-Renee] Myriad Genet Labs Inc, Salt Lake City, UT USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Petersen, GM (reprint author), Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. EM petersen.gloria@mayo.edu RI Gallinger, Steven/E-4575-2013; OI Zhen, David/0000-0003-3375-5912; albright, lisa/0000-0003-2602-3668 FU National Cancer Institute (NCI) [R01 CA97075]; National Institutes of Health NCI SPORE [P50 CA102701, P50 CA62924, K24113433]; Sol Goldman Pancreatic Cancer Research Center [N01-PC35145, P30 CA22453]; Karp Family H.H. & M. Metals, Inc. Fund; Sheikh Ahmed Center for Pancreatic Cancer Research; American Association for Cancer Research Innovation [11-60-25-CANN] FX The authors thank the probands and their families. They also thank study assistants Ryan Wuertz, Bridget Eversman, Sarah Amundson, Megan Reichmann, Denesia Parris, Chinedu Ukaegbu, Chelsea Michael, and Diane Echavarria, for their contributions to the study. The Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium is funded by National Cancer Institute (NCI) grant R01 CA97075. Other funding support for this study includes National Institutes of Health NCI SPORE grants P50 CA102701 and P50 CA62924, Susan Wojcicki, Dennis Troper, grant K24113433, the Sol Goldman Pancreatic Cancer Research Center (grants N01-PC35145 and P30 CA22453), the Karp Family H.H. & M. Metals, Inc. Fund, the Sheikh Ahmed Center for Pancreatic Cancer Research, and the American Association for Cancer Research Innovation (grant 11-60-25-CANN, awarded to L.A.C.-A.). This work was presented at the American Society of Human Genetics annual meeting, Boston, MA, 24 October 2013. NR 40 TC 23 Z9 23 U1 1 U2 16 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 JUL PY 2015 VL 17 IS 7 BP 569 EP 577 DI 10.1038/gim.2014.153 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CM0ID UT WOS:000357360700007 PM 25356972 ER PT J AU Baran, Y Subramaniam, M Biton, A Tukiainen, T Tsang, EK Rivas, MA Pirinen, M Gutierrez-Arcelus, M Smith, KS Kukurba, KR Zhang, R Eng, C Torgerson, DG Urbanek, C Li, JB Rodriguez-Santana, JR Burchard, EG Seibold, MA MacArthur, DG Montgomery, SB Zaitlen, NA Lappalainen, T AF Baran, Yael Subramaniam, Meena Biton, Anne Tukiainen, Taru Tsang, Emily K. Rivas, Manuel A. Pirinen, Matti Gutierrez-Arcelus, Maria Smith, Kevin S. Kukurba, Kim R. Zhang, Rui Eng, Celeste Torgerson, Dara G. Urbanek, Cydney Li, Jin Billy Rodriguez-Santana, Jose R. Burchard, Esteban G. Seibold, Max A. MacArthur, Daniel G. Montgomery, Stephen B. Zaitlen, Noah A. Lappalainen, Tuuli CA GTEx Consortium TI The landscape of genomic imprinting across diverse adult human tissues SO GENOME RESEARCH LA English DT Article ID RANDOM MONOALLELIC EXPRESSION; ALLELE-SPECIFIC EXPRESSION; GENE-EXPRESSION; HUMAN GRB10; HUMAN-CELLS; ORIGIN; BRAIN; IDENTIFICATION; TRANSCRIPTOME; DISEASE AB Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender. specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. C1 [Baran, Yael] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Subramaniam, Meena; Biton, Anne; Eng, Celeste; Torgerson, Dara G.; Burchard, Esteban G.; Zaitlen, Noah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Tukiainen, Taru; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Tukiainen, Taru; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Tsang, Emily K.; Smith, Kevin S.; Kukurba, Kim R.; Montgomery, Stephen B.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Tsang, Emily K.] Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA. [Rivas, Manuel A.] Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Pirinen, Matti] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Gutierrez-Arcelus, Maria] Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Li, Jin Billy; Montgomery, Stephen B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Urbanek, Cydney; Seibold, Max A.] Natl Jewish Hlth, Integrated Ctr Genes Environm & Hlth, Denver, CO 80206 USA. [Rodriguez-Santana, Jose R.] Ctr Neumol Pediat, San Juan, PR 00917 USA. [Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. [Seibold, Max A.] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA. [Seibold, Max A.] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80045 USA. [MacArthur, Daniel G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lappalainen, Tuuli] New York Genome Ctr, New York, NY 10013 USA. [Lappalainen, Tuuli] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA. RP Lappalainen, T (reprint author), New York Genome Ctr, New York, NY 10013 USA. EM noah.zaitlen@ucsf.edu; tlappalainen@nygenome.org OI Lappalainen, Tuuli/0000-0002-7746-8109; Pirinen, Matti/0000-0002-1664-1350 FU National Institutes of Health [1K25HL121295-01A1, HHSN26820100029C, R01MH101814, 1R01HL124285-01, 1R01GM110251-01]; Edmond J. Safra Center for Bioinformatics at Tel-Aviv University; Israel Science Foundation [989/08]; German-Israeli Foundation [1094-33.2/2010]; Binational Science Foundation [2012304]; Hewlett-Packard Stanford Graduate Fellowship; Natural Science and Engineering Research Council of Canada; Clarendon Scholarship; NDM Studentship; Green Templeton College Award from the University of Oxford; Finnish Cultural Foundation; Orion-Farmos Research Foundation; Emil Aaltonen Foundation; Common Fund of the Office of the Director of the National Institutes of Health; National Cancer Institute (NCI); National Human Genome Research Institute (NHGRI); National Heart, Lung, and Blood Institute (NHLBI); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS); NCI \ SAIC-Frederick, Inc. (SAIC-F) [10XS170, 10XS171, X10S172]; SAIC-F [10ST1035]; University of Miami grant [DA006227]; University of Geneva [MH090941]; University of Chicago [MH090951, MH090937]; University of North Carolina-Chapel Hill [MH090936]; Harvard University [MH090948]; National Human Genome Research Institute Medical Sequencing Program grant [U54 HG003067]; [HHSN268201000029C] FX We thank all the members of the GTEx Consortium, Marta Mele, Ferran Reverter, Carlos D. Bustamante, Emmanouil Dermitzakis, Joseph Pickrell, and Ana Pascoini. N.Z. was supported by National Institutes of Health grant 1K25HL121295-01A1, and T.L. was supported by National Institutes of Health grants HHSN26820100029C and R01MH101814. Y.B. was supported in part by a Fellowship from the Edmond J. Safra Center for Bioinformatics at Tel-Aviv University, by Israel Science Foundation grant no. 989/08, German-Israeli Foundation grant no. 1094-33.2/2010, and Binational Science Foundation grant no. 2012304. A.B. was supported by National Institutes of Health grants 1R01HL124285-01 and 1R01GM110251-01. E.K.T. was supported by a Hewlett-Packard Stanford Graduate Fellowship and a fellowship from the Natural Science and Engineering Research Council of Canada. M.A.R. was supported by a Clarendon Scholarship, NDM Studentship, and Green Templeton College Award from the University of Oxford. T.T. was supported in part by personal grants from the Finnish Cultural Foundation, Orion-Farmos Research Foundation, and Emil Aaltonen Foundation. The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (commonfund.nih.gov/GTEx). Additional funds were provided by the National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), and National Institute of Neurological Disorders and Stroke (NINDS). Donors were enrolled at Biospecimen Source Sites funded by NCI \ SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by a supplement to University of Miami grant DA006227. Statistical methods development grants were made to the University of Geneva (MH090941), the University of Chicago (MH090951 and MH090937), the University of North Carolina-Chapel Hill (MH090936), and Harvard University (MH090948). Exome sequencing of the muscle disease families was supported by National Human Genome Research Institute Medical Sequencing Program grant U54 HG003067. The authors thank the families and patients for their participation in the GALA II study and the numerous health care providers and community clinics for their support and participation in GALA II. In particular, the authors thank the GALA II study coordinator, Sandra Salazar, and the recruiters who obtained the data: Gaby Ayala-Rodriguez, Jaime Colon, and Vivian Medina. NR 55 TC 23 Z9 23 U1 6 U2 26 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 JUL PY 2015 VL 25 IS 7 BP 927 EP 936 DI 10.1101/gr.192278.115 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CM0GR UT WOS:000357356900001 PM 25953952 ER PT J AU Eddy, KT Thomas, JJ Hastings, E Edkins, K Lamont, E Nevins, CM Patterson, RM Murray, HB Bryant-Waugh, R Becker, AE AF Eddy, Kamryn T. Thomas, Jennifer J. Hastings, Elizabeth Edkins, Katherine Lamont, Evan Nevins, Caitlin M. Patterson, Rebecca M. Murray, Helen B. Bryant-Waugh, Rachel Becker, Anne E. TI Prevalence of DSM-5 Avoidant/Restrictive Food Intake Disorder in a Pediatric Gastroenterology Healthcare Network SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE avoidant/restrictive food intake disorder; feeding disorder; DSM-5 ID EATING-DISORDERS; FEEDING DISORDERS; ADOLESCENTS; CHILDREN; CHILDHOOD; CLASSIFICATION; COMORBIDITY; BEHAVIORS; CRITERIA; IV AB Objective: Few published studies have evaluated the clinical utility of new diagnostic criteria for avoidant/restrictive food intake disorder (ARFID), a DSM-5 reformulation of feeding and eating disorder of infancy or early childhood. We examined the prevalence of ARFID and inter-rater reliability of its diagnostic criteria in a pediatric gastrointestinal sample. Method: We conducted a retrospective chart review of 2,231 consecutive new referrals (ages 8-18 years) to 19 Boston-area pediatric gastroenterology clinics for evidence of DSM-5 ARFID. Results: We identified 33 (1.5%) ARFID cases; 22 of whom (67%) were male. Most were characterized by insufficient intake/little interest in feeding (n = 19) or limited diet due to sensory features of the food (n = 7). An additional 54 cases (2.4%) met one or more ARFID criteria but there was insufficient information in the medical record to confer or exclude the diagnosis. Diagnostic agreement between coders was adequate (kappa = 0.72). Common challenges were (i) distinguishing between diagnoses of ARFID and anorexia nervosa or anxiety disorders; (ii) determination of whether the severity of the eating/feeding disturbance was sufficient to warrant diagnosis in the presence of another medical or psychiatric disorder; and (iii) assessment of psychosocial impairment related to eating/feeding problems. Discussion: In a pediatric treatment-seeking sample where ARFID features were common, cases meeting full criteria were rare, suggesting that the diagnosis is not over-inclusive even in a population where eating/feeding difficulties are expected. (C) 2014 Wiley Periodicals Inc. C1 [Eddy, Kamryn T.; Thomas, Jennifer J.; Hastings, Elizabeth; Edkins, Katherine; Lamont, Evan; Nevins, Caitlin M.; Patterson, Rebecca M.; Murray, Helen B.; Becker, Anne E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.; Thomas, Jennifer J.; Becker, Anne E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bryant-Waugh, Rachel] Great Ormond St Hosp Children NHS Fdn Trust, Dept Child & Adolescent Mental Hlth, London, England. [Becker, Anne E.] Boston Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02118 USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Long Fellow Pl,Suite 200, Boston, MA 02114 USA. EM keddy@mgh.harvard.edu NR 30 TC 6 Z9 6 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2015 VL 48 IS 5 BP 464 EP 470 DI 10.1002/eat.22350 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA CL1ED UT WOS:000356684500003 PM 25142784 ER PT J AU Sokoloff, NC Eguiguren, ML Wargo, K Ackerman, KE Baskaran, C Singhal, V Clarke, H Slattery, M Lee, H Eddy, KT Misra, M AF Sokoloff, Natalia Cano Eguiguren, Maria L. Wargo, Katherine Ackerman, Kathryn E. Baskaran, Charumathi Singhal, Vibha Clarke, Hannah Slattery, Meghan Lee, Hang Eddy, Kamryn T. Misra, Madhusmita TI Bone parameters in relation to attitudes and feelings associated with disordered eating in oligo-amenorrheic athletes, eumenorrheic athletes, and nonathletes SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE female athlete triad; oligomenorrhea; disordered eating; cognitive eating restraint; bone microarchitecture; bone mineral density ID COGNITIVE DIETARY RESTRAINT; SUBCLINICAL OVULATORY DISTURBANCES; HEALTHY-YOUNG WOMEN; MINERAL DENSITY; CORTISOL; MASS; ADOLESCENCE; INVENTORY-2; RUNNERS; BULIMIA AB ObjectivesDisordered eating may negatively impact bone in athletes. However, it is not known whether this effect is independent of the associated amenorrhea and relative hypercortisolemia. We aimed to compare attitudes, feelings, and cognitions associated with disordered eating using the Three-Factor Eating Questionnaire (TFEQ) and Eating Disorder Inventory-2 (EDI-2) in normal-weight oligomenorrheic athletes (OA), eumenorrheic athletes (EA), and nonathletes, and determine the associations with bone independent of confounders. Method109 OA, 39 EA, and 36 nonathletes (14-25 years) completed the TFEQ and EDI-2. Dual-energy X-ray absorptiometry was used to assess spine bone mineral density (BMD), and high-resolution pQCT to assess radius microarchitecture. We measured integrated cortisol (q 20, 11 PM-7 AM), bone formation (procollagen Type 1 N-terminal propeptide, P1NP), and resorption (C-telopeptide, CTX) markers in a subset. ResultsOA had lower spine BMD Z-scores than EA. Cognitive eating restraint (CER), drive for thinness (DT), ineffectiveness, and interoceptive awareness (IA) were higher in OA than EA (p<0.05); CER was higher in OA versus nonathletes (p=0.03). Pulsatile cortisol was positively associated with DT, ineffectiveness, and IA (p<0.03). CER was inversely associated with BMD Z-scores and P1NP, and ineffectiveness with radius cross-sectional area even after controlling for age, BMI, amenorrhea duration, and cortisol (p<0.03). DiscussionHigher CER in athletes independently predicts lower BMD. (c) 2015 Wiley Periodicals, Inc (Int J Eat Disord 2015; 48:522-526). C1 [Sokoloff, Natalia Cano; Eguiguren, Maria L.; Wargo, Katherine; Ackerman, Kathryn E.; Baskaran, Charumathi; Singhal, Vibha; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Sokoloff, Natalia Cano; Eguiguren, Maria L.; Wargo, Katherine; Ackerman, Kathryn E.; Baskaran, Charumathi; Singhal, Vibha; Clarke, Hannah; Slattery, Meghan; Lee, Hang; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Baskaran, Charumathi; Singhal, Vibha; Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Sokoloff, NC (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. EM ncanosokoloff@partners.org OI Cano Sokoloff, Natalia/0000-0002-4840-5686 NR 20 TC 1 Z9 1 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2015 VL 48 IS 5 BP 522 EP 526 DI 10.1002/eat.22405 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA CL1ED UT WOS:000356684500011 ER PT J AU Rauh-Hain, JA Connor, SC Clemmer, JT Foley, OW Clark, RM Hall, TR Boruta, DM Schorge, JO del Carmen, MG AF Rauh-Hain, Jose Alejandro Connor, Sarah C. Clemmer, Joel T. Foley, Olivia W. Clark, Rachel M. Hall, Tracilyn R. Boruta, David M. Schorge, John O. del Carmen, Marcela G. TI Trends in Treatment of Uterine Serous Cancer in the Medicare Population SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Uterine serous carcinoma; Chemotherapy; Radiotherapy ID RECURRENT ENDOMETRIAL CANCER; PLATINUM-BASED CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA UPSC; BREAST-CANCER; CLEAR-CELL; PAPILLARY; PACLITAXEL; STAGE; CARBOPLATIN AB Objective The objectives of this study were to evaluate the rates of chemotherapy and radiotherapy delivery in the treatment of uterine serous carcinoma in the Medicare population and to compare clinical outcomes in treated and untreated patients. Methods The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients with a diagnosis of uterine serous carcinoma between 1992 and 2009. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results A total of 2188 patients met study eligibility criteria. Stages I, II, III, and IV diseases accounted for 890 (41%), 174 (8%), 470 (21%), and 654 (30%) of the study population, respectively. Chemotherapy, radiotherapy, both, or none, were administered as adjuvant therapy in 635 (29%), 536 (24%), 308 (14%), and 709 (32%) of the study population, respectively. Use of chemotherapy became more frequent over time. Over the study period, and after adjusting for race, time of diagnosis, SEER registry, marital status, stage, age, surgery, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between receipt of radiotherapy alone (hazard ratio [HR], 1.3; 95% CI, 1.04-1.67) and not receiving any treatment (HR, 1.5; 95% CI, 1.2-2.01) and worst survival. Survival was not improved over time. Conclusion Although adjuvant chemotherapy and combination treatment with chemotherapy and radiation were associated with improved survival in our model, there was no significant improvement in survival over time. C1 [Rauh-Hain, Jose Alejandro; Connor, Sarah C.; Clemmer, Joel T.; Foley, Olivia W.; Clark, Rachel M.; Hall, Tracilyn R.; Boruta, David M.; Schorge, John O.; 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, Vincent Obstet & Gynecol, Div Gynecol Oncol, Yawkey Ctr, 55 Fruit St,Suite 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX This work was supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 35 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JUL PY 2015 VL 25 IS 6 BP 1023 EP 1030 DI 10.1097/IGC.0000000000000464 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL9HB UT WOS:000357286900012 PM 25914960 ER PT J AU DiPasquale, DM Strangman, GE Harris, NS Muza, SR AF DiPasquale, D. M. Strangman, G. E. Harris, N. S. Muza, S. R. TI Acute Mountain Sickness, Hypoxia, Hypobaria and Exercise Duration each Affect Heart Rate SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article DE altitude; normobaric; hypobaric; cardiovascular ID PULMONARY ARTERIAL BARORECEPTORS; EXHALED NITRIC-OXIDE; NORMOBARIC HYPOXIA; HIGH-ALTITUDE; PHYSIOLOGICAL-RESPONSES; SIMULATED ALTITUDE; BODY-TEMPERATURE; EXPOSURE; HUMANS; SUSCEPTIBILITY AB In this study, we quantified the changes in post-exercise resting heart rate (HRrst) associated with acute mountain sickness (AMS), and compared the effects of hypobaric hypoxia (HH) and normobaric hypoxia (NH) on HRrst. We also examined the modulating roles of exercise duration and exposure time on HRrst. Each subject participated in 2 of 6 conditions: normobaric normoxia (NN), NH, or HH (4400m altitude equivalent) combined with either 10 or 60min of moderate cycling at the beginning of an 8-h exposure. AMS was associated with a 2bpm higher HRrst than when not sick, after taking into account the ambient environment, exercise duration, and SpO(2). In addition, HRrst was elevated in both NH and HH compared to NN with HRrst being 50% higher in HH than in NH. Participating in long duration exercise led to elevated resting HRs (0.8-1.4bpm higher) compared with short exercise, while short exercise caused a progressive increase in HRrst over the exposure period in both NH and HH (0.77-1.2bpm/h of exposure). This data suggests that AMS, NH, HH, exercise duration, time of exposure, and SpO(2) have independent effects on HRrst. It further suggests that hypobaria exerts its own effect on HRrst in hypoxia. Thus NH and HH may not be interchangeable environments. C1 [DiPasquale, D. M.] Univ Pittsburgh, Dept Sports Med & Nutr, Pittsburgh, PA 15203 USA. [DiPasquale, D. M.; Strangman, G. E.] Massachusetts Gen Hosp, Psychiat, Charlestown, MA USA. [Harris, N. S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [DiPasquale, D. M.; Strangman, G. E.; Harris, N. S.] Harvard Univ, Sch Med, Boston, MA USA. [Muza, S. R.] US Army Res Inst Environm Med, Thermal & Mt Med Div, Natick, MA USA. RP DiPasquale, DM (reprint author), Univ Pittsburgh, Dept Sports Med & Nutr, 3830 South Water St, Pittsburgh, PA 15203 USA. EM dmd116@pitt.edu FU DOD CDMRP program; [W81-XWH1020199] FX We gratefully acknowledge the support of the DOD CDMRP program and grant W81-XWH1020199. We also thank the following individuals for their assistance: Andrea Gunn, Richard Goldstein, Janet Staab, Chuck Fulco, Beth Beidleman, Ingrid Sills, Vincent Forte, Marie Grunbeck, Sean Andrew, Katylin Guerriere and Myra Jones. Approved for public release; distribution is unlimited. The views, opinions and/or findings contained in this publication are those of the authors and should not be construed as an official Dept. of the Army position, policy or decision unless so designated by other documentation. For the protection of human subjects, the investigators adhered to policies of applicable Federal Law CFR 46. Human subjects participated in these studies after giving their free and informed consent. Investigators adhered to AR 70-25 and USAMRMC Regulation 70-25 on the use of volunteers in research. Any citations of commercial organizations and trade names in this report do not constitute an official Dept. of the Army endorsement of approval of the products or services of the organizations. NR 40 TC 6 Z9 6 U1 1 U2 8 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0172-4622 EI 1439-3964 J9 INT J SPORTS MED JI Int. J. Sports Med. PD JUL PY 2015 VL 36 IS 8 BP 609 EP 614 DI 10.1055/s-0034-1398623 PG 6 WC Sport Sciences SC Sport Sciences GA CL8HL UT WOS:000357215100001 PM 25837245 ER PT J AU Mueller, AE Segal, DL Gavett, B Marty, MA Yochim, B June, A Coolidge, FL AF Mueller, Anne E. Segal, Daniel L. Gavett, Brandon Marty, Meghan A. Yochim, Brian June, Andrea Coolidge, Frederick L. TI Geriatric Anxiety Scale: item response theory analysis, differential item functioning, and creation of a ten-item short form (GAS-10) SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE geriatric; anxiety assessment; anxiety; item response theory; short form ID OLDER-ADULTS; PSYCHOMETRIC PROPERTIES; GENDER-DIFFERENCES; DEPRESSION; DISORDERS; INVENTORY; LIFE; ASSOCIATION; PREVALENCE; SYMPTOMS AB Background: The Geriatric Anxiety Scale (GAS; Segal et al. (Segal, D. L., June, A., Payne, M., Coolidge, F. L. and Yochim, B. (2010). Journal of Anxiety Disorders, 24, 709-714. doi: 10.1016/j.janxdis.2010.05.002) is a self-report measure of anxiety that was designed to address unique issues associated with anxiety assessment in older adults. This study is the first to use item response theory (IRT) to examine the psychometric properties of a measure of anxiety in older adults. Method: A large sample of older adults (n = 581; mean age = 72.32 years, SD = 7.64 years, range = 60 to 96 years; 64% women; 88% European American) completed the GAS. IRT properties were examined. The presence of differential item functioning (DIF) or measurement bias by age and sex was assessed, and a ten-item short form of the GAS (called the GAS-10) was created. Results: All GAS items had discrimination parameters of 1.07 or greater. Items from the somatic subscale tended to have lower discrimination parameters than items on the cognitive or affective subscales. Two items were flagged for DIF, but the impact of the DIF was negligible. Women scored significantly higher than men on the GAS and its subscales. Participants in the young-old group (60 to 79 years old) scored significantly higher on the cognitive subscale than participants in the old-old group (80 years old and older). Conclusions: Results from the IRT analyses indicated that the GAS and GAS-10 have strong psychometric properties among older adults. We conclude by discussing implications and future research directions. C1 [Mueller, Anne E.] Vet Affairs Puget Sound Hlth Care Syst, Amer Lake Div, Washington, DC USA. [Segal, Daniel L.; Gavett, Brandon; Yochim, Brian; Coolidge, Frederick L.] Univ Colorado, Dept Psychol, Colorado Springs, CO 80918 USA. [Marty, Meghan A.] Transit Profess Ctr, Portland, OR USA. [Yochim, Brian] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, VA Palo Alto Hlth Care Syst, Stanford, CA 94305 USA. [June, Andrea] Cent Connecticut State Univ, Dept Psychol Sci, New Britain, CT 06050 USA. RP Segal, DL (reprint author), Univ Colorado, Dept Psychol, Colorado Springs, CO 80918 USA. EM dsegal@uccs.edu OI Gavett, Brandon/0000-0003-1938-1854 NR 35 TC 3 Z9 3 U1 4 U2 8 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 JUL PY 2015 VL 27 IS 7 SI SI BP 1099 EP 1111 DI 10.1017/S1041610214000210 PG 13 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CL5TW UT WOS:000357025400006 PM 24576589 ER PT J AU Chatterjee, S Herrmann, HC Wilensky, RL Hirshfeld, J McCormick, D Frankel, DS Yeh, RW Armstrong, EJ Kumbhani, DJ Giri, J AF Chatterjee, Saurav Herrmann, Howard C. Wilensky, Robert L. Hirshfeld, John McCormick, Daniel Frankel, David S. Yeh, Robert W. Armstrong, Ehrin J. Kumbhani, Dharam J. Giri, Jay TI Safety and Procedural Success of Left Atrial Appendage Exclusion With the Lariat Device A Systematic Review of Published Reports and Analytic Review of the FDAMAUDE Database SO JAMA INTERNAL MEDICINE LA English DT Article ID CLINICAL-EXPERIENCE; ORAL ANTICOAGULANTS; WARFARIN THERAPY; PREVENT STROKE; FIBRILLATION; CLOSURE; EFFICACY; METAANALYSIS; OCCLUSION; RISK AB IMPORTANCE The Lariat device has received US Food and Drug Administration (FDA) 510(k) clearance for soft-tissue approximation and is being widely used off-label for left atrial appendage (LAA) exclusion. A comprehensive analysis of safety and effectiveness has not been reported. OBJECTIVES To perform a systematic review of published literature to assess safety and procedural success, defined as successful closure of the LAA during the index procedure, of the Lariat device. We performed a formal analytic review of the FDAMAUDE (Manufacturer and User Facility Device Experience) database to compile adverse event reports from real-world practice with the Lariat. DATA SOURCES For the systematic review, PubMed, EMBASE, CINAHL, and the Cochrane Library were searched from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in 3 or more patients. The FDA MAUDE database was queried for adverse events reports related to Lariat use. DATA EXTRACTIONS AND SYNTHESIS Data were abstracted in duplicate by 2 physician reviewers. Events from published literature were pooled using a generic inverse variance weighting with a random effects model. Cumulative and individual adverse events were also reported using the FDAMAUDE data set. MAIN OUTCOMES AND MEASURES Procedural adverse events and procedural success. RESULTS In the systematic review, 5 reports of Lariat device use in 309 participants were identified. Specific complications weighted for inverse of variance of individual studies were urgent need for cardiac surgery (2.3%; 7 of 309 procedures) and death (0.3%; 1 of 309 procedures). Procedural success was 90.3%(279 of 309 procedures). In the FDAMAUDE database, there were 35 unique reports of adverse events with use of the Lariat device. Among these, we identified 5 adverse event reports that noted pericardial effusion and death and an additional 23 reported urgent cardiac surgery without mention of death. CONCLUSIONS AND RELEVANCE This review of published reports and case reports identified risks of adverse events with off-label use of the Lariat device for LAA exclusion. Formal, controlled investigations into the safety and efficacy of the device for this indication are warranted. C1 [Chatterjee, Saurav] St Lukes Roosevelt Hosp, Ctr Mt Sinai Hlth Syst, Div Cardiol, New York, NY 10025 USA. [Herrmann, Howard C.; Wilensky, Robert L.; Hirshfeld, John; McCormick, Daniel; Frankel, David S.; Giri, Jay] Univ Penn, Div Cardiovasc Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Armstrong, Ehrin J.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. [Kumbhani, Dharam J.] Univ Texas Dallas, Div Cardiol, SW Med Sch, Dallas, TX 75230 USA. RP Giri, J (reprint author), Hosp Univ Penn, Div Cardiovasc Med, Gates Pavil,Ninth Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM giri.jay@gmail.com FU Harvard Clinical Research Institute; Edwards Lifesciences Inc; Medtronic Inc; St Jude Medical Inc; Siemens Medical Inc; Abbott Vascular Corp; W. L. Gore; Boston Scientific Corp. FX Dr Yeh is on the advisory board for Abbott Vascular; is a consultant for Gilead Sciences; and receives research support and salary from Harvard Clinical Research Institute. Dr Armstrong is on the advisory board for Abbott Vascular and is a consultant for Angioscore. Dr Kumbhani is a consultant for the American College of Cardiology. Dr Herrmann has received research funding for the University of Pennsylvania from Edwards Lifesciences Inc, Medtronic Inc, and St Jude Medical Inc; is a consultant for and has received research funding from Siemens Medical Inc; and has equity in Microinterventional Devices Inc. Dr Wilensky reports that he is a member of the scientific advisor boards of Cardiostem, GenWay, Soteria, and Vascular Magnetics and has equity interest in Johnson & Johnson. Dr McCormick has received research grants from Abbott Vascular Corp, W. L. Gore, and Boston Scientific Corp. Dr Hirshfeld has served as a member of the FDA Circulatory Systems Device Advisory Panel. No other disclosures are reported. NR 34 TC 18 Z9 18 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2015 VL 175 IS 7 BP 1104 EP 1109 DI 10.1001/jamainternmed.2015.1513 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400011 PM 25938303 ER PT J AU Reddy, A Pollack, CE Asch, DA Canamucio, A Werner, RM AF Reddy, Ashok Pollack, Craig E. Asch, David A. Canamucio, Anne Werner, Rachel M. TI The Effect of Primary Care Provider Turnover on Patient Experience of Care and Ambulatory Quality of Care SO JAMA INTERNAL MEDICINE LA English DT Article ID MEDICAL HOME; HEALTH-CARE; CONTINUITY; ORGANIZATIONS; SATISFACTION; VETERANS AB IMPORTANCE Primary care provider (PCP) turnover is common and can disrupt patient continuity of care. Little is known about the effect of PCP turnover on patient care experience and quality of care. OBJECTIVE To measure the effect of PCP turnover on patient experiences of care and ambulatory care quality. DESIGN, SETTING, AND PARTICIPANTS Observational, retrospective cohort study of a nationwide sample of primary care patients in the Veterans Health Administration (VHA). We included all patients enrolled in primary care at the VHA between 2010 and 2012 included in 1 of 2 national data sets used to measure our outcome variables: 326 374 patients in the Survey of Healthcare Experiences of Patients (SHEP; used to measure patient experience of care) associated with 8441 PCPs and 184 501 patients in the External Peer Review Program (EPRP; used to measure ambulatory care quality) associated with 6973 PCPs. EXPOSURES Whether a patient experienced PCP turnover, defined as a patient whose provider (physician, nurse practitioner, or physician assistant) had left the VHA (ie, had no patient encounters for 12 months). MAIN OUTCOMES AND MEASURES Five patient care experience measures (from SHEP) and 11 measures of quality of ambulatory care (from EPRP). RESULTS Nine percent of patients experienced a PCP turnover in our study sample. Primary care provider turnover was associated with a worse rating in each domain of patient care experience. Turnover was associated with a reduced likelihood of having a positive rating of their personal physician of 68.2% vs 74.6%(adjusted percentage point difference, -5.3; 95% CI, -6.0 to -4.7) and a reduced likelihood of getting care quickly of 36.5% vs 38.5%(adjusted percentage point difference, -1.1; 95% CI, -2.1 to -0.1). In contrast, PCP turnover was not associated with lower quality of ambulatory care except for a lower likelihood of controlling blood pressure of 78.7% vs 80.4%(adjusted percentage point difference, -1.44; 95% CI, -2.2 to -0.7). In 9 measures of ambulatory care quality, the difference between patients who experienced no PCP turnover and those who had a PCP turnover was less than 1 percentage point. These effects were moderated by the patients' continuity with their PCP prior to turnover, with a larger detrimental effect of PCP turnover among those with higher continuity prior to the turnover. CONCLUSIONS AND RELEVANCE Primary care provider turnover was associated with worse patient experiences of care but did not have a major effect on ambulatory care quality. C1 [Reddy, Ashok; Asch, David A.; Canamucio, Anne; Werner, Rachel M.] Philadelphia VA Med Ctr, VISN Ctr Evaluat PACT 4, Philadelphia, PA USA. [Reddy, Ashok; Asch, David A.; Werner, Rachel M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Reddy, Ashok; Asch, David A.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Reddy, Ashok; Asch, David A.] Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. [Pollack, Craig E.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Reddy, A (reprint author), Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Perelman Sch Med, Blockley Hall 1303,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ashokr@upenn.edu FU Robert Wood Johnson Foundation Clinical Scholars Program; National Institutes of Health career development award [K07CA151910] FX Dr Reddy was supported by the Robert Wood Johnson Foundation Clinical Scholars Program. Dr Pollack was supported by a National Institutes of Health career development award (K07CA151910). NR 21 TC 5 Z9 5 U1 1 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 JUL PY 2015 VL 175 IS 7 BP 1157 EP 1162 DI 10.1001/jamainternmed.2015.1853 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400023 PM 25985320 ER PT J AU Jena, AB Ho, O Goldman, DP Karaca-Mandic, P AF Jena, Anupam B. Ho, Oliver Goldman, Dana P. Karaca-Mandic, Pinar TI The Impact of the US Food and Drug Administration Chlorofluorocarbon Ban on Out-of-pocket Costs and Use of Albuterol Inhalers Among Individuals With Asthma SO JAMA INTERNAL MEDICINE LA English DT Article ID EVALUATING PATIENT ADHERENCE; HEALTH-CARE NEEDS; ANTIDEPRESSANT THERAPY; STRATOSPHERIC OZONE; PHARMACY BENEFITS; CONTROLLED-TRIAL; CHRONICALLY ILL; UNITED-STATES; CHILDREN; MEDICATION AB IMPORTANCE The US Clean Air Act prohibits use of nonessential ozone-depleting substances. In 2005, the US Food and Drug Administration announced the ban of chlorofluorocarbon (CFC) albuterol inhalers by December 31, 2008. The policy resulted in the controversial replacement of generic CFC inhalers by more expensive, branded hydrofluoroalkane inhalers. The policy's impact on out-of-pocket costs and utilization of albuterol is unknown. OBJECTIVE To study the impact of the US Food and Drug Administration's CFC ban on out-of-pocket costs and utilization of albuterol inhalers. DESIGN, SETTING, AND PARTICIPANTS Using private insurance data from January 1, 2004, to December 31, 2010, we investigated the effect of the CFC ban on out-of-pocket costs and utilization of albuterol inhalers among individuals with asthma (109 428 adults; 37 281 children), as well as asthma-related hospitalizations, emergency department visits, and outpatient visits. We estimated multivariable models adjusted for age, sex, comorbidities, and mean out-of-pocket costs of albuterol inhalers in an individual's drug plan. We analyzed whether effects varied between adults vs children and those with persistent vs nonpersistent asthma. MAIN OUTCOMES AND MEASURES Pharmacy claims for albuterol inhalers, as well as asthma-related hospitalizations, emergency department visits, and outpatient visits. RESULTS The mean out-of-pocket albuterol cost rose from $13.60 (95% CI, $13.40-$13.70) per prescription in 2004 to $25.00 (95% CI, $24.80-$25.20) immediately after the 2008 ban. By the end of 2010, costs had lowered to $21.00 (95% CI, $20.80-$21.20) per prescription. Overall albuterol inhaler use steadily declined from 2004 to 2010. Steep declines in use of generic CFC inhalers occurred after the fourth quarter of 2006 and were almost fully offset by increases in use of hydrofluoroalkane inhalers. In multivariable analyses, a $10 increase in out-of-pocket albuterol prescription costs was estimated to lower utilization by 0.92 percentage points (95% CI, -1.39 to -0.44; P < .001) for adults and 0.54 percentage points (95% CI, -0.84 to -0.24; P = .001) for children, with no difference between adults vs children and patients with persistent vs nonpersistent asthma and with no impact on asthma-related hospitalizations, emergency department visits, and outpatient visits. CONCLUSIONS AND RELEVANCE The Federal ban of CFC inhalers led to large relative increases in out-of-pocket albuterol costs among privately insured individuals with asthma and modest declines in utilization. The policy's impact on individuals without insurance, who faced greater cost increases, is unknown. C1 [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.; Goldman, Dana P.; Karaca-Mandic, Pinar] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Jena, Anupam B.; Ho, Oliver] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Goldman, Dana P.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Karaca-Mandic, Pinar] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU Health Early Independence Award from the National Institutes of Health [1DP5OD017897-01]; National Institute on Aging [5P01AG033559, 5K01AG036740]; University of Minnesota Academic Health Center Faculty Development Grant FX This study was funded by Health Early Independence Award 1DP5OD017897-01 from the National Institutes of Health (Dr Jena), by grants 5P01AG033559 (Dr Goldman) and 5K01AG036740 (Dr. Karaca-Mandic) from the National Institute on Aging, and by a University of Minnesota Academic Health Center Faculty Development Grant (Dr Karaca-Mandic). NR 33 TC 7 Z9 7 U1 1 U2 4 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 JUL PY 2015 VL 175 IS 7 BP 1171 EP 1179 DI 10.1001/jamainternmed.2015.1665 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400026 PM 25962128 ER PT J AU Ornstein, KA Leff, B Covinsky, KE Ritchie, CS Federman, AD Roberts, L Kelley, AS Siu, AL Szanton, SL AF Ornstein, Katherine A. Leff, Bruce Covinsky, Kenneth E. Ritchie, Christine S. Federman, Alex D. Roberts, Laken Kelley, Amy S. Siu, Albert L. Szanton, Sarah L. TI Epidemiology of the Homebound Population in the United States SO JAMA INTERNAL MEDICINE LA English DT Article ID HOME-BASED PRIMARY; LATE-LIFE DISABILITY; OF-CARE STANDARDS; OLDER PERSONS; HEALTH-CARE; ADULTS; PROGRAM; PREVALENCE; CAREGIVERS; DEPRESSION AB IMPORTANCE Increasing numbers of older, community-dwelling adults have functional impairments that prevent them from leaving their homes. It is uncertain how many people who live in the United States are homebound. OBJECTIVES To develop measures of the frequency of leaving and ability to leave the home and to use these measures to estimate the size of the homebound population in the US population. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional data from the National Health and Aging Trends Study collected in 2011 in the contiguous United States. Participants were a nationally representative sample of 7603 noninstitutionalized Medicare beneficiaries 65 years and older. MAIN OUTCOMES AND MEASURES We defined homebound persons as those who never (completely homebound) or rarely (mostly homebound) left the home in the last month. We defined semihomebound persons as those who only left the home with assistance or had difficulty or needed help leaving the home. We compared demographic, clinical, and health care utilization characteristics across different homebound status categories. RESULTS In 2011, the prevalence of homebound individuals was 5.6%(95% CI, 5.1%-6.2%), including an estimated 395 422 people who were completely homebound and 1 578 984 people who were mostly homebound. Among semihomebound individuals, the prevalence of those who never left home without personal assistance was 3.3%(95% CI, 2.8%-3.8%), and the prevalence of those who required help or had difficulty was 11.7%(95% CI, 10.9%-12.6%). Completely homebound individuals were more likely to be older (83.2 vs 74.3 years, P < .001), female (67.9% vs 53.4%, P < .006), and of nonwhite race (34.1% vs 17.6%, P < .001) and have less education and income than nonhomebound individuals. They also had more chronic conditions (4.9 vs 2.5) and were more likely to have been hospitalized in the last 12 months (52.1% vs 16.2%) (P < .001 for both). Only 11.9% of completely homebound individuals reported receiving primary care services at home. CONCLUSIONS AND RELEVANCE In total, 5.6% of the elderly, community-dwelling Medicare population (approximately 2 million people) were completely or mostly homebound in 2011. Our findings can inform improvements in clinical and social services for these individuals. C1 [Ornstein, Katherine A.; Kelley, Amy S.; Siu, Albert L.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Ornstein, Katherine A.] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Ornstein, Katherine A.; Federman, Alex D.] Icahn Sch Med Mt Sinai, Dept Med, Div Gen Internal Med, New York, NY 10029 USA. [Leff, Bruce] Johns Hopkins Univ, Dept Med, Div Geriatr Med, Baltimore, MD USA. [Leff, Bruce; Roberts, Laken; Szanton, Sarah L.] Johns Hopkins Univ, Dept Community & Publ Hlth, Sch Nursing, Baltimore, MD USA. [Leff, Bruce; Szanton, Sarah L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Covinsky, Kenneth E.; Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Kelley, Amy S.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Ornstein, KA (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, POB 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM katherine.ornstein@mssm.edu FU National Institute on Aging [NIA U01AG32947, K01AG047923, 1K23AG040774-01A1]; National Palliative Care Research Center; American Federation for Aging Research; Robert Wood Johnson Foundation Nurse Faculty Scholars [69351] FX The National Health and Aging Trends Study is sponsored by grant NIA U01AG32947 from the National Institute on Aging. Dr Ornstein was supported by grant K01AG047923 from the National Institute on Aging and by the National Palliative Care Research Center. Dr Kelley was supported by grant 1K23AG040774-01A1 from the National Institute on Aging and by the American Federation for Aging Research. Dr Szanton was supported by program 69351 from the Robert Wood Johnson Foundation Nurse Faculty Scholars. NR 36 TC 15 Z9 15 U1 2 U2 4 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 JUL PY 2015 VL 175 IS 7 BP 1180 EP 1186 DI 10.1001/jamainternmed.2015.1849 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400028 PM 26010119 ER PT J AU Wierman, ME AF Wierman, Margaret E. TI Risks of Different Testosterone Preparations Too Much, Too Little, Just Right SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID THERAPY; MEN C1 [Wierman, Margaret E.] Univ Colorado, Dept Med, Sch Med, Aurora, CO 80045 USA. [Wierman, Margaret E.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO USA. RP Wierman, ME (reprint author), Univ Colorado, Dept Med, Sch Med, 12801 E 17th St,Bldg RC1S,Mail Stop 8106, Aurora, CO 80045 USA. EM margaret.wierman@ucdenver.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 JUL PY 2015 VL 175 IS 7 BP 1197 EP 1198 DI 10.1001/jamainternmed.2015.1580 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400030 PM 25961437 ER PT J AU Rothberg, MB Sivalingam, SK Kleppel, R Schweiger, M Hu, B Sepucha, KR AF Rothberg, Michael B. Sivalingam, Senthil K. Kleppel, Reva Schweiger, Marc Hu, Bo Sepucha, Karen R. TI Informed Decision Making for Percutaneous Coronary Intervention for Stable Coronary Disease SO JAMA INTERNAL MEDICINE LA English DT Article ID OPTIMAL MEDICAL THERAPY; PATIENT-CENTERED CARE; CARDIOVASCULAR ANGIOGRAPHY; HEART-ASSOCIATION; ARTERY-DISEASE; BENEFITS; CONSENT; SURGERY; REVASCULARIZATION; PERCEPTIONS AB IMPORTANCE Patients with stable coronary disease undergoing percutaneous coronary intervention (PCI) are frequently misinformed about the benefits of PCI. Little is known about the quality of decision making before angiography and possible PCI. OBJECTIVE To assess the quality of informed decision making and its association with patient decisions. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional analysis of recorded conversations between August 1, 2008, and August 31, 2012, among adults with known or suspected stable coronary disease at outpatient cardiology practices. MAIN OUTCOMES AND MEASURES Presence of 7 elements of informed decision making and the decision to undergo angiography and possible PCI. RESULTS Of 59 conversations conducted by 23 cardiologists, 2 (3%) included all 7 elements of informed decision making; 8 (14%) met a more limited definition of procedure, alternatives, and risks. Specific elements significantly associated with not choosing angiography and possible PCI included discussion of uncertainty (odds ratio [OR], 20.5; 95% CI, 2.3-204.9), patient's role (OR, 5.3; 95% CI, 1.3-21.3), exploration of alternatives (OR, 9.5; 95% CI, 2.5-36.5), and exploration of patient preference (OR, 4.8; 95% CI, 1.2-19.4). Neither the presence of angina nor severity of symptoms was associated with choosing angiography and possible PCI. In a multivariable analysis using the total number of elements as a predictor, better informed patients were less likely to choose angiography and possible PCI (OR per additional element, 3.2; 95% CI, 1.4-7.1; P = .005). CONCLUSIONS AND RELEVANCE In conversations between cardiologists and patients with stable angina, informed decision making is often incomplete. More complete discussions are associated with patients choosing not to undergo angiography and possible PCI. C1 [Rothberg, Michael B.] Cleveland Clin, Ctr Value Based Care Res, Inst Med, Cleveland, OH 44195 USA. [Sivalingam, Senthil K.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Kleppel, Reva] Baystate Med Ctr, Div Gen Med, Springfield, MA USA. [Schweiger, Marc] Baystate Med Ctr, Div Cardiol, Springfield, MA USA. [Hu, Bo] Cleveland Clin, Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Sepucha, Karen R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hlth Decis Sci, Boston, MA USA. RP Rothberg, MB (reprint author), Cleveland Clin, Ctr Value Based Care Res, Inst Med, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM rothbem@ccf.org FU Informed Medical Decisions Foundation FX The study was funded by a grant from the Informed Medical Decisions Foundation. NR 32 TC 8 Z9 8 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2015 VL 175 IS 7 BP 1199 EP 1206 DI 10.1001/jamainternmed.2015.1657 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400031 PM 25984988 ER PT J AU Austin, CA Mohottige, D Sudore, RL Smith, AK Hanson, LC AF Austin, C. Adrian Mohottige, Dinushika Sudore, Rebecca L. Smith, Alexander K. Hanson, Laura C. TI Tools to Promote Shared Decision Making in Serious Illness A Systematic Review SO JAMA INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CARDIOPULMONARY-RESUSCITATION VIDEO; MECHANICAL VENTILATION; CONSORT STATEMENT; FEEDING OPTIONS; CANCER-PATIENTS; INTENSIVE-CARE; BREAST-CANCER; SUPPORT TOOL; AID AB IMPORTANCE Serious illness impairs function and threatens survival. Patients facing serious illness value shared decision making, yet few decision aids address the needs of this population. OBJECTIVE To perform a systematic review of evidence about decision aids and other exportable tools that promote shared decision making in serious illness, thereby (1) identifying tools relevant to the treatment decisions of seriously ill patients and their caregivers, (2) evaluating the quality of evidence for these tools, and (3) summarizing their effect on outcomes and accessibility for clinicians. EVIDENCE REVIEW We searched PubMed, CINAHL, and PsychInfo from January 1, 1995, through October 31, 2014, and identified additional studies from reference lists and other systematic reviews. Clinical trials with random or nonrandom controls were included if they tested print, video, or web-based tools for advance care planning (ACP) or decision aids for serious illness. We extracted data on the study population, design, results, and risk for bias using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Each tool was evaluated for its effect on patient outcomes and accessibility. FINDINGS Seventeen randomized clinical trials tested decision tools in serious illness. Nearly all the trials were of moderate or high quality and showed that decision tools improve patient knowledge and awareness of treatment choices. The available tools address ACP, palliative care and goals of care communication, feeding options in dementia, lung transplant in cystic fibrosis, and truth telling in terminal cancer. Five randomized clinical trials provided further evidence that decision tools improve ACP documentation, clinical decisions, and treatment received. CONCLUSIONS AND RELEVANCE Clinicians can access and use evidence-based tools to engage seriously ill patients in shared decision making. This field of research is in an early stage; future research is needed to develop novel decision aids for other serious diagnoses and key decisions. Health care delivery organizations should prioritize the use of currently available tools that are evidence based and effective. C1 [Austin, C. Adrian; Hanson, Laura C.] Univ N Carolina, Ctr Aging & Hlth, Div Geriatr, Chapel Hill, NC 27599 USA. [Mohottige, Dinushika] Duke Univ, Dept Med, Durham, NC USA. [Sudore, Rebecca L.; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Sudore, Rebecca L.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hanson, Laura C.] Univ N Carolina, Palliat Care Program, Chapel Hill, NC 27599 USA. RP Hanson, LC (reprint author), Univ N Carolina, Ctr Aging & Hlth, Div Geriatr, 5003 Old Clin Bldg,Campus Box 7550, Chapel Hill, NC 27599 USA. EM laura_hanson@med.unc.edu FU National Institute on Aging [R01AG037483] FX This study was supported by grant R01AG037483 from the National Institute on Aging (principal investigator, Dr Hanson). NR 53 TC 10 Z9 10 U1 11 U2 38 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 JUL PY 2015 VL 175 IS 7 BP 1213 EP 1221 DI 10.1001/jamainternmed.2015.1679 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400033 PM 25985438 ER PT J AU Song, ZR Wallace, J Neprash, HT McKellar, MR Chernew, ME McWilliams, JM AF Song, Zirui Wallace, Jacob Neprash, Hannah T. McKellar, Michael R. Chernew, Michael E. McWilliams, J. Michael TI Medicare Fee Cuts and Cardiologist-Hospital Integration SO JAMA INTERNAL MEDICINE LA English DT Letter ID PHYSICIAN C1 [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wallace, Jacob; Neprash, Hannah T.; McKellar, Michael R.; Chernew, Michael E.; McWilliams, J. Michael] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Song, ZR (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM zirui_song@post.harvard.edu FU NIA NIH HHS [F30 AG039175] NR 6 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2015 VL 175 IS 7 BP 1229 EP 1231 DI 10.1001/jamainternmed.2015.2017 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400038 PM 26011666 ER PT J AU Cimino, T Steinman, MA Mitchell, SL Miao, YH Bharel, M Barnhart, CE Brown, RT AF Cimino, Theora Steinman, Michael A. Mitchell, Susan L. Miao, Yinghui Bharel, Monica Barnhart, Caroline E. Brown, Rebecca T. TI The Course of Functional Impairment in Older Homeless Adults: Disabled on the Street SO JAMA INTERNAL MEDICINE LA English DT Letter ID POPULATION C1 [Cimino, Theora] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Steinman, Michael A.; Barnhart, Caroline E.; Brown, Rebecca T.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Steinman, Michael A.; Miao, Yinghui; Barnhart, Caroline E.; Brown, Rebecca T.] San Francisco VA Med Ctr, Geriatr & Extended Care Serv, San Francisco, CA 94121 USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Bharel, Monica] Boston Hlth Care Homeless Program, Boston, MA USA. [Bharel, Monica] Boston Med Ctr, Dept Med, Boston, MA USA. [Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, Geriatr & Extended Care Serv, UCSF Box VA-181G,4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU NCATS NIH HHS [KL2 TR000143, KL2TR000143]; NIA NIH HHS [K23 AG030999, K23 AG045290, K23AG030999, K23AG045290, K24 AG049057, P30 AG044281, P30AG044281] NR 5 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2015 VL 175 IS 7 BP 1237 EP 1239 DI 10.1001/jamainternmed.2015.1562 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CM3SM UT WOS:000357604400044 PM 26011591 ER PT J AU Hoffmann, U Douglas, PS AF Hoffmann, Udo Douglas, Pamela S. TI The PROMISE trial: An inside perspective SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Editorial Material ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; CT ANGIOGRAPHY; CHEST-PAIN; CLINICAL-OUTCOMES; MORTALITY; DIAGNOSIS; RISK C1 [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Douglas, Pamela S.] Duke Univ, Med Ctr, Dept Med, Duke Clin Res Inst, Durham, NC 27710 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, 165 Cambridge St Suite 400, Boston, MA 02114 USA. EM uhoffmann@mgh.harvard.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2015 VL 9 IS 4 BP 252 EP 254 DI 10.1016/j.jcct.2015.05.002 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CL7JL UT WOS:000357148200003 PM 26025047 ER PT J AU Truong, QA Thai, WE Wai, B Cordaro, K Cheng, T Beaudoin, J Xiong, GL Cheung, JW Altman, R Min, JK Singh, JP Barrett, CD Danik, S AF Truong, Quynh A. Thai, Wai-ee Wai, Bryan Cordaro, Kevin Cheng, Teresa Beaudoin, Jonathan Xiong, Guanglei Cheung, Jim W. Altman, Robert Min, James K. Singh, Jagmeet P. Barrett, Conor D. Danik, Stephan TI Myocardial scar imaging by standard single-energy and dual-energy late enhancement CT: Comparison with pathology and electroanatomic map in an experimental chronic infarct porcine model SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Computed tomography; Electrophysiology; Imaging; Myocardial infarction; Myocardial scar ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; VENTRICULAR-TACHYCARDIA; DIAGNOSTIC-ACCURACY; CATHETER ABLATION; CARDIOMYOPATHY; ARRHYTHMIAS; PROTOCOLS; HEART AB Background: Myocardial scar is a substrate for ventricular tachycardia and sudden cardiac death. Late enhancement CT imaging can detect scar, but it remains unclear whether newer late enhancement dual-energy (LE-DECT) acquisition has benefit over standard single-energy late enhancement (LE-CT). Objective: We aim to compare late enhancement CT using newer LE-DECT acquisition and single-energy LE-CT acquisitions with pathology and electroanatomic map (EAM) in an experimental chronic myocardial infarction (MI) porcine study. Methods: In 8 pigs with chronic myocardial infarction (59 +/- 5 kg), we performed dual-source CT, EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes after contrast administration: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with 2 postprocessing software settings. Results: Of the sequences, LE-CT 100 kV provided the best contrast-to-noise ratio (all P <= .03) and correlation to pathology for scar (p = 0.88). LE-DECT overestimated scar (both P = .02), whereas LE-CT images did not (both P = .08). On a segment basis (n = 136), all CT sequences had high specificity (87%-93%) and modest sensitivity (50%-67%), with LE-CT 100 kV having the highest specificity of 93% for scar detection compared to pathology and agreement with EAM (kappa = 0.69). Conclusions: Standard single-energy LE-CT, particularly 100 kV, matched better to pathology and EAM than dual-energy LE-DECT for scar detection. Larger human trials as well as more technical studies that optimize varying different energies with newer hardware and software are warranted. (C) 2015 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Truong, Quynh A.; Xiong, Guanglei; Min, James K.] Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, New York, NY 10021 USA. [Truong, Quynh A.; Xiong, Guanglei; Cheung, Jim W.; Min, James K.] New York Presbyterian Hosp, New York, NY 10021 USA. [Truong, Quynh A.; Cheung, Jim W.; Min, James K.] Weill Cornell Med Coll, Div Cardiol, New York, NY 10021 USA. [Thai, Wai-ee; Wai, Bryan] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Div Cardiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cordaro, Kevin; Cheng, Teresa; Beaudoin, Jonathan; Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Altman, Robert; Barrett, Conor D.; Danik, Stephan] Mt Sinai St Lukes Roosevelt Hosp Ctr, Al Sabah Arrhythmia Inst, New York, NY USA. RP Truong, QA (reprint author), Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, 413 E 69th St,Suite 108, New York, NY 10021 USA. EM qat9001@med.cornell.edu FU National Institutes of Health's National Heart, Lung, and Blood Institute [K23HL098370, L30HL093896]; St. Jude Medical; American College of Radiology Imaging Network; Duke Clinical Research Institute; Harvard Catalyst and Qi Imaging, LLC FX Quynh A. Truong receives grant support from St. Jude Medical, American College of Radiology Imaging Network, and Duke Clinical Research Institute. She was also supported by National Institutes of Health's National Heart, Lung, and Blood Institute grants K23HL098370 and L30HL093896.; The study was funded by Harvard Catalyst and Qi Imaging, LLC. NR 19 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2015 VL 9 IS 4 BP 313 EP 320 DI 10.1016/j.jcct.2015.03.003 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CL7JL UT WOS:000357148200013 PM 25977115 ER PT J AU Blasi, F Herisson, F Wang, SX Mao, JR Ayata, C AF Blasi, Francesco Herisson, Fanny Wang, Shuxing Mao, Jianren Ayata, Cenk TI Late-onset thermal hypersensitivity after focal ischemic thalamic infarcts as a model for central post-stroke pain in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE central post-stroke pain; endothelin-1; hyperalgesia; stroke; thalamus ID STROKE; LESION; PATHOPHYSIOLOGY AB Central post-stroke pain (CPSP) is a neuropathic pain syndrome that often develops in a delayed manner after thalamic stroke. Here, we describe a new model of CPSP by stereotaxic thalamic injection of endothelin-1. Stroke rats (n = 12), but not saline-injected controls (n = 12), developed a progressive, contralateral cutaneous thermal hyperalgesia over 4 weeks, without motor deficits. Lesions were highly focal and mainly affected the ventral posterior thalamic complex. Tchis model reproduces the infarct location and delayed hypersensitivity typical of CPSP, and may be useful to investigate its pathophysiology and test therapies targeting recovery and pain after thalamic stroke. C1 [Blasi, Francesco; Herisson, Fanny; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Wang, Shuxing; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Department Anesthesia Crit Care & Pain Med, Boston, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Neurosci Intens Care Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Blasi, Francesco/G-1055-2015 OI Blasi, Francesco/0000-0002-6616-8418 FU National Institutes of Health [NS061505, NS055104]; Fondation Leducq; Neuroendovascular Research Fund from the Andrew David Heitman Foundation; Ellison Foundation FX This study was funded by the National Institutes of Health (NS061505 and NS055104), Fondation Leducq, Neuroendovascular Research Fund from the Andrew David Heitman Foundation, and The Ellison Foundation. NR 15 TC 4 Z9 5 U1 0 U2 0 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 JUL PY 2015 VL 35 IS 7 BP 1100 EP 1103 DI 10.1038/jcbfm.2015.73 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CL7FI UT WOS:000357137500006 PM 25899295 ER PT J AU Nayar, R Wilbur, DC AF Nayar, Ritu Wilbur, David C. TI The Pap Test and Bethesda 2014 SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE cervical cytology; Pap test; terminology; Bethesda system ID OF-AMERICAN-PATHOLOGISTS; TERMINOLOGY STANDARDIZATION PROJECT; CANCER SCREENING-TESTS; ASCUS-LSIL TRIAGE; CONSENSUS GUIDELINES; INTEROBSERVER REPRODUCIBILITY; CERVICAL PATHOLOGY; CYTOLOGY; MANAGEMENT; SOCIETY AB The Bethesda System for gynecologic cytopathology has standardized reporting terminology over the past quarter of a century. In doing so, it has allowed for improved communication among practitioners around the world, facilitated large research projects and clinical trials, and has provided the basis from which uniformly accepted risk-based management strategies have been developed. Over time, changes in terminology and the underlying science require revisions, and the third edition of the Bethesda Atlas is the result of a yearlong effort to provide such an update. New material was developed and proposed via an Internet bulletin board, allowing for wide commentary that was compiled and incorporated. New images were collected, which comprised many new examples of equivocal presentations and mimics. New background material on the scientific basis supporting the terminology categories, the most current management algorithms, and comprehensive references were included. The effort completely refurbishes this standard reference that forms an inexpensive and, therefore, widely available resource for the world's cytology community. C1 [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilbur, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Nayar, R (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM r-nayar@northwestern.edu NR 22 TC 3 Z9 3 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1089-2591 EI 1526-0976 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JUL PY 2015 VL 19 IS 3 BP 175 EP 184 DI 10.1097/LGT.0000000000000115 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL4PL UT WOS:000356935300001 PM 25943863 ER PT J AU Tyekucheva, S Martin, NE Stack, EC Wei, W Vathipadiekal, V Waldron, L Fiorentino, M Lis, RT Stampfer, MJ Loda, M Parmigiani, G Mucci, LA Birrer, M AF Tyekucheva, Svitlana Martin, Neil E. Stack, Edward C. Wei, Wei Vathipadiekal, Vinod Waldron, Levi Fiorentino, Michelangelo Lis, Rosina T. Stampfer, Meir J. Loda, Massimo Parmigiani, Giovanni Mucci, Lorelei A. Birrer, Michael TI Comparing Platforms for Messenger RNA Expression Profiling of Archival Formalin-Fixed, Paraffin-Embedded Tissues SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID PROBE LEVEL DATA; GENE-EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; OVARIAN-CANCER; CLEAR-CELL; SAMPLES; BIOINFORMATICS; CHEMOTHERAPY; MICROARRAYS AB Archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens represent a readily available but largely untapped resource for gene expression profiling based biomarker discovery. Severaltechnologies have been proposed to cope with the bias from RNA cross-linking and degradation associated with archival specimens to generate data comparable with RNA from fresh-frozen materials. Direct comparison studies of these RNA expression platforms remain rare. We compared two commercially available platforms for RNA expression profiling of archival FFPE specimens from clinical studies of prostate and ovarian cancer: the Affymetrix Human Gene 1.0ST Array following whole-transcriptome amplification using the NuGen WT-Ovation FFPE System V2, and the NanoString nCounter without amplification. For each assay, we profiled 7 prostate and 11 ovarian cancer specimens, with a block age of 4 to 21 years. Both platforms produced gene expression profiles with high sensitivity and reproducibility through technical repeats from FFPE materials. Sensitivity and reproducibility remained high across block age within each cohort. A strong concordance was shown for the transcript expression values for genes detected by both platforms. We showed the biological validity of specific gene signatures generated by both platforms for both cohorts. Our study supports the feasibility of gene expression profiling and Large-scale signature validation on archival prostate and ovarian tumor specimens using commercial platforms. These approaches have the potential to aid precision medicine with biomarker discovery and validation. C1 [Tyekucheva, Svitlana; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Martin, Neil E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stack, Edward C.; Lis, Rosina T.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Tyekucheva, Svitlana; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Stack, Edward C.; Lis, Rosina T.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wei, Wei; Vathipadiekal, Vinod; Birrer, Michael] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Waldron, Levi] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London, England. RP Tyekucheva, S (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. EM svitlana@jimmy.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Vathipadiekal, Vinod/0000-0002-8181-6890; WEI, WEI/0000-0002-2315-3558; Waldron, Levi/0000-0003-2725-0694 FU National Cancer Institute/NIH [1RC4CA156551-01, 5R01CA142832-05, 5R01CA141298, CA136578, CA090381]; Julie Fund; Prostate Cancer Foundation; NIH [R01CA131945, P50CA90381] FX Supported by National Cancer Institute/NIH grants 1RC4CA156551-01 and 5R01CA142832-05 (M.B.), 5R01CA141298 (M.J.S.), and CA136578 and CA090381 (L.A.M.); The Julie Fund; the Prostate Cancer Foundation; and by NIH grants R01CA131945 and P50CA90381 (M.L.). NR 39 TC 4 Z9 4 U1 1 U2 6 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 JUL PY 2015 VL 17 IS 4 BP 374 EP 381 DI 10.1016/j.jmoldx.2015.02.002 PG 8 WC Pathology SC Pathology GA CM1LE UT WOS:000357441600006 PM 25937617 ER PT J AU Yang, Y Keene, CD Peskind, ER Galasko, DR Hu, SC Cudaback, E Wilson, AM Li, G Yu, CE Montine, KS Zhang, J Baird, GS Hyman, BT Montine, TJ AF Yang, Yue Keene, C. Dirk Peskind, Elaine R. Galasko, Douglas R. Hu, Shu-Ching Cudaback, Eiron Wilson, Angela M. Li, Ge Yu, Chang-En Montine, Kathleen S. Zhang, Jing Baird, Geoffrey S. Hyman, Bradley T. Montine, Thomas J. TI Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Biomarkers; Cerebrospinal fluid; Cognitive impairment; Neurodegenerative disease; Parkinson disease ID APOLIPOPROTEIN-A-I; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; MILD COGNITIVE IMPAIRMENT; TARGETED REPLACEMENT MICE; HUMAN-PLASMA-LIPOPROTEINS; GENOME-WIDE ASSOCIATION; CEREBRAL SPINAL-FLUID; E APOE POLYMORPHISM; EXTRACELLULAR VESICLES AB Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ-, and amyloid (A) (42)-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitive impairment (MCI), Alzheimer disease (AD) dementia, or Parkinson disease. APOE epsilon 4/epsilon 4 participants had CSF apoE-positive particles that were more frequently larger but at an 88% lower level versus those in APOE epsilon 3/epsilon 3 or APOE epsilon 3/epsilon 4 patients; this finding was reproduced in conditioned medium from mouse primary glial cell cultures with targeted replacement of apoE. Cerebrospinal fluid apoE-positive and -amyloid (A(42))-positive particle concentrations were persistently reduced one-third to one-half in middle and older age subjects; apoAI-positive particle concentration progressively increased approximately 2-fold with age. Both apoAI-positive and annexin V-positive CSF particle levels were reduced one-third to one-half in CSF of MCI and/or AD dementia patients versus age-matched controls. Our approach provides new methods to investigate CNS lipid biology in relation to neurodegeneration and perhaps develop new biomarkers for diagnosis or treatment monitoring. C1 [Yang, Yue; Keene, C. Dirk; Cudaback, Eiron; Wilson, Angela M.; Montine, Kathleen S.; Zhang, Jing; Baird, Geoffrey S.; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Peskind, Elaine R.; Li, Ge] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, VA Northwest Network Mental Illness Res Educ & Cl, Seattle, WA USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Hu, Shu-Ching] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Yu, Chang-En] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Yu, Chang-En] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Baird, Geoffrey S.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, POB 357470, Seattle, WA 98195 USA. EM tmontine@u.washington.edu RI Keene, Christopher/N-1806-2015 FU Department of Veterans Affairs [P50 AG05136, P50 NS62684, P50 AG05131]; Nancy and Buster Alvord Endowment FX This work was supported by P50 AG05136, P50 NS62684, P50 AG05131, the Department of Veterans Affairs, and the Nancy and Buster Alvord Endowment. NR 130 TC 8 Z9 8 U1 1 U2 11 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 JUL PY 2015 VL 74 IS 7 BP 672 EP 687 DI 10.1097/NEN.0000000000000207 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CL4QA UT WOS:000356937000003 PM 26083568 ER PT J AU Nigim, F Cavanaugh, J Patel, AP Curry, WT Esaki, S Kasper, EM Chi, AS Louis, DN Martuza, RL Rabkin, SD Wakimoto, H AF Nigim, Fares Cavanaugh, Jill Patel, Anoop P. Curry, William T. Esaki, Shin-ichi Kasper, Ekkehard M. Chi, Andrew S. Louis, David N. Martuza, Robert L. Rabkin, Samuel D. Wakimoto, Hiroaki TI Targeting Hypoxia-Inducible Factor 1 alpha in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Glioblastoma; Glioblastoma stem cells; Hypoxia; Hypoxia inducible factor 1 (HIF-1); Molecular targeted therapy; Necrosis; Orthotopic xenograft model ID HUMAN GLIOMA-CELLS; PRIMARY BRAIN-TUMORS; STEM-CELLS; CANCER-THERAPY; FACTOR-1-ALPHA PROTEIN; MALIGNANT GLIOMAS; XENOGRAFT MODELS; EXPRESSION; PROGRESSION; PATHWAY AB Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1 (HIF-1) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1 and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 m distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1 expression in cultured MGG123 cells, which was abrogated by the HIF-1 inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1 expression, vascular endothelial growth factor mRNA levels, and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness and is a suitable platform for studying disease biology and developing hypoxia-targeted agents. C1 [Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P.; Curry, William T.; Esaki, Shin-ichi; Martuza, Robert L.; Rabkin, Samuel D.; Wakimoto, Hiroaki] Harvard Univ, Dept Neurosurg, Sch Med, Boston, MA 02114 USA. [Kasper, Ekkehard M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02114 USA. [Chi, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Div Hematol Oncol,Dept Neurol,Sch Med, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Wakimoto, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM hwakimoto@mgh.harvard.edu FU National Institute of Health [R01NS032677]; ABTA discovery grant FX This work was supported by a grant from the National Institute of Health (Grant Number R01NS032677) and the ABTA discovery grant. NR 60 TC 3 Z9 3 U1 0 U2 6 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 JUL PY 2015 VL 74 IS 7 BP 710 EP 722 DI 10.1097/NEN.0000000000000210 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CL4QA UT WOS:000356937000006 PM 26083570 ER PT J AU LaVela, SL Landers, K Etingen, B Karalius, VP Miskevics, S AF LaVela, Sherri L. Landers, Kelsie Etingen, Bella Karalius, Vytas P. Miskevics, Scott TI Factors related to caregiving for individuals with spinal cord injury compared to caregiving for individuals with other neurologic conditions SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Caregiving; Spinal cord injury; Sleep; Coronary heart disease; Obesity ID QUALITY-OF-LIFE; CORONARY-HEART-DISEASE; TRAUMATIC BRAIN-INJURY; SHORT-SLEEP DURATION; FAMILY CAREGIVERS; SPOUSAL CAREGIVERS; HEALTH; DEPRESSION; PEOPLE; BURDEN AB Context/objective: To compare outcomes among caregivers of adults with spinal cord injuries (SCIs) to caregivers of adults with other neurological conditions, and determine if caregiving for SCI is associated with poor health status and chronic conditions. Design: Secondary data analysis of 2009/2010 Behavioral Risk Factor Surveillance System survey. Participants: Informal caregivers of adults with neurological conditions. Outcome measures: Sociodemographics, caregiving factors (e.g. role, emotional support, life satisfaction), lifestyle behaviors, chronic conditions, and health status. Results: Demographics and lifestyle behaviors did not differ in caregivers of adults with SCI vs. caregivers of adults with other neurological conditions (except younger age of SCI caregivers). Greater proportions of caregivers of adults with SCI had coronary heart disease (CHD) (12% vs. 6%, P = 0.06) and were obese (43% vs. 28%, P = 0.03). Frequent physical distress was reported by 20% of caregivers of persons with SCI (vs. 12% of other caregivers, P = 0.09), but mental health did not differ between caregiver groups. A greater proportion of caregivers of adults with SCI experienced insufficient sleep (47% vs. 30%, P = 0.008) and more days without enough sleep (13 vs. 9 days, P = 0.008). Odds of being younger, caregiver of a spouse, having CHD, and being obese were associated with being a caregiver of an adult with SCI. Conclusion: Caregivers of adults with SCI report similar mental health status, but more poor sleep, and have increased odds of CHD and obesity. Interventions to address physical distress, improve sleep, and address CHD and obesity are needed in this cohort. C1 [LaVela, Sherri L.; Landers, Kelsie; Etingen, Bella; Miskevics, Scott] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hlth Serv Res & Dev, Hines, IL 60141 USA. [LaVela, Sherri L.; Etingen, Bella; Karalius, Vytas P.; Miskevics, Scott] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat S, Hines, IL 60141 USA. [LaVela, Sherri L.; Landers, Kelsie; Etingen, Bella; Miskevics, Scott] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Evaluat Practices & Experiences Patient Ctr C, Hines, IL 60141 USA. [LaVela, Sherri L.] Northwestern Univ, Ctr Healthcare Studies, Inst Publ Hlth & Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Karalius, Vytas P.] Loyola Univ, Dept Publ Hlth Sci, Stritch Sch Med, Maywood, IL 60153 USA. RP Etingen, B (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hlth Serv Res & Dev, 151-H,Bldg 1,Off D 322,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM Bella.Etingen@va.gov FU Veterans Health Administration, Health Services Research and Development (HSRD) Service [LIP 42-125] FX This work was supported by the Veterans Health Administration, Health Services Research and Development (HSR&D) Service (LIP 42-125). NR 54 TC 0 Z9 0 U1 3 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2015 VL 38 IS 4 BP 505 EP 514 DI 10.1179/2045772314Y.0000000240 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CL4RS UT WOS:000356941800013 PM 24993244 ER PT J AU Udler, MS Nadkarni, GN Belbin, G Lotay, V Wyatt, C Gottesman, O Bottinger, EP Kenny, EE Peter, I AF Udler, Miriam S. Nadkarni, Girish N. Belbin, Gillian Lotay, Vaneet Wyatt, Christina Gottesman, Omri Bottinger, Erwin P. Kenny, Eimear E. Peter, Inga TI Effect of Genetic African Ancestry on eGFR and Kidney Disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE epidemiology and outcomes; ethnicity; genetic renal disease; GFR; renal function; apolipoprotein L1 ID GLOMERULAR-FILTRATION-RATE; ARTERY RISK DEVELOPMENT; GENOME-WIDE PATTERNS; YOUNG-ADULTS CARDIA; RENAL-DISEASE; PERSONALIZED MEDICINE; POPULATION-STRUCTURE; APOL1 VARIANTS; AMERICANS; ASSOCIATION AB Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P1x10(-7)). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m(2), and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of 50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. C1 [Udler, Miriam S.; Nadkarni, Girish N.; Wyatt, Christina; Gottesman, Omri; Bottinger, Erwin P.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Udler, Miriam S.; Belbin, Gillian; Kenny, Eimear E.; Peter, Inga] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Udler, Miriam S.; Nadkarni, Girish N.; Belbin, Gillian; Lotay, Vaneet; Gottesman, Omri; Bottinger, Erwin P.; Kenny, Eimear E.; Peter, Inga] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Nadkarni, Girish N.; Wyatt, Christina; Bottinger, Erwin P.] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY 10029 USA. [Kenny, Eimear E.] Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY 10029 USA. [Kenny, Eimear E.; Peter, Inga] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. RP Udler, MS (reprint author), Massachusetts Gen Hosp, Thier 11-1101,50 Blossom St, Boston, MA 02114 USA. EM mudler@mgh.harvard.edu FU Andrea and Charles Bronfman Philantropies; eMERGE Network Grant [U01-HG006380]; National Human Genome Research Institute [U01-HG006380, U01-HG006828, U01-HG006830, U01-HG006389, U01-HG006382, U01-HG006375, U01-HG006379, U01-HG006388, U01-HG006378, U01-HG006385] FX The BioMe Biobank program is supported by The Andrea and Charles Bronfman Philantropies. O.G., E.P.B., E.E.K. and I.P. were supported, in part, by eMERGE Network Grant U01-HG006380 (to E.P.B.). The Electronic Medical Records and Genomics Network was initiated and funded by the National Human Genome Research Institute through Grants U01-HG006828 (to Cincinnati Children's Hospital Medical Center/Harvard), U01-HG006830 (to Children's Hospital of Philadelphia), U01-HG006389 (to Essentia Institute of Rural Health), U01-HG006382 (to Geisinger Clinic), U01-HG006375 (to Group Health Cooperative), U01-HG006379 (to Mayo Clinic), U01-HG006380 (to Icahn School of Medicine at Mount Sinai), U01-HG006388 (to Northwestern University), U01-HG006378 (to Vanderbilt University), and U01-HG006385 (to Vanderbilt University serving as the Coordinating Center). NR 43 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2015 VL 26 IS 7 BP 1682 EP 1692 DI 10.1681/ASN.2014050474 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CM0UE UT WOS:000357393300022 PM 25349204 ER PT J AU Saraceni, C Li, PM Gainor, JF Stopyra, GA Friedman, EL AF Saraceni, Christine Li, P. Mark Gainor, Justin F. Stopyra, Gary A. Friedman, Eliot L. TI Cystic Brain Metastases in NSCLC Harboring the EML4-ALK Translocation after Treatment with Crizotinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; CENTRAL-NERVOUS-SYSTEM; PROGRESSION; SAFETY C1 [Saraceni, Christine; Li, P. Mark; Stopyra, Gary A.; Friedman, Eliot L.] Lehigh Valley Hlth Network, Allentown, PA USA. [Gainor, Justin F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Lehigh Valley Hlth Network, Hlth Network Labs, Allentown, PA USA. RP Friedman, EL (reprint author), Div Hematol & Med Oncol, 1240 S Cedar Crest Blvd,Suite 401, Allentown, PA 18103 USA. EM Eliot_L.Friedman@lvhn.org NR 12 TC 5 Z9 5 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUL PY 2015 VL 10 IS 7 BP 1116 EP 1117 DI 10.1097/JTO.0000000000000409 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CL4SK UT WOS:000356944100018 PM 26134230 ER PT J AU Mesar, T Martin, D Lawless, R Podbielski, J Cook, M Underwood, S Larentzakis, A Cotton, B Fagenholz, P Schreiber, M Holcomb, JB Marini, J Sharma, U Rago, AP King, DR AF Mesar, Tomaz Martin, David Lawless, Ryan Podbielski, Jeanette Cook, Mackenzie Underwood, Sam Larentzakis, Andreas Cotton, Bryan Fagenholz, Peter Schreiber, Martin Holcomb, John B. Marini, John Sharma, Upma Rago, Adam P. King, David R. TI Human dose confirmation for self-expanding intra-abdominal foam: A translational, adaptive, multicenter trial in recently deceased human subjects SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Scientific Assembly of the Eastern-Association-for-the-Surgery-of-Trauma CY JAN 13-17, 2015 CL Lake Buena Vista, FL SP Eastern Assoc Surg Trauma DE Trauma; foam; noncompressible hemorrhage; translational; dosing ID COMBAT CASUALTY CARE; BODY HABITUS; PREHOSPITAL TREATMENT; ABDOMINAL HEMORRHAGE; LAPAROSCOPIC ACCESS; IMPROVES SURVIVAL; CLOSED-ABDOMEN; RECENTLY DEAD; INJURY; BATTLEFIELD AB BACKGROUND Noncompressible abdominal bleeding accounts for significant mortality in both military and civilian populations. There is an emergent need for a temporary hemostatic intervention whenever surgical care is not immediately available. Our team previously described a self-expanding polyurethane foam for the treatment of exsanguinating abdominal hemorrhage. The objective of this study was to translate a safe and effective swine dose into an appropriate human dose through foam administration in recently deceased humans with representative tissue compliance. METHODS With institutional review board oversight and informed consent at three centers, terminal patients were identified. Within 3 hours of death, the abdomen was accessed, and fluid was added to simulate hemorrhage. Foam was percutaneously administered using a prototype delivery system at multiple doses (45, 55, 65, 75, and 100 mL). Intra-abdominal pressure was monitored for 15 minutes, and then, foam was removed via laparotomy to assess abdominal tissue contact. RESULTS Twenty-one recently deceased patients ranging in age from 20 years to 92 years and body mass index from 18 kg/m(2) to 39 kg/m(2) were enrolled in the study. Foam was administered at a mean (SD) of 146 (34) minutes after death. Three subjects were screen failures, and three subjects were excluded from the analysis because of experimental errors. Change in intra-abdominal pressure and semiquantitative organ contact were used as surrogates to compare findings between humans and swine. Doses of 45, 55, and 65 mL resulted in peak pressures of 37 (20), 28 (8.1), and 33 (20) mmHg, respectively, within the acceptable range established in swine studies. Foam deployments of 75 mL and 100 mL exceeded acceptable pressures defined in swine. Higher foam doses tended to improve contact with the diaphragm, paracolic gutters, and liver. CONCLUSION The use of recently deceased humans demonstrates a novel approach to device evaluation in representative human anatomy, particularly when tissue compliance is critical. Sixty-five milliliters was determined to be the clinically appropriate dose for foam treatment in bleeding human patients. C1 [Mesar, Tomaz; Larentzakis, Andreas; Fagenholz, Peter; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02141 USA. [Mesar, Tomaz; Larentzakis, Andreas; Fagenholz, Peter; King, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Marini, John; Sharma, Upma; Rago, Adam P.] Arsenal Med Inc, Watertown, MA USA. [Lawless, Ryan; Podbielski, Jeanette; Cotton, Bryan; Holcomb, John B.] Univ Texas Hlth Sci Ctr Houston, Div Acute Care Surg, Dept Surg, Ctr Translat Injury Res, Houston, TX 77030 USA. [Martin, David; Cook, Mackenzie; Underwood, Sam; Schreiber, Martin] Oregon Hlth & Sci Univ, Dept Surg, Div Trauma Crit Care & AcuteCare Surg, Portland, OR 97201 USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@mgh.harvard.edu; dking3@mgh.harvard.edu OI King, David/0000-0003-1028-1478 FU DARPA; MRMC; ARO [W911NF-12-C-0066] FX This work was supported by DARPA, MRMC, and ARO contract W911NF-12-C-0066. NR 35 TC 2 Z9 2 U1 1 U2 3 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 JUL PY 2015 VL 79 IS 1 BP 39 EP 47 DI 10.1097/TA.0000000000000696 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CL7LN UT WOS:000357153700006 PM 26091312 ER PT J AU Yeh, DD Naraghi, L Larentzakis, A Nielsen, N Dzik, W Bittner, EA Chang, YC Kaafarani, HMA Fagenholz, P Lee, J DeMoya, M King, DR Velmahos, G AF Yeh, Daniel Dante Naraghi, Leily Larentzakis, Andreas Nielsen, Nathan Dzik, Walter Bittner, Edward A. Chang, Yuchiao Kaafarani, Haytham M. A. Fagenholz, Peter Lee, Jarone DeMoya, Marc King, David R. Velmahos, George TI Peer-to-peer physician feedback improves adherence to blood transfusion guidelines in the surgical intensive care unit SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Scientific Assembly of the Eastern-Association-for-the-Surgery-of-Trauma CY JAN 13-17, 2015 CL Lake Buena Vista, FL SP Eastern Assoc Surg Trauma DE Transfusion; ICU; feedback ID DIAGNOSTIC-TESTS; INTERVENTIONS; STRATEGIES; BEHAVIOR; TRIAL AB BACKGROUND Translation of evidence to practice regarding adherence to published guidelines for transfusion of red blood cells (RBCs) in critically ill patients is sometimes suboptimal. We sought to use a multimodal intervention founded on peer-to-peer feedback and monthly audit to increase adherence to restrictive RBC transfusion guidelines. METHODS We conducted a prospective interventional study with a preintervention and postintervention comparison in our tertiary care center. For the 6-month preintervention period (January 1, 2013, to June 31, 2013) and the 6-month postintervention period (October 1, 2013, to March 31, 2014), all RBCs transfused in the surgical intensive care unit (SICU) were evaluated for pretransfusion hemoglobin (Hgb) trigger (TRIG). During the intervention, if stable low-risk patients were transfused outside of restrictive guidelines, the clinicians received e-mail notification and education from a surgeon colleague within 72 hours of transfusion. The mean TRIG, percentage of transfusions with TRIG greater than 8.0 g/dL, and rate of overtransfusion (posttransfusion Hgb > 10) were compared before and after intervention. RESULTS For stable, low-risk patients, mean TRIG decreased from 7.6 g/dL to 7.1 g/dL (p < 0.001) and percentage of transfusions with TRIG greater than 8.0 g/dL decreased from 25% to 2% (p < 0.001) The overtransfusion rate decreased from 11%to 3% (p = 0.001). Total 6-month transfusions decreased from 284 U to 181 U, a 36% decrease. There were no significant differences in median SICU or hospital lengths of stay. Although SICU discharge Hgb and hospital discharge Hgb were significantly lower in the intervention period (8.4 vs. 8.6 [p = 0.037] and 8.6 vs. 9.0 [p = 0.003]), 30-day readmission and mortality rates were similar. CONCLUSION A blood management program based on peer e-mail feedback was effective in improving adherence to guideline recommendations for transfusion of RBCs in stable, low-risk SICU patients. LEVEL OF EVIDENCE Therapeutic/care management study, level IV. C1 [Yeh, Daniel Dante; Larentzakis, Andreas; Dzik, Walter; Bittner, Edward A.; Chang, Yuchiao; Kaafarani, Haytham M. A.; Fagenholz, Peter; Lee, Jarone; DeMoya, Marc; King, David R.; Velmahos, George] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Naraghi, Leily] Maimonides Hosp, Brooklyn, NY 11219 USA. [Nielsen, Nathan] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. RP Yeh, DD (reprint author), Massachusetts Gen Hosp, 165 Cambridge St 810, Boston, MA 02114 USA. EM Dyeh2@partners.org OI King, David/0000-0003-1028-1478 NR 23 TC 2 Z9 2 U1 1 U2 3 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 JUL PY 2015 VL 79 IS 1 BP 65 EP 70 DI 10.1097/TA.0000000000000683 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CL7LN UT WOS:000357153700010 PM 26091316 ER PT J AU Matsushita, K Coresh, J Sang, YY Chalmers, J Fox, C Guallar, E Jafar, T Jassal, SK Landman, GWD Muntner, P Roderick, P Sairenchi, T Schottker, B Shankar, A Shlipak, M Tonelli, M Townend, J van Zuilen, A Yamagishi, K Yamashita, K Gansevoort, R Sarnak, M Warnock, DG Woodward, M Arnlov, J AF Matsushita, Kunihiro Coresh, Josef Sang, Yingying Chalmers, John Fox, Caroline Guallar, Eliseo Jafar, Tazeen Jassal, Simerjot K. Landman, Gijs W. D. Muntner, Paul Roderick, Paul Sairenchi, Toshimi Schoettker, Ben Shankar, Anoop Shlipak, Michael Tonelli, Marcello Townend, Jonathan van Zuilen, Arjan Yamagishi, Kazumasa Yamashita, Kentaro Gansevoort, Ron Sarnak, Mark Warnock, David G. Woodward, Mark Arnlov, Johan CA CKD Prognosis Consortium TI Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; ARTERY-DISEASE; CYSTATIN C; RISK; CREATININE; MORTALITY; HEART; CKD; ASSOCIATION; EQUATION AB Background The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. Methods We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2-19.0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0.0139 [95% CI 0.0105- 0.0174] for ACR and 0.0065 [0.0042-0.0088] for eGFR) and heart failure (0.0196 [0.0108-0.0284] and 0.0109 [0.0059-0.0159]) than for coronary disease (0.0048 [0.0029-0.0067] and 0.0036 [0.0019-0.0054]) and stroke (0.0105 [0.0058-0.0151]and 0.0036 [0.0004-0.0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0.0227 (0.0158-0.0296) after omission of eGFR and ACR compared with less than 0.007 for any single modifiable traditional predictor. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. C1 [Matsushita, Kunihiro; Coresh, Josef; Sang, Yingying; Guallar, Eliseo; Woodward, Mark] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chalmers, John; Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Fox, Caroline] NHLBI, Framingham Heart Study & Ctr Populat Studies, Framingham, MA USA. [Jafar, Tazeen] Duke NUS Grad Med Sch, Singapore, Singapore. [Jassal, Simerjot K.] VA San Diego Healthcare, San Diego, CA USA. [Jassal, Simerjot K.] Univ Calif San Diego, San Diego, CA 92103 USA. [Landman, Gijs W. D.] Isala Hosp, Diabet Ctr Zwolle, Zwolle, Netherlands. [Muntner, Paul; Warnock, David G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Roderick, Paul] Univ Southampton, Fac Med, Primary Care & Populat Sci, Southampton SO9 5NH, Hants, England. [Sairenchi, Toshimi] Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Shimotsuga, Tochigi, Japan. [Schoettker, Ben] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Shlipak, Michael] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA 94143 USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tonelli, Marcello] Univ Calgary, Dept Med, Calgary, AB, Canada. [Townend, Jonathan] Queen Elizabeth Hosp, Dept Cardiol, Birmingham B15 2TH, W Midlands, England. [van Zuilen, Arjan] Univ Utrecht, Med Ctr, Dept Hypertens & Nephrol, Utrecht, Netherlands. [Yamagishi, Kazumasa] Univ Tsukuba, Fac Med, Dept Publ Hlth Med, Tsukuba, Ibaraki, Japan. [Yamashita, Kentaro] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi 4648601, Japan. [Gansevoort, Ron] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [Sarnak, Mark] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England. [Arnlov, Johan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Arnlov, Johan] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden. RP Coresh, J (reprint author), Data Coordinating Ctr, Chron Kidney Dis Prognosis Consortium, Baltimore, MD 21205 USA. EM ckdpc@jhmi.edu RI Wetzels, Jack/A-1720-2014; Woodward, Mark/D-8492-2015; Tonelli, Marcello/B-3028-2009; Stengel, Benedicte/G-5730-2015; Brenner, Hermann/B-4627-2017; Moyes, Simon/D-2574-2017 OI Emberson, Jonathan/0000-0001-7792-9422; Grams, Morgan/0000-0002-4430-6023; yamagishi, kazumasa/0000-0003-3301-5519; Kenealy, Timothy/0000-0001-6002-4766; Brenner, Hermann/0000-0002-6129-1572; Moyes, Simon/0000-0001-9580-1545 FU US National Kidney Foundation; National Institute of Diabetes and Digestive and Kidney Diseases FX US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases. NR 33 TC 56 Z9 57 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JUL PY 2015 VL 3 IS 7 BP 514 EP 525 DI 10.1016/S2213-8587(15)00040-6 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM1DC UT WOS:000357419500027 PM 26028594 ER PT J AU Goede, SL Kuntz, KM van Ballegooijen, M Knudsen, AB Lansdorp-Vogelaar, I Tangka, FK Howard, DH Chin, J Zauber, AG Seeff, LC AF Goede, Simon L. Kuntz, Karen M. van Ballegooijen, Marjolein Knudsen, Amy B. Lansdorp-Vogelaar, Iris Tangka, Florence K. Howard, David H. Chin, Joseph Zauber, Ann G. Seeff, Laura C. TI Cost-Savings to Medicare From Pre-Medicare Colorectal Cancer Screening SO MEDICAL CARE LA English DT Article DE colorectal cancer; screening; computer simulation; prevention and control ID SOCIETY-TASK-FORCE; LARGE-BOWEL; AMERICAN-COLLEGE; LARGE-INTESTINE; UNITED-STATES; COLONOSCOPY; POLYPS; AUTOPSY; COLON; CARE AB Background:Many individuals have not received recommended colorectal cancer (CRC) screening before they become Medicare eligible at the age of 65. We aimed to estimate the long-term implications of increased CRC screening in the pre-Medicare population (50-64 y) on costs in the pre-Medicare and Medicare populations (65+ y).Methods:We used 2 independently developed microsimulation models [Microsimulation Screening Analysis Colon (MISCAN) and Simulation Model of CRC (SimCRC)] to project CRC screening and treatment costs under 2 scenarios, starting in 2010: current trends (60% of the population up-to-date with screening recommendations) and enhanced participation (70% up-to-date). The population was scaled to the projected US population for each year between 2010 and 2060. Costs per year were derived by age group (50-64 and 65+ y).Results:By 2060, the discounted cumulative total costs in the pre-Medicare population were $35.7 and $28.1 billion higher with enhanced screening participation, than in the current trends scenario ($252.1 billion with MISCAN and $239.5 billion with SimCRC, respectively). Because of CRC treatment savings with enhanced participation, cumulative costs in the Medicare population were $18.3 and $32.7 billion lower (current trends: $423.5 billion with MISCAN and $372.8 billion with SimCRC). Over the 50-year time horizon an estimated 60% (MISCAN) and 89% (SimCRC) of the increased screening costs could be offset by savings in Medicare CRC treatment costs.Conclusion:Increased CRC screening participation in the pre-Medicare population could reduce CRC incidence and mortality, whereas the additional screening costs can be largely offset by long-term Medicare treatment savings. C1 [Goede, Simon L.; van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris] Erasmus Univ, Dept Publ Hlth, Med Ctr, NL-3000 CA Rotterdam, Netherlands. [Kuntz, Karen M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA. [Knudsen, Amy B.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Tangka, Florence K.; Seeff, Laura C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Howard, David H.] Emory Univ, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Chin, Joseph] Ctr Medicare Serv, Coverage & Anal Grp, Baltimore, MD USA. [Chin, Joseph] Ctr Medicaid Serv, Coverage & Anal Grp, Baltimore, MD USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Goede, SL (reprint author), Erasmus Univ, Dept Publ Hlth, Med Ctr, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM s.goede@erasmusmc.nl FU National Cancer Institute at the National Institutes of Health [U01-CA-088204, U01-CA-097426, U01-CA-115953, U01-CA-152959]; Centers for Disease Control and Prevention FX Supported by the National Cancer Institute at the National Institutes of Health (grants: U01-CA-088204, U01-CA-097426, U01-CA-115953, and U01-CA-152959) for the Cancer Intervention and Surveillance Modeling Network with supplemental funding from the Centers for Disease Control and Prevention. D.H.H.'s time on the project was supported by an Interagency Personnel Agreement with the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, the National Cancer Institute, or the National Institutes of Health. NR 47 TC 2 Z9 2 U1 0 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 JUL PY 2015 VL 53 IS 7 BP 630 EP 638 DI 10.1097/MLR.0000000000000380 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CL4QE UT WOS:000356937400010 PM 26067885 ER PT J AU Wong, HKA El Fatimy, R Onodera, C Wei, ZY Yi, M Mohan, A Gowrisankaran, S Karmali, P Marcussont, E Wakimoto, H Stephens, R Uhlmann, EJ Song, JS Tannous, B Krichevsky, AM AF Wong, Hon-Kit Andus El Fatimy, Rachid Onodera, Courtney Wei, Zhiyun Yi, Ming Mohan, Athul Gowrisankaran, Sindhuja Karmali, Priya Marcussont, Eric Wakimoto, Hiroaki Stephens, Robert Uhlmann, Erik J. Song, Jun S. Tannous, Bakhos Krichevsky, Anna M. TI The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma SO MOLECULAR THERAPY LA English DT Article ID HYPOXIA-INDUCIBLE FACTORS; TUMOR-INITIATING CELLS; STEM-CELLS; ENDOTHELIAL-CELLS; IN-VIVO; GLIOMA; NOTCH; PATHWAY; MAINTENANCE; INHIBITION AB Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two "risky" miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two nniRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1 alpha and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of unconnplexed antagomirs in orthotopic glioma. C1 [Wong, Hon-Kit Andus; El Fatimy, Rachid; Wei, Zhiyun; Mohan, Athul; Gowrisankaran, Sindhuja; Uhlmann, Erik J.; Krichevsky, Anna M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wong, Hon-Kit Andus; El Fatimy, Rachid; Wei, Zhiyun; Mohan, Athul; Gowrisankaran, Sindhuja; Uhlmann, Erik J.; Krichevsky, Anna M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Onodera, Courtney; Song, Jun S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yi, Ming; Stephens, Robert] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res & Technol Program, Frederick, MD USA. [Karmali, Priya; Marcussont, Eric] Regulus Therapeut Inc, San Diego, CA USA. [Wakimoto, Hiroaki] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Tannous, Bakhos] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Tannous, Bakhos] Harvard Univ, Sch Med, Charlestown, MA USA. RP Krichevsky, AM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Neurol,Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. EM akrichevsky@rics.bwh.harvard.edu RI Wei, Zhiyun/E-2008-2016 OI Wei, Zhiyun/0000-0002-3554-4142 FU NIH/NCI [R01CA138734, R01CA163336]; Sontag Foundation Distinguished Scientist Award; National Brain Tumor Society; Brain Science Foundation FX This work was supported by grants from NIH/NCI (R01CA138734), Sontag Foundation Distinguished Scientist Award, National Brain Tumor Society, and Brain Science Foundation to AMK, and NIH/NCI R01CA163336 and Sontag Foundation Distinguished Scientist Award to J.S.S. We thank Regulus Therapeutics, Inc. for providing us with specific antagomirs. There is no potential conflict of interest NR 51 TC 13 Z9 14 U1 1 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 JUL PY 2015 VL 23 IS 7 BP 1234 EP 1247 DI 10.1038/mt.2015.72 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CM0FY UT WOS:000357355000013 PM 25903473 ER PT J AU Guo, ZD Xu, L Wang, XY Sun, XC AF Guo, Zongduo Xu, Liang Wang, Xiaoying Sun, Xiaochuan TI MMP-9 expression and activity is concurrent with endothelial cell apoptosis in the basilar artery after subarachnoid hemorrhaging in rats SO NEUROLOGICAL SCIENCES LA English DT Article DE Matrix metalloproteinase 9; Subarachnoid hemorrhage; Vascular endothelial cell; Basilar artery ID EARLY BRAIN-INJURY; MODEL; INHIBITION; PATHWAY AB Subarachnoid hemorrhage refers to one kind of lethal stroke. While several studies have shown the role of matrix metalloproteinase 9 in cerebral tissues and microvasculature after subarachnoid hemorrhage the role of matrix metalloproteinase 9 in large cerebral vasculature is limited, The present study aimed at investigating the relationship between the expression and activity of matrix metalloproteinase 9 and vascular endothelial cell apoptosis in the basilar artery at early-stage post-subarachnoid hemorrhaging in rats. The expression and activity of matrix metalloproteinase 9 in the basilar artery increased at 12 h after subarachnoid hemorrhage and peaked at 24 h. Concurrently, the number of apoptotic cells in the basilar artery increased at 12 h and peaked at 24 h following subarachnoid hemorrhage. Additionally, laminin and cleaved caspase 3 reached to their lowest and highest levels at 24 h after subarachnoid hemorrhage, respectively. Our results suggested that the change in expression and activity of matrix metalloproteinase 9 paralleled that of apoptotic cells in the basilar artery following subarachnoid hemorrhage. Matrix metalloproteinase 9 may be contributing to the injury of the basilar artery after subarachnoid hemorrhage via laminin degradation. Although the underlying mechanisms need to be explored further, our study has shown a potential association of matrix metalloproteinase 9 with injury of the basilar artery and can be associated with early-stage brain injury following subarachnoid hemorrhage. C1 [Guo, Zongduo; Sun, Xiaochuan] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing, Peoples R China. [Xu, Liang] Zhejiang Univ, Dept Neurosurg, Affiliated Hosp 2, Sch Med, Hangzhou 310027, Zhejiang, Peoples R China. [Wang, Xiaoying] Harvard Univ, Neuroprotect Res Lab, Dept Neurol & Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. RP Guo, ZD (reprint author), Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing, Peoples R China. EM stonegzd@gmail.com FU National Natural Science Foundation of China [81100865] FX This work was undertaken at the First Affiliated Hospital of Chongqing Medical University, which received funding from project (No. 81100865) supported by National Natural Science Foundation of China. NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 1590-1874 EI 1590-3478 J9 NEUROL SCI JI Neurol. Sci. PD JUL PY 2015 VL 36 IS 7 BP 1241 EP 1245 DI 10.1007/s10072-015-2092-6 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL5ZH UT WOS:000357043900023 PM 25627354 ER PT J AU Papp, KV Amariglio, RE Mormino, EC Hedden, T Dekhytar, M Johnson, KA Sperling, RA Rentz, DM AF Papp, Kathryn V. Amariglio, Rebecca E. Mormino, Elizabeth C. Hedden, Trey Dekhytar, Maria Johnson, Keith A. Sperling, Reisa A. Rentz, Dorene M. TI Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer's disease SO NEUROPSYCHOLOGIA LA English DT Article DE Free and cued memory; Biomarker stages; Preclinical Alzheimer's disease ID MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT; NORMAL INDIVIDUALS; PRODROMAL AD; DEMENTIA; VALIDATION; DEPRESSION; RECALL; AGE AB Objectives: Furthering our understanding of the relationship between amyloidosis (A beta), neurodegeneration (ND), and cognition is imperative for early identification and early intervention of Alzheimer's disease (AD). However, the subtle cognitive decline differentially associated with each biomarker-defined stage of preclinical AD has yet to be fully characterized. Recent work indicates that different components of memory performance (free and cued recall) may be differentially specific to memory decline in prodromal AD. We sought to examine the relationship between free and cued recall paradigms, in addition to global composites of memory, executive functioning, and processing speed in relation to stages of predinical AD. Methods: A total of 260 clinically normal (CN) older adults (CDR=0) from the Harvard Aging Brain study were grouped according to predinical AD stages including Stage 0 (A beta-/ND-), Stage 1 (A beta+/ND-), Stage 2 (A beta+/ND+), and suspected non-Alzheimer's associated pathology (SNAP; A beta-/ND+). General linear models controlling for age, sex, and education were used to assess for stage-based performance differences on cognitive composites of executive functioning, processing speed, and memory in addition to free and cued delayed recall on the Selective Reminding Test (SRT) and Memory Capacity Test (MCT). Results: Global memory performance differed between preclinical stages with Stage 2 performing worse compared with Stage 0. When examining free and cued paradigms by memory test, only the MCT (and not the SRT) revealed group differences. More specifically, Stage 1 was associated with decrements in free recall compared with Stage 0 while Stage 2 was associated with decrements in both free and cued recall. There was a trend for the SNAP group to perform worse on free recall compared with Stage 0. Finally, there was no association between preclinical stage and global composites of executive functioning or processing speed. Conclusions: Clinically normal older adults with underlying evidence of amyloidosis and neurodegeneration exhibit subtle, yet measurable differences in memory performance, but only on a challenging associative test. The sensitivity of free vs. cued memory paradigms may be dependent on predinical stage such that reduced free recall is associated with amyloidosis alone (Stage 1) while a decline in cued recall may represent progression to amyloidosis and neurodegeneration (Stage 2). These findings may have practical applications for clinical assessment and clinical trial design. (C) 2015 Published by Elsevier Ltd. C1 [Papp, Kathryn V.; Amariglio, Rebecca E.; Dekhytar, Maria; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimers Res & Treatment, Boston, MA 02115 USA. [Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Hedden, Trey; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Hedden, Trey; Johnson, Keith A.; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Papp, KV (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimers Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA. EM kpapp@partners.org FU NIA NIH HHS [P50AG0051341, 5T32AG023480-08, F32 AG044054, F32AG044054, K01 AG040197, K01AG040197, K23 AG044431, K23AG044431, K24 AG035007, K24AG035007, P01 AG036694, P01AG036694, P50 AG005134, P50AG005134, R01 AG027435, R01 AG034556, R01 AG037497, R01AG027435, R01AG034556, R01AG037497, T32 AG023480, U01 AG024904, U01 AG032438, U01AG024904, U01AG032438, U19 AG010483, U19AG010483] NR 41 TC 9 Z9 9 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUL PY 2015 VL 73 BP 169 EP 175 DI 10.1016/j.neuropsychologia.2015.04.034 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CM1KQ UT WOS:000357440200016 PM 26002757 ER PT J AU Palombo, DJ Kapson, HS Lafleche, G Vasterling, JJ Marx, BP Franz, M Verfaellie, M AF Palombo, Daniela J. Kapson, Heather S. Lafleche, Ginette Vasterling, Jennifer J. Marx, Brian P. Franz, Molly Verfaellie, Mieke TI Alterations in Autobiographical Memory for a Blast Event in Operation Enduring Freedom and Operation Iraqi Freedom Veterans With Mild Traumatic Brain Injury SO NEUROPSYCHOLOGY LA English DT Article DE mild traumatic brain injury; autobiographical memory; coherence ID POSTTRAUMATIC-STRESS-DISORDER; OEF/OIF VETERANS; MENTAL-HEALTH; SELF-REPORT; CONCUSSION; EXPOSURE; OUTCOMES; RECOLLECTION; NARRATIVES; COHERENCE AB Objective: Although loss of consciousness associated with moderate or severe traumatic brain injury (TBI) is thought to interfere with encoding of the TBI event, little is known about the effects of mild TBI (mTBI), which typically involves only transient disruption in consciousness. Method: Blast-exposed Afghanistan and Iraq War veterans were asked to recall the blast event. Participants were stratified based on whether the blast was associated with probable mTBI (n = 50) or not (n = 25). Narratives were scored for organizational structure (i.e., coherence) using the Narrative Coherence Coding Scheme (Reese et al., 2011) and episodic recollection using the Autobiographical Interview Coding Procedures (Levine et al., 2002). Results: The mTBI group produced narratives that were less coherent but contained more episodic details than those of the no-TBI group. Conclusion: These results suggest that mTBI interferes with the organizational quality of memory in a manner that is independent of episodic detail generation. C1 [Palombo, Daniela J.; Kapson, Heather S.; Lafleche, Ginette; Franz, Molly; Verfaellie, Mieke] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. [Palombo, Daniela J.; Lafleche, Ginette; Vasterling, Jennifer J.; Marx, Brian P.; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Kapson, Heather S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Vasterling, Jennifer J.; Marx, Brian P.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. RP Palombo, DJ (reprint author), Vet Affairs Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM palombo@bu.edu OI Palombo, Daniela/0000-0001-8082-3522 FU United States Department of Veterans Affairs, Office of Rehabilitation Research & Development Grant [IO1RX000216]; Canadian Institutes of Health Research FX This research was supported by United States Department of Veterans Affairs, Office of Rehabilitation Research & Development Grant IO1RX000216 awarded to Mieke Verfaellie. Daniela J. Palombo was supported by the Canadian Institutes of Health Research. The authors thank Meredith Charney, Keely Burke, Elizabeth Race, and Matthew Grilli. NR 43 TC 0 Z9 0 U1 2 U2 5 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 JUL PY 2015 VL 29 IS 4 BP 543 EP 549 DI 10.1037/neu0000198 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA CL5CA UT WOS:000356976200005 PM 25893970 ER PT J AU O'Connor, MK Deason, RG Reynolds, E Tat, MJ Flannery, S Solomon, PR Vassey, EA Budson, AE AF O'Connor, Maureen K. Deason, Rebecca G. Reynolds, Erin Tat, Michael J. Flannery, Sean Solomon, Paul R. Vassey, Elizabeth A. Budson, Andrew E. TI The Imagination Inflation Effect in Healthy Older Adults and Patients With Mild Alzheimer's Disease SO NEUROPSYCHOLOGY LA English DT Article DE Alzheimer's disease; imagination inflation; source monitoring; familiarity; visual imagery; false memory ID MEMORY-IMPAIRED INDIVIDUALS; FALSE RECOGNITION; RESPONSE BIAS; CATEGORIZED PICTURES; NEUROLOGICAL DAMAGE; EPISODIC MEMORY; GIST MEMORY; IMAGERY; DEMENTIA; EVENTS AB Objective: The imagination inflation effect is a type of memory distortion defined as an increased tendency to falsely remember that an item has been seen, or an action has been performed, when it has only been imagined. For patients with very mild Alzheimer's disease (AD), susceptibility to the imagination inflation effect could have significant functional consequences in daily life. Method: We assessed whether patients with very mild AD were more or less susceptible to the imagination inflation effect when compared with healthy older adults. In the first session, participants were read an action statement such as "fill the pillbox" and engaged in 1 of 3 activities: listened to the statement being read, performed the action, or imagined performing the action. During the second session, participants imagined action statements from the first session, as well as new action statements. During the recognition test, participants were asked to determine whether action statements were or were not performed during the first session. Results: We found that imagining performing actions increased the tendency of patients with very mild AD to falsely recall the action as having been performed to an extent similar to that of healthy older adults. Conclusion: We concluded that, similar to healthy older adults, patients with very mild AD were susceptible to the imagination inflation effect, which we attributed to difficulties with source monitoring and reliance on familiarity. C1 [O'Connor, Maureen K.] Bedford Vet Affairs Hosp, Dept Psychol, Bedford, MA USA. [O'Connor, Maureen K.; Tat, Michael J.; Flannery, Sean; Vassey, Elizabeth A.; Budson, Andrew E.] Boston Univ, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Boston, MA 02215 USA. [Deason, Rebecca G.] Texas State Univ, Dept Psychol, San Marcos, TX 78666 USA. [Reynolds, Erin] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA 15260 USA. [Tat, Michael J.; Flannery, Sean; Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA 02130 USA. [Solomon, Paul R.; Vassey, Elizabeth A.] Boston Ctr Memory, Chestnut Hill, MA USA. [Solomon, Paul R.] Williams Coll, Psychol, Williamstown, MA 01267 USA. [Solomon, Paul R.] Williams Coll, Program Neurosci, Williamstown, MA 01267 USA. RP O'Connor, MK (reprint author), VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, 150 South Huntington Ave Mailstop 151-C, Boston, MA 02130 USA. EM maureen.oconnor@va.gov FU National Institute on Aging [R01 AG025815, P30 AG13846]; Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award FX This research was supported by National Institute on Aging Grants R01 AG025815 (AEB), P30 AG13846 (AEB), and a Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award (RGD). This material is also the result of work supported with resources and the use of facilities at the Bedford VA Hospital in Bedford, MA, the VA Boston Healthcare System in Boston, MA, and The Memory Clinic in Bennington, VT. We thank our healthy older adults and patients with AD and their families for their time and participation in this study. We would also like to thank Mr. Ryan Daley for his assistance editing the manuscript. NR 50 TC 1 Z9 1 U1 4 U2 10 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 JUL PY 2015 VL 29 IS 4 BP 550 EP 560 DI 10.1037/neu0000195 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA CL5CA UT WOS:000356976200006 PM 25893972 ER PT J AU Corliss, BM Hooten, KG Gul, SS Neal, D Murad, GJA Rahman, M AF Corliss, Brian M. Hooten, Kristopher G. Gul, Sarah Shireen Neal, Dan Murad, Gregory J. A. Rahman, Maryam TI Establishing Standard Performance Measures in Adult Traumatic Brain Injury Patients SO NEUROSURGERY LA English DT Article DE Adult brain injury; Hospital-acquired condition; Outcome measures; Patient safety indicator; Traumatic brain injury ID INPATIENT SAMPLE DATABASE; CLINICAL ARTICLE; SAFETY AB BACKGROUND:The Agency for Healthcare Research and Quality patient safety indicators (PSIs) and Centers for Medicare and Medicaid Services hospital-acquired conditions (HACs) are publicly reported metrics that illustrate the overall quality of care provided at an institution. The national incidences of PSIs and HACs in traumatic brain injury (TBI) patients were estimated using the Nationwide Inpatient Sample database.OBJECTIVE:To establish baseline incidences of PSIs and HACs among surgical TBI patients treated at nonfederal hospitals in the United States, and to identify patient factors contributing to these adverse events.METHODS:The Nationwide Inpatient Sample database was queried for patients admitted with International Classification of Diseases, Ninth Revision diagnosis codes consistent with TBI between 2002 and 2011. The incidences of PSIs and HACs were estimated for TBI patients and evaluated for correlation with multiple factors, including comorbidity score, teaching hospital status, and insurance status.RESULTS:There were 15403 total PSIs among 24012 TBI patients. There were only 165 HACs among 24012 TBI patients. Only sepsis, deep vein thrombosis, and pressure ulcers occurred in more than 1% of patients. Patient age, sex, comorbidity score, and teaching hospital status were all found to significantly impact PSI incidence. Comorbidity score was found to significantly impact HAC incidence. Compared with private insurance, Medicaid patients developed significantly more HACs.CONCLUSION:These data may be used as reference values for hospitals reporting their own rates and seeking to improve the quality of care they provide for TBI patients.ABBREVIATIONS:AHRQ, Healthcare Research and QualityHAC, hospital-acquired conditionICP, intracranial pressureLOS, length of stayMS-DRG, Medicare Severity Diagnosis Related GroupNIS, Nationwide Inpatient SamplePSI, patient safety indicatorTBI, traumatic brain injury C1 [Corliss, Brian M.; Hooten, Kristopher G.; Neal, Dan; Murad, Gregory J. A.; Rahman, Maryam] Univ Florida, Dept Neurol Surg, Gainesville, FL 32610 USA. [Gul, Sarah Shireen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Corliss, BM (reprint author), Univ Florida, Dept Neurol Surg, Box 100265, Gainesville, FL 32610 USA. EM brianmatthew.corliss@neurosurgery.ufl.edu NR 14 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 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2015 VL 77 IS 1 BP 44 EP 50 DI 10.1227/NEU.0000000000000734 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CL2LS UT WOS:000356776100012 PM 25790069 ER PT J AU Hamani, C Pilitsis, J Rughani, AI Rosenow, JM Patil, PG Slavin, K Abosch, A Eskandar, E Mitchell, L Kalkanis, S AF Hamani, Clement Pilitsis, Julie Rughani, Anand I. Rosenow, Joshua M. Patil, Parag G. Slavin, Konstantin Abosch, Aviva Eskandar, Emad Mitchell, Laura Kalkanis, Steven TI In Reply: Stereotactic Microanatomy of the Nucleus Accumbens Stimulation for Obsessive-Compulsive Disorder: Reported Coordinates and Mavridis' Area SO NEUROSURGERY LA English DT Letter C1 [Hamani, Clement] Toronto Western Hosp, Ctr Addict & Mental Hlth, Div Neurosurg, Toronto, ON M5T 2S8, Canada. [Pilitsis, Julie] Albany Med Coll, Dept Neurosurg, Albany, NY 12208 USA. [Pilitsis, Julie] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Rughani, Anand I.] Maine Med Ctr, Neurosci Inst, Portland, ME 04102 USA. [Rosenow, Joshua M.] Northwestern Univ, Dept Neurosurg, Chicago, IL 60611 USA. [Patil, Parag G.] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Patil, Parag G.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Patil, Parag G.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Patil, Parag G.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Slavin, Konstantin] Univ Illinois, Dept Neurosurg, Chicago, IL USA. [Abosch, Aviva] Univ Colorado, Dept Neurosurg, Denver, CO 80202 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Mitchell, Laura] Congress Neurol Surg, Schaumburg, IL USA. [Kalkanis, Steven] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. RP Hamani, C (reprint author), Toronto Western Hosp, Ctr Addict & Mental Hlth, Div Neurosurg, Toronto, ON M5T 2S8, Canada. 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 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2015 VL 77 IS 1 BP E156 EP E157 DI 10.1227/NEU.0000000000000795 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CL2LU UT WOS:000356776400006 PM 25938691 ER PT J AU Collins, LC Gelber, S Marotti, JD White, S Ruddy, K Brachtel, EF Schapira, L Come, SE Borges, VF Schedin, P Warner, E Wensley, T Tamimi, RM Winer, EP Partridge, AH AF Collins, Laura C. Gelber, Shari Marotti, Jonathan D. White, Sarah Ruddy, Kathryn Brachtel, Elena F. Schapira, Lidia Come, Steven E. Borges, Virginia F. Schedin, Pepper Warner, Ellen Wensley, Taylor Tamimi, Rulla M. Winer, Eric P. Partridge, Ann H. TI Molecular Phenotype of Breast Cancer According to Time Since Last Pregnancy in a Large Cohort of Young Women SO ONCOLOGIST LA English DT Article DE Breast cancer; Molecular phenotypes; Young women; Pregnancy-associated breast cancer ID FULL-TERM PREGNANCY; BASAL-LIKE SUBTYPE; CARCINOMA IN-SITU; GENE-EXPRESSION; GENOMIC SIGNATURE; TUMOR SUBTYPES; RISK-FACTORS; ADULT WOMEN; SURVIVAL; AGE AB Background. The increase in breast cancer risk during pregnancy and postpartum is well known; however, the molecular phenotype of breast cancers occurring shortly after pregnancy has not been well studied. Given this, we investigated whether nulliparity and the time interval since pregnancy among parous women affects the breast cancer phenotype in young women. Materials and Methods. We examined molecular phenotype in relation to time since pregnancy in a prospective cohort of 707 young women (aged <= 40 years) with breast cancer. Parity was ascertained from study questionnaires. Using tumor histologic grade on central review and biomarker expression, cancers were categorized as luminal A- or B-like, HER2 enriched, and triple negative. Results. Overall, 32% were luminal A-like, 41% were luminal B-like, 9% were HER2 enriched, and 18% were triple negative. Although, numerically, patients diagnosed >5 years after pregnancy had more luminal A-like subtypes than women with shorter intervals since pregnancy, there was no evidence of a relationship between these intervals and molecular subtypes once family history of breast cancer and age at diagnosis were considered. Conclusion. Distribution of breast cancer molecular phenotype did not differ significantly among young women by parity or time interval since parturition when important predictors of tumor phenotype such as age and family history were considered. C1 [Collins, Laura C.; Come, Steven E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Gelber, Shari; Wensley, Taylor; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marotti, Jonathan D.] Dartmouth & Dartmouth Hitchcock Med Ctr, Geisel Sch Med, Lebanon, NH USA. [White, Sarah] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Collins, Laura C.; Brachtel, Elena F.; Schapira, Lidia; Come, Steven E.; Tamimi, Rulla M.; Winer, Eric P.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. [Ruddy, Kathryn] Mayo Clin, Rochester, MN USA. [Brachtel, Elena F.; Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Borges, Virginia F.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Schedin, Pepper] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Warner, Ellen] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Collins, LC (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM lcollins@bidmc.harvard.edu FU Susan G. Komen Foundation FX Funding was provided by a grant from the Susan G. Komen Foundation. NR 47 TC 2 Z9 2 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 JUL PY 2015 VL 20 IS 7 BP 713 EP 718 DI 10.1634/theoncologist.2014-0412 PG 6 WC Oncology SC Oncology GA CL9DK UT WOS:000357275500006 PM 26025931 ER PT J AU Peters, KB Lou, E Desjardins, A Reardon, DA Lipp, ES Miller, E Herndon, JE McSherry, F Friedman, HS Vredenburgh, JJ AF Peters, Katherine B. Lou, Emil Desjardins, Annick Reardon, David A. Lipp, Eric S. Miller, Elizabeth Herndon, James E., II McSherry, Frances Friedman, Henry S. Vredenburgh, James J. TI Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma SO ONCOLOGIST LA English DT Article ID PRERADIATION CHEMOTHERAPY; MALIGNANT GLIOMAS; RADIATION-THERAPY; EXTENT; RADIOTHERAPY; MULTIFORME; RESECTION; SURVIVAL AB Background. Extent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection. We conducted a phase II trial of upfront therapy with bevacizumab (BV), irinotecan (CPT-11), and temozolomide (TMZ) prior to chemoradiation in patients with unresectable, subtotally resected, and/or multifocal GBM. Methods. Patients received up to 4 cycles of TMZ at 200 mg/m(2) per day on days 1-5 (standard dosing) and BV at 10 mg/kg every 2 weeks on a 28-day cycle. CPT-11 was given every 2 weeks on a 28-day cycle at 125 mg/m(2) or 340 mg/m(2) depending on anti-epileptic drugs. Magnetic resonance imaging of the brain was done every 4 weeks, and treatment continued as long as there was no tumor progression or unmanageable toxicity. The primary endpoint was tumor response rate, with a goal of 26% or greater. Results. Forty-one patients were enrolled from December 2009 to November 2010. Radiographic responses were as follows: 9 patients (22.0%) had partial response, 25 (61.0%) had stable disease, and 2 (4.9%) had progression; 5 patients were not assessed. Cumulative response rate was 22%. Median overall survival was 12 months (95% confidence interval: 7.2-13.5 months). Conclusion. Upfront treatment with BV, TMZ, and CPT-11 is tolerable and can lead to radiographic response in unresectable and/or subtotally resected GBM. C1 [Peters, Katherine B.; Desjardins, Annick] Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27710 USA. [Lipp, Eric S.; Miller, Elizabeth] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Herndon, James E., II; McSherry, Frances] Duke Univ, Med Ctr, Dept Biostat, Durham, NC 27710 USA. [Friedman, Henry S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Lou, Emil] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Reardon, David A.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Vredenburgh, James J.] St Francis Med Canc Ctr, Div Med Oncol, Hartford, CT USA. RP Peters, KB (reprint author), Duke Univ, Med Ctr, DUMC 3624, Durham, NC 27710 USA. EM katherine.peters@duke.edu FU Genentech, Inc. FX Genentech, Inc. NR 18 TC 6 Z9 6 U1 1 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 JUL PY 2015 VL 20 IS 7 BP 727 EP 728 DI 10.1634/theoncologist.2015-0135 PG 2 WC Oncology SC Oncology GA CL9DK UT WOS:000357275500009 PM 26025933 ER PT J AU Maki, RG Blay, JY Demetri, GD Fletcher, JA Joensuu, H Martin-Broto, J Nishida, T Reichardt, P Schoffski, P Trent, JC AF Maki, Robert G. Blay, Jean-Yves Demetri, George D. Fletcher, Jonathan A. Joensuu, Heikki Martin-Broto, Javier Nishida, Toshirou Reichardt, Peter Schoffski, Patrick Trent, Jonathan C. TI Key Issues in the Clinical Management of Gastrointestinal Stromal Tumors: An Expert Discussion SO ONCOLOGIST LA English DT Article DE Gastrointestinal stromal tumor; GIST; Imatinib; Sunitinib; Regorafenib; KIT; PDGFRA; SDH; Carney-Stratakis syndrome ID ADJUVANT IMATINIB MESYLATE; GIST FOLLOWING FAILURE; RANDOMIZED-TRIAL; RESIDUAL DISEASE; PDGFRA MUTATIONS; TYROSINE KINASE; PHASE-3 TRIAL; C-KIT; SUNITINIB; THERAPY AB After the revelation of kinase targeting with orally available small molecules, the use of imatinib in chronic myelogenous leukemia and in gastrointestinal stromal tumor (GIST) has now become commonplace and just two of many examples of the use of kinase inhibitors in cancer. In this article, we discuss important practice points that may impact upon questions of therapy of primary and metastatic GIST, with the hope that the questions addressed in this rare solid tumor can serve as examples of what can be achieved with kinase-directed therapies in other cancers. We present cases that highlight some of the key issues in GIST management and afterward discuss both points of consensus and controversial issues in what is now recognized as one of the most common forms of sarcoma. C1 [Maki, Robert G.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. [Blay, Jean-Yves] Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Joensuu, Heikki] Helsinki Univ Hosp, Helsinki, Finland. [Joensuu, Heikki] Univ Helsinki, Helsinki, Finland. [Martin-Broto, Javier] Fdn Inst Valenciano Oncol, Serv Oncol Med, Valencia, Spain. [Nishida, Toshirou] Natl Canc Ctr Hosp East, Dept Surg, Kashiwa, Chiba, Japan. [Reichardt, Peter] HELIOS Klinikum Berlin Buch, Interdisciplinary Oncol, Berlin, Germany. [Schoffski, Patrick] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Leuven Canc Inst, Gen Med Oncol, Leuven, Belgium. [Trent, Jonathan C.] Univ Miami, Sylvester Canc Ctr, Sarcoma Med Oncol Program, Miami, FL USA. RP Maki, RG (reprint author), Mt Sinai Med Ctr, Tisch Canc Inst, 1425 Madison Ave, New York, NY 10029 USA. EM bobmakimd@gmail.com RI IBIS, BIOMARCADORES/P-3515-2015; Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU Eisai; Tracon; Lilly; Novartis; Pfizer; Bayer; GlaxoSmithKline; Blueprint Medicines FX Robert G. Maki: Bayer (C/A, H), Eisai (C/A, H, RF), Tracon (C/A, RF), Lilly (H, RF), Sarcoma Alliance for Research through Collaboration (participation/leadership); Jean-Yves Blay: Novartis, Pfizer, Bayer (C/A, RF); George D. Demetri: Blueprint Medicines Board of Directors (C/A, E, OI), Dana-Farber (IP), Novartis (C/A, IP, RF), Pfizer, Bayer, GlaxoSmithKline (C/A, RF), Ariad, AstraZeneca (C/A), Kolltan (C/A, OI); Jonathan A. Fletcher: Bayer, Ariad (C/A); Heikki Joensuu: Blueprint Medicines (RF); Javier Martin-Broto: PharmaMar, GlaxoSmithKline, Bayer, Amgen (C/A); Toshirou Nishida: Bayer, Pfizer (H); Peter Reichardt: Pfizer, Bayer (C/A, H), Ariad (C/A), Novartis (RF); Patrick Schoffski: Novartis (C/A, RF), Bayer (C/A). The other author indicated no financial relationships. NR 39 TC 5 Z9 7 U1 0 U2 4 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 JUL PY 2015 VL 20 IS 7 BP 823 EP 830 DI 10.1634/theoncologist.2014-0471 PG 8 WC Oncology SC Oncology GA CL9DK UT WOS:000357275500022 PM 26070915 ER PT J AU Dion, NT Bragdon, C Muratoglu, O Freiberg, AA AF Dion, Neil T. Bragdon, Charles Muratoglu, Orhun Freiberg, Andrew A. TI Durability of Highly Cross-Linked Polyethylene in Total Hip and Total Knee Arthroplasty SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Highly cross-linked polyethylene; Total hip arthroplasty; Total knee arthroplasty; Osteolysis; Vitamin E ID MOLECULAR-WEIGHT POLYETHYLENE; RADIOSTEREOMETRIC ANALYSIS; CONVENTIONAL POLYETHYLENE; UNCEMENTED SOCKETS; WEAR PERFORMANCE; FEMORAL HEADS; PARTICLES; OUTCOMES; UHMWPE; LINERS AB This article reviews the history of the development of highly cross-linked polyethylene (HXLPE) and provides an in-depth review of the clinical results regarding the durability of HXLPE used in total hip arthroplasty (THA) and total knee arthroplasty (TKA). The use of polyethylene as a bearing surface has contributed to the success of THA and TKA; however, polyethylene wear and osteolysis can lead to failure. Ongoing clinical and retrieval studies are required to analyze outcomes at longer-term follow-up. C1 [Dion, Neil T.; Bragdon, Charles; Muratoglu, Orhun; Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Dion, NT (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Suite 3700, Boston, MA 02114 USA. EM NDion1@Partners.org FU Zimmer; Depuy/Synthes; Biomet; Stryker FX Disclosures: Charles Bragdon, PhD receives research support and royalties from Zimmer; Orhun Muratoglu, PhD receives research support from Depuy/Synthes, Biomet, Zimmer, and Stryker. He receives royalties from Biomet, Zimmer, Corin, Conformis, Alchimist, Aston Medical, Ceramtech, Maxx Orthopedics, Iconacy, Renovis, Arthrex, Stryker, Orthopedic Technology Group, and Cambridge Polymer Group; Andrew Freiberg, MD is a consultant for Zimmer, Medtronic and CeramTec. He receives royalties from Zimmer and Biomet. He has ownership in ArthroSurface. NR 35 TC 1 Z9 2 U1 4 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-5898 EI 1558-1373 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JUL PY 2015 VL 46 IS 3 BP 321 EP + DI 10.1016/j.ocl.2015.02.001 PG 8 WC Orthopedics SC Orthopedics GA CL5KY UT WOS:000357000000002 PM 26043046 ER PT J AU Konopka, JF Hansen, VJ Rubash, HE Freiberg, AA AF Konopka, Joseph F. Hansen, Viktor J. Rubash, Harry E. Freiberg, Andrew A. TI Risk Assessment Tools Used to Predict Outcomes of Total Hip and Total Knee Arthroplasty SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Total knee arthroplasty; Total hip arthroplasty; Prediction tools; Nomograms ID TOTAL JOINT ARTHROPLASTY; QUALITY-OF-LIFE; PREOPERATIVE PREDICTION; EXTERNAL VALIDATION; SINGLE INSTITUTION; COST-EFFECTIVENESS; UNITED-STATES; REPLACEMENT; CARE; DISCHARGE AB This article reviews recently proposed clinical tools for predicting risks and outcomes in total hip arthroplasty and total knee arthroplasty patients. Additionally, we share the Massachusetts General Hospital experience with using the Risk Assessment and Prediction Tool to predict the need for an extended care facility after total joint arthroplasty. C1 [Konopka, Joseph F.; Hansen, Viktor J.; Rubash, Harry E.; Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Hansen, VJ (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey Ctr Outpatient Care, Suite 3B,55 Fruit St, Boston, MA 02114 USA. EM jkonopka@partners.org NR 43 TC 1 Z9 1 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-5898 EI 1558-1373 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JUL PY 2015 VL 46 IS 3 BP 351 EP + DI 10.1016/j.ocl.2015.02.004 PG 14 WC Orthopedics SC Orthopedics GA CL5KY UT WOS:000357000000005 PM 26043049 ER PT J AU Kang, WS Sun, ST Nguyen, K Kashemirov, B McKenna, CE Hacking, SA Quesnel, AM Sewell, WF McKenna, MJ Jung, DH AF Kang, Woo Seok Sun, Shuting Nguyen, Kim Kashemirov, Boris McKenna, Charles E. Hacking, S. Adam Quesnel, Alicia M. Sewell, William F. McKenna, Michael J. Jung, David H. TI Non-Ototoxic Local Delivery of Bisphosphonate to the Mammalian Cochlea SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Bisphosphonates; Fluorescence imaging; Inner ear drug delivery; Otosclerosis ID FLUORESCENTLY-LABELED BISPHOSPHONATES; SENSORINEURAL HEARING-LOSS; FAR-ADVANCED OTOSCLEROSIS; ROUND WINDOW MEMBRANE; SCALA TYMPANI; IN-VIVO; CONCENTRATION GRADIENT; BONE TURNOVER; IMPLANTATION; PHARMACOKINETICS AB Hypothesis Local delivery of bisphosphonates results in superior localization of these compounds for the treatment of cochlear otosclerosis, without ototoxicity. Background Otosclerosis is a common disorder of abnormal bone remodeling within the human otic capsule. It is a frequent cause of conductive hearing loss from stapes fixation. Large lesions that penetrate the cochlear endosteum and injure the spiral ligament result in sensorineural hearing loss. Nitrogen-containing bisphosphonates (e.g., zoledronate) are potent inhibitors of bone remodeling with proven efficacy in the treatment of metabolic bone diseases, including otosclerosis. Local delivery to the cochlea may allow for improved drug targeting, higher local concentrations, and the avoidance of systemic complications. In this study, we use a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) to determine drug localization and concentration within the otic capsule. Various methods for delivery are compared. Ototoxicity is evaluated by auditory brainstem responses and distortion product otoacoustic emissions. Methods 6-FAM-ZOL was administered to guinea pigs via intraperitoneal injection, placement of alginate beads onto the round window membrane, or microfluidic pump infusion via a cochleostomy. Hearing was evaluated. Specimens were embedded into resin blocks, ground to a mid-modiolar section, and quantitatively imaged using fluorescence microscopy. Results There was a dose-dependent increase in fluorescent signal after systemic 6-FAM-ZOL treatment. Local delivery via the round window membrane or a cochleostomy increased delivery efficiency. No significant ototoxicity was observed after either systemic or local 6-FAM-ZOL delivery. Conclusion These findings establish important preclinical parameters for the treatment of cochlear otosclerosis in humans. C1 [Kang, Woo Seok; Quesnel, Alicia M.; McKenna, Michael J.; Jung, David H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kang, Woo Seok; Quesnel, Alicia M.; Sewell, William F.; McKenna, Michael J.; Jung, David H.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Kang, Woo Seok; Quesnel, Alicia M.; McKenna, Michael J.; Jung, David H.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Sun, Shuting; Nguyen, Kim; Kashemirov, Boris; McKenna, Charles E.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Hacking, S. Adam] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. RP Jung, DH (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM david_jung@meei.harvard.edu FU NIDCD [R01 DC009837]; Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard Catalyst | The Harvard Clinical and Translational Science Center (Harvard University) FX The authors thank Doug Hayden, PhD, for assistance with the biostatistical analyses, and Kris Kristiansen for excellent technical support. This work was primarily supported by NIDCD grant R01 DC009837, with additional support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, or the National Institutes of Health. NR 43 TC 5 Z9 5 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2015 VL 36 IS 6 BP 953 EP 960 DI 10.1097/MAO.0000000000000786 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CL3TO UT WOS:000356873700002 PM 25996080 ER PT J AU Kelly, VE Johnson, CO McGough, EL Shumway-Cook, A Horak, FB Chung, KA Espay, AJ Revilla, FJ Devoto, J Wood-Siverio, C Factor, SA Cholerton, B Edwards, KL Peterson, AL Quinn, JF Montine, TJ Zabetian, CP Leverenz, JB AF Kelly, V. E. Johnson, C. O. McGough, E. L. Shumway-Cook, A. Horak, F. B. Chung, K. A. Espay, A. J. Revilla, F. J. Devoto, J. Wood-Siverio, C. Factor, S. A. Cholerton, B. Edwards, K. L. Peterson, A. L. Quinn, J. F. Montine, T. J. Zabetian, C. P. Leverenz, J. B. TI Association of cognitive domains with postural instability/gait disturbance in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Cognition; Executive function; Balance; Gait; Freezing of gait ID RATING-SCALE; DEMENTIA; IMPAIRMENT; GAIT; DYSFUNCTION; FEATURES; COHORT AB Introduction: Research suggests an association between global cognition and postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the relationship between specific cognitive domains and PIGD symptoms is not clear. This study examined the association of cognition (global and specific cognitive domains) with PIGD symptoms in a large, well-characterized sample of individuals with PD. Methods: Cognitive function was measured with a detailed neuropsychological assessment, including global cognition, executive function, memory, visuospatial function, and language. PIGD symptoms were measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses were performed to assess the relationship between cognition and PIGD symptoms with models adjusting for age, sex, education, enrollment site, disease duration, and motor symptom severity. Results: The analysis included 783 participants, with mean (standard deviation) age of 67.3 (9.7) years and median (interquartile range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global cognition, executive function, memory, and phonemic fluency were associated with more severe PIGD symptoms. Deficits in executive function were associated with impairments in gait, freezing, and postural stability, while visuospatial impairments were associated only with more severe freezing, and poorer memory function was associated only with greater postural instability. Discussion: While impairments in global cognition and aspects of executive functioning were associated with more severe PIGD symptoms, specific cognitive domains were differentially related to distinct PIGD components, suggesting the presence of multiple neural pathways contributing to associations between cognition and PIGD symptoms in persons with PD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Kelly, V. E.; McGough, E. L.; Shumway-Cook, A.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Johnson, C. O.; Edwards, K. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Horak, F. B.; Chung, K. A.; Peterson, A. L.; Quinn, J. F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Horak, F. B.; Chung, K. A.; Peterson, A. L.] Portland VA Med Ctr, Portland, OR USA. [Espay, A. J.; Revilla, F. J.; Devoto, J.] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Revilla, F. J.] Greenville Hlth Syst, Div Neurol, Greenville, SC USA. [Revilla, F. J.] Univ S Carolina, Sch Med, Greenville, SC USA. [Wood-Siverio, C.; Factor, S. A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Cholerton, B.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Cholerton, B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Edwards, K. L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Montine, T. J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Zabetian, C. P.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, J. B.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. RP Kelly, VE (reprint author), 1959 NE Pacific St,Box 356490, Seattle, WA USA. EM vekelly@u.washington.edu; johnsoco@uw.edu; emcg@uw.edu; ashumway@uw.edu; horakf@ohsu.edu; chungka@ohsu.edu; alberto.espay@uc.edu; fredy.revilla@uc.edu; devotoj@ucmail.uc.edu; cwoodsi@emory.edu; sfactor@emory.edu; bchol@uw.edu; kedwardl@uci.edu; peterami@ohsu.edu; quinnj@ohsu.edu; tmontine@uw.edu; zabetian@u.washington.edu; leverej@ccf.org OI Kelly, Valerie E./0000-0002-0099-9219 FU Department of Veterans Affairs from American Parkinson Disease Association; National Institutes of Health [P50 NS062684, R01 NS065070]; Consolidated Anti-Aging Foundation; Jane and Lee Seidman Fund FX This work was supported by the Department of Veterans Affairs, grants from the American Parkinson Disease Association, National Institutes of Health (P50 NS062684 and R01 NS065070), Consolidated Anti-Aging Foundation, and the Jane and Lee Seidman Fund. The funding sources did not provide scientific input for this study. NR 28 TC 14 Z9 14 U1 5 U2 20 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 JUL PY 2015 VL 21 IS 7 BP 692 EP 697 DI 10.1016/j.parkreldis.2015.04.002 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CM0HW UT WOS:000357360000004 PM 25943529 ER PT J AU Khawaja, RDA Singh, S Otrakji, A Padole, A Lim, R Nimkin, K Westra, S Kalra, MK Gee, M AF Khawaja, Ranish Deedar Ali Singh, Sarabjeet Otrakji, Alexi Padole, Atul Lim, Ruth Nimkin, Katherine Westra, Sjirk Kalra, Mannudeep K. Gee, Michael S. TI Dose reduction in pediatric abdominal CT: use of iterative reconstruction techniques across different CT platforms SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Dose reduction; ALARA; Iterative reconstruction technique; Pediatric ID IMAGE QUALITY; COMPUTED-TOMOGRAPHY; BODY CT; FEASIBILITY; PROTOCOLS; CHILDREN; ASIR AB Dose reduction in children undergoing CT scanning is an important priority for the radiology community and public at large. Drawbacks of radiation reduction are increased image noise and artifacts, which can affect image interpretation. Iterative reconstruction techniques have been developed to reduce noise and artifacts from reduced-dose CT examinations, although reconstruction algorithm, magnitude of dose reduction and effects on image quality vary. We review the reconstruction principles, radiation dose potential and effects on image quality of several iterative reconstruction techniques commonly used in clinical settings, including 3-D adaptive iterative dose reduction (AIDR-3D), adaptive statistical iterative reconstruction (ASIR), iDose, sinogram-affirmed iterative reconstruction (SAFIRE) and model-based iterative reconstruction (MBIR). We also discuss clinical applications of iterative reconstruction techniques in pediatric abdominal CT. C1 [Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Otrakji, Alexi; Padole, Atul; Lim, Ruth; Nimkin, Katherine; Westra, Sjirk; Kalra, Mannudeep K.; Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, MGH Imaging, Sch Med, Boston, MA 02114 USA. RP Khawaja, RDA (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Imaging, Sch Med, 25 New Chardon St,4th Floor, Boston, MA 02114 USA. EM rkhawaja@mgh.harvard.edu NR 21 TC 5 Z9 5 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JUL PY 2015 VL 45 IS 7 BP 1046 EP 1055 DI 10.1007/s00247-014-3235-2 PG 10 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CL5ZJ UT WOS:000357044200014 PM 25427434 ER PT J AU Ferraresi, C Beltrame, T Fabrizzi, F do Nascimento, ESP Karsten, M Francisco, CD Borghi-Silva, A Catai, AM Cardoso, DR Ferreira, AG Hamblin, MR Bagnato, VS Parizotto, NA AF Ferraresi, Cleber Beltrame, Thomas Fabrizzi, Fernando Pereira do Nascimento, Eduardo Sanches Karsten, Marlus Francisco, Cristina de Oliveira Borghi-Silva, Audrey Catai, Aparecida Maria Cardoso, Daniel Rodrigues Ferreira, Antonio Gilberto Hamblin, Michael R. Bagnato, Vanderlei Salvador Parizotto, Nivaldo Antonio TI Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner SO PHYSIOTHERAPY THEORY AND PRACTICE LA English DT Article DE Fatigue; LEDT; LLLT; muscle damage; NMR; oxygen uptake; photobiomodulation ID BIPHASIC DOSE-RESPONSE; CYTOCHROME-C-OXIDASE; LEVEL LASER THERAPY; SLOW COMPONENT; O-2 UPTAKE; SKELETAL-MUSCLE; UPTAKE KINETICS; HEAVY EXERCISE; RADIATION; PHOTOTHERAPY AB Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase - CK and alanine), and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy (H-1 NMR). A LED cluster with 50 LEDs (lambda = 850 nm; 50 mW 15s; 37.5J) was applied on legs, arms, and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (similar to-9 s), decreased O-2 deficit (similar to-10 L), increased the VO2 from the slow component phase (similar to+348 ml min(-1)), and increased the time limit of exercise (similar to+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance. C1 [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Lab Electrothermophototherapy, Dept Phys Therapy, Sao Paulo, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Postgrad Program Biotechnol, Sao Paulo, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei Salvador] Univ Sao Paulo, Phys Inst Sao Carlos, Opt Grp, Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Hamblin, Michael R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Beltrame, Thomas; Karsten, Marlus; Francisco, Cristina de Oliveira; Borghi-Silva, Audrey; Catai, Aparecida Maria] Univ Fed Sao Carlos, Dept Phys Therapy, Nucleus Res Phys Exercise, Lab Cardiovasc Phys Therapy, Sao Paulo, Brazil. [Beltrame, Thomas] Univ Waterloo, Fac Appl Hlth Sci, Waterloo, ON N2L 3G1, Canada. [Fabrizzi, Fernando] Univ Fed Sao Carlos, Dept Genet & Evolut, Lab Biochem Adapt, Sao Paulo, Brazil. [Pereira do Nascimento, Eduardo Sanches; Cardoso, Daniel Rodrigues] Univ Sao Paulo, Inst Chem Sao Carlos, Lab Inorgan & Analyt Chem, Sao Carlos, SP, Brazil. [Ferreira, Antonio Gilberto] Univ Fed Sao Carlos, Dept Chem, Lab Nucl Magnet Resonance, BR-13560 Sao Carlos, SP, Brazil. [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 Ferraresi, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM cleber.ferraresi@gmail.com RI USP, CePOF/J-3608-2015; Bagnato, Vanderlei/C-3133-2012; Borghi-Silva, Audrey/F-5702-2012; Cardoso, Daniel/B-9775-2012; Ferraresi, Cleber/B-2458-2014; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; OI Karsten, Marlus/0000-0002-2476-7981 FU NIAID NIH HHS [R01 AI050875, R01AI050875] NR 41 TC 5 Z9 5 U1 3 U2 23 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0959-3985 EI 1532-5040 J9 PHYSIOTHER THEOR PR JI Physiother. Theory Pract. PD JUL PY 2015 VL 31 IS 5 BP 354 EP 361 DI 10.3109/09593985.2014.1003118 PG 8 WC Rehabilitation SC Rehabilitation GA CL8NA UT WOS:000357230200007 PM 25585514 ER PT J AU Yu, BL Muenster, S Blaesi, AH Bloch, DB Zapol, WM AF Yu, Binglan Muenster, Stefan Blaesi, Aron H. Bloch, Donald B. Zapol, Warren M. TI Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID PERSISTENT PULMONARY-HYPERTENSION; DIELECTRIC BARRIER; HEART-FAILURE; NEWBORN; ARC; NO AB Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $ 14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O-2 and 10% N-2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O-3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O-3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. C1 [Yu, Binglan; Muenster, Stefan; Blaesi, Aron H.; Bloch, Donald B.; Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res,Med Sch, Boston, MA 02114 USA. [Bloch, Donald B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res,Med Sch, Boston, MA 02114 USA. EM wzapol@mgh.harvard.edu FU Department of Anesthesia, Critical Care and Pain Medicine, MGH FX This study was supported by funds of the Department of Anesthesia, Critical Care and Pain Medicine, MGH. NR 38 TC 2 Z9 2 U1 2 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUL 1 PY 2015 VL 7 IS 294 AR 294ra107 DI 10.1126/scitranslmed.aaa3097 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CM0CJ UT WOS:000357345500007 PM 26136478 ER PT J AU Fathi, AT Wander, SA Faramand, R Emadi, A AF Fathi, Amir T. Wander, Seth A. Faramand, Rowan Emadi, Ashkan TI Biochemical, Epigenetic, and Metabolic Approaches to Target IDH Mutations in Acute Myeloid Leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID ISOCITRATE DEHYDROGENASE MUTATIONS; HYPOMETHYLATING AGENTS; PROGNOSTIC IMPACT; MUTANT IDH1; ASPARAGINASE; DIFFERENTIATION; INHIBITION; GLUTAMINE; DISEASE; CELLS AB Acute myeloid leukemia (AML) is a lethal hematologic malignancy associated with poor clinical outcomes. In recent years, mutations in the IDH1 and IDH2 genes have been discovered across a range of malignancies, including AML, raising hope for effective targeted therapies. An intriguing aspect of IDH1/2-mutant malignancies is the aberrant production of the oncometabolite 2-hydroxyglutarate (2-HG), which likely play a pivotal oncogenic role. We recently reported that 2-HG is dramatically elevated in the sera, marrow and urine of IDH1/2-mutant AML patients, and that levels of this oncometabolite directly correlate with disease burden and therapeutic response. The discovery of IDH1/2 mutations and their impact on important proteomic and metabolic pathways has triggered intensive efforts to develop novel and targeted therapies. IDH1/2 inhibitors are currently under early phase clinical investigation, with promising suggestion of efficacy. Other therapeutic approaches under preclinical and clinical investigation in this population include DNA methyltransferase inhibitors and agents that target glutamine metabolism through inhibition of glutaminase or depletion of serum glutamine by asparaginase products. C1 [Fathi, Amir T.; Wander, Seth A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol & Med Oncol, Boston, MA 02114 USA. [Faramand, Rowan; Emadi, Ashkan] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA. RP Emadi, A (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Sch Med, Med, 22 S Greene St,Room N9E24, Baltimore, MD 21201 USA. EM afathi@partners.org; aemadi@umm.edu FU Jazz Pharmaceutical FX A.E. is an inventor on the patent "Metabolic Inhibitor Against Tumors Having an IDH Mutation", and research funding to University of Maryland from Jazz Pharmaceutical for clinical trial involving AML patients with IDH mutations. A.T.F. has participated in advisory board meetings of Agios Pharmaceuticals. Other co-authors report no relevant conflict of interest. NR 57 TC 7 Z9 7 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2015 VL 52 IS 3 BP 165 EP 171 DI 10.1053/j.seminhematol.2015.03.002 PG 7 WC Hematology SC Hematology GA CM1IF UT WOS:000357433800003 PM 26111463 ER PT J AU Wang, WH Yu, SL Zimmerman, G Wang, YW Myers, J Yu, VWC Huang, D Huang, XR Shim, J Huang, YS Xin, W Qiao, P Yan, MH Xin, W Scadden, DT Stanley, P Lowe, JB Huang, AY Siebel, CW Zhou, L AF Wang, Weihuan Yu, Shuiliang Zimmerman, Grant Wang, Yiwei Myers, Jay Yu, Vionnie W. C. Huang, Dan Huang, Xiaoran Shim, Jeongsup Huang, Yuanshuai Xin, William Qiao, Peter Yan, Minhong Xin, Wei Scadden, David T. Stanley, Pamela Lowe, John B. Huang, Alex Y. Siebel, Christian W. Zhou, Lan TI Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention SO STEM CELLS LA English DT Article DE HSC quiescence and niche retention; HSC egress and mobilization; Notch receptor-ligand interactions; O-fucosylglycans on Notch ID BONE-MARROW NICHE; O-FUCOSYL-TRANSFERASE; INHIBITS TUMOR-GROWTH; PROTEIN O-FUCOSYL-TRANSFERASE-1; PROGENITOR CELLS; MESENCHYMAL PROGENITORS; BINDING DOMAIN; SELF-RENEWAL; LOCALIZATION; ANGIOGENESIS AB Notch is long recognized as a signaling molecule important for stem cell self-renewal and fate determination. Here, we reveal a novel adhesive role of Notch-ligand engagement in hematopoietic stem and progenitor cells (HSPCs). Using mice with conditional loss of O-fucosylglycans on Notch EGF-like repeats important for the binding of Notch ligands, we report that HSPCs with faulty ligand binding ability display enhanced cycling accompanied by increased egress from the marrow, a phenotype mainly attributed to their reduced adhesion to Notch ligand-expressing stromal cells and osteoblastic cells and their altered occupation in osteoblastic niches. Adhesion to Notch ligand-bearing osteoblastic or stromal cells inhibits wild type but not O-fucosylglycan-deficient HSPC cycling, independent of RBP-J(K)-mediated canonical Notch signaling. Furthermore, Notch-ligand neutralizing antibodies induce RBP-J(K)-independent HSPC egress and enhanced HSPC mobilization. We, therefore, conclude that Notch receptor-ligand engagement controls HSPC quiescence and retention in the marrow niche that is dependent on O-fucosylglycans on Notch. Stem Cells 2015;33:2280-2293 C1 [Wang, Weihuan; Yu, Shuiliang; Zimmerman, Grant; Wang, Yiwei; Huang, Dan; Huang, Xiaoran; Qiao, Peter; Xin, Wei; Zhou, Lan] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Myers, Jay; Huang, Alex Y.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Yu, Vionnie W. C.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Yu, Vionnie W. C.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Yu, Vionnie W. C.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Shim, Jeongsup; Lowe, John B.] Luzhou Med Coll, Affiliated Hosp, Dept Pathol, Luzhou, Sichuan, Peoples R China. [Huang, Yuanshuai] Luzhou Med Coll, Affiliated Hosp, Dept Blood Transfus, Luzhou, Sichuan, Peoples R China. [Xin, William] Univ Sch, Hunting Valley, OH USA. [Yan, Minhong; Siebel, Christian W.] Genentech Inc, Dept Mol Biol Oncol, San Francisco, CA USA. [Stanley, Pamela] Albert Einstein Coll Med, Dept Cell Biol, New York, NY USA. RP Zhou, L (reprint author), Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. EM lan.zhou@case.edu OI Yu, Vionnie W. C./0000-0002-6658-0285; Huang, Alex/0000-0002-5701-4521 FU American Cancer Society [LIB-125064, HL103827, RO195022, RO1GM106417]; MGH Federal Share of the Program Income [C06 CA059267]; Proton Therapy Research and Treatment Center; BD Biosciences Stem Cell Grant; Bullock-Wellman Fellowship Award; Tosteson; Fund for Medical Discovery Fellowship; [HL097794]; [HL044851]; [HL100402]; [HL96372]; [EB14703] FX We thank Dr. Guang Zhou for assisting in the isolation of calvarium osteoblasts. This work was supported by grants from American Cancer Society LIB-125064 and HL103827 (to L.Z.); RO195022 and RO1GM106417 (to P.S.); MGH Federal Share of the Program Income under C06 CA059267, Proton Therapy Research and Treatment Center, BD Biosciences Stem Cell Grant, Bullock-Wellman Fellowship Award, as well as Tosteson and Fund for Medical Discovery Fellowship (to V.W.C.Y.); HL097794, HL044851, HL100402, HL96372, and EB14703 (to D.T.S). NR 65 TC 7 Z9 9 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JUL PY 2015 VL 33 IS 7 BP 2280 EP 2293 DI 10.1002/stem.2031 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA CL0YE UT WOS:000356668200018 PM 25851125 ER PT J AU Begum, G Yuan, H Kahle, KT Li, LL Wang, SX Shi, YJ Shmukler, BE Yang, SS Lin, SH Alper, SL Sun, DD AF Begum, Gulnaz Yuan, Hui Kahle, Kristopher T. Li, Liaoliao Wang, Shaoxia Shi, Yejie Shmukler, Boris E. Yang, Sung-Sen Lin, Shih-Hua Alper, Seth L. Sun, Dandan TI Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery After Stroke SO STROKE LA English DT Article DE bumetanide; KCC2 cotransporter; NKCC1 cotransporter; OSR1 kinase; SPAK Kinase ID FOCAL CEREBRAL-ISCHEMIA; K+-CL-COTRANSPORTER; NA-K-2CL COTRANSPORTER; BLOOD-PRESSURE; CELL-VOLUME; MEDIATED EXCITOTOXICITY; MOLECULAR PHYSIOLOGY; NA+/CA2+ EXCHANGER; ARTERY OCCLUSION; PROTEIN-KINASES AB Background and Purpose WNK kinases, including WNK3, and the associated downstream Ste20/SPS1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinases, comprise an important signaling cascade that regulates the cation-chloride cotransporters. Ischemia-induced stimulation of the bumetanide-sensitive Na+-K+-Cl- cotransporter (NKCC1) plays an important role in the pathophysiology of experimental stroke, but the mechanism of its regulation in this context is unknown. Here, we investigated the WNK3-SPAK/OSR1 pathway as a regulator of NKCC1 stimulation and their collective role in ischemic brain damage. Method Wild-type WNK3 and WNK3 knockout mice were subjected to ischemic stroke via transient middle cerebral artery occlusion. Infarct volume, brain edema, blood brain barrier damage, white matter demyelination, and neurological deficits were assessed. Total and phosphorylated forms of WNK3 and SPAK/OSR1 were assayed by immunoblotting and immunostaining. In vitro ischemia studies in cultured neurons and immature oligodendrocytes were conducted using the oxygen-glucose deprivation/reoxygenation method. Results WNK3 knockout mice exhibited significantly decreased infarct volume and axonal demyelination, less cerebral edema, and accelerated neurobehavioral recovery compared with WNK3 wild-type mice subjected to middle cerebral artery occlusion. The neuroprotective phenotypes conferred by WNK3 knockout were associated with a decrease in stimulatory hyperphosphorylations of the SPAK/OSR1 catalytic T-loop and of NKCC1 stimulatory sites Thr(203)/Thr(207)/Thr(212), as well as with decreased cell surface expression of NKCC1. Genetic inhibition of WNK3 or small interfering RNA knockdown of SPAK/OSR1 increased the tolerance of cultured primary neurons and oligodendrocytes to in vitro ischemia. Conclusions These data identify a novel role for the WNK3-SPAK/OSR1-NKCC1 signaling pathway in ischemic neuroglial injury and suggest the WNK3-SPAK/OSR1 kinase pathway as a therapeutic target for neuroprotection after ischemic stroke. C1 [Begum, Gulnaz; Yuan, Hui; Li, Liaoliao; Wang, Shaoxia; Shi, Yejie; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Kahle, Kristopher T.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis, Boston, MA USA. [Shmukler, Boris E.; Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shmukler, Boris E.; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. [Shmukler, Boris E.; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Vasc Biol Ctr, Boston, MA 02215 USA. [Yang, Sung-Sen; Lin, Shih-Hua] Natl Def Med Ctr, Triserv Gen Hosp, Dept Med, Div Nephrol, Taipei, Taiwan. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Sun, DD (reprint author), Univ Pittsburgh, Dept Neurol, S-598 S Biomed Sci Tower BST,3500 Terranc St, Pittsburgh, PA 15213 USA. EM sund@upmc.edu OI Shi, Yejie/0000-0001-7502-9201 FU National Institute of Health [R01 NS038118, R01 HL07765, R25]; Manton Center for Orphan Disease Research; Harvard-MIT Basic Neuroscience Award; Ministry of Science and Technology, Taiwan FX This study was supported by the National Institute of Health Grants R01 NS038118 (Dr Sun) and R01 HL07765 (Dr Alper) and R25 (Dr Kahle), and the Manton Center for Orphan Disease Research (Dr Kahle), and a Harvard-MIT Basic Neuroscience Award (Dr Kahle), and the Ministry of Science and Technology, Taiwan (Dr Yang). NR 54 TC 9 Z9 9 U1 1 U2 6 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 JUL PY 2015 VL 46 IS 7 BP 1956 EP 1965 DI 10.1161/STROKEAHA.115.008939 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CL0ZY UT WOS:000356672800030 PM 26069258 ER PT J AU Liebeskind, DS Albers, GW Crawford, K Derdeyn, CP George, MS Palesch, YY Toga, AW Warach, S Zhao, WL Brott, TG Sacco, RL Khatri, P Saver, JL Cramer, SC Wolf, SL Broderick, JP Wintermark, M AF Liebeskind, David S. Albers, Gregory W. Crawford, Karen Derdeyn, Colin P. George, Mark S. Palesch, Yuko Y. Toga, Arthur W. Warach, Steven Zhao, Wenle Brott, Thomas G. Sacco, Ralph L. Khatri, Pooja Saver, Jeffrey L. Cramer, Steven C. Wolf, Steven L. Broderick, Joseph P. Wintermark, Max TI Imaging in StrokeNet Realizing the Potential of Big Data SO STROKE LA English DT Article DE collateral circulation; diagnostic imaging; stroke ID ACUTE ISCHEMIC-STROKE; TRIALS; REPERFUSION; COLLATERALS; DIFFUSION; STANDARDS; DISEASE; PROFILE; DEFUSE C1 [Liebeskind, David S.] Univ Calif Los Angeles, Neurovasc Imaging Res Core, Los Angeles, CA 90095 USA. [Liebeskind, David S.; Saver, Jeffrey L.] Univ Calif Los Angeles, Geffen Sch Med, Comprehens Stroke Ctr, Dept Neurol, Los Angeles, CA 90095 USA. [Albers, Gregory W.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Wintermark, Max] Stanford Univ, Dept Radiol, Palo Alto, CA 94304 USA. [Crawford, Karen; Toga, Arthur W.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA 90033 USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, Dept Neurol, St Louis, MO 63110 USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, Dept Neurol Surg, St Louis, MO 63110 USA. [George, Mark S.] Med Univ S Carolina, Dept Psychiat Radiol & Neurosci, Charleston, SC 29425 USA. [Palesch, Yuko Y.; Zhao, Wenle] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Warach, Steven] Univ Texas SW Med Ctr Dallas, Austin, TX USA. [Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Coral Gables, FL 33124 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Human Genet, Coral Gables, FL 33124 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurosurg, Coral Gables, FL 33124 USA. [Khatri, Pooja; Broderick, Joseph P.] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Cramer, Steven C.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Wolf, Steven L.] Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA. [Wolf, Steven L.] Atlanta VA Med Ctr, Ctr Visual & Cognit Neurorehabil, Atlanta, GA USA. RP Liebeskind, DS (reprint author), Univ Calif Los Angeles, Dept Neurol, Neurovasc Imaging Res Core, Neurosci Res Bldg,635 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM davidliebeskind@yahoo.com OI Derdeyn, Colin/0000-0002-5932-2683 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke [U01NS087748, K24NS072272, R01NS077706, R13NS089280] FX This work has been funded by National Institutes of Health-National Institute of Neurological Disorders and Stroke awards U01NS087748, K24NS072272, R01NS077706, and R13NS089280. NR 25 TC 3 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2015 VL 46 IS 7 BP 2000 EP 2006 DI 10.1161/STROKEAHA.115.009479 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CL0ZY UT WOS:000356672800039 PM 26045600 ER PT J AU Hemphill, JC Greenberg, SM Anderson, CS Becker, K Bendok, BR Cushman, M Fung, GL Goldstein, JN Macdonald, RL Mitchell, PH Scott, PA Selim, MH Woo, D AF Hemphill, J. Claude, III Greenberg, Steven M. Anderson, Craig S. Becker, Kyra Bendok, Bernard R. Cushman, Mary Fung, Gordon L. Goldstein, Joshua N. Macdonald, R. Loch Mitchell, Pamela H. Scott, Phillip A. Selim, Magdy H. Woo, Daniel CA Amer Heart Assoc Stroke Council Council Cardiovasc Stroke Nursing Council Clinical Cardiology TI Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association SO STROKE LA English DT Review DE AHA Scientific Statements; blood pressure; coagulopathy; diagnosis; intracerebral hemorrhage; intraventricular hemorrhage; surgery; treatment ID PROTHROMBIN COMPLEX CONCENTRATE; ACTIVATED FACTOR-VII; RANDOMIZED CONTROLLED-TRIALS; MINIMALLY-INVASIVE SURGERY; ACUTE ISCHEMIC-STROKE; SEVERE INTRAVENTRICULAR HEMORRHAGE; PREDICTS HEMATOMA EXPANSION; ACUTE-CEREBRAL-HEMORRHAGE; IN-HOSPITAL MORTALITY; DEEP-VEIN THROMBOSIS AB Purpose The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. Methods A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. Results Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. Conclusions Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage. C1 [Hemphill, J. Claude, III] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Greenberg, Steven M.; Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anderson, Craig S.] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Anderson, Craig S.] Royal Prince Alfred Hosp, Camperdown, NSW, Australia. [Becker, Kyra] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Bendok, Bernard R.] Northwestern Med Fac Fdn, Chicago, IL USA. [Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [Fung, Gordon L.] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. [Mitchell, Pamela H.] Univ Washington, Seattle, WA 98195 USA. [Scott, Phillip A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Selim, Magdy H.] Harvard Med Fac Phys, Boston, MA USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. RP Hemphill, JC (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Goldstein, Joshua/H-8953-2016 FU NIH/NINDS; Avid Radiopharmaceuticals; NIH; NINDS; National Health and Medical Research (NHMRC) of Australia; NIH/NHLBI; CSL Behring; Brain Aneurysm Foundation; Canadian Institutes of Health Research; Heart and Stroke Foundation of Canada; Physicians Services Incorporated Foundation; NINDS [NS030678, NS036695, 1U01NS069763, NINDS 2P50NS044283]; Novo Nordisk (NINDS) FX J. Claude Hemphill III University of California, San Francisco NIH/NINDS* None None None None None None; Steven M. Greenberg Massachusetts General Hospital Avid Radiopharmaceuticals dagger; NIH dagger; NINDS dagger; None None None None None None; Craig S. Anderson The George Institute for Global Health, University of Sydney; Royal Prince Alfred Hospital The National Health and Medical Research (NHMRC) of Australia dagger None Takeda China*; Covidien*; Bayer* None None Pfizer*; The Medicines Company* None; Mary Cushman University of Vermont NIH/NHLBI dagger; NIH/NINDS dagger None None None None None None; Joshua N. Goldstein Massachusetts General Hospital CSL Behring dagger; NIH*; NINDS dagger None None None None CSL Behring* None; R. Loch Macdonald Independent Medical Practitioner Brain Aneurysm Foundation*; Canadian Institutes of Health Research*; Heart and Stroke Foundation of Canada*; Physicians Services Incorporated Foundation* None None None Edge Therapeutics* Actelion Pharmaceuticals* None; Matthew L. Flaherty University of Cincinnati Academic Health Center NINDS (Coinvestigator on NINDS-funded grants NS030678, NS036695,1U01NS069763)dagger; NINDS (Principal Investigator, NINDS 2P50NS044283, "STOP-IT Study")dagger Novo Nordisk (Principal Investigator of NINDS-funded STOP-IT Study, study drug supplied by Novo Nordisk)* CSL Behring* None Sense Diagnostics, LLC dagger CSL Behring* None NR 330 TC 166 Z9 171 U1 12 U2 38 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 JUL PY 2015 VL 46 IS 7 BP 2032 EP 2060 DI 10.1161/STR.0000000000000069 PG 29 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CL0ZY UT WOS:000356672800044 PM 26022637 ER PT J AU Meredith, ME Salameh, TS Banks, WA AF Meredith, M. Elizabeth Salameh, Therese S. Banks, William A. TI Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases SO AAPS JOURNAL LA English DT Review DE blood-brain barrier; cognition; intranasal; memory ID GALANIN-LIKE PEPTIDE; BLOOD-BRAIN-BARRIER; GLUCAGON-LIKE PEPTIDE-1; CYCLASE-ACTIVATING POLYPEPTIDE; MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; NASAL DRUG-DELIVERY; ADENYLATE-CYCLASE; ALZHEIMERS-DISEASE; ACETYLCHOLINE-RELEASE AB The blood-brain barrier (BBB) is a major impediment to the therapeutic delivery of peptides and proteins to the brain. Intranasal delivery often provides a non-invasive means to bypass the BBB. Advantages of using intranasal delivery include minimizing exposure to peripheral organs and tissues, thus reducing systemic side effects. It also allows substances that typically have rapid degradation in the blood time to exert their effect. Intranasal delivery provides the ability to target proteins and peptides to specific regions of the brain when administered with substrates like cyclodextrins. In this review, we examined the use of intranasal delivery of various proteins and peptides that have implications in the treatment of neurodegenerative diseases, focusing especially on albumin, exendin/GLP-1, GALP, insulin, leptin, and PACAP. We have described their rationale for use, distribution in the brain after intranasal injection, how intranasal administration differed from other modes of delivery, and their use in clinical trials, if applicable. Intranasal delivery of drugs, peptides, and other proteins could be very useful in the future for the prevention or treatment of brain related diseases. C1 [Meredith, M. Elizabeth] Univ Washington, Dept Pathol, Seattle, WA 98108 USA. [Meredith, M. Elizabeth; Salameh, Therese S.; Banks, William A.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med,VAPSHCS, Seattle, WA 98108 USA. [Meredith, M. Elizabeth; Salameh, Therese S.; Banks, William A.] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Banks, WA (reprint author), Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med,VAPSHCS, 1660S Columbian Way,810A Bldg 1, Seattle, WA 98108 USA. EM bankswa@slu.edu FU NIA NIH HHS [T32 AG000057] NR 73 TC 13 Z9 13 U1 5 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUL PY 2015 VL 17 IS 4 BP 780 EP 787 DI 10.1208/s12248-015-9719-7 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CL0DV UT WOS:000356610300002 PM 25801717 ER PT J AU Patel, MS AF Patel, Mitesh S. TI Health Policy in Medical Education: A Renewed Look at a Timely and Achievable Imperative Reply SO ACADEMIC MEDICINE LA English DT Letter ID STUDENT PERCEPTIONS C1 [Patel, Mitesh S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Patel, Mitesh S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Patel, MS (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu NR 3 TC 0 Z9 0 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2015 VL 90 IS 7 BP 838 EP 838 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CL6QZ UT WOS:000357093500003 PM 26414047 ER PT J AU Pojednic, RM Trilk, J Phillips, EM AF Pojednic, Rachele M. Trilk, Jennifer Phillips, Edward M. TI Lifestyle Medicine Curricula: An Initiative to Include Lifestyle Medicine in Our Nation's Medical Schools SO ACADEMIC MEDICINE LA English DT Letter ID EDUCATION C1 [Pojednic, Rachele M.; Phillips, Edward M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med, Boston, MA 02115 USA. [Trilk, Jennifer] Univ S Carolina, Dept Biomed Sci, Sch Med, Greenville, SC USA. [Phillips, Edward M.] Harvard Univ, Sch Med, Phys Med & Rehabil, Boston, MA USA. RP Pojednic, RM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med, Boston, MA 02115 USA. EM Rachele.pojednic@joslin.harvard.edu NR 4 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 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2015 VL 90 IS 7 BP 840 EP 841 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CL6QZ UT WOS:000357093500007 PM 26414051 ER PT J AU Zafar, HM Yang, JN Armstrong, K Groeneveld, P AF Zafar, Hanna M. Yang, Jianing Armstrong, Katrina Groeneveld, Peter TI Cost Differences After Initial CT Colonography Versus Optical Colonoscopy in the Elderly SO ACADEMIC RADIOLOGY LA English DT Article DE Colorectal cancer; health care utilization; health care costs; radiology; gastroenterology ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; EXTRACOLONIC FINDINGS; VIRTUAL COLONOSCOPY; MEDICARE BENEFICIARIES; SCREENING POPULATION; REGIONAL-VARIATIONS; BARIUM ENEMA; NEOPLASIA; IMPACT AB Rationale and Objectives: To compare differences in Medicare costs 1 year after initial computed tomographic colonography (CTC) or initial optical colonoscopy (OC). Materials and Methods: We performed a retrospective cohort study of asymptomatic Medicare outpatients aged >= 66 years who received initial CTC (n = 531) or OC (n = 17,593) between January 2007 and December 2008; initial OC patients were matched on county of residence and year of screening. Outcomes included differences in total inpatient and outpatient Medicare costs 1 year after initial CTC or OC and differences in outpatient testing of potential findings in the colon, abdomen, pelvis, and lungs. Results: Higher adjusted costs per patient were revealed in the year after initial CTC compared to initial OC for outpatient testing related to potential colonic ($50; 95% confidence interval [CI], $12-$88; P =.010) and extracolonic findings ($64; 95% CI, $23-$106; P =.002). However, there were no differences in adjusted total costs per patient in the year after either modality ($2065; 95% CI, $1672-$5803; P =.28). Similarly, adjusted costs did not differ between cohorts for inpatient ($267; 95% CI, $1017-$1550; P = .68) or outpatient care ($2828; 95% CI, $311-$5966; P = .08). Conclusions: Despite higher adjusted costs of outpatient testing potentially related to colonic and extracolonic findings among asymptomatic elderly patients 1 year after initial CTC compared to OC, we found no differences in adjusted total, inpatient, or outpatient costs between cohorts. Although Medicare does not cover screening CTC, our results suggest that these modalities generate comparable downstream costs to payers. C1 [Zafar, Hanna M.] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Yang, Jianing] Amer Acad Dermatol, Schaumburg, IL USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Groeneveld, Peter] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Zafar, HM (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM hanna.zafar@uphs.upenn.edu OI Zafar, Hanna/0000-0001-5874-7607 FU American Cancer Society [IRG-78-002-31]; National Institutes of Health [1-KM-CA156715-01] FX This study was supported by grant IRG-78-002-31 from the American Cancer Society and grant 1-KM-CA156715-01 from the National Institutes of Health. NR 45 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2015 VL 22 IS 7 BP 807 EP 813 DI 10.1016/j.acra.2015.03.002 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5IN UT WOS:000356993200002 PM 25890873 ER PT J AU Lee, CI Bogart, A Hubbard, RA Obadina, ET Hill, DA Haas, JS Tosteson, ANA Alford-Teaster, JA Sprague, BL DeMartini, WB Lehman, CD Onega, TL AF Lee, Christoph I. Bogart, Andy Hubbard, Rebecca A. Obadina, Eniola T. Hill, Deirdre A. Haas, Jennifer S. Tosteson, Anna N. A. Alford-Teaster, Jennifer A. Sprague, Brian L. DeMartini, Wendy B. Lehman, Constance D. Onega, Tracy L. TI Advanced Breast Imaging Availability by Screening Facility Characteristics SO ACADEMIC RADIOLOGY LA English DT Article DE Screening; breast cancer; mammography; diagnostic imaging ID DIAGNOSTIC MAMMOGRAPHY; GEOGRAPHIC ACCESS; CANCER; PERFORMANCE; LEGISLATION; ULTRASOUND; MORTALITY AB Rationale and Objectives: To determine the relationship between screening mammography facility characteristics and on-site availability; of advanced breast imaging services required for supplemental screening and the diagnostic evaluation of abnormal screening findings. Materials and Methods: We analyzed data from all active imaging facilities across six regional registries of the National Cancer Institute-funded Breast Cancer Surveillance Consortium offering screening mammography in calendar years 2011-2012 (n = 105). We used generalized estimating equations regression models to identify associations between facility characteristics (eg, academic affiliation, practice type) and availability of on-site advanced breast imaging (eg, ultrasound [US], magnetic-resonance imaging [MRI]) and image guided biopsy services. Results: Breast MRI was not available at any nonradiology or breast imaging-only facilities. A combination of breast US, breast MRI, and imaging-guided breast biopsy services was available at 76.0% of multispecialty breast centers compared-to 22.2% of full diagnostic radiology practices (P = .0047) and 75.0% of facilities with academic affiliations compared to 29.0% of those without academic affiliations (P = .04). Both supplemental screening breast US and screening breast MRI were available at 28.0% of multispecialty breast centers compared to 4.7% of full diagnostic radiology practices (P < .01) and 25.0% of academic facilities compared to 8.5% of nonacademic facilities (P = .02). Conclusions: Screening facility characteristics are strongly associated with the availability of on-site advanced breast imaging and image-guided biopsy service. therefore, the type of imaging facility a woman attends for screening may have important implications on her timely access to supplemental screening and diagnostic breast imaging services. C1 [Lee, Christoph I.; Obadina, Eniola T.; Lehman, Constance D.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98109 USA. [Lee, Christoph I.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Bogart, Andy; Hubbard, Rebecca A.] Grp Hlth Res Inst, Seattle, WA USA. [Hill, Deirdre A.] Univ New Mexico, Dept Internal Med, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Haas, Jennifer S.] Harvard Univ, Sch Med, Dept Med, Dana Farber Harvard Canc Inst, Boston, MA USA. [Haas, Jennifer S.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tosteson, Anna N. A.; Alford-Teaster, Jennifer A.; Onega, Tracy L.] Geisel Sch Med, Norris Cotton Canc Ctr, Dartmouth Inst Hlth Policy & Clin Practice, Dept Med, Lebanon, NH USA. [Alford-Teaster, Jennifer A.; Onega, Tracy L.] Geisel Sch Med, Norris Cotton Canc Ctr, Dartmouth Inst Hlth Policy & Clin Practice, Dept Community & Family Med, Lebanon, NH USA. [Sprague, Brian L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA. [Sprague, Brian L.] Univ Vermont, Off Hlth Promot Res, Burlington, VT 05405 USA. [DeMartini, Wendy B.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Lee, CI (reprint author), Univ Washington, Sch Med, Dept Radiol, 825 Eastlake Ave East, Seattle, WA 98109 USA. EM stophlee@uw.edu FU National Cancer Institute [RC2CA148577, P01CA154292, HHSN261201100031C]; American Cancer Society [MRSG-14-160-01-CPHPS] FX This work was supported by grants from the National Cancer Institute (RC2CA148577 and P01CA154292 and, for the Breast Cancer Surveillance Consortium, HHSN261201100031C) and the American Cancer Society (MRSG-14-160-01-CPHPS). The design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. NR 24 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2015 VL 22 IS 7 BP 846 EP 852 DI 10.1016/j.acra.2015.02.011 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5IN UT WOS:000356993200008 PM 25851643 ER PT J AU Hahn, PF Guimaraes, AR Arellano, RS Mueller, PR Gervais, DA AF Hahn, Peter F. Guimaraes, Alexander R. Arellano, Ronald S. Mueller, Peter R. Gervais, Debra A. TI Nonvascular Interventional Procedures in an Urban General Hospital: Analysis of 2001-2010 with Comparison to the Previous Decade SO ACADEMIC RADIOLOGY LA English DT Article DE Radiology; interventional; utilization; image-guided biopsy; abdominal abscess ID COMPUTED-TOMOGRAPHY; MANAGEMENT; GASTROSTOMY; DATABASE; BIOPSY AB Rationale and Objectives: To determine trends in nonvascular image-guided procedures at an urban general hospital over a 10-year period and to compare utilization of nonvascular interventional radiology (IR) over the decade 2001-2010 to a previously reported analysis for 1991-2000. Methods: With institutional review board approval, a 20-year quality assurance database verified against the radiology information system was queried for procedure location (eg, pleura, liver, bowel, and abdomen) and type (eg, biopsy, catheter insertion, and transient drainage), demographics, and change over time. Yearly admissions and new hospital numbers assigned each year served to normalize for overall hospital activity. Results: A total of 50,195 IR procedures were performed in 24,309 distinct patients (male:female, 12,625:11,684; average age, 60 years), 940 procedures performed in age <20 years, and 571 procedures performed in patients aged >= 90 years. A total of 15345, 4377, and 1754 patients had one, two, or three procedures, respectively; 470 had >= 10 procedures. Twenty-seven supervising radiologists and 277 individuals participated as operators, double the previous decade. Biopsy (4.8% average yearly increase), abdominal drainage (7.3%), paracentesis (12.9%), tube manipulation (13.0%), suprapubic bladder tube insertion (21.0%), and gastrostomy (44.6%) all increased strongly (P < .001) over 120 months but not biliary drainage, nephrostomy, or chest tubes. Procedures increased faster than either admissions or new hospital numbers (P < .001). For each 1000 new hospital numbers, IR service performed 48 procedures versus 31 the previous decade (P < .0005). Conclusions: Referrals for nonvascular IR procedures have doubled over 2 decades, outpacing growth in new hospital patients and requiring increased resource allocation. C1 [Hahn, Peter F.; Guimaraes, Alexander R.; Arellano, Ronald S.; Mueller, Peter R.; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hahn, Peter F.; Guimaraes, Alexander R.; Arellano, Ronald S.; Mueller, Peter R.; Gervais, Debra A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 220,55 Fruit St, Boston, MA 02114 USA. EM phahn@partners.org FU Covidien, Ireland FX A.R.G. serves on the Siemens Medical Solutions Speakers Bureau, and D.A.G. received a research grant from Covidien, Ireland. All other authors have no potential conflicts of interest related to this research. NR 16 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2015 VL 22 IS 7 BP 904 EP 908 DI 10.1016/j.acra.2015.01.002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5IN UT WOS:000356993200015 PM 25704589 ER PT J AU Auther, AM Cadenhead, KS Carrion, RE Addington, J Bearden, CE Cannon, TD McGlashan, TH Perkins, DO Seidman, L Tsuang, M Walker, EF Woods, SW Cornblatt, BA AF Auther, A. M. Cadenhead, K. S. Carrion, R. E. Addington, J. Bearden, C. E. Cannon, T. D. McGlashan, T. H. Perkins, D. O. Seidman, L. Tsuang, M. Walker, E. F. Woods, S. W. Cornblatt, B. A. TI Alcohol confounds relationship between cannabis misuse and psychosis conversion in a high-risk sample SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE cannabis use; alcohol use; substance use; clinical high-risk; prodromal states; psychosis ID CLINICAL HIGH-RISK; ULTRA-HIGH-RISK; YOUNG-ADULTS; SYMPTOMS; SCHIZOPHRENIA; ADOLESCENCE; PSYCHOPATHOLOGY; EXPERIENCES; PREVALENCE; PREDICTION AB ObjectiveCannabis use has been examined as a predictor of psychosis in clinical high-risk (CHR) samples, but little is known about the impact of other substances on this relationship. MethodSubstance use was assessed in a large sample of CHR participants (N=370, mean age=18.3) enrolled in the multisite North American Prodrome Longitudinal Study Phase 1 project. Three hundred and forty-one participants with cannabis use data were divided into groups: No Use (NU, N=211); Cannabis Use without impairment (CU, N=63); Cannabis Abuse/Dependence (CA/CD, N=67). Participants (N=283) were followed for 2years to determine psychosis conversion. ResultsAlcohol (45.3%) and cannabis (38.1%) were the most common substances. Cannabis use groups did not differ on baseline attenuated positive symptoms. Seventy-nine of 283 participants with cannabis and follow-up data converted to psychosis. Survival analysis revealed significant differences between conversion rates in the CA/CD group compared with the No Use (P=0.031) and CU group (P=0.027). CA/CD also significantly predicted psychosis in a regression analysis, but adjusting for alcohol use weakened this relationship. ConclusionThe cannabis misuse and psychosis association was confounded by alcohol use. Non-impairing cannabis use was not related to psychosis. Results highlight the need to control for other substance use, so as to not overstate the cannabis/psychosis connection. C1 [Auther, A. M.; Carrion, R. E.; Cornblatt, B. A.] Zucker Hillside Hosp, Div Psychiat Res, North Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY 11004 USA. [Auther, A. M.; Carrion, R. E.; Cornblatt, B. A.] Hofstra North Shore LIJ Sch Med, Dept Psychiat, Hempstead, NY USA. [Cadenhead, K. S.; Tsuang, M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Carrion, R. E.; Cornblatt, B. A.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Addington, J.] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Bearden, C. E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Cannon, T. D.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT USA. [Cannon, T. D.; McGlashan, T. H.; Woods, S. W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Perkins, D. O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, L.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, L.] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Walker, E. F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. RP Auther, AM (reprint author), Zucker Hillside Hosp, Dept Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM aauther@lij.edu FU National Institute of Mental Health [R01 MH061523, U01 MH081857, R18 MH43518, U01 MH081928, P50 MH080272, P50 MH066286, R01 MH65079, RO1 MH062066, 5U01 MH081988, R01 MH60720, K24 MH76191, K05 MH01654, U01MH081902-05, R01 MH081861, R01 MH085560, U01 MH082022, U01 MH 066160, U01 MH066134] FX This study was supported by the National Institute of Mental Health (grant R01 MH061523, U01 MH081857 to Dr. Cornblatt; grants R18 MH43518, U01 MH081928, and P50 MH080272 to Dr. Seidman; grant P50 MH066286 and R01 MH65079 to Drs. Cannon and Bearden; grants RO1 MH062066 and 5U01 MH081988 to Dr. Walker; grants R01 MH60720 and K24 MH76191 to Dr. Cadenhead; grant K05 MH01654 to Dr. McGlashan; grant U01MH081902-05 to Dr. Perkins; grant R01 MH081861 and R01 MH085560 to Dr. Tsuang; grants U01 MH082022 and U01 MH 066160 to Dr. Woods; grant U01 MH066134 to Dr. Addington). NR 46 TC 6 Z9 6 U1 6 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 2015 VL 132 IS 1 BP 60 EP 68 DI 10.1111/acps.12382 PG 9 WC Psychiatry SC Psychiatry GA CL1EW UT WOS:000356686500007 PM 25572323 ER PT J AU Rodriguez, D Sacco, DE AF Rodriguez, Dayron Sacco, Dianne E. TI Minimally Invasive Surgical Treatment for Kidney Stone Disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Nephrolithiasis; Ureteroscopy; Extracorporeal shock wave lithotripsy; Percutaneous nephrolithotomy ID SHOCK-WAVE LITHOTRIPSY; COMPUTED-TOMOGRAPHY; RENAL STONE; PERCUTANEOUS NEPHROSTOLITHOTOMY; URETERAL CALCULI; RANDOMIZED-TRIAL; SOLITARY KIDNEY; ENERGY; URETEROSCOPY; MANAGEMENT AB Minimally invasive interventions for stone disease in the United States are mainly founded on 3 surgical procedures: extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy. With the advancement of technology, treatment has shifted toward less invasive strategies and away from open or laparoscopic surgery. The treatment chosen for a patient with stones is based on the stone and patient characteristics. Each of the minimally invasive techniques uses an imaging source, either fluoroscopy or ultrasound, to localize the stone and an energy source to fragment the stone. Extracorporeal shock wave lithotripsy uses a shock wave energy source generated outside the body to fragment the stone. In contrast, with ureteroscopy, laser energy is placed directly on the stone using a ureteroscope that visualizes the stone. Percutaneous nephrolithotomy requires dilation of a tract through the back into the renal pelvis so that instruments can be inserted directly onto the stone to fragment or pulverize it. The success of the surgical intervention relies on performing the least invasive technique with the highest success of stone removal. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Rodriguez, Dayron; Sacco, Dianne E.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sacco, DE (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM dsacco@partners.org NR 58 TC 3 Z9 3 U1 3 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JUL PY 2015 VL 22 IS 4 BP 266 EP 272 DI 10.1053/j.ackd.2015.03.005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CL5LH UT WOS:000357000900004 PM 26088070 ER PT J AU Shoag, J Tasian, GE Goldfarb, DS Eisner, BH AF Shoag, Jonathan Tasian, Greg E. Goldfarb, David S. Eisner, Brian H. TI The New Epidemiology of Nephrolithiasis SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Nephrolithiasis; Epidemiology; Pediatrics; Systemic disease; Risk factors ID INCIDENT KIDNEY-STONES; BODY-MASS INDEX; UNITED-STATES; RENAL STONE; DIETARY CALCIUM; NATIONAL-HEALTH; US CHILDREN; NHANES-III; RISK; DISEASE AB Historically nephrolithiasis was considered a disease of dehydration and abnormal urine composition. However, over the past several decades, much has been learned about the epidemiology of this disease and its relation to patient demographic characteristics and common systemic diseases. Here we review the latest epidemiologic studies in the field. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Urol, New York, NY USA. Childrens Hosp Philadelphia, Div Urol, Philadelphia, PA 19104 USA. NYU, Langone Med Ctr, Dept Med, New York, NY USA. New York Harbor Vet Affairs Hlth Care Syst, Nephrol Sect, New York, NY USA. [Eisner, Brian H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org OI Goldfarb, David/0000-0002-9215-1273 NR 66 TC 9 Z9 9 U1 3 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JUL PY 2015 VL 22 IS 4 BP 273 EP 278 DI 10.1053/j.ackd.2015.04.004 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CL5LH UT WOS:000357000900005 PM 26088071 ER PT J AU Esrick, EB McConkey, M Lin, K Frisbee, A Ebert, BL AF Esrick, Erica B. McConkey, Marie Lin, Katherine Frisbee, Alyse Ebert, Benjamin L. TI Inactivation of HDAC1 or HDAC2 induces gamma globin expression without altering cell cycle or proliferation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FETAL-HEMOGLOBIN PRODUCTION; QUALITY-OF-LIFE; GENE-EXPRESSION; HYDROXYUREA; DISEASE; ANEMIA; CHILDREN; TRIAL; INDUCTION; MORBIDITY AB Other than hydroxyurea, no pharmacologic agents are clinically available for fetal hemoglobin (HbF) induction in sickle cell disease (SCD). An optimal candidate would induce HbF without causing cell cycle inhibition and would act independently of hydroxyurea in order to yield additional HbF induction when combined. We explored whether inhibition of histone deacetylase (HDAC) 1 or HDAC2 could achieve these goals. In human erythroid progenitor cells, shRNA knockdown of the HDAC1 or HDAC2 genes induced gamma globin, without altering cellular proliferation in vitro, and without altering cell cycle phase. Treatment with hydroxyurea in combination with HDAC2 knockdown yielded a further increase in gamma globin expression. Additionally, when CD34+ cells were treated with both hydroxyurea and MS-275 (an inhibitor of HDAC 1, 2, and 3), an additive induction of relative gamma globin expression was achieved. Our findings support further clinical investigation of HDAC inhibitors in combination with hydroxyurea in SCD patients. Am. J. Hematol. 90:624-628, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Esrick, Erica B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Esrick, Erica B.; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [McConkey, Marie; Lin, Katherine; Frisbee, Alyse; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Ebert, BL (reprint author), 1 Blackfan Circle,Karp 5-210, Boston, MA 02115 USA. EM bebert@partners.org FU National Institutes of Health [U01HL117720]; Doris Duke Charitable Foundation FX Contract grant sponsor: National Institutes of Health; Contract grant number: U01HL117720.; Contract grant sponsor: Doris Duke Charitable Foundation. NR 31 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2015 VL 90 IS 7 BP 624 EP 628 DI 10.1002/ajh.24019 PG 5 WC Hematology SC Hematology GA CL1JS UT WOS:000356699300016 PM 25808664 ER PT J AU Terry, AR Merker, VL Barker, FG Leffert, L Bateman, BT Souter, I Plotkin, SR AF Terry, Anna R. Merker, Vanessa L. Barker, Fred G., II Leffert, Lisa Bateman, Brian T. Souter, Irene Plotkin, Scott R. TI Pregnancy complications in women with rare tumor suppressor syndromes affecting central and peripheral nervous system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID VON-HIPPEL-LINDAU; TUBEROUS SCLEROSIS; DISEASE C1 [Terry, Anna R.] George Washington Univ, Med Fac Associates, Dept Neurosurg, Washington, DC 20037 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Leffert, Lisa; Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Souter, Irene] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Terry, AR (reprint author), George Washington Univ, Med Fac Associates, Dept Neurosurg, Washington, DC 20037 USA. EM aterry@mfa.gwu.edu OI Merker, Vanessa/0000-0002-4542-5227 NR 5 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2015 VL 213 IS 1 BP 108 EP 109 DI 10.1016/j.ajog.2015.02.013 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL3FQ UT WOS:000356836200039 PM 25687565 ER PT J AU Dugel, PU Regillo, C Eliott, D AF Dugel, Pravin U. Regillo, Carl Eliott, Dean TI Characterization of Anatomic and Visual Function Outcomes in Patients With Full-Thickness Macular Hole in Ocriplasmin Phase 3 Trials SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID VITREOMACULAR TRACTION; SURGERY; VITRECTOMY; ADHESION; SIZE; MICROPLASMIN; VITREOLYSIS; STAGE-2 AB PURPOSE: To characterize anatomic and visual outcomes in patients with full-thickness macular hole (FTMH) at baseline in ocriplasmin phase 3 clinical trials, focusing on the relationship between resolution of vitreomacular adhesion and FTMH closure. DESIGN: Two multicenter, randomized, double-masked clinical trials. METHODS: Pharmacologic FTMH closure was one of multiple secondary endpoints. OCT scans were obtained at baseline and at all postinjection visits, and for patients with baseline FTMH, evaluated for FTMH width, vitreomacular adhesion, and epiretinal membrane. RESULTS: FTMH closure was observed in a greater proportion of ocriplasmin- vs vehicle-injected patients with baseline FTMH width <= 250 mu m (58.3% vs 16.0%, P <.001) and >250 to <= 400 mu m (36.8% vs 5.3%, P =.009). Among FTMH patients in the ocriplasmin group, >= 2-line visual acuity gains at month 6 were achieved by a greater percentage of those who achieved hole closure at day 28 vs those who did not achieve this outcome (72.1% vs 25.4%). CONCLUSIONS: Ocriplasmin demonstrated efficacy in closure of small and medium FTMH, and in FTMH without epiretinal membrane at baseline. Visual acuity gains occurred more frequently when hole closure was achieved after ocriplasmin treatment compared to when this outcome did not occur. Ocriplasmin treatment is an additional option for the management of patients with FTMH and vitreomacular adhesion. (C) 2015 by Elsevier Inc. All rights reserved. C1 [Dugel, Pravin U.] Retinal Consultants Arizona, Phoenix, AZ USA. [Dugel, Pravin U.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Regillo, Carl] Wills Eye Hosp & Res Inst, Philadelphia, PA USA. [Regillo, Carl] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Eliott, Dean] Harvard Univ, Sch Med, Boston, MA USA. RP Dugel, PU (reprint author), 1101 E Missouri Ave, Phoenix, AZ 85014 USA. EM pdugel@gmail.com FU Abbott (Abbott Park, IL); Abbott Medical Optics (Santa Ana, CA); Aerpio (Cincinnati, OH); Alcon (Fort Worth, TX); Alimera Sciences (Alpharetta, GA); Allergan (Irvine, CA); Acucela (Seattle, WA); Annidis (Ottawa, Canada); DigiSight Technologies (Porto la Valley, CA); Genentech (South San Francisco, CA); Lutronic (Trevose, PA); Novartis (New York, NY); Opthea (South Yarra, Australia); PentaVision (Ambler, PA); Regeneron (Tarrytown, NY); Stealth Biotherapeutics (Newton, MA); ThromboGenics (Iselin, NJ); Advanced Cell Technology (Marlborough, MA); Dutch Ophthalmic (Exeter, NH); ThomboGenics (Iselin, NJ) FX Dr Dugel reports personal fees from Abbott (Abbott Park, IL), Abbott Medical Optics (Santa Ana, CA), personal fees and stock/stock options from Aerpio (Cincinnati, OH), personal fees and payment for lectures from Alcon (Fort Worth, TX), personal fees and stock/stock options from Alimera Sciences (Alpharetta, GA), personal fees and payment for lectures from Allergan (Irvine, CA), personal fees from Acucela (Seattle, WA), personal fees from Annidis (Ottawa, Canada), personal fees and stock/stock options from DigiSight Technologies (Porto la Valley, CA), personal fees and payment for lectures from Genentech (South San Francisco, CA), personal fees from Lutronic (Trevose, PA), personal fees and payment for lectures from Novartis (New York, NY), personal fees from Opthea (South Yarra, Australia), personal fees from PentaVision (Ambler, PA), personal fees from Regeneron (Tarrytown, NY), personal fees from Stealth Biotherapeutics (Newton, MA), personal fees from ThromboGenics (Iselin, NJ), stock/stock options from Ophthotech (New York, NY) outside the submitted work. Dr Eliott reports research grants from Advanced Cell Technology (Marlborough, MA), payment for participation in educational symposia from Allergan (Irvine, CA), payment for participation in educational symposia and other from ThromboGenics (Iselin, NJ), payments for participation in educational symposia from Dutch Ophthalmic (Exeter, NH), other from Bausch & Lomb (Rochester, NY), other from Alimera Sciences (Alpharetta, GA), other from Acucela (Seattle, WA), other from ArcticDx (Toronto, Canada), other from Avalanche (Menlo Park, CA), other from Alcon (Fort Worth, TX), other from Biogen Idec (Cambridge, MA), other from Genentech (South San Francisco, CA), other from Regeneron (Tarrytown, NY) outside the submitted work. Dr Regillo reports personal fees from ThomboGenics (Iselin, NJ), research grants for other ocriplasmin Clinical trials outside the submitted work. The authors indicate no funding support. All authors attest that they meet the current ICMJE requirements to qualify as authors. NR 20 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2015 VL 160 IS 1 BP 94 EP 99 DI 10.1016/j.ajo.2015.03.017 PG 6 WC Ophthalmology SC Ophthalmology GA CL4FS UT WOS:000356908600012 PM 25818925 ER PT J AU Naunheim, MR Remenschneider, AK Bunting, GW Deschler, DG AF Naunheim, Matthew R. Remenschneider, Aaron K. Bunting, Glenn W. Deschler, Daniel G. TI Placement of a 16-French voice prosthesis at the time of secondary tracheoesophageal voice restoration SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID TOTAL LARYNGECTOMY; VOCAL REHABILITATION; PUNCTURE; EXPERIENCE; PROVOX AB Purpose: Tracheoesophageal voice restoration (TEVR) has traditionally been described with fistula tract creation, catheter placement, and prosthesis placement. Prosthesis placement at the time of tracheoesophageal puncture (TEP) utilizing 20-French prostheses has been previously described. Smaller initial prostheses may allow fluent speech with reduced long-term complications, such as widening of the fistula and pen-prosthesis leakage. This study evaluates the safety and efficacy of the 16-French prostheses placement at the time of secondary TEP. Methods: All cases of 16-French tracheoesophageal voice prosthesis (TEVP) placement at the time of secondary TEP were reviewed from 1/2011 through 12/2013 at a large academic medical center. Perioperative complications attributable to device placement were recorded, including inability to place prosthesis, intraoperative complications, post-operative infection, prosthesis dislodgement, prosthesis leakage, and inability to obtain voice. Results: Twenty-one patients received placement of a 16-French TEVP at the time of secondary TEP. All prostheses were placed without intraoperative complications. The proportion of patients who had minor complications within the first postoperative month was 23.8%, including leakage through the prosthesis (3 of 21), granulation tissue near the prosthesis (1 of 21), retained sheath (1 of 21) and prosthesis displacement (1 of 21). Leakage and displacement were addressed with change and replacement, respectively. Fluent voicing was achieved in 85.7% patients, with a median time to voicing of 18.5 days. Conclusions: Placement of 16-French TEVPs is effective and safe, with an acceptable rate of minor complications attributable to the prosthesis. Therefore, a smaller prosthesis may be primarily placed at the time of secondary TEP and is our preference. (C) 2015 Elsevier Inc. All rights reserved. C1 [Naunheim, Matthew R.; Remenschneider, Aaron K.; Bunting, Glenn W.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Naunheim, Matthew R.; Remenschneider, Aaron K.; Bunting, Glenn W.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Naunheim, MR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Matthew_Naunheim@meei.harvard.edu; Aaron_Remenschneider@meei.harvard.edu; Glenn_Bunting@meei.harvard.edu; Daniel_Deschler@meei.harvard.edu NR 23 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JUL-AUG PY 2015 VL 36 IS 4 BP 509 EP 512 DI 10.1016/j.amjoto.2015.01.026 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CL4FG UT WOS:000356907400003 PM 25891859 ER PT J AU Garhyan, J Bhuyan, S Pulu, I Kalita, D Das, B Bhatnagar, R AF Garhyan, Jaishree Bhuyan, Seema Pulu, Ista Kalita, Deepjyoti Das, Bikul Bhatnagar, Rakesh TI Preclinical and Clinical Evidence of Mycobacterium tuberculosis Persistence in the Hypoxic Niche of Bone Marrow Mesenchymal Stem Cells after Therapy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MICROBIAL ENUMERATION TECHNIQUE; TUBERCLE BACILLI; MOUSE TISSUES; LATENT TUBERCULOSIS; INFECTION; MICE; REACTIVATION; MODEL; PYRAZINAMIDE; CHEMOTHERAPY AB Mycobacterium tuberculosis (MTB), the causative agent of pulmonary tuberculosis, is difficult to eliminate by antibiotic therapy. We recently identified CD271(+) bone marrow-mesenchymal stem cells (BM-MSCs) as a potential site of MTB persistence after therapy. Herein, we have characterized the potential hypoxic Localization of the post-therapy MTB-infected CD271(+) BM-MSCs in both mice and human subjects. We first demonstrate that in a Cornell model of MTB persistence in mice, green fluorescent protein-labeled virulent MTB-strain H37Rv was localized to pimonidazole (an in vivo hypoxia marker) positive CD271(+) BM-MSCs after 90 days of isoniazid and pyrazinamide therapy that rendered animal's lung noninfectious. The recovered CD271(+) BM-MSCs from post-therapy mice, when injected into healthy mice, caused active tuberculosis infection in the animal's Lung. Moreover, MTB infection significantly increased the hypoxic phenotype of CD271(+) BM-MSCs. Next, in human subjects, previously treated for pulmonary tuberculosis, the MTB-containing CD271(+) BM-MSCs exhibited high expression of hypoxia-inducible factor 1 alpha and Low expression of CD146, a hypoxia down-regulated cell surface marker of human BM-MSCs. These data collectively demonstrate the potential Localization of MTB harboring CD271(+) BM-MSCs in the hypoxic niche, a critical microenvironmental factor that is well known to induce the MTB dormancy phenotype. C1 [Garhyan, Jaishree; Bhuyan, Seema; Pulu, Ista; Kalita, Deepjyoti; Das, Bikul] Indian Inst Technol, KaviKrishna Lab, Gauhati, India. [Garhyan, Jaishree; Bhatnagar, Rakesh] Jawaharlal Nehru Univ, Sch Biotechnol, Mol Biol & Genet Engn Lab, New Delhi 110067, India. [Das, Bikul] Forsyth Inst, Dept Immun & Infect Dis, Cambridge, MA 01247 USA. RP Das, B (reprint author), Forsyth Inst, 245 First St, Cambridge, MA 01247 USA. EM bdas@forsyth.org; rakeshbhatnagar@jnu.ac.in FU Research Institute of World's Ancient Traditions, Cultures and Heritage (Roing, Arunachal Pradesh, India) FX We thank the Idu-Mishmi tribe for participation in our clinical study; the government of Arunachal Pradesh (India) for allowing us to conduct the clinical study; Research Institute of World's Ancient Traditions, Cultures and Heritage (Roing, Arunachal Pradesh, India) for supporting the clinical study; Dr. Antonio Campos Neto (Forsyth Institute, Cambridge, MA) for reviewing and making valuable comments on the manuscript; All Advanced Instrumentation Research Facility, Jawaharlal Nehru University, for providing an instrumentation facility for immunofluorescence and histopathology; Dr. Sabine Ehrt (Weill Cornell Medical College, New York, NY) for the pUVGFP+ plasmid; and Prof. Stewart T. Cole (Global Health Institute, Ecole Polytechinque Federale de Lausanne, Lausanne, Switzerland) for providing the M. tuberculosis H37Rv, green fluorescent protein H37Rv, and streptomycin-auxotrophic mutant M. tuberculosis strain 18b. NR 33 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2015 VL 185 IS 7 BP 1924 EP 1934 DI 10.1016/j.ajpath.2015.03.028 PG 11 WC Pathology SC Pathology GA CL5KA UT WOS:000356997600013 PM 26066709 ER PT J AU Dadras, SS Lin, RJ Fishert, DE AF Dadras, Soheil S. Lin, Richard J. Fishert, David E. TI Microphthalmia-Associated Transcription Factor A Central Regulator of Pigment Epithelium-Derived Factor Controlling Human Melanoma Progression Reply SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Letter C1 [Dadras, Soheil S.; Fishert, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Dadras, Soheil S.; Fishert, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Charlestown, MA USA. [Lin, Richard J.; Fishert, David E.] Melanoma Program Med Oncol, Dept Pediat Hematol Oncol, Boston, MA USA. RP Dadras, SS (reprint author), Univ Connecticut, Dept Dermatol, Farmington, CT 06030 USA. NR 2 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 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2015 VL 185 IS 7 BP 2070 EP 2070 DI 10.1016/j.ajpath.2015.05.002 PG 1 WC Pathology SC Pathology GA CL5KA UT WOS:000356997600027 PM 26093987 ER PT J AU Zhang, YJ Chee, A Shi, P Wang, R Moss, I Chen, EY He, TC An, HS AF Zhang, Yejia Chee, Ana Shi, Peng Wang, Rui Moss, Isaac Chen, Er-Yun He, Tong-Chuan An, Howard S. TI Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene Expression in the Degenerating Rabbit Intervertebral Disk In Vivo SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Cell Therapy; Inflammation; Intervertebral Disk; Articular Chondrocytes ID MESENCHYMAL STEM-CELLS; NUCLEUS PULPOSUS CELLS; BONE MORPHOGENETIC PROTEINS; EXTRACELLULAR-MATRIX; CLINICAL-EXPERIENCE; SOX9 OVEREXPRESSION; CANINE MODEL; SAND RAT; REPAIR; INJECTION AB Objective The aim of this study was to investigate whether repopulating the degenerating intervertebral disk (IVD) with articular chondrocytes will decrease inflammation in the degenerating rabbit IVD. Design This was a biologic study in a rabbit IVD-injury model in vivo. Dual cell tracking methods (infrared dye labeling and adenovirus transduction) were used to demonstrate the viability of allogeneic articular chondrocytes injected into degenerating rabbit IVDs. Interleukin 8 gene expression was determined via real-time polymerase chain reaction. Infiltrating inflammatory cells (macrophages, T cells, or neutrophils) were examined with immunohistochemistry. The IVDs were also examined by routine histology. Results Articular chondrocytes labeled with infrared dye were detected in the degenerating IVDs at both 2 and 8 wks after injection. At the 2-wk time point, interleukin 8 gene expression was comparable in IVDs injected with chondrocytes and in intact disks as control (P = 0.647), whereas its expression in IVDs injected with saline increased 50-fold (P = 0.028). Transgene expression of red fluorescent protein, -galactosidase, and human bone morphogenetic protein 7 diminished at 8 wks after injection. IVDs injected with chondrocytes overexpressing human bone morphogenetic protein 7 did not show lower interleukin 8 gene expression or improved histology. Macrophages were consistently detected by immunohistochemistry in the cartilage formed around the needle insertion sites in both the saline and chondrocyte groups, whereas neither T cells nor neutrophils were detected. Conclusions Allogeneic rabbit articular chondrocyte survived in the degenerating rabbit IVDs for at least 8 wks. Cell treatment resulted in reduced IVD inflammation but did not significantly improve IVD structure. C1 [Zhang, Yejia; Chee, Ana; Shi, Peng; Wang, Rui; An, Howard S.] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA. [Zhang, Yejia] Vet Affairs Med Ctr, Philadelphia, PA 19146 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19146 USA. [Moss, Isaac] Univ Connecticut, Ctr Hlth, Dept Orthoped Surg, Hartford, CT 06112 USA. [Chen, Er-Yun] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [He, Tong-Chuan] Univ Chicago, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA. RP Zhang, YJ (reprint author), Vet Affairs Med Ctr, 1800 Lombard St,1st Floor, Philadelphia, PA 19146 USA. FU Cervical Spine Research Society (CSRS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [1K08 HD049598] FX Supported, in part, by a research grant from the Cervical Spine Research Society (CSRS).; Yejia Zhang, MD, PhD, is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, 1K08 HD049598). 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 37 TC 4 Z9 4 U1 5 U2 12 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 JUL PY 2015 VL 94 IS 7 BP 530 EP 538 DI 10.1097/PHM.0000000000000194 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CK8NA UT WOS:000356493700004 PM 25133623 ER PT J AU Turkbey, B Agarwal, HK Shih, J Bernardo, M McKinney, YL Daar, D Griffiths, GL Sankineni, S Johnson, L Grant, KB Weaver, J Rais-Bahrami, S Harisinghani, M Jacobs, P Dahut, W Merino, MJ Pinto, PA Choyke, PL AF Turkbey, Baris Agarwal, Harsh K. Shih, Joanna Bernardo, Marcelino McKinney, Yolanda L. Daar, Dagane Griffiths, Gary L. Sankineni, Sandeep Johnson, Linda Grant, Kinzya B. Weaver, Juanita Rais-Bahrami, Soroush Harisinghani, Mukesh Jacobs, Paula Dahut, William Merino, Maria J. Pinto, Peter A. Choyke, Peter L. TI A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ferumoxytol; lymph node; metastases; prostate cancer; staging; ultrasmall superparamagnetic iron oxide (USPIO) ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; LYMPH-NODE METASTASES; RADICAL PROSTATECTOMY; BLADDER; NANOPARTICLE; PROGRESSION; EXPERIENCE; CARCINOMA; EFFICACY; OUTCOMES AB OBJECTIVE. The objective of our study was to determine the optimal dose of ferumoxytol for performing MR lymphography (MRL) at 3 T in patients with prostate cancer. SUBJECTS AND METHODS. This phase I trial enrolled patients undergoing radical prostatectomy (RP) with bilateral pelvic lymph node dissection (PLND). Three groups of five patients each (total of 15 patients) received IV ferumoxytol before RP with bilateral PLND at each of the following doses of iron: 4, 6, and 7.5 mg Fe/kg. Patients underwent abdominopelvic MRI at 3 T before and 24 hours after ferumoxytol injection using T2-and T2*-weighted sequences. Normalized signal intensity (SI) and normalized SD changes from baseline to 24 hours after injection within visible lymph nodes were calculated for each dose level. Linear mixed effects models were used to estimate the effects of dose on the percentage SI change and log-transformed SD change within visible lymph nodes to determine the optimal dose of ferumoxytol for achieving uniform low SI in normal nodes. RESULTS. One patient who was excluded from the study group had a mild allergic reaction requiring treatment after approximately 2.5 mg Fe/kg ferumoxytol injection whereupon the injection was interrupted. The 15 study group patients tolerated ferumoxytol at all dose levels. The mean percentage SI change in 13 patients with no evidence of lymph metastasis was -36.4%, -45.4%, and -65.1% for 4, 6, and 7.5 mg Fe/kg doses, respectively (p = 0.041). CONCLUSION. A dose level of 7.5 mg Fe/kg ferumoxytol was safe and effective in deenhancing benign lymph nodes. This dose therefore can be the starting point for future phase II studies regarding the efficacy of ferumoxytol for MRL. C1 [Turkbey, Baris; Agarwal, Harsh K.; Bernardo, Marcelino; McKinney, Yolanda L.; Daar, Dagane; Sankineni, Sandeep; Johnson, Linda; Grant, Kinzya B.; Weaver, Juanita; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Agarwal, Harsh K.] Philips Healthcare Res North Amer, Briarcliff Manor, NY USA. [Shih, Joanna] NCI, Biomet Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Griffiths, Gary L.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Frederick, MD USA. [Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol,Sch Med, Boston, MA USA. [Jacobs, Paula] NCI, Canc Imaging Program, NIH, Rockville, MD USA. [Dahut, William] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Rm B3B85, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 NR 22 TC 9 Z9 9 U1 0 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 JUL PY 2015 VL 205 IS 1 BP 64 EP 69 DI 10.2214/AJR.14.13009 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000028 PM 26102381 ER PT J AU Mangano, MD Bennett, SE Gunn, AJ Sahani, DV Choy, G AF Mangano, Mark D. Bennett, Susan E. Gunn, Andrew J. Sahani, Dushyant V. Choy, Garry TI Creating a Patient-Centered Radiology Practice Through the Establishment of a Diagnostic Radiology Consultation Clinic SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE patient-centered radiology; quality improvement; radiology clinic; value ID PREFERENCES; COMMUNICATION; PHYSICIANS; CARE AB OBJECTIVE. The purposes of this study were to assess the feasibility of and to create a referral mechanism for a diagnostic radiology consultation clinic. SUBJECTS AND METHODS. A pilot program was instituted with patients from a single primary care clinic over a 3-week period. Patients with findings of common problems at routine imaging, such as atherosclerosis, emphysema, and hepatic steatosis, were eligible to participate. As the patients arrived for their routine primary care visits, office staff informed them of the opportunity to formally meet with a radiologist to review their most recent imaging findings. The office staff of the primary care clinic then contacted the radiologist covering the diagnostic radiology consultation clinic to schedule a consultation. A survey was administered before and after the session. RESULTS. Twenty-two patients participated (88% participation rate). Participants rated the consultation as very helpful (mean, 4.8 on 1-5 scale), and all participants would take the opportunity to review studies with the radiologist again. Significantly more patients preferred the involvement of the radiologist in communicating the results of an imaging examination after the consultation compared with before the consultation (p = 0.001). After the consultation session, patients had significantly improved understanding of a radiologist's role (p = 0.004), and all participants were able to correctly identify the radiologist as a physician who interprets medical images. CONCLUSION. A referral mechanism for a diagnostic radiology consultation clinic can be effectively integrated into the everyday workflow of both the referring physician and the radiologist. The consultations are useful to patients and help to increase their awareness of the role of the radiologist. C1 [Mangano, Mark D.; Gunn, Andrew J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mangano, Mark D.; Bennett, Susan E.; Gunn, Andrew J.; Sahani, Dushyant V.; Choy, Garry] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bennett, Susan E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sahani, Dushyant V.] Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol, Vasc & Intervent Radiol Ctr, Baltimore, MD 21287 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging, Dept Radiol, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Div Emergency Radiol & Teleradiol, Dept Radiol, Boston, MA 02114 USA. RP Mangano, MD (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND216, Boston, MA 02114 USA. EM mark.mangano@mgh.harvard.edu NR 21 TC 14 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2015 VL 205 IS 1 BP 95 EP 99 DI 10.2214/AJR.14.14165 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000033 PM 26102386 ER PT J AU Chang, CY Simeone, FJ Nelson, SB Taneja, AK Huang, AJ AF Chang, Connie Y. Simeone, F. Joseph Nelson, Sandra B. Taneja, Atul K. Huang, Ambrose J. TI Is Biopsying the Paravertebral Soft Tissue as Effective as Biopsying the Disk or Vertebral Endplate? 10-Year Retrospective Review of CT-Guided Biopsy of Diskitis-Osteomyelitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT-guided biopsy; culture; diskitis-osteomyelitis; spine ID PERCUTANEOUS BIOPSY; SPINAL INFECTIONS; JOINT INFECTION; CULTURE; IMPACT AB OBJECTIVE. The purpose of this study was to determine whether there is a difference in biopsying bone (endplate), disk, or paravertebral soft tissue to culture the pathogenic organism causing diskitis-osteomyelitis. MATERIALS AND METHODS. A retrospective review was conducted of 111 spinal biopsies performed between 2002 and 2011. Pathologic examination was used as the reference standard for detecting diskitis-osteomyelitis. Microbiologic yield, sensitivity, and specificity were calculated. The yields for different groups were compared by use of Fisher exact test. The analysis was repeated with biopsy samples from patients not being treated with antibiotics at the time of biopsy. RESULTS. A total of 122 biopsy specimens were obtained from 111 spinal biopsy procedures on 102 patients. Overall, 27 (22%) biopsies were performed on the endplate-disk, 61 (50%) on the disk only, and 34 (28%) on paravertebral soft tissue only. The microbiologic yield was 36% for all biopsies, 19% for endplate-disk biopsies, 39% for disk-only biopsies, and 44% for soft-tissue biopsies. The sensitivity and specificity of the microbiologic results for all specimens were 57% and 89%; endplate-disk, 38% and 86%; disk only, 57% and 89%; and paravertebral soft tissue, 68% and 92%. There was no statistically significant difference between the yields of the endplate-disk, disk-only, and paravertebral soft-tissue biopsies. CONCLUSION. Paravertebral soft-tissue changes, when present, may be considered a viable target for biopsy in cases of diskitis-osteomyelitis, even in the absence of a paravertebral abscess. C1 [Chang, Connie Y.; Simeone, F. Joseph; Huang, Ambrose J.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Nelson, Sandra B.] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. [Taneja, Atul K.] Hosp Coracao & Teleimagem, Hosp Israelita Albert Einstein, Ctr Diagnost, Dept Imaging,Musculoskeletal Radiol Div, Sao Paulo, Brazil. RP Chang, CY (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 22 TC 2 Z9 2 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2015 VL 205 IS 1 BP 123 EP 129 DI 10.2214/AJR.14.13545 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000037 PM 26102390 ER PT J AU Jhaveri, KS Elmi, A Hosseini-Nik, H Hedgire, S Evans, A Jewett, M Harisinghani, M AF Jhaveri, Kartik S. Elmi, Azadeh Hosseini-Nik, Hooman Hedgire, Sandeep Evans, Andrew Jewett, Michael Harisinghani, Mukesh TI Predictive Value of Chemical-Shift MRI in Distinguishing Clear Cell Renal Cell Carcinoma From Non-Clear Cell Renal Cell Carcinoma and Minimal-Fat Angiomyolipoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chemical-shift MRI; clear cell renal cell carcinoma; minimal-fat angiomyolipoma; signal intensity drop ID PATHOLOGICAL FEATURES; CORTICAL TUMORS; PARTIAL NEPHRECTOMY; HISTOGRAM ANALYSIS; CENTER EXPERIENCE; LESS-THAN-4 CM; VISIBLE FAT; CORE BIOPSY; HELICAL CT; MASSES AB OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of chemical-shift MRI in the differentiation of clear cell renal cell carcinoma (RCC) from minimal-fat angiomyolipoma (AML) and non-clear cell RCC. MATERIALS AND METHODS. In this retrospective study, 97 patients with solid renal tumors without macroscopic fat and with a pathologic diagnosis of clear cell RCC (n = 40), non-clear cell RCC (n = 31), or minimal-fat AML (n = 26) who had undergone renal chemical-shift MRI were included. Size, location, morphology, and signal intensity (SI) of the tumors and the contralateral normal kidneys on T2-weighted and in-phase and opposed-phase images were recorded by readers blinded to the pathology. Percentage tumor-to-renal parenchymal SI drop (percentage SI drop) was calculated and correlated to tumor histology. The statistical analysis was done using Kruskal-Wallis, one-way ANOVA, chi-square, and Fisher exact tests. RESULTS. The percentage SI drop was significantly higher in clear cell RCC compared with non-clear cell RCC and minimal-fat AML (p < 0.001). Percentage SI drop of greater than 20% had 57.5% sensitivity, 96.5% specificity, and 92% positive predictive value (PPV); and percentage SI drop greater than 29% had 40% sensitivity and 100% specificity for diagnosis of clear cell RCC within the cohort of clear cell RCC, minimal-fat AML, and non-clear cell RCC. A significant proportion of minimal-fat AML (46.2%) displayed homogeneous low T2-weighted SI as opposed to clear cell RCC (5%) and non-clear cell RCC (29%) (p < 0.001). CONCLUSION. The percentage SI drop on chemical-shift MRI had high specificity and moderate sensitivity in predicting clear cell RCC over non-clear cell RCC and minimal-fat AML. A percentage SI drop greater than 20% in a renal mass without macroscopically visible fat has high PPV for clear cell RCC over minimal-fat AML and non-clear cell RCC. Among morphologic features, homogeneous low T2 SI favors minimal-fat AML over RCC. C1 [Jhaveri, Kartik S.; Hosseini-Nik, Hooman] Univ Toronto, Joint Dept Med Imaging, Univ Hlth Network, Mt Sinai Hosp, Toronto, ON M5G 2M9, Canada. [Jhaveri, Kartik S.; Hosseini-Nik, Hooman] Univ Toronto, Womens Coll Hosp, Toronto, ON M5G 2M9, Canada. [Elmi, Azadeh; Hedgire, Sandeep; Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA USA. [Evans, Andrew] Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Jewett, Michael] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Dept Surg Oncol,Div Urol, Toronto, ON, Canada. RP Jhaveri, KS (reprint author), Univ Toronto, Joint Dept Med Imaging, Univ Hlth Network, Mt Sinai Hosp, Toronto, ON M5G 2M9, Canada. EM kartik.jhaveri@uhn.ca NR 53 TC 6 Z9 6 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2015 VL 205 IS 1 BP W79 EP W86 DI 10.2214/AJR.14.13245 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000011 PM 26102422 ER PT J AU Patino, M Fuentes, JM Singh, S Hahn, PF Sahani, DV AF Patino, Manuel Fuentes, Jorge M. Singh, Sarabjeet Hahn, Peter F. Sahani, Dushyant V. TI Iterative Reconstruction Techniques in Abdominopelvic CT: Technical Concepts and Clinical Implementation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; CT radiation dose; filtered back projection; image quality; iterative reconstruction ID FILTERED BACK-PROJECTION; ABDOMINAL COMPUTED-TOMOGRAPHY; AUTOMATIC EXPOSURE CONTROL; RADIATION-DOSE REDUCTION; PEDIATRIC BODY CT; LOW-TUBE-VOLTAGE; DUAL-ENERGY CT; X-RAY CT; IMAGE-QUALITY; NOISE-REDUCTION AB OBJECTIVE. This article discusses the clinical challenge of low-radiation-dose examinations, the commonly used approaches for dose optimization, and their effect on image quality. We emphasize practical aspects of the different iterative reconstruction techniques, along with their benefits, pitfalls, and clinical implementation. CONCLUSION. The widespread use of CT has raised concerns about potential radiation risks, motivating diverse strategies to reduce the radiation dose associated with CT. CT manufacturers have developed alternative reconstruction algorithms intended to improve image quality on dose-optimized CT studies, mainly through noise and artifact reduction. Iterative reconstruction techniques take unique approaches to noise reduction and provide distinct strength levels or settings. C1 [Patino, Manuel; Fuentes, Jorge M.; Singh, Sarabjeet; Hahn, Peter F.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent,Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 71 TC 7 Z9 7 U1 2 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 JUL PY 2015 VL 205 IS 1 BP W19 EP W31 DI 10.2214/AJR.14.13402 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000005 PM 26102414 ER PT J AU Rehani, MM AF Rehani, Madan M. TI I Am Confused About the Cancer Risks Associated With CT: How Can We Summarize What Is Currently Known? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE cancer risk; CT risk; low-dose CT risk; radiation risk C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rehani, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 8 TC 2 Z9 2 U1 0 U2 1 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 JUL PY 2015 VL 205 IS 1 BP W2 EP W3 DI 10.2214/AJR.15.14363 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000002 PM 26102415 ER PT J AU Whitesell, RT Steenburg, SD Shen, CY Lin, HB AF Whitesell, Ryan T. Steenburg, Scott D. Shen, Changyu Lin, Hongbo TI Facial Fracture in the Setting of Whole-Body CT for Trauma: Incidence and Clinical Predictors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE emergency; maxillofacial; MDCT; trauma ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; MAXILLOFACIAL TRAUMA; CONCOMITANT INJURIES; HELICAL CT; MULTIDETECTOR; MANAGEMENT; ANGIOGRAPHY; EPIDEMIOLOGY; EXPERIENCE; VIOLENCE AB OBJECTIVE. The objective of our study was to identify the incidence and clinical predictors of facial fracture in the setting of whole-body MDCT for trauma. MATERIALS AND METHODS. The clinical data from the electronic medical records, including the final radiology reports, of 486 consecutive patients who underwent MDCT for trauma (head, cervical spine, chest, abdomen, and pelvis examinations) with dedicated maxillofacial reconstructions from October 1, 2011, to July 31, 2013, were studied. The clinical variables were compared between cohorts of patients with and those without facial fracture. The two-sample t test was used to compare continuous variables, and the Fisher exact test was used to compare categoric variables. RESULTS. Two hundred sixteen (44.4%) patients had at least one fracture on the dedicated maxillofacial CT examinations, 215 of whom had facial physical examination findings (sensitivity = 99.5%). Of the 28 patients without documented physical examination findings, 27 did not have a facial fracture (negative predictive value = 96.4%). Statistically significant differences were found between positive and negative cases of facial fracture in patients with a Glasgow coma scale (GCS) score of 8 or less (p < 0.0001), an injury severity score of 16 or greater (p < 0.0001), acute alcohol intoxication according to blood alcohol concentration (BAC) (p = 0.0387), intubation at presentation (p < 0.0001), positive physical examination findings (p < 0.0001), and loss of consciousness (p = 0.0364). Falls from a height greater than standing height and open-vehicle collisions had the highest fracture rates (80.0% and 58.3%, respectively). CONCLUSION. A negative finding at facial physical examination reliably excluded fracture. Clinical variables positively associated with facial fracture included the following: GCS score of 8 or less, ISS of 16 or greater, alcohol intoxication according to BAC, intubation at presentation, loss of consciousness, and the presence of abnormal facial findings at physical examination. C1 [Whitesell, Ryan T.; Steenburg, Scott D.] Indiana Univ Sch Med, Div Emergency Radiol, Dept Radiol & Imaging Sci, Indianapolis, IN 46202 USA. [Shen, Changyu; Lin, Hongbo] Indiana Univ Sch Med, Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Shen, Changyu; Lin, Hongbo] Indiana Univ Sch Med, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46202 USA. RP Whitesell, RT (reprint author), Massachusetts Gen Hosp, Div Emergency Imaging, Dept Radiol, 55 Fruit St,FND 210, Boston, MA 02114 USA. EM rwhitesell@partners.org NR 37 TC 2 Z9 2 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2015 VL 205 IS 1 BP W4 EP W10 DI 10.2214/AJR.14.13589 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2NK UT WOS:000356781000003 PM 26102417 ER PT J AU Parry-Jones, AR Di Napoli, M Goldstein, JN Schreuder, FHBM Tetri, S Tatlisumak, T Yan, B van Nieuwenhuizen, KM Dequatre-Ponchelle, N Lee-Archer, M Horstmann, S Wilson, D Pomero, F Masotti, L Lerpiniere, C Godoy, DA Cohen, AS Houben, R Al-Shahi Salman, R Pennati, P Fenoglio, L Werring, D Veltkamp, R Wood, E Dewey, HM Cordonnier, C Klijn, CJM Meligeni, F Davis, SM Huhtakangas, J Staals, J Rosand, J Meretoja, A AF Parry-Jones, Adrian R. Di Napoli, Mario Goldstein, Joshua N. Schreuder, Floris H. B. M. Tetri, Sami Tatlisumak, Turgut Yan, Bernard van Nieuwenhuizen, Koen M. Dequatre-Ponchelle, Nelly Lee-Archer, Matthew Horstmann, Solveig Wilson, Duncan Pomero, Fulvio Masotti, Luca Lerpiniere, Christine Godoy, Daniel Agustin Cohen, Abigail S. Houben, Rik Al-Shahi Salman, Rustam Pennati, Paolo Fenoglio, Luigi Werring, David Veltkamp, Roland Wood, Edith Dewey, Helen M. Cordonnier, Charlotte Klijn, Catharina J. M. Meligeni, Fabrizio Davis, Stephen M. Huhtakangas, Juha Staals, Julie Rosand, Jonathan Meretoja, Atte TI Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage SO ANNALS OF NEUROLOGY LA English DT Article ID PROTHROMBIN COMPLEX CONCENTRATE; FRESH-FROZEN PLASMA; ORAL ANTICOAGULANT; WARFARIN REVERSAL; HEMATOMA GROWTH; ASSOCIATION; MULTICENTER; GUIDELINES; MANAGEMENT; EFFICACY AB ObjectiveThere is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies. MethodsWe pooled individual ICH patient data from 16 stroke registries in 9 countries (n=10 282), of whom 1,797 (17%) were on VKA. After excluding 250 patients with international normalized ratio<1.3 and/or missing data required for analysis, we compared all-cause 30-day case fatality using Cox regression. ResultsWe included 1,547 patients treated with FFP (n=377, 24%), PCC (n=585, 38%), both (n=131, 9%), or neither (n=454, 29%). The crude case fatality and adjusted hazard ratio (HR) were highest with no reversal (61.7%, HR=2.540, 95% confidence interval [CI]=1.784-3.616, p<0.001), followed by FFP alone (45.6%, HR=1.344, 95% CI=0.934-1.934, p=0.112), then PCC alone (37.3%, HR=1.445, 95% CI=1.014-2.058, p=0.041), compared to reversal with both FFP and PCC (27.8%, reference). Outcomes with PCC versus FFP were similar (HR=1.075, 95% CI=0.874-1.323, p=0.492); 4-factor PCC (n=441) was associated with higher case fatality compared to 3-factor PCC (n=144, HR=1.441, 95% CI=1.041-1.995, p=0.027). InterpretationThe combination of FFP and PCC might be associated with the lowest case fatality in reversal of VKA-ICH, and FFP may be equivalent to PCC. Randomized controlled trials with functional outcomes are needed to establish the most effective treatment. Ann Neurol 2015;78:54-62 C1 [Parry-Jones, Adrian R.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Salford Royal Natl Hlth Serv Fdn Trust, Salford, Lancs, England. [Parry-Jones, Adrian R.; Wood, Edith] Salford Royal Natl Hlth Serv Fdn Trust, Greater Manchester Neurosci Ctr, Salford, Lancs, England. [Di Napoli, Mario] San Camillo de Lellis Gen Hosp, Neurol Serv, Rieti, Italy. [Di Napoli, Mario] Ctr Cardiovasc Med & Cerebrovasc Dis Prevent SMDN, Neurol Sect, Sulmona, Italy. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schreuder, Floris H. B. M.; Houben, Rik; Staals, Julie] Maastricht Univ, Med Ctr, Dept Neurol, NL-6200 MD Maastricht, Netherlands. [Tetri, Sami; Huhtakangas, Juha] Oulu Univ Hosp, Dept Neurol, Oulu, Finland. [Tatlisumak, Turgut; Meretoja, Atte] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [Yan, Bernard; Davis, Stephen M.; Meretoja, Atte] Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3050, Australia. [van Nieuwenhuizen, Koen M.; Klijn, Catharina J. M.] Univ Med Ctr Utrecht, Rudolf Magnus Brain Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Dequatre-Ponchelle, Nelly; Cordonnier, Charlotte] Univ Lille Nord France UDSL, Dept Neurol, Lille Univ Hosp Ctr, Lille, France. [Lee-Archer, Matthew; Dewey, Helen M.] Austin Hosp, Dept Neurol, Heidelberg, Vic 3084, Australia. [Horstmann, Solveig; Veltkamp, Roland] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Wilson, Duncan; Werring, David] UCL, London, England. [Pomero, Fulvio; Fenoglio, Luigi] Santa Croce e Carle Hosp, Dept Internal Med, Cuneo, Italy. [Masotti, Luca; Pennati, Paolo] Cecina Hosp, Internal Med, Cecina, Italy. [Lerpiniere, Christine; Al-Shahi Salman, Rustam] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Godoy, Daniel Agustin] Pasteur Sanat, Neurointens Care Unit, Catamarca, Argentina. [Godoy, Daniel Agustin] San Juan Bautista Hosp, Intens Care Unit, Catamarca, Argentina. [Cohen, Abigail S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Veltkamp, Roland] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Meligeni, Fabrizio] San Camillo de Lellis Gen Hosp, Dept Emergency Med, Rieti, Italy. [Davis, Stephen M.; Meretoja, Atte] Univ Melbourne, Dept Med, Melbourne, Vic, Australia. [Davis, Stephen M.; Meretoja, Atte] Univ Melbourne, Florey Inst, Melbourne, Vic, Australia. RP Meretoja, A (reprint author), Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic 3050, Australia. EM atte.meretoja@unimelb.edu.au RI Klijn, C.J.M. (Karin)/E-1700-2016; Goldstein, Joshua/H-8953-2016; OI Al-Shahi Salman, Rustam/0000-0002-2108-9222 FU University of Manchester; Salford Royal NHS Foundation Trust; Academy of Medical Sciences; Dowager Countess Eleanor Peel Trust; Natalie Kate Moss Trust; Italian National Health Service; Helsinki University Central Hospital; Dutch Heart Foundation [2012T077]; ASPASIA grant from the Netherlands Organization for Health Research and Development [015008048]; Finnish Brain Foundation; Finnish Medical Foundation; NIH National Institute of Neurological Disorders and Stroke [R01 NS059727]; Academy of Finland; National Health and Medical Research Council (Australia); British Heart Foundation; Stroke Association (UK); MRC senior clinical fellowship; MRC/Stroke Association clinical research training fellowship FX This study was supported by the University of Manchester (A.R.P.-J.), the Salford Royal NHS Foundation Trust (A.R.P.-J.), the Academy of Medical Sciences (A.R.P.-J.), the Dowager Countess Eleanor Peel Trust (A.R.P.-J.), the Natalie Kate Moss Trust (A.R.P.-J.), the Italian National Health Service (M.D.N.), a grant from the Helsinki University Central Hospital for research on intracerebral hemorrhage (T.T.), a clinical established investigator grant from the Dutch Heart Foundation (2012T077, C.J.M.K.), an ASPASIA grant from the Netherlands Organization for Health Research and Development (015008048, C.J.M.K.), the Finnish Brain Foundation (J.H.), the Finnish Medical Foundation (J.H., A.M.), the NIH National Institute of Neurological Disorders and Stroke (R01 NS059727, J.R.), the Academy of Finland (A.M.), and the National Health and Medical Research Council (Australia; A.M.). CROMIS-2 was funded by a grant from the British Heart Foundation and the Stroke Association (UK; chief investigator: D.We.). LATCH was funded by an MRC senior clinical fellowship (R.A.-S.S.) and an MRC/Stroke Association clinical research training fellowship. NR 33 TC 26 Z9 26 U1 1 U2 12 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 JUL PY 2015 VL 78 IS 1 BP 54 EP 62 DI 10.1002/ana.24416 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL3AQ UT WOS:000356821200005 PM 25857223 ER PT J AU Shapiro, KA McGuone, D Deshpande, V Sadow, PM Stemmer-Rachamimov, A Staley, KJ AF Shapiro, Kevin A. McGuone, Declan Deshpande, Vikram Sadow, Peter M. Stemmer-Rachamimov, Anat Staley, Kevin J. TI Failure to detect human papillomavirus in focal cortical dysplasia type IIb SO ANNALS OF NEUROLOGY LA English DT Article ID VERTICAL TRANSMISSION; BRAIN MALFORMATIONS; INFECTION; CONJUNCTIVA; EPILEPSY; GRADE; DNA; HPV AB ObjectiveRecent studies have reported evidence of human papillomavirus 16 (HPV-16) in a very high proportion of pathological specimens of focal cortical dysplasia type IIb, but not in control specimens, motivating the proposal that viral infection during fetal development may play a causal role in the pathogenesis of focal cortical dysplasias. However, the significance of the association between HPV infection and focal cortical dysplasia type IIb, and its reproducibility across surgical centers, remain unclear. Here we sought evidence for HPV-16 in an independent cohort of surgical specimens. MethodsWe identified 14 specimens of focal cortical dysplasia type IIb from a single surgical center between 1995 and 2013. Multiple methods were used to establish presence or absence of HPV, including DNA polymerase chain reaction, conventional in situ hybridization, chromogenic in situ hybridization, and immunohistochemistry for p16. ResultsWe found no conclusive evidence of HPV in any of the specimens. All but 1 of the cases were negative by >1 method. InterpretationThese results raise questions about the prevalence of HPV infection in focal cortical dysplasias and about its potential importance as a causative agent. Ann Neurol 2015;78:63-67 C1 [Shapiro, Kevin A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [McGuone, Declan; Deshpande, Vikram; Sadow, Peter M.; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shapiro, KA (reprint author), Dept Neurol, Box 0663,675 Nelson Rising Lane,Room 405, San Francisco, CA 94143 USA. EM kevin.shapiro@ucsf.edu FU NIH National Institute of Neurologic Disorders and Stroke [R01 NS034700] FX The research reported here was supported by the NIH National Institute of Neurologic Disorders and Stroke (R01 NS034700, K.J.S.). NR 22 TC 5 Z9 5 U1 1 U2 1 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 JUL PY 2015 VL 78 IS 1 BP 63 EP 67 DI 10.1002/ana.24422 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL3AQ UT WOS:000356821200006 PM 25893423 ER PT J AU Stanley, MPH Berger, J Misra, S Rodriguez, I Elliott, V Brown, RH Mateen, FJ AF Stanley, Michael P. H. Berger, Joseph Misra, Shri Rodriguez, Ildefonso Elliott, Victoria Brown, Robert H., Jr. Mateen, Farrah J. TI International engagement by United States academic neurology departments: A national survey SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Stanley, Michael P. H.] Tufts Univ, Boston, MA 02111 USA. [Berger, Joseph] Univ Penn, Philadelphia, PA 19104 USA. [Misra, Shri] Univ Calif Los Angeles, Los Angeles, CA USA. [Rodriguez, Ildefonso] Hosp Cent Dr Ignacio Morones Prieto, San Luis Potosi, Mexico. [Elliott, Victoria] Amer Neurol Assoc, Washington, DC USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Stanley, MPH (reprint author), Tufts Univ, Boston, MA 02111 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2015 VL 78 IS 1 BP 150 EP 152 DI 10.1002/ana.24366 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL3AQ UT WOS:000356821200015 PM 25612320 ER PT J AU Criscione-Schreiber, LG Sloane, RJ Hawley, J Jonas, BL O'Rourke, KS Bolster, MB AF Criscione-Schreiber, Lisa G. Sloane, Richard J. Hawley, Jeffrey Jonas, Beth L. O'Rourke, Kenneth S. Bolster, Marcy B. TI Expert Panel Consensus on Assessment Checklists for a Rheumatology Objective Structured Clinical Examination SO ARTHRITIS CARE & RESEARCH LA English DT Article ID EXAMINATION SKILLS; INTERNAL-MEDICINE; EXAMINATION OSCE; VALIDATION; INSTRUMENT; CONFIDENCE; RESIDENTS; STUDENTS AB ObjectiveWhile several regional fellowship groups conduct rheumatology objective structured clinical examinations (ROSCEs), none have been validated for use across programs. We aimed to establish agreement among subspecialty experts regarding checklist items for several ROSCE stations. MethodsWe administered a 1-round survey to assess the importance of 173 assessment checklist items for 11 possible ROSCE stations. We e-mailed the survey to 127 rheumatology educators from across the US. Participants rated each item's importance on a 5-point Likert scale (1=not important to 5=very important). Consensus for high importance was predefined as a lower bound of the 95% confidence interval 4.0. ResultsTwenty-five individuals (20%) completed the expert panel survey. A total of 133 of the 173 items (77%) met statistical cutoff for consensus to retain. Several items that had population means of 4.0 but did not meet the predetermined definition for consensus were rejected. The percentage of retained items for individual stations ranged from 24% to 100%; all items were retained for core elements of patient counseling and radiograph interpretation tasks. Only 24% of items were retained for a rehabilitation medicine station and 60% for a microscope use/synovial fluid analysis station. ConclusionThis single-round expert panel survey established consensus on 133 items to assess on 11 proposed ROSCE stations. The method used in this study, which can engage a diverse geographic representation and employs rigorous statistical methods to establish checklist content agreement, can be used in any medical field. C1 [Criscione-Schreiber, Lisa G.; Sloane, Richard J.; Hawley, Jeffrey] Duke Univ, Durham, NC 27710 USA. [Jonas, Beth L.] Univ N Carolina, Chapel Hill, NC USA. [O'Rourke, Kenneth S.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Bolster, Marcy B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Criscione-Schreiber, LG (reprint author), Duke Univ, Med Ctr, Box 3490, Durham, NC 27710 USA. EM crisc001@dm.duke.edu FU Duke University Graduate Medical Innovations Grant [01-12-05]; Rheumatology Research Foundation Clinician Scholar Educator Award; Eli Lilly FX Supported by a Duke University Graduate Medical Innovations Grant (01-12-05). Dr. Criscione-Schreiber's work was supported by a Rheumatology Research Foundation Clinician Scholar Educator Award.; Dr. Bolster owns stock or stock options in Johnson & Johnson, has received research grants from Eli Lilly, serves on the Rheumatology Subspecialty Board and Test Writing Committee for the American Board of Internal Medicine, and is on the Board of Directors of the American College of Rheumatology and the Rheumatology Research Foundation. NR 24 TC 2 Z9 2 U1 1 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 JUL PY 2015 VL 67 IS 7 BP 898 EP 904 DI 10.1002/acr.22543 PG 7 WC Rheumatology SC Rheumatology GA CL3WR UT WOS:000356883000002 PM 25580581 ER PT J AU Nikiforow, S Ritz, J AF Nikiforow, Sarah Ritz, Jerome TI Reconstitution of T Cell Immunity after Umbilical Cord Blood Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID RECOVERY C1 [Nikiforow, Sarah; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM jerome_ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [R01CA183560]; NHLBI NIH HHS [R01HL118774] NR 12 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2015 VL 21 IS 7 BP 1151 EP 1152 DI 10.1016/j.bbmt.2015.04.027 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CL2AY UT WOS:000356747200002 PM 25985916 ER PT J AU Shah, N Callander, N Ganguly, S Gul, Z Hamadani, M Costa, L Sengsayadeth, S Abidi, M Hari, P Mohty, M Chen, YB Koreth, J Landau, H Lazarus, H Leather, H Majhail, N Nath, R Osman, K Perales, MA Schriber, J Shaughnessy, P Vesole, D Vij, R Wingard, J Giralt, S Savani, BN AF Shah, Nina Callander, Natalie Ganguly, Siddhartha Gul, Zartash Hamadani, Mehdi Costa, Luciano Sengsayadeth, Salyka Abidi, Muneer Hari, Parameswaran Mohty, Mohamad Chen, Yi-Bin Koreth, John Landau, Heather Lazarus, Hillard Leather, Helen Majhail, Navneet Nath, Rajneesh Osman, Keren Perales, Miguel-Angel Schriber, Jeffrey Shaughnessy, Paul Vesole, David Vij, Ravi Wingard, John Giralt, Sergio Savani, Bipin N. TI Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Multiple myeloma; Transplantation; Recommendations; Guidelines ID HIGH-DOSE THERAPY; TERM-FOLLOW-UP; NEWLY-DIAGNOSED MYELOMA; THALIDOMIDE PLUS DEXAMETHASONE; CONDITIONING ALLOGENEIC TRANSPLANTATION; FRONT AUTOLOGOUS TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIALS; ADVERSE PROGNOSTIC-FACTOR; TOTAL-BODY IRRADIATION; MELPHALAN 100 MG/M(2) AB Therapeutic strategies for multiple myeloma (MM) have changed dramatically over the past decade. Thus, the role of hematopoietic stem cell transplantation (HCT) must be considered in the context of this evolution. In this evidence-based review, we have critically analyzed the data from the most recent clinical trials to better understand how to incorporate HCT and when HCT is indicated. We have provided our recommendations based on Strength of evidence with the knowledge that ongoing clinical trials make this a dynamic field. Within this document, we discuss the decision to proceed with autologous HCT, factors to consider before proceeding to HCT, the role of tandem autologous HCT, post-HCT maintenance therapy, and the role of allogeneic HCT for patients with MM. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Shah, Nina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Callander, Natalie] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Ganguly, Siddhartha] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Gul, Zartash] Univ Kentucky, Lexington, KY USA. [Hamadani, Mehdi; Hari, Parameswaran] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Hamadani, Mehdi; Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Costa, Luciano; Savani, Bipin N.] Univ Alabama Birmingham, Birmingham, AL USA. [Sengsayadeth, Salyka; Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Abidi, Muneer] Spectrum Hlth, Grand Rapids, MI USA. [Mohty, Mohamad] Hop St Antoine, AP HP, F-75571 Paris, France. [Mohty, Mohamad] Univ Paris 06, Paris, France. [Mohty, Mohamad] INSERM, UMRs 938, Paris, France. [Chen, Yi-Bin] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Koreth, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Landau, Heather; Perales, Miguel-Angel; Giralt, Sergio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lazarus, Hillard] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Leather, Helen] HLL Commun, Gainesville, FL USA. [Majhail, Navneet] Cleveland Clin, Cleveland, OH 44106 USA. [Nath, Rajneesh] Univ Massachusetts, Worcester, MA 01605 USA. [Osman, Keren] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Schriber, Jeffrey] Canc Transplant Inst Scottsdale Healthcare, Scottsdale, AZ USA. [Shaughnessy, Paul] Texas Transplant Inst, San Antonio, TX USA. [Vesole, David] Hackensack Univ Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Wingard, John] Univ Florida, Coll Med, Gainesville, FL USA. RP Shah, N (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd Unit 432, Houston, TX 77030 USA. EM nshah@mdanderson.org OI Abidi, Muneer/0000-0002-9936-6031; Hari, Parameswaran/0000-0002-8800-297X FU Celgene; Onyx; Millenium/Takeda; Sanofi; Celegene; Janssen; Millenium; Otsuka; Celegne FX N.S. has a consulting role with Sanofi and receives research support from Celgene. M.H. receives honoraria from Celgene. L.C. receives research support from Onyx. P.H. has a consulting role with and receives research support from Millenium/Takeda, Celgene and Sanofi. M.M. receives honoraria and research support from Celegene, Janssen and Sanofi. Y.-B.C. receives research support from Celgene. J.K. has a consulting role with Takeda and receives research support from Millenium and Otsuka. H.L. serves as a promotional speaker for Celgene. J.S. has a consulting role with and receives speaker honoraria from Celgene. P.S. receives honoraria from Millennium, Celgene, and Sanofi. R.V. has a consulting role with Celgene, Millennium, Onyx, Bristol-Myers Squibb, Novartis, and Sanofi. S.G. receives research support from Celegne, Onyx and Sanofi. NR 134 TC 24 Z9 25 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2015 VL 21 IS 7 BP 1155 EP 1166 DI 10.1016/j.bbmt.2015.03.002 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CL2AY UT WOS:000356747200004 PM 25769794 ER PT J AU Carpenter, PA Kitko, CL Elad, S Flowers, MED Gea-Banacloche, JC Halter, JP Hoodin, F Johnston, L Lawitschka, A McDonald, GB Opipari, AW Savani, BN Schultz, KR Smith, SR Syrjala, KL Treister, N Vogelsang, GB Williams, KM Pavletic, SZ Martin, PJ Lee, SJ Couriel, DR AF Carpenter, Paul A. Kitko, Carrie L. Elad, Sharon Flowers, Mary E. D. Gea-Banacloche, Juan C. Halter, Jorg P. Hoodin, Flora Johnston, Laura Lawitschka, Anita McDonald, George B. Opipari, Anthony W. Savani, Bipin N. Schultz, Kirk R. Smith, Sean R. Syrjala, Karen L. Treister, Nathaniel Vogelsang, Georgia B. Williams, Kirsten M. Pavletic, Steven Z. Martin, Paul J. Lee, Stephanie J. Couriel, Daniel R. TI National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Allogeneic hematopoietic cell transplantation; Supportive care; Consensus; Guidelines ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; BRONCHIOLITIS OBLITERANS SYNDROME; SEVERE DRY EYE; RANDOMIZED CONTROLLED-TRIAL; CASE-MATCHED CONTROLS; DOUBLE-BLIND; INTRAVENOUS IMMUNOGLOBULIN; CHRONIC GVHD AB The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Carpenter, Paul A.; Flowers, Mary E. D.; McDonald, George B.; Syrjala, Karen L.; Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kitko, Carrie L.; Couriel, Daniel R.] Univ Michigan, Ctr Comprehens Canc, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA. [Elad, Sharon] Univ Rochester, Med Ctr, Div Oral Med, Eastman Inst Oral Hlth, Rochester, NY 14642 USA. [Elad, Sharon] Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA. [Gea-Banacloche, Juan C.; Williams, Kirsten M.; Pavletic, Steven Z.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Halter, Jorg P.] Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. [Hoodin, Flora] Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. [Johnston, Laura] Stanford Univ, Med Ctr, Dept Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Lawitschka, Anita] Med Univ, St Anna Childrens Hosp, Vienna, Austria. [Opipari, Anthony W.] Univ Michigan Hlth Syst, Dept Obstet & Gynecol, Ann Arbor, MI USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Schultz, Kirk R.] BC Childrens Hosp, Michael Cuccione Childhood Canc Res Program, Vancouver, BC, Canada. [Schultz, Kirk R.] Univ British Columbia, Vancouver, BC, Canada. [Smith, Sean R.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Treister, Nathaniel] Dana Farber Brigham & Womens Canc Ctr, Div Oral Med & Dent, Boston, MA USA. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Carpenter, PA (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,POB 19024, Seattle, WA 98109 USA. EM pcarpent@fredhutch.org FU National Institutes of Health's (NIH) National Cancer Institute, Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Disease; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources FX This project was supported by the National Institutes of Health's (NIH) National Cancer Institute, Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Disease; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources. The authors want to acknowledge the following individuals and organizations that, by their participation, made this project possible: American Society for Blood and Marrow Transplantation, Center for International Bone and Marrow Transplant Research, US Chronic GVHD Consortium (supported by ORD and NCI), German-Austrian-Swiss GVHD Consortium, National Marrow Donor Program, the Health Resources and Services Administration, Division of Transplantation, US Department of Human Health and Services, Canadian Blood and Marrow Transplant Group, European Group for Blood and Marrow Transplantation, Pediatric Blood and Marrow Transplant Consortium, and the representatives of the Brazilian Chronic GVHD consortium (Drs. Maria Claudia Moreira, Marcia and Vaneuza Funke) and Deutsche Jose Carreras Leukarnie-Stiftung. The organizers are in debt to patients and patient and research advocacy groups, who made this process much more meaningful by their engagement. Acknowledgement goes to the Meredith Cowden GVHD foundation for facilitating the initial planning meeting in Cleveland in November of 2013 in conjunction with the National GVHD Symposium. The project group also recognizes the contributions of numerous colleagues in the field of blood and marrow transplantation in the US and internationally, medical specialists and consultants, the pharmaceutical industry, and the NIH and US Food and Drug Administration professional staff for their intellectual input, dedication, and enthusiasm on the road to completion of these documents. Project participants also recognize Drs. Joseph Antin and Gerard Socie for their independent expert reviews and comments on final documents at the June 2014 meeting. NR 182 TC 19 Z9 21 U1 1 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 JUL PY 2015 VL 21 IS 7 BP 1167 EP 1187 DI 10.1016/j.bbmt.2015.03.024 PG 21 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CL2AY UT WOS:000356747200005 PM 25838185 ER PT J AU Mehta, PA Zhang, MJ Eapen, M He, WS Seber, A Gibson, B Camitta, BM Kitko, CL Dvorak, CC Nemecek, ER Frangoul, HA Abdel-Azim, H Kasow, KA Lehmann, L Vicent, MG Perez, MAD Ayas, M Qayed, M Carpenter, PA Jodele, S Lund, TC Leung, WH Davies, SM AF Mehta, Parinda A. Zhang, Mei-Jie Eapen, Mary He, Wensheng Seber, Adriana Gibson, Brenda Camitta, Bruce M. Kitko, Carrie L. Dvorak, Christopher C. Nemecek, Eneida R. Frangoul, Haydar A. Abdel-Azim, Hisham Kasow, Kimberly A. Lehmann, Leslie Gonzalez Vicent, Marta Diaz Perez, Miguel A. Ayas, Mouhab Qayed, Muna Carpenter, Paul A. Jodele, Sonata Lund, Troy C. Leung, Wing H. Davies, Stella M. TI Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hypodiploid acute lymphoblastic leukemia; Hematopoietic stem cell transplantation ID VERSUS-HOST-DISEASE; ONCOLOGY-GROUP; CANCER-GROUP; RISK; ADOLESCENTS; CLASSIFICATION; SURVIVAL; TRIALS AB Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk-adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplantation between 1990 and 2010. Thirty-nine (50%) patients had <= 43 chromosomes, 12 (15%) had 44 chromosomes, and 27 (35%) had 45 chromosomes. Forty-three (55%) patients underwent transplantation in first remission (CR1) and 35 (45%) underwent transplantation in >= second remission (CR2). Twenty-nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival, overall survival, relapse, and treatment-related mortality for the entire cohort were 51%, 56%, 27%, and 22%, respectively. Multivariate analysis confirmed that mortality risks were higher for patients who underwent transplantation in CR2 (hazard ratio, 2.16; P =.05), with number of chromosomes <= 43 (hazard ratio, 2.15; P = .05), and for those who underwent transplantation in the first decade of the study period (hazard ratio, 2.60; P = .01). Similarly, treatment failure risks were higher with number of chromosomes <= 43 (hazard ratio, 2.28; P = .04) and the earlier transplantation period (hazard ratio, 2.51; P = .01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Mehta, Parinda A.; Jodele, Sonata; Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Zhang, Mei-Jie; Eapen, Mary; He, Wensheng] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Seber, Adriana] Hosp Samaritano, Pediat Oncol Inst, Sao Paulo, Brazil. [Gibson, Brenda] NHS Greater Glasgow & Clyde, Royal Hosp Sick Children, Schiehall Day Care Unit, Glasgow, Lanark, Scotland. [Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Kitko, Carrie L.] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Dvorak, Christopher C.] Univ Calif San Francisco, Dept Pediat, Med Ctr, San Francisco, CA USA. [Nemecek, Eneida R.] Doernbecher Childrens Hosp, Dept Pediat, Pediat Blood & Marrow Transplant Program, Portland, OR USA. [Nemecek, Eneida R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Frangoul, Haydar A.] Vanderbilt Univ, Dept Pediat, Div Hematol Oncol, Sch Med, Nashville, TN USA. [Abdel-Azim, Hisham] Univ So Calif, Keck Sch Med, Div Hematol Oncol & Blood & Marrow Transplantat, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Kasow, Kimberly A.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA. [Lehmann, Leslie] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Gonzalez Vicent, Marta; Diaz Perez, Miguel A.] Hosp Infantil Univ Nino Jesus, Stem Cell Transplant Unit, Madrid, Spain. [Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia. [Qayed, Muna] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Dept Pediat, Seattle, WA 98104 USA. [Lund, Troy C.] Univ Minnesota, Dept Pediat, Med Ctr, Minneapolis, MN 55455 USA. [Leung, Wing H.] St Jude Childrens Res Hosp, Div Bone Marrow Transplantat, Memphis, TN 38105 USA. RP Mehta, PA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA. EM Parinda.mehta@cchmc.org FU Public Health Service from the National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; 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; 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, 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; WellPoint FX The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants, N00014-13-1-0039 and N00014-14-1-0028, from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen; an 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; 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 *WellPoint. 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 22 TC 4 Z9 4 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 JUL PY 2015 VL 21 IS 7 BP 1273 EP 1277 DI 10.1016/j.bbmt.2015.04.008 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CL2AY UT WOS:000356747200017 PM 25865650 ER PT J AU Swinnen, LJ Li, HL Quon, A Gascoyne, R Hong, F Ranheim, EA Habermann, TM Kahl, BS Horning, SJ Advani, RH AF Swinnen, Lode J. Li, Hailun Quon, Andrew Gascoyne, Randy Hong, Fangxin Ranheim, Erik A. Habermann, Thomas M. Kahl, Brad S. Horning, Sandra J. Advani, Ranjana H. TI Response-adapted therapy for aggressive non-Hodgkin's lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE diffuse large B-cell lymphoma; interim positron emission tomography scan; R-CHOP; R-ICE; response-adapted therapy ID POSITRON-EMISSION-TOMOGRAPHY; B-CELL LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; PROGNOSTIC VALUE; F-18 FLUORODEOXYGLUCOSE; INTERNATIONAL WORKSHOP; GA-67 SCINTIGRAPHY; CHOP CHEMOTHERAPY; ELDERLY-PATIENTS; INTERIM AB A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B-cell lymphoma (DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R-ICE, PET-negative patients received two more cycles of R-CHOP. A 45% 2-year progression-free survival (PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival (OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R-ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. C1 [Swinnen, Lode J.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA. [Li, Hailun; Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Quon, Andrew; Advani, Ranjana H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Gascoyne, Randy] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Ranheim, Erik A.; Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. RP Swinnen, LJ (reprint author), Johns Hopkins Univ, Dept Oncol, 1650 Orleans St, Baltimore, MD 21231 USA. EM lswinne1@jhmi.edu FU Public Health Service [CA21115, CA23318, CA66636, CA180820, CA180794, CA16116, CA180802, CA180816, CA21076, CA180799, CA13650, CA180790]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA21115, CA23318, CA66636, CA180820, CA180794, CA16116, CA180802, CA180816, CA21076, CA180799, CA13650, CA180790 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Biospecimens were provided by the ECOG-ACRIN Pathology Coordinating Office and Reference Laboratory. NR 40 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2015 VL 170 IS 1 BP 56 EP 65 DI 10.1111/bjh.13389 PG 10 WC Hematology SC Hematology GA CL1PQ UT WOS:000356716500009 PM 25823885 ER PT J AU Dytfeld, D Rosebeck, S Kandarpa, M Mayampurath, A Mellacheruvu, D Alonge, MM Ngoka, L Jasielec, J Richardson, PG Volchenboum, S Nesvizhskii, AI Sreekumar, A Jakubowiak, AJ AF Dytfeld, Dominik Rosebeck, Shaun Kandarpa, Malathi Mayampurath, Anoop Mellacheruvu, Dattatreya Alonge, Mattina M. Ngoka, Lambert Jasielec, Jagoda Richardson, Paul G. Volchenboum, Samuel Nesvizhskii, Alexey I. Sreekumar, Arun Jakubowiak, Andrzej J. TI Proteomic profiling of naive multiple myeloma patient plasma cells identifies pathways associated with favourable response to bortezomib-based treatment regimens SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; lenalidomide; bortezomib; proteomics ID LENALIDOMIDE PLUS DEXAMETHASONE; MINIMAL RESIDUAL DISEASE; QUANTITATIVE PROTEOMICS; CEREBLON EXPRESSION; DOSE DEXAMETHASONE; MASS-SPECTROMETRY; CANCER CELLS; THERAPY; TRANSPLANTATION; RESISTANCE AB Toward our goal of personalized medicine, we comprehensively profiled pre-treatment malignant plasma cells from multiple myeloma patients and prospectively identified pathways predictive of favourable response to bortezomib-based treatment regimens. We utilized two complementary quantitative proteomics platforms to identify differentially-regulated proteins indicative of at least a very good partial response (VGPR) or complete response/near complete response (CR/nCR) to two treatment regimens containing either bortezomib, liposomal doxorubicin and dexamethasone (VDD), or lenalidomide, bortezomib and dexamethasone (RVD). Our results suggest enrichment of universal response' pathways that are common to both treatment regimens and are probable predictors of favourable response to bortezomib, including a subset of endoplasmic reticulum stress pathways. The data also implicate pathways unique to each regimen that may predict sensitivity to DNA-damaging agents, such as mitochondrial dysfunction, and immunomodulatory drugs, which was associated with acute phase response signalling. Overall, we identified patterns of tumour characteristics that may predict response to bortezomib-based regimens and their components. These results provide a rationale for further evaluation of the protein profiles identified herein for targeted selection of anti-myeloma therapy to increase the likelihood of improved treatment outcome of patients with newly-diagnosed myeloma. C1 [Dytfeld, Dominik; Rosebeck, Shaun; Alonge, Mattina M.; Jasielec, Jagoda; Jakubowiak, Andrzej J.] Univ Chicago, Chicago, IL 60637 USA. [Dytfeld, Dominik] Poznan Univ Med Sci, Poznan, Poland. [Kandarpa, Malathi] Univ Michigan, Ctr Comprehens Canc, Hematol Oncol, Ann Arbor, MI 48109 USA. [Mayampurath, Anoop; Volchenboum, Samuel] Univ Chicago, Ctr Res Informat, Computat Inst, Chicago, IL 60637 USA. [Mayampurath, Anoop; Volchenboum, Samuel] Univ Chicago, Ctr Res Informat, Dept Pediat, Chicago, IL 60637 USA. [Mellacheruvu, Dattatreya; Nesvizhskii, Alexey I.; Sreekumar, Arun] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Mellacheruvu, Dattatreya] Dept Computat Med & Bioinformat, Ann Arbor, MI USA. [Ngoka, Lambert] Med Coll Georgia, Augusta, GA 30912 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jakubowiak, AJ (reprint author), Univ Chicago, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM ajakubowiak@medicine.bsd.uchicago.edu RI Nesvizhskii, Alexey/A-5410-2012; OI Nesvizhskii, Alexey/0000-0002-2806-7819; Rosebeck, Shaun/0000-0003-1781-4601 FU Multiple Myeloma Research Foundation; Leukemia and Lymphoma Society; Janssen-Cilag FX This study was supported by grants to A.S. and A.J.J. from the Multiple Myeloma Research Foundation and the Leukemia and Lymphoma Society. D.D. received a research grant from Janssen-Cilag. NR 50 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2015 VL 170 IS 1 BP 66 EP 79 DI 10.1111/bjh.13394 PG 14 WC Hematology SC Hematology GA CL1PQ UT WOS:000356716500010 PM 25824111 ER PT J AU Cao, Y Yang, G Hunter, ZR Liu, X Xu, L Chen, J Tsakmaklis, N Hatjiharissi, E Kanan, S Davids, MS Castillo, JJ Treon, SP AF Cao, Yang Yang, Guang Hunter, Zachary R. Liu, Xia Xu, Lian Chen, Jie Tsakmaklis, Nickolas Hatjiharissi, Evdoxia Kanan, Sandra Davids, Matthew S. Castillo, Jorge J. Treon, Steven P. TI The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and idelalisib mediated cytotoxicity in CXCR4(Wild-type) and CXCR4(WHIM) mutated Waldenstrom macroglobulinaemia cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Waldenstrom macroglobulinemia; CXCR4; BCL2; Ibrutinib; ABT-199 ID MYD88; LYMPHOMA C1 [Cao, Yang; Yang, Guang; Hunter, Zachary R.; Liu, Xia; Xu, Lian; Chen, Jie; Tsakmaklis, Nickolas; Kanan, Sandra; Davids, Matthew S.; Castillo, Jorge J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Cao, Yang; Yang, Guang; Liu, Xia; Davids, Matthew S.; Castillo, Jorge J.; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Hunter, Zachary R.; Hatjiharissi, Evdoxia] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Hunter, Zachary R.; Hatjiharissi, Evdoxia] Theagenio Canc Hosp, Thessaloniki, Greece. RP Cao, Y (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu OI Hunter, Zachary/0000-0002-1689-1691 NR 10 TC 22 Z9 22 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2015 VL 170 IS 1 BP 134 EP 138 DI 10.1111/bjh.13278 PG 5 WC Hematology SC Hematology GA CL1PQ UT WOS:000356716500020 PM 25582069 ER PT J AU Tremmel, JA Bhatt, DL Pinto, DS Grines, CL AF Tremmel, Jennifer A. Bhatt, Deepak L. Pinto, Duane S. Grines, Cindy L. TI Late breaking trials of 2014 in coronary artery disease: Commentary covering ACC, EuroPCR, SCAI, TCT, ESC, and AHA SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stents; antithrombotics; myocardial infarction; review ID ELEVATION MYOCARDIAL-INFARCTION; RANDOMIZED CLINICAL-TRIAL; DUAL ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; EFFICACY; OUTCOMES; POLYMER; SAFETY AB With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the SCAI Publications Committee concisely summarizes and provides editorial commentary on the most important coronary trials from the large international meetings of 2014. The intent is to allow quick assimilation of trial results into interventional practice. (c) 2015 Wiley Periodicals, Inc. C1 [Tremmel, Jennifer A.] Stanford Univ, Med Ctr, Dept Med Cardiovasc, Stanford, CA 94305 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Med Cardiovasc, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.; Pinto, Duane S.] Harvard Univ, Sch Med, Boston, MA USA. [Pinto, Duane S.] Beth Israel Deaconess Med Ctr, Dept Med Cardiovasc, Boston, MA 02215 USA. [Grines, Cindy L.] Detroit Med Ctr, Cardiovasc Inst, Dept Med Cardiovasc, Detroit, MI USA. RP Tremmel, JA (reprint author), Stanford Univ, Med Ctr, 300 Pasteur Dr,Room H2103, Stanford, CA 94305 USA. EM jtremmel@stanford.edu FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Forest Laboratories; Ischemix; Medtronic; Pfizer; Roche; Sanofi Aventis; Medicines Company FX Dr. Jennifer Tremmel discloses the following relationships-Consulting/Honoraria: Terumo Medical, Boston Scientific, Medtronic, Amgen, Recor Medical. Dr. Deepak L. Bhatt discloses the following relationships-Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Associate Editor; Section Editor, Pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor); Research Funding: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Dr. Duane S. Pinto has nothing to disclose. Dr. Cindy L. Grines discloses the following relationships-Advisory Board: Abbott Vascular, The Medicines Company. NR 16 TC 0 Z9 0 U1 1 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 JUL PY 2015 VL 86 IS 1 BP 73 EP 79 DI 10.1002/ccd.25942 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL1GJ UT WOS:000356690500019 PM 25854985 ER PT J AU Rocha-Singh, KJ Bosiers, M Schultz, G Jaff, MR Mehta, M Matsumura, JS AF Rocha-Singh, Krishna J. Bosiers, Marc Schultz, Greg Jaff, Michael R. Mehta, Manish Matsumura, Jon S. CA Durability II Investigators TI A single stent strategy in patients with lifestyle limiting claudication: 3-year results from the Durability II trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral arterial disease; claudication; stents ID SUPERFICIAL FEMORAL-ARTERY; RESILIENT RANDOMIZED-TRIAL; NITINOL STENTS; BALLOON ANGIOPLASTY; PROXIMAL POPLITEAL; LESIONS; IMPLANTATION; DISEASE; RESTENOSIS; FRACTURES AB ObjectivesTo evaluate longer-term safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral (SFA) and proximal popliteal arteries. BackgroundAngioplasty and stenting are options for revascularization of symptomatic peripheral artery disease. While angioplasty alone is effective in short lesions, outcomes in longer lesions (i.e., mean 8.7 cm) show suboptimal patency rates of 33% at one year. MethodsTwo hundred eighty-seven patients (mean age 68 years, 66% male) were treated with the EverFlex Self-Expanding Peripheral Stent System. Patients were followed through 3 years with yearly core lab adjudicated duplex ultrasonography for patency, radiographic assessment of stent fractures, and resting ankle brachial indices. ResultsOverall freedom from loss of primary patency at 3 years was 60.0%. Patency was significantly higher for lesions 8 cm compared with lesions >8 cm (71.0 vs. 50.5%, P<0.0001). There was no significant difference in patency between single-stent and multistent recipients (60.4 vs. 52.4%, P=0.343). The three-year freedom from clinically driven target lesion revascularization was 70.0%. At 3 years, the overall stent fracture rate was 0.9%. ConclusionsDURABILITY II is the first investigational device exemption trial to report 3-year duplex Doppler defined stent patency and CD-TLR outcomes in long SFA and proximal popliteal lesions and demonstrated acceptable stent patency and freedom from CD-TLR with a low fracture rate. These data suggest that use of a single long stent provides reasonable long-term outcomes when intervention is required for symptomatic SFA and proximal popliteal arterial disease. (c) 2015 Wiley Periodicals, Inc. C1 [Rocha-Singh, Krishna J.] St Johns Hosp, Prairie Heart Inst, Springfield, IL 62191 USA. [Bosiers, Marc] AZ Sint Blasius, Dendermonde, Belgium. [Schultz, Greg] Sanford Hlth, Sioux Falls, SD USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matsumura, Jon S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Rocha-Singh, KJ (reprint author), St Johns Hosp, Prairie Heart Inst, 619 E Mason St, Springfield, IL 62191 USA. EM ksingh@prairieheart.com FU Abbott Vascular; Aptus Endosystems Inc; Bolton Medical Inc; Cook Medical; Cordis Corporation; Lombard Medical Technologies; MEDRAD Inc; Medtronic Inc; Silroad Medical Inc; Terumo; Trivascular Inc; WL Gore; Covidien; Endologix FX Contract grant sponsors: Abbott Vascular, Aptus Endosystems Inc, Bolton Medical Inc, Cook Medical, Cordis Corporation, Lombard Medical Technologies, MEDRAD Inc, Medtronic Inc, Silroad Medical Inc, Terumo, Trivascular Inc, WL Gore, Covidien, Endologix. NR 19 TC 6 Z9 6 U1 0 U2 0 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 JUL PY 2015 VL 86 IS 1 BP 164 EP 170 DI 10.1002/ccd.25895 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL1GJ UT WOS:000356690500034 PM 25676568 ER PT J AU Roberts, AL Koenen, KC Lyall, K Robinson, EB Weisskopf, MG AF Roberts, Andrea L. Koenen, Karestan C. Lyall, Kristen Robinson, Elise B. Weisskopf, Marc G. TI Association of autistic traits in adulthood with childhood abuse, interpersonal victimization, and posttraumatic stress SO CHILD ABUSE & NEGLECT LA English DT Article DE Child physical abuse; Child sexual abuse; Autistic traits; Broad autism spectrum; Posttraumatic stress disorder; Violence victimization ID SPECTRUM DISORDER; SEXUAL ASSAULT; SOCIAL RESPONSIVENESS; GENERAL-POPULATION; RISK RECOGNITION; TRAUMATIC EVENTS; MALTREATMENT; CHILDREN; IMPAIRMENT; COMMUNITY AB Persons with autistic traits may be at elevated risk for interpersonal victimization across the life course. Children with high levels of autistic traits may be targeted for abuse, and deficits in social awareness may increase risk of interpersonal victimization. Additionally, persons with autistic traits may be at elevated risk of posttraumatic stress disorder (PTSD) symptoms subsequent to trauma. We examined retrospectively reported prevalence of childhood abuse, trauma victimization and PTSD symptoms by autistic traits among adult women in a population-based longitudinal cohort, the Nurses' Health Study II (N= 1,077). Autistic traits were measured by the 65-item Social Responsiveness Scale. We estimated odds ratios (OR) for childhood sexual and physical/emotional abuse and PTSD symptoms by quintiles of autistic traits. We examined possible mediation of PTSD risk by abuse and trauma type. Women in the highest versus lowest quintile of autistic traits were more likely to have been sexually abused (40.1% versus 26.7%), physically/emotionally abused (23.9% versus 14.3%), mugged (17.1% versus 10.1%), pressured into sexual contact (25.4% versus 15.6%) and have high PTSD symptoms (10.7% versus 4.5%). Odds of PTSD were elevated in women in the top three quintiles of autistic traits compared with the reference group (OR range =1.4 to 1.9). Childhood abuse exposure partly accounted for elevated risk of PTSD in women with autistic traits. We identify for the first time an association between autistic traits, childhood abuse, trauma victimization, and PTSD. Levels of autistic traits that are highly prevalent in the general population are associated with abuse, trauma and PTSD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Roberts, Andrea L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02138 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Lyall, Kristen] Univ Calif Davis, Davis, CA 95616 USA. [Robinson, Elise B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Roberts, AL (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02138 USA. OI Robinson, Elise/0000-0003-2314-2792 FU DOD [W81XWH-08-1-0499]; United States Army Medical Research and Material Command (USAMRMC) [A-14917]; NIH [T32MH073124-08, P60AR047782, UM1 CA176726]; Autism Speaks [1788, 2210] FX This study was funded by DOD W81XWH-08-1-0499, United States Army Medical Research and Material Command (USAMRMC) A-14917, NIH T32MH073124-08 and P60AR047782, and Autism Speaks grants 1788 and 2210. The Nurses' Health Study II is funded in part by NIH UM1 CA176726. NR 58 TC 6 Z9 7 U1 10 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 EI 1873-7757 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JUL PY 2015 VL 45 BP 135 EP 142 DI 10.1016/j.chiabu.2015.04.010 PG 8 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA CL4FH UT WOS:000356907500013 PM 25957197 ER EF